Research - Alzheimers + Dementia
Synergistic neuroprotection by coffee components eicosanoyl-5-hydroxytryptamide and caffeine in models of Parkinson's disease and DLB
Run Yan, Jie Zhang, Hye-Jin Park, Eun S. Park, Stephanie Oh, Haiyan Zheng, Eunsung Junn, Michael Voronkov, Jeffry B. Stock, and M. Maral Mouradian
Coffee consumption is linked with reduced risk of Parkinson’s disease (PD), and caffeine is generally believed to be the protective agent. However, several lines of evidence suggest the presence of additional compound(s) in coffee that can be protective as well. Here we show that eicosanoyl-5-hydroxytryptamide, which we purified from coffee as an agent that leads to enhanced enzymatic activity of the specific phosphatase PP2A that dephosphorylates the pathogenic protein α-synuclein, works in synergy with caffeine in protecting against mouse models of PD and Dementia with Lewy bodies. The mechanism of this synergy is also through enhancing PP2A, which is dysregulated in the brains of individuals with these α-synucleinopathies.
Hyperphosphorylated α-synuclein in Lewy bodies and Lewy neurites is a characteristic neuropathological feature of Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB). The catalytic subunit of the specific phosphatase, protein phosphatase 2A (PP2A) that dephosphorylates α-synuclein, is hypomethylated in these brains, thereby impeding the assembly of the active trimeric holoenzyme and reducing phosphatase activity. This phosphatase deficiency contributes to the accumulation of hyperphosphorylated α-synuclein, which tends to fibrillize more than unmodified α-synuclein. Eicosanoyl-5-hydroxytryptamide (EHT), a fatty acid derivative of serotonin found in coffee, inhibits the PP2A methylesterase so as to maintain PP2A in a highly active methylated state and mitigates the phenotype of α-synuclein transgenic (SynTg) mice. Considering epidemiologic and experimental evidence suggesting protective effects of caffeine in PD, we sought, in the present study, to test whether there is synergy between EHT and caffeine in models of α-synucleinopathy. Coadministration of these two compounds orally for 6 mo at doses that were individually ineffective in SynTg mice and in a striatal α-synuclein preformed fibril inoculation model resulted in reduced accumulation of phosphorylated α-synuclein, preserved neuronal integrity and function, diminished neuroinflammation, and improved behavioral performance. These indices were associated with increased levels of methylated PP2A in brain tissue. A similar profile of greater PP2A methylation and cytoprotection was found in SH-SY5Y cells cotreated with EHT and caffeine, but not with each compound alone. These findings suggest that these two components of coffee have synergistic effects in protecting the brain against α-synuclein−mediated toxicity through maintenance of PP2A in an active state.
Source : PNAS - Proceedings of the National Academy of Sciences
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Antioxidant and acetylcholinesterase inhibitory activities of ginger root (Zingiber officinale Roscoe) extract
Bui Thanh Tung / Dang Kim Thu / Nguyen Thi Kim Thu
Zingiber officinale Roscoe has been used in traditional medicine for the treatment of neurological disorder. This study aimed to investigate the phenolic contents, antioxidant, acetylcholinesterase enzyme (AChE) inhibitory activities of different fraction of Z. officinale root grown in Vietnam.
The roots of Z. officinale are extracted with ethanol 96 % and fractionated with n-hexane, ethyl acetate (EtOAc) and butanol (BuOH) solvents. These fractions evaluated the antioxidant activity by 1,1-Diphenyl -2-picrylhydrazyl (DPPH) assay and AChE inhibitory activity by Ellman’s colorimetric method.
Our data showed that the total phenolic content of EtOAc fraction was highest equivalents to 35.2±1.4 mg quercetin/g of fraction. Our data also demonstrated that EtOAc fraction had the strongest antioxidant activity with IC50 was 8.89±1.37 µg/mL and AChE inhibitory activity with an IC50 value of 22.85±2.37 μg/mL in a dose-dependent manner, followed by BuOH fraction and the n-hexane fraction is the weakest. Detailed kinetic analysis indicated that EtOAc fraction was mixed inhibition type with Ki (representing the affinity of the enzyme and inhibitor) was 30.61±1.43 µg/mL.
Our results suggest that the EtOAc fraction of Z. officinale may be a promising source of AChE inhibitors for Alzheimer’s disease.
Source : Journal Complementary and Integrative Medicine
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Sunlight Incidence, Vitamin D Deficiency, and Alzheimer's Disease
Alice Barros Câmara, Iara Dantas de Souza, and Rodrigo Juliani Siqueira Dalmolin
Vitamin D (VD) deficiency is a growing problem, affecting a significant portion of the population in many countries. VD deficiency may be related to several diseases, including Alzheimer's disease (AD). This study aimed to review the relationship between VD deficiency and AD. We describe the proteins involved in AD pathogenesis and how those proteins can be influenced by VD deficiency. We also investigated a relationship between AD death rate and solar radiation and we found an increased AD death rate in countries with low sunlight. It was also observed that amyloid precursor protein, ryanodine receptor, mammalian target of rapamycin complex 1, and receptor for advanced glycation end products are associated with a worse prognosis in AD. While the tho protein, phosphatase and tensin homologue, and VD receptor are associated with a better prognosis in the disease. The literature suggests that decline in VD concentrations may be involved in the establishment and progression of AD. According to sunlight data, we can conclude that countries with low average sunlight have high AD death rate.
Source : Journal of Medicinal Food
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The Effect of Acupressure on Agitation and Salivary Cortisol in People with Dementia: A Pilot Study
Rick Y.C. Kwan, RN, MSc,1 Mason C.P. Leung, MCP, PDPT, PhD,2 and Claudia K.Y. Lai, RN, PhD3
Objectives: This study aimed to identify the acupressure effect over time, compare the efficacy in different dosages, and identify feasibility issues with saliva sample collection and acupressure implementation in agitated nursing home residents with dementia.
Design: Time serial design with eight dosage-combination groups.
Setting: Three residential care homes (RCHs) in Hong Kong.
Participants: Agitated RCH residents with dementia.
Interventions: Acupressure was performed for 9 minutes altogether on five acupoints: Fengchi (GB 20), Baihui(GV 20), Shenmen (HT 7), Niguan (PC 6), and Yingtang (EX-HN 3). Two frequencies (once and twice a day) and four durations (1, 2, 3, and 4 weeks) formed eight dosage combinations.
Outcome measures: The primary outcome was agitation, measured by the Cohen Mansfield Agitation Inventory. The secondary outcome was stress, measured by salivary cortisol.
Results: Twenty-four participants from three RCHs completed the study. Acupressure was successfully completed for 88% of total sessions, and 79.17% of participants completed more than 80% of expected sessions. The effect of acupressure on agitation onset was seen immediately at week 1 (p < 0.001), resurged at week 4 (p = 0.001), and was sustained until week 6 (p < 0.001). The effect on stress began immediately to a mild extent at week 1 (p = 0.011) and peaked at week 4 (p = 0.010). Acupressure was observed to show the largest effect when it was performed twice a day (p = 0.026) for 2 weeks (p = 0.005). Valid saliva samples were collected for 53.33% of participants. Hyposalivation caused this unsatisfactory yield of valid saliva samples.
Conclusion: Acupressure can be conducted on agitated RCH residents with dementia, but low yield of saliva samples related to participants' hyposalivation is a problem. Preliminary findings suggest that acupressure is effective in reducing both agitation and stress. Its onset of effect was immediate, and the effect was sustained until 6 weeks after the intervention. The optimal dosage appears to be a course of acupressure twice a day for 2 weeks.
Source : Sci-Hub via Journal Alternative and Complementary Medicine
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Memory Impairment, Dementia, and Alzheimer's Disease in Classical and Contemporary Traditional Chinese Medicine
May Brian H., Feng Mei, Zhou Iris W., Chang Su-yueh, Lu Shao-chen, Zhang Anthony L., Guo Xin-feng, Lu Chuan-jian, and Xue Charlie C.L..
Objectives: To identify and analyze records of the treatment of dementia and memory disorders in the classical Chinese medical literature that were consistent with the signs and symptoms of Alzheimer's disease (AD), with the aim of determining which traditional medicines have histories of use for these disorders.
Methods: Encyclopedia of Traditional Chinese Medicine (Zhong Hua Yi Dian), a database of more than 1000 classical and premodern Chinese medical books, was systematically searched. Search terms were identified from dictionaries, medical nomenclatures, guidelines, and specialist clinical manuals on aging, neurology, or brain disorders. Inclusion and exclusion criteria were used to identify citations of conditions whose signs and symptoms were consistent with the clinical features of AD. Passages of text identified by these terms were copied to Microsoft Excel spreadsheets, together with the identity of the source book and all relevant information on the disorder and the intervention. Each distinct passage of text was considered a citation. The frequencies of the traditional formulas used as interventions and their constituent ingredients were calculated.
Results: The selection criteria identified 1498 citations of dementia and memory impairments derived from 277 different books written from circa 363 to 1945 AD. In 91 of these citations, memory impairment was associated with aging and was broadly consistent with the clinical features of AD. Although the interventions varied in name,Poria cocos, Polygala tenuifolia, Rehmannia glutinosa, Panax ginseng, and Acorus species consistently appeared as ingredients in multiple formulas for memory impairment in the context of aging.
Conclusions: Memory impairment in older age was a recognized condition in the classical literature. Many of the traditional medicines frequently used as ingredients in classical formulas for memory impairment consistent with clinical features of AD remain in contemporary use, and experimental studies suggest biological activities relevant to AD.
Source : Journal Alternative and Complementary Medicine
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Aromatherapy for the Treatment of Patients with Behavioral and Psychological Symptoms of Dementia: A Descriptive Analysis of RCTs
Sandler Olga, Freud Tamar, Volkov Ilya, Peleg Roni, and Press Yan.
Background: Behavioral and psychological symptoms of dementia (BPSD) are a common problem among patients with dementia. This problem is usually treated by drugs, but they have limited efficacy and often cause adverse effects. Aromatherapy is a nonpharmacologic treatment that is simple to use and devoid of significant adverse effects.
Objectives: To review the literature on the effectiveness of aromatherapy treatment in patients with BPSD.
Design: A descriptive analysis of randomized clinical trials (RCTs) published in the English-language literature and cited in PubMed.
Results: Eleven articles on RCTs were found, of which 1 had fewer than 10 participants, 2 were mistakenly presented as RCTs, and another did not report treatment for BPSD. In all, 7 articles with 417 participants total (range, 15–114) were reviewed. The mean age in all studies was greater than 69 years (range, 69–85 years), and the percentage of women was 55% (range, 50%–57%). The intervention period ranged from 10 days to 12 weeks. Two studies used Melissa oil and 5 others used lavender oil. The studies described different methods of administration for the oils, including spraying and rubbing over various body organs. The duration of treatment differed among the studies. In 3 studies the investigators concluded that the treatment was not effective and in 3 that it was effective; in 1 study no clear conclusion could be drawn.
Conclusions: The difference between positive and negative studies was not explained by differences in the study population, the type of oil, or the duration of treatment. The significant difference apparently stems from the method of administration. When the oil was applied close to the olfactory system the outcome was positive. A study should be designed to assess the effect of the site of application of aromatherapy.
Source : Journal of Alternative and Complementary Medicine
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Influence of the Melissa officinalis Leaf Extract on Long-Term Memory in Scopolamine Animal Model with Assessment of Mechanism of Action
Marcin Ozarowski,1,2 Przemyslaw L. Mikolajczak,2,3 Anna Piasecka,4 Piotr Kachlicki,4 Radoslaw Kujawski,2 Anna Bogacz,5,6 Joanna Bartkowiak-Wieczorek,5 Michal Szulc,3 Ewa Kaminska,3 Malgorzata Kujawska,7 Jadwiga Jodynis-Liebert,7 Agnieszka Gryszczynska,2 Bogna Opala,2 Zdzislaw Lowicki,2 Agnieszka Seremak-Mrozikiewicz,2,8,9 and Boguslaw Czerny6,10
Melissa officinalis (MO, English: lemon balm, Lamiaceae), one of the oldest and still most popular aromatic medicinal plants, is used in phytomedicine for the prevention and treatment of nervous disturbances. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 50% ethanol extract of MOleaves (200 mg/kg, p.o.) compared with rosmarinic acid (RA, 10 mg/kg, p.o.) and huperzine A (HU, 0.5 mg/kg, p.o.) on behavioral and cognitive responses in scopolamine-induced rats. The results were linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex of rats. In our study, MO and HU, but not RA, showed an improvement in long-term memory. The results were in line with mRNA levels, since MOproduced a decrease of AChE mRNA level by 52% in the cortex and caused a strong significant inhibition of BACE1 mRNA transcription (64% in the frontal cortex; 50% in the hippocampus). However, the extract produced only an insignificant inhibition of AChE activity in the frontal cortex. The mechanisms of MO action are probably more complicated, since its role as a modulator of beta-secretase activity should be taken into consideration.
Source : Evidence Based Complementary and Alternative Medicine
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Association of Vitamin D Status with Dual Task Physical Performance in Older Adults1.
Johanna Lopez1, Adriana Campa1, John E. Lewis3, Fatma G. Ercanli-Huffman1, Juan P. Liuzzi1, Tan Li2, Ana H. Martinez3 and Serena M Ferris3
Objective To evaluate the association of vitamin D status with age-relatedchanges in mobility and higher order cognitive function using a single and dual task physical performance test.
Methods After consenting, participants completed the baseline assessments that included serum levels of vitamin D, vitals, anthropometrics and body composition, as well as completing surveys to evaluate physical activity, depressive symptoms and fear of falling. Participants performed in random order the physical performance tests, which included 1) walking (single gait task); 2) counting backwards from 50 by 1 (single cognitive task); and 3) walking while counting backwards from 50 by 1 (dual task). The dual task physical performance variables measured were: 1) dual task gait velocity; 2) single task gait velocity; 3) difference in dual and single task gait velocity; 4) dual task counting rate; 5) single task counting rate; 6) difference in dual and single counting rate. Paired t-tests were used to compare single and dual task variables within the whole population andeach vitamin D status group. Spearman’s correlations, independent t-tests, repeated measures ANOVAs and multiple logistic regressions were used to examine the relationship between vitamin D insufficiency (25OHD<30ng/mL) andsufficiency (25OHD≥30ng/mL) and dual task physical performance variables. The significance level was set at α≤0.05, and statistical analyzes were performed using SPSS 21.
Results The mean +/− SD of serum vitamin D levels were 30.73 +/− 8.73 ng/ml and 46% of the participants were vitamin D insufficient. Dual and single task counting rate were significantly lower in the vitamin D insufficient group compared to the sufficient group (mean difference: −0.14, P=0.018 and meandifference: −0.06, P=0.028, respectively). Using Spearman correlations, a slower single (r=0.258, P=0.011) and dual counting rate (r=0.278, P=0.006) were significantly associated with vitamin D insufficiency.
Conclusions Cognitive performance for dual or single tasking were worse in thevitamin D insufficient group. Since counting backward is a mental tracking task, which is a component of executive function, our results support a relationship between vitamin D insufficiency and executive dysfunction.
Source : The FASEB Journal
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Rg3-enriched ginseng extract ameliorates scopolamine-induced learning deficits in mice
- Jiyoung Kim†,
- Jaesung Shim†,
- Siyoung Lee,
- Woo-Hyun Cho,
- Eunyoung Hong,
- Jin Hee Lee,
- Jung-Soo Han,
- Hyong Joo Lee†Email author and
- Ki Won Lee†
Ginseng (Panax ginseng C.A. Meyer) has been used as a traditional herb in the treatment of many medical disorders. Ginsenosides, which are triterpene derivatives that contain sugar moieties, are the main pharmacological ingredients in ginseng. This study was designed to investigate the effect of ginsenoside Rg3-enriched ginseng extract (Rg3GE) on scopolamine-induced memory impairment in mice.
Rg3GE (50 and 100 mg/kg) were administered to C57BL/6 mice by oral gavage for 14 days (days 1–14). Memory impairment was induced by scopolamine (1 mg/kg, intraperitoneal injection) for 6 days (days 914). The Morris water maze test was used to assess hippocampus-dependent spatial memory. The effects of scopolamine with or without Rg3GE on acetylcholinesterase and nuclear factor-κB (NF-κB) in the hippocampus were also examined.
Mice with scopolamine treatment alone showed impairments in the acquisition and retention of spatial memory. Mice that received Rg3GE and scopolamine showed no scopolamine-induced impairment in the acquisition of spatial memory. Oral administration of Rg3GE suppressed the scopolamine-mediated increase in acetylcholinesterase activity and stimulation of the NF-κB pathway (i.e., phosphorylation of p65) in the hippocampus.
These findings suggest that Rg3GE may stabilize scopolamine-induced memory deficits through the inhibition of acetylcholinesterase activity and NF-κB signaling in the hippocampus.
Source : BMC Complementary and Alternative Medicine
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Salvia miltiorrhiza extract protects white matter and the hippocampus from damage induced by chronic cerebral hypoperfusion in rats
Min-Soo Kim14, Ji Hye Bang12, Jun Lee15, Hyeon Woo Kim3, Sang Hyun Sung3, Jung-Soo Han4 and Won Kyung Jeon1*
Salvia miltiorrhiza (SM), an herbal plant, is traditionally used in the treatment of cardiovascular and cerebrovascular diseases in Asian countries. SM has multiple biological effects including anti-inflammatory activity. The present study is aimed at investigating the effects of SM extract in rats with chronic cerebral hypoperfusion.
Chronic cerebral hypoperfusion was induced in male Wistar rats by permanent bilateral common carotid artery occlusion (BCCAo). The rats were divided into 3 groups: sham-control, BCCAo treated with vehicle, and BCCAo treated with SM extract. Vehicle or SM extract (200 mg/kg) were administered daily by oral gavage beginning on day 21 after BCCAo and continuing to day 42. Immunohistochemical analyses were used to measure Iba-1-positive microglia and myelin basic protein (MBP) in white matter and hippocampal tissue. In addition, the expression levels of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, and the toll-like receptor (TLR) pathway in the hippocampus, were analyzed by western blot.
Administration of SM extract attenuated the activation of microglial cells in the white matter and hippocampus after BCCAo. SM extract also prevented neuroinflammation after BCCAo by reducing hippocampal levels of TNF-α, IL-1β, and IL-6, and increasing the reduced levels of MBP in the white matter and hippocampus. Further, the administration of SM extract alleviated the up-regulation of hippocampal TLR4 and myeloid differentiation primary response gene 88 (MyD88) in rats with chronic BCCAo.
Our findings suggest that SM may be a promising therapeutic candidate in vascular dementia because of its protective effects against damage to the white matter and hippocampus after BCCAo.
Source : BMC Complementary and Alternative Medicine
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Playing a Musical Instrument as a Protective Factor against Dementia and Cognitive Impairment: A Population-Based Twin Study
M. Alison Balbag,1 Nancy L. Pedersen,2,3 and Margaret Gatz2,3
Increasing evidence supports that playing a musical instrument may benefit cognitive development and health at young ages. Whether playing an instrument provides protection against dementia has not been established. In a population-based cotwin control study, we examined the association between playing a musical instrument and whether or not the twins developed dementia or cognitive impairment. Participation in playing an instrument was taken from informant-based reports of twins’ leisure activities. Dementia diagnoses were based on a complete clinical workup using standard diagnostic criteria. Among 157 twin pairs discordant for dementia and cognitive impairment, 27 pairs were discordant for playing an instrument. Controlling for sex, education, and physical activity, playing a musical instrument was significantly associated with less likelihood of dementia and cognitive impairment (odds ratio [OR] = 0.36 [95% confidence interval 0.13–0.99]). These findings support further consideration of music as a modifiable protective factor against dementia and cognitive impairment.
Source : Intl Journal of Alzheimer's Disease
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Vitamin D and Alzheimer’s Disease: Neurocognition to Therapeutics
Anindita Banerjee,1,2 Vineet Kumar Khemka,1,2 Anirban Ganguly,2 Debashree Roy,2 Upasana Ganguly,2 and Sasanka Chakrabarti1
Alzheimer’s disease (AD), the major cause of dementia worldwide, is characterized by progressive loss of memory and cognition. The sporadic form of AD accounts for nearly 90% of the patients developing this disease. The last century has witnessed significant research to identify various mechanisms and risk factors contributing to the complex etiopathogenesis of AD by analyzing postmortem AD brains and experimenting with animal and cell culture based models. However, the treatment strategies, as of now, are only symptomatic. Accumulating evidences suggested a significant association between vitamin D deficiency, dementia, and AD. This review encompasses the beneficial role of vitamin D in neurocognition and optimal brain health along with epidemiological evidence of the high prevalence of hypovitaminosis D among aged and AD population. Moreover, disrupted signaling, altered utilization of vitamin D, and polymorphisms of several related genes including vitamin D receptor (VDR) also predispose to AD or AD-like neurodegeneration. This review explores the relationship between this gene-environmental influence and long term vitamin D deficiency as a risk factor for development of sporadic AD along with the role and rationale of therapeutic trials with vitamin D. It is, therefore, urgently warranted to further establish the role of this potentially neuroprotective vitamin in preventing and halting progressive neurodegeneration in AD patients.
Source : Intl Journal Alzheimer's Disease
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Vitamin D deficiency is associated with increased risk of Alzheimer’s disease and dementia: evidence from meta-analysis
Liang Shen and Hong-Fang Ji*
In recent years, the associations between vitamin D status and Alzheimer’s disease (AD) and dementia have gained increasing interests. The present meta-analysis was designed to estimate the association between vitamin D deficiency and risk of developing AD and dementia.
A literature search conducted until February 2015 identified 10 study populations, which were included in the meta-analysis. Pooled risk ratios (RRs) and 95 % confidence interval (CI) were calculated with a random-effect model using Stata software package.
Results of our meta-analysis showed that subjects with deficient vitamin D status (25(OH)D level < 50 nmol/L) were at increased risk of developing AD by 21 % compared with those possessing 25(OH)D level > 50 nmol/L. Similar analysis also found a significantly increased dementia risk in vitamin D deficient subjects. There is no evidence for significant heterogeneity among the included studies.
Available data indicates that lower vitamin D status may be associated with increased risk of developing AD and dementia. More studies are needed to further confirm the associations and to evaluate the beneficial effects of vitamin D supplementation in preventing AD and dementia.
Source : Nutrition Journal
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Cognition: the new frontier for nuts and berries1,2,3
The inclusion of nuts in the diet is associated with a decreased risk of coronary artery disease, hypertension, gallstones, diabetes, cancer, metabolic syndrome, and visceral obesity. Frequent consumption of berries seems to be associated with improved cardiovascular and cancer outcomes, improved immune function, and decreased recurrence of urinary tract infections; the consumption of nuts and berries is associated with reduction in oxidative damage, inflammation, vascular reactivity, and platelet aggregation, and improvement in immune functions. However, only recently have the effects of nut and berry consumption on the brain, different neural systems, and cognition been studied. There is growing evidence that the synergy and interaction of all of the nutrients and other bioactive components in nuts and berries can have a beneficial effect on the brain and cognition. Regular nut consumption, berry consumption, or both could possibly be used as an adjunctive therapeutic strategy in the treatment and prevention of several neurodegenerative diseases and age-related brain dysfunction. A number of animal and a growing number of human studies show that moderate-duration dietary supplementation with nuts, berry fruit, or both is capable of altering cognitive performance in humans, perhaps forestalling or reversing the effects of neurodegeneration in aging.
Source : American Society of Nutrition
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The Synergistic Beneficial Effects of Ginkgo Flavonoid and Coriolus versicolor Polysaccharide for Memory Improvements in a Mouse Model of Dementia
Xianying Fang, 1 , 2 Yan Jiang, 1 , 2 Hui Ji, 3 Linguo Zhao, 1 , 2 , * Wei Xiao, 4 , * Zhenzhong Wang, 4 and Gang Ding 4
This study reports the combination of Ginkgo flavonoid (GF) and Coriolus versicolor polysaccharide (CVP) in the prevention and treatment of a mouse model of Alzheimer's disease (AD). GF is a traditional health product, and CVP is the main active ingredient of the medicinal fungus Coriolus versicolor. The Morris water maze test, the Y maze, and the step-through test showed that the combinational use of CVP and GF synergistically improved memory in a mouse model of AD. Based on H&E staining analysis, the combination of CVP and GF decreased the severity of the pathological findings in the brain. Given that the expression of IL-1β, IL-6, and TNF-α was downregulated, the inflammation response in AD mice was considered to be inhibited. The downregulation of GFAP further demonstrated that inflammation was reduced in the brain of AD mice following treatment. Moreover, the expression levels of superoxide dismutase (SOD) and catalase (CAT) were elevated in the brains of treated mice, indicating that oxidation levels were reduced upon the combination treatment. Our results provide new insights into the efficient utilization of traditional medicine for preventing dementia.
Source ; eCAM
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Medicinal value of asiaticoside for Alzheimer’s disease as assessed using single-molecule-detection fluorescence correlation spectroscopy, laser-scanning microscopy, transmission electron microscopy, and in silico docking
Shahdat Hossain12, Michio Hashimoto1*, Masanori Katakura1, Abdullah Al Mamun1 and Osamu Shido1
Identifying agents that inhibit amyloid beta peptide (Aβ) aggregation is the ultimate goal for slowing Alzheimer’s disease (AD) progression. This study investigated whether the glycoside asiaticoside inhibits Aβ 1–42 fibrillation in vitro
Fluorescence correlation spectroscopy (FCS), evaluating the Brownian diffusion times of moving particles in a small confocal volume at the single-molecule level, was used. If asiaticoside inhibits early Aβ 1–42 fibrillation steps, more Aβs would remain free and rapidly diffuse in the confocal volume. In contrast, “weaker or no inhibition” permits a greater number of Aβs to polymerize into oligomers, leading to fibers and gives rise to slow diffusion times in the solution. Trace amounts of 5-carboxyte
tramethylrhodamine (TAMRA)-labeled Aβ 1–42 in the presence of excess unlabeled Aβ 1–42 (10μM) was used as a fluorescent probe. Steady-state and kinetic-Thioflavin T (ThT) fluorospectroscopy, laser-scanning fluorescencemicroscopy (LSM), and transmission electron microscopy (TEM) were also used to monitor fibrillation. Binding of asiaticoside with Aβ 1–42
at the atomic level was computationally examined using the Molegro Virtual Docker and Patch Dock.
With 1 h of incubation time for aggregation, FCS data analysis revealed that the diffusion time of TAMRA-Aβ 1–42 was 208 ± 4μs, which decreased to 164 ± 8.0μs in the presence of asiaticoside, clearly indicating that asiaticoside inhibited the early stages Aβ 1–42 of fibrillation, leaving more free Aβs in the solution and permitting their rapid diffusion in the confocal volume. The inhibitory effects were also evidenced by reduced fiber formation as assessed by steady-state and kinetic ThT fluorospec
troscopy, LSM, and TEM. Asiaticoside elongated the lag phase of Aβ 1–42 fibrillation, indicating the formation of smaller
amyloid species were impaired in the presence of asiaticoside. Molecular docking revealed that asiaticoside binds with amyloid intra- and inter-molecular amino acid residues, which are responsible for β-sheet formation and longitudinal extension of fibrils.
Finally, asiaticoside prevents amyloidogenesis that precedes neurodegeneration in patients with Alzheimer’s disease.
Source : BMC Complementary and Alternative Medicine
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Association between intake of B vitamins and cognitive function in elderly Koreans with cognitive impairment
Hyesook Kim1, Ggotpin Kim1, Won Jang1, Seong Yoon Kim2 and Namsoo Chang1
Background It is possible that blood B vitamins level and cognitive function may be affected by dietary intake of these vitamins, no study however has yet been conducted on relationships between B vitamins intake and cognitive function among elderly population in Korea. This study examined the relationship between B vitamins intake and cognitive function among elderly in South Korea.
Methods Participants consisted of 100 adults with mild cognitive impairment (MCI), 100 with Alzheimer’s disease (AD), and 121 normal subjects. Dietary intake data that included the use of dietary supplements were obtained using a 24-hour recall method by well-trained interviewers. Plasma folate and vitamin B12 concentrations were analyzed by radioimmunoassay, and homocysteine (Hcy) was assessed by a high performance liquid chromatography-fluorescence method.
Results Plasma levels of folate and vitamin B12 were positively correlated with B vitamins intake; and plasma Hcy was negatively correlated with total intake of vitamin B2, vitamin B6, vitamin B12 and folate. In the AD group, a multiple regression analysis after adjusting for covariates revealed positive relationships between vitamin B2 intake and test scores for the MMSE-KC, Boston Naming, Word Fluency, Word List Memory and Constructional Recall Tests; and between vitamin B6 intake and the MMSE-KC, Boston Naming, Word Fluency, Word List Memory, Word List Recognition, Constructional Recall and Constructional Praxis Tests. Positive associations were observed between vitamin B12 intake and the MMSE-KC, Boston Naming, Constructional Recall and Constructional Praxis Tests, and between folate intake and the Constructional Recall Test. In the MCI group, vitamin B2 intake was positively associated with the MMSE-KC and Boston Naming Test, vitamin B6 intake was positively associated with the Boston Naming Test, and folate intake was positively associated with the MMSE-KC and Word List Memory test. No associations were observed in the normal group.
Conclusion These results suggested that total B vitamins intake is associated with cognitive function in cognitively impaired AD and MCI elderly, and the association is stronger in AD patients.
Source : Nutrition Journal
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Mechanisms of Action of Phytochemicals from Medicinal Herbs in the Treatment of Alzheimerʼs Disease
Mi Hye Kim1, Sung-Hoon Kim2, Woong Mo Yang1
- 1College of Korean Medicine and Institute of Korean Medicine, Kyung Hee University, Seoul, Korea
- 2Cancer Preventive Material Development Research Center, College of Korean Medicine, Kyung Hee University, Seoul, Korea
Alzheimerʼs disease is a chronic neurodegenerative disorder characterized by progressive dementia and deterioration of cognitive function. Although several drugs currently used for the treatment of Alzheimerʼs disease delay its onset and slow its progression, still there is no drug with profound disease-modifying effects. Studies aiming the treatment of this neurodegenerative disorder explore various disease mechanisms. Since antiquity, medicinal herbs have been used in traditional medicine. Recent studies suggest that the neurobiological effects of phytochemicals from medicinal herbs may contribute to clinical benefits in in vitro and in vivo models of Alzheimerʼs disease. This review focuses on five phytochemicals, berberine, curcumin, ginsenoside Rg1, puerarin, and silibinin, which have been mostly investigated to treat the development and progression of this neurodegenerative disorder.
....To date, evidence from recent studies suggests that commonly used medicinal herbs and their phytochemicals could potentially be used to treat AD. Although these studies focus on the efficacy of inhibiting AD development, and research on humans is limited, numerous findings demonstrate the possibilities of the use of medicinal herbs for the treatment of AD. The approach to investigate the potential treatment of AD may support drug development from herbal medicine.
Source : Planta Medica
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The Effect of Crocus sativus L. and Its Constituents on Memory: Basic Studies and Clinical Applications
Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Thessaly, Panepistimiou 3, Biopolis, 41500 Larissa, Greece
Memory-related disorders are a common public health issue. Memory impairment is frequent in degenerative diseases (such as Alzheimer’s disease and Parkinson disease), cerebral injuries, and schizophrenia. The dried stigma of the plant Crocus sativus L. (C. sativus), commonly known as saffron, is used in folk medicine for various purposes. Several lines of evidence suggest that C. sativus and its constituents are implicated in cognition. Here we critically review advances in research of these emerging molecular targets for the treatment of memory disorders, and discuss their advantages over currently used cognitive enhancers as well remaining challenges. Current analysis has shown that C. sativus and its components might be a promising target for cognition impairments.
Source : Journal Evidence Based Complementary and Alternative Medicine
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Huperzine A for Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
- Guoyan Yang
- Yuyi Wang
- Jinzhou Tian
- Jian-Ping Liu
Huperzine A is a Chinese herb extract used for Alzheimer’s disease. We conducted this review to evaluate the beneficial and harmful effect of Huperzine A for treatment of Alzheimer’s disease.
We searched for randomized clinical trials (RCTs) of Huperzine A for Alzheimer’s disease in PubMed, Cochrane Library, and four major Chinese electronic databases from their inception to June 2013. We performed meta-analyses using RevMan 5.1 software. (Protocol ID: CRD42012003249)
20 RCTs including 1823 participants were included. The methodological quality of most included trials had a high risk of bias. Compared with placebo, Huperzine A showed a significant beneficial effect on the improvement of cognitive function as measured by Mini-Mental State Examination (MMSE) at 8 weeks, 12 weeks and 16 weeks, and by Hastgawa Dementia Scale (HDS) and Wechsler Memory Scale (WMS) at 8 weeks and 12 weeks. Activities of daily living favored Huperzine A as measured by Activities of Daily Living Scale (ADL) at 6 weeks, 12 weeks and 16 weeks. One trial found Huperzine A improved global clinical assessment as measured by Clinical Dementia Rating Scale (CDR). One trial demonstrated no significant change in cognitive function as measured by Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and activity of daily living as measured by Alzheimer’s disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) in Huperzine A group. Trials comparing Huperzine A with no treatment, psychotherapy and conventional medicine demonstrated similar findings. No trial evaluated quality of life. No trial reported severe adverse events of Huperzine A.
Huperzine A appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment in participants with Alzheimer’s disease. However, the findings should be interpreted with caution due to the poor methodological quality of the included trials.
Source : PLOS On
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Aluminium and its likely contribution to Alzheimer's disease
A world authority on the link between human exposure to aluminium in everyday life and its likely contribution to Alzheimer's disease, Professor Christopher Exley of Keele University, UK, says in a new report that it may be inevitable that aluminium plays some role in the disease.
He says the human brain is both a target and a sink for aluminium on entry into the body – "the presence of aluminium in the human brain should be a red flag alerting us all to the potential dangers of the aluminium age. We are all accumulating a known neurotoxin in our brain from our conception to our death. Why do we treat this inevitability with almost total complacency?"
Exley, Professor in Bioinorganic Chemistry, Aluminium and Silicon Research Group in The Birchall Centre, Lennard-Jones Laboratories at Keele University, writes in Frontiers in Neurology about the 'Aluminium Age' and its role in the 'contamination' of humans by aluminium.
He says a burgeoning body burden of aluminium is an inevitable consequence of modern living and this can be thought of as 'contamination', as the aluminium in our bodies is of no benefit to us it can only be benign or toxic.
Professor Exley says: "The biological availability of aluminium or the ease with which aluminium reacts with human biochemistry means that aluminium in the body is unlikely to be benign, though it may appear as such due to the inherent robustness of human physiology. The question is raised as to 'how do you know if you are suffering from chronic aluminium toxicity?' How do we know that Alzheimer's disease is not the manifestation of chronic aluminium toxicity in humans?
"At some point in time the accumulation of aluminium in the brain will achieve a toxic threshold and a specific neurone or area of the brain will stop coping with the presence of aluminium and will start reacting to its presence. If the same neurone or brain tissue is also suffering other insults, or another on-going degenerative condition, then the additional response to aluminium will exacerbate these effects. In this way aluminium may cause a particular condition to be more aggressive and perhaps to have an earlier onset - such occurrences have already been shown in Alzheimer's disease related to environmental and occupational exposure to aluminium."
Professor Exley argues that the accumulation of aluminium in the brain inevitably leads to it contributing negatively to brain physiology and therefore exacerbating on-going conditions such as Alzheimer's disease. He suggests that this is a testable hypothesis and offers a non-invasive method of the removal of aluminium from the body and the brain. He says the aluminium hypothesis of Alzheimer's disease will only be tested if we are able to lower the body and hence brain burden of aluminium and determine if such has any impact upon the incidence, onset or aggressiveness of Alzheimer's disease.
Professor Exley adds: "There are neither cures nor effective treatments for Alzheimer's disease. The role of aluminium in Alzheimer's disease can be prevented by reducing human exposure to aluminium and by removing aluminium from the body by non-invasive means. Why are we choosing to miss out on this opportunity? Surely the time has come to test the aluminium hypothesis of Alzheimer's disease once and for all?"
Source : Medical Xpress
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Worry, Jealousy, Moodiness Linked to Higher Risk of Alzheimer’s in Women
Women who are anxious, jealous, or moody and distressed in middle age may be at a higher risk of developing Alzheimer’s disease later in life, according to a nearly 40-year-long study published in the October 1, 2014, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“Most Alzheimer’s research has been devoted to factors such as education, heart and blood risk factors, head trauma, family history and genetics,” said study author Lena Johannsson, PhD, of the University of Gothenburg in Gothenburg, Sweden. “Personality may influence the individual’s risk for dementia through its effect on behavior, lifestyle or reactions to stress.”
For the study, 800 women with an average age of 46 were followed for 38 years and given personality tests that looked at their level of neuroticism and extraversion or introversion, along with memory tests. Of those, 19 percent developed dementia.
Neuroticism involves being easily distressed and personality traits such as worrying, jealousy or moodiness. People who are neurotic are more likely to express anger, guilt, envy, anxiety or depression. Introversion is described as shyness and reserve and extraversion is associated with being outgoing.
The women were also asked if they had experienced any period of stress that lasted one month or longer in their work, health, or family situation. Stress referred to feelings of irritability, tension, nervousness, fear, anxiety or sleep disturbances. Responses were categorized as zero to five, with zero representing never experiencing any period of stress, to five, experiencing constant stress during the last five years. Women who chose responses from 3 and 5 were considered to have distress.
The study found that women who scored highest on the tests for neuroticism had double the risk of developing dementia compared to those who scored lowest on the tests. However, the link depended on long-standing stress.
Being either withdrawn or outgoing did not appear to raise dementia risk alone, however, women who were both easily distressed and withdrawn had the highest risk of Alzheimer’s disease in the study. A total of 16 of the 63 women, or 25 percent, who were easily distressed and withdrawn developed Alzheimer’s disease, compared to eight out of the 64 people, or 13 percent, of those who were not easily distressed and were outgoing.
Source : Newswise
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Green Tea Consumption Affects Cognitive Dysfunction in the Elderly: A Pilot Study
Kazuki Ide 1, Hiroshi Yamada 1,* , Norikata Takuma 2, Mijong Park 1, Noriko Wakamiya 1, Junpei Nakase 3, Yuuichi Ukawa 3 and Yuko M. Sagesaka 3
Green tea is known to have various health benefits for humans. However, the effect of green tea consumption on cognitive dysfunction remains to be clinically verified. We conducted a clinical study to investigate the effects of green tea consumption on cognitive dysfunction. Twelve elderly nursing home residents with cognitive dysfunction (Mini-Mental State Examination Japanese version (MMSE-J) score: <28) participated in the study (2 men, 10 women; mean age, 88 years). The participants consumed green tea powder 2 g/day for 3 months. After three months of green tea consumption, the participants’ MMSE-J scores were significantly improved (before, 15.3 ± 7.7; after, 17.0 ± 8.2; p = 0.03). This result suggests that green tea consumption may be effective in improving cognitive function or reducing the progression of cognitive dysfunction; however, long-term large-scale controlled studies are needed to further clarify the effect.
Source : Journal Nutrients
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New study provides insight into relationship between depression and dementia
A new study by neuropsychiatric researchers at Rush University Medical Center gives insight into the relationship between depression and dementia. The study is published in the July 30, 2014, online issue of Neurology®, the medical journal of the American Academy of Neurology.
"Studies have shown that people with symptoms of depression are more likely to develop dementia, but we haven't known how the relationship works," said study author Robert S. Wilson, PhD, neuropsychiatrist at the Rush Alzheimer's Disease Center and lead study investigator. "Is the depression a consequence of the dementia? Do both problems develop from the same underlying problems in the brain? Or does the relationship of depression with dementia have nothing to do with dementia-related pathology?"
The current study indicates that the association of depression with dementia is independent of dementia-related brain changes. "These findings are exciting because they suggest depression truly is a risk factor for dementia, and if we can target and prevent or treat depression and causes of stress we may have the potential to help people maintain their thinking and memory abilities into old age," Wilson said.
The study involved 1,764 people from the Religious Orders Study and the Rush Memory and Aging Project with an average age of 77 who had no thinking or memory problems at the start of the study. Participants were screened every year for symptoms of depression, such as loneliness and lack of appetite, and took tests on their thinking and memory skills for an average of eight years. A total of 680 people died during the study, and autopsies were performed on 582 of them to look for the plaques and tangles in the brain that are the signs of dementia and other signs of damage in the brain.
During the study, 922 people, or 52 percent of the participants, developed mild cognitive impairment (MCI), or mild problems with memory and thinking abilities that is often a precursor to Alzheimer's disease. A total of 315 people, or 18 percent, developed dementia.
The researchers found no relationship between how much damage was found in the brain and the level of depression symptoms people had or in the change in depression symptoms over time.
People who developed mild cognitive impairment were more likely to have a higher level of symptoms of depression before they were diagnosed, but they were no more likely to have any change in symptoms of depression after the diagnosis than people without MCI. People with dementia were also more likely to have a higher level of depression symptoms before the dementia started, but they had a more rapid decrease in depression symptoms after dementia developed.
Having a higher level of depression symptoms was associated with more rapid decline in thinking and memory skills, accounting for 4.4 percent of the difference in decline that could not be attributed to the level of damage in the brain.
Source : News Medical
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Long-term use of pills for insomnia and anxiety linked to Alzheimer’s risk
New research bolsters the belief that long-term use of a prescription drug commonly used to alleviate anxiety, panic attacks and sleep problems is linked in aging patients to a higher risk of Alzheimer’s disease.
Researchers in France and Canada, using data from Quebec’s health insurance program, found that Alzheimer’s risk was up to 51 percent higher in elderly people who used benzodiazepines for three months or more. The researchers said the link appeared even stronger with longer duration of use or longer-acting benzodiazepines.
The team said it wasn’t clear whether the link between Alzheimer’s and benzodiazepines — which are marketed under brands such as Xanax, Ativan, Valium and Klonopin — was causal. The researchers also noted that it was possible that anxiety and sleep disorders could be associated with early symptoms of Alzheimer’s.
But the researchers also said the link between duration and use of the drugs suggests a possible direct connection worthy of further investigation. They urged physicians to use caution in prescribing the drugs to elderly patients.
The researchers — led by Sophie Billioti de Gage and Antoine Pariente at the University of Bordeaux — used data from Quebec’s public drug plan to track 1,796 Alzheimer’s cases over six years. The patients were at least 66 years old, living in the community and covered by the drug plan between 2000 and 2009. All had used benzodiazepines at least five years prior to the first diagnosis of Alzheimer’s — a criterion selected by the researchers to guard against finding possible reverse causation. The patients’ records were then compared with 7,184 control cases.
The study — which appeared Tuesday in the British Medical Journal — was in line with five previous studies that found an increased risk of Alzheimer’s and long-term use of benzodiazepines. An accompanying editorial in the medical journal — co-authored by Kristine Yaffe at the University of California at San Francisco and Malaz Boustani at Indiana University’s Center for Aging Research — noted that the 2012 American Geriatrics Society’s list of inappropriate drugs for older adults was updated to include benzodiazepines because of undesirable side effects on cognition.
Source : Dangerous Prescription Drugs
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Three Herbs for Cognition
Three HerbClips in this issue focus on cognition. HC 011456-496 covers a meta-analysis of bacopa (Bacopa monnieri; Scrophulariaceae).1 Bacopa has been used in Ayurvedic medicine for centuries to improve memory and intellect. Nine clinical trials were included in the meta-analysis, with a total of 231 subjects receiving bacopa and 206 subjects receiving placebo. Memory function (6 studies) and attention (7 studies) were the outcome effects. The authors conclude that bacopa may aid in improving cognitive function, particularly attention speed, but that more study is needed, especially a "head to head" trial with a proven existing medication and standardized bacopa extract. As mentioned in the previous HC News, a green tea (Camellia sinensis; Theaceae) extract was found to enhance working memory between the frontal and parietal brain regions in 12 healthy subjects (See HC 041431-496).2 The authors suggest that green tea extract could be used to treat cognitive impairments, such as dementia, by creating short-term plasticity between the brain regions. This increased connectivity could provide enhanced cognitive function for both healthy individuals as well as those with cognitive impairment. The study used a whey-based soft drink. Additionally studies with a standardized green tea extract are warranted. HC 121314-496 reviews a pilot study on pomegranate (Punica granatum; Lythraceae) supplement POMx™ (POM Wonderful; Los Angeles, California) which demonstrated that the supplement may improve postoperative cognitive dysfunction (POCD) for patients who have had heart surgery.3 Memory retention can be mildly to severely affected after heart surgery, possibly due to anesthesia or lack of oxygen/glucose to the brain. In this small study (5 active; 5 placebo), the researchers found that the pomegranate group was protected against POCD and even improved their memory retention compared to baseline.
Cognition domains include "motor functioning, attention, language, memory, executive control, vision, emotion, sensory functions, and consciousness."1 With an increased aging population, evidence of cognitive decline has also increased. Other impairments among the younger generations, such as attention deficit hyperactivity disorder, have had a notable escalation as well. Finding ways to enhance brain activity, such as word puzzles, studying new subjects, exercising to increase oxygen capacity, and some form of meditation to relax the mind, can maintain and even enhance cognitive function. Bacopa, green tea, and pomegranate, among other herbs, can also support the brain's various processes.
1Kongkeaw C, Dilokthornsakul P, Thanarangsarit P, Limpeanchob N, Scholfield CN. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. J Ethnopharmacol. 2014;151(1):528-535.
2Schmidt A, Hammann F, Wölnerhanssen B, et al. Green tea extract enhances parieto-frontal connectivity during working memory processing. Psychopharmacology. 2014; [epub ahead of print]. doi: 10.1007/s00213-014-3526-1.
3Ropacki SA, Patel SM, Hartman RE. Pomegranate supplementation protects against memory dysfunction after heart surgery: A pilot study. Evid Based Complement Alternat Med. 2013;2013:932401. doi: 10.1155/2013/932401.
Source : HerbClip-ABC
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Do soy isoflavones improve cognitive function in postmenopausal women? A meta-analysis
Cheng PF1, Chen JJ, Zhou XY, Ren YF, Huang W, Zhou JJ, Xie P.
OBJECTIVE: Several studies have demonstrated that soy isoflavone (SIF) supplementation can improve aspects of cognitive function. However, these findings remain controversial. We aimed to quantify the effects of SIF supplementation on improving cognitive function in postmenopausal women.
METHODS: Databases and relevant Web sites were searched for relevant studies up to March 2014. Two reviewers independently verified all potentially suitable randomized controlled trials (RCTs) using inclusion and exclusion criteria, and the quality of identified RCTs was assessed using the Jadad scale and the Risk of Bias Tool from the "Cochrane handbook for systematic reviews of interventions." Any disagreement on study quality or data extraction was resolved by consensus; a third reviewer was consulted if needed. Standardized mean differences (SMDs) in cognitive function test scores were calculated between SIF-treated and placebo-treated groups.
RESULTS: We conducted a meta-analysis of 10 placebo-controlled RCTs of SIF supplementation (1,024 participants; treatment duration of 6 wk to 30 mo). The overall SMD in summary cognitive function test scores (0.08) was statistically significant (95% CI, 0.02-0.15; P = 0.014). The summary SMD for visual memory (0.10) was statistically significant (95% CI, 0.02-0.18; P = 0.016). In subgroup analyses, the statistically significant SMDs were as follows: 0.12 (95% CI, 0-0.25; P = 0.044) for non-US countries; 0.16 (95% CI, 0.05-0.28; P = 0.004) for mean age younger than 60 years; and 0.15 (95% CI, 0.03-0.27; P = 0.011) for treatment duration less than 12 months.
CONCLUSIONS: SIF supplementation seems to have a positive effect on improving summary cognitive function and visual memory in postmenopausal women. There may be a critical window of opportunity in initiating SIF use at an earlier age in postmenopausal women, and geography and treatment duration seem to be factors influencing the effects of SIF supplementation. All individuals in the included studies should be followed up to observe the incidence rates of Alzheimer's disease and dementia, and future studies should report any adverse effects of SIF supplementation.
Source : Journal Menopause
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Antioxidants prevent memory deficits provoked by chronic variable stress in rats.
Tagliari B1, Scherer EB, Machado FR, Ferreira AG, Dalmaz C, Wyse AT.Author information
Learning and memory deficits occur in depression and other stress related disorders. Although the pathogenesis of cognitive impairment after stress has not been fully elucidated, factors such as oxidative stress and neurotrophins are thought to play possible roles. Here we investigated the effect of treatment with vitamin E (40 mg/kg) and vitamin C (100 mg/kg) on the effects elicited by chronic variable stress on rat performance in Morris water maze. Brain-derived neurotrophic factor (BDNF) immunocontent was also evaluated in hippocampus of rats. Sixty-day old Wistar rats were submitted to different stressors for 40 days (stressed group). Half of stressed group received administration of vitamins once a day, during the period of stress. Chronically stressed rats presented a marked decrease in reference memory in the water maze task as well as a reduced efficiency to find the platform in the working memory task. Rats treated with vitamins E and C had part of the above effects prevented, suggesting the participation of oxidative stress in such effects. The BDNF levels were not altered in hippocampus of stressed group when compared to controls. Our findings lend support to a novel therapeutic strategy, associated with these vitamins, to the cognitive dysfunction observed in depression and other stress related diseases.
Source : Neurochem Res
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Nutrition and the Risk of Alzheimer's Disease
Nan Hu,1 Jin-Tai Yu,1,2 Lin Tan,1 Ying-Li Wang,1 Lei Sun,1 and Lan Tan1,2
1Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Number 5 Donghai Middle Road, Qingdao 266071, China
2College of Medicine and Pharmaceutics, Ocean University of China, Qingdao 266003, China
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for the major cause of dementia, and the increasing worldwide prevalence of AD is a major public health concern. Increasing epidemiological studies suggest that diet and nutrition might be important modifiable risk factors for AD. Dietary supplementation of antioxidants, B vitamins, polyphenols, and polyunsaturated fatty acids are beneficial to AD, and consumptions of fish, fruits, vegetables, coffee, and light-to-moderate alcohol reduce the risk of AD. However, many of the results from randomized controlled trials are contradictory to that of epidemiological studies. Dietary patterns summarizing an overall diet are gaining momentum in recent years. Adherence to a healthy diet, the Japanese diet, and the Mediterranean diet is associated with a lower risk of AD. This paper will focus on the evidence linking many nutrients, foods, and dietary patterns to AD.
Source : Biomed Research International
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A Molecular Link Between the Active Component of Marijuana and Alzheimer's Disease Pathology
Lisa M. Eubanks,† Claude J. Rogers,† Albert E. Beuscher, IV,‡ George F. Koob,§ Arthur J. Olson,‡ Tobin J. Dickerson,† and Kim D. Janda
Alzheimer's disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer's disease are expected to triple over the next 50 years. Consequently, the development of treatments that slow or halt the disease progression have become imperative to both improve the quality of life for patients as well as reduce the health care costs attributable to Alzheimer's disease. Here, we demonstrate that the active component of marijuana, Δ9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid β-peptide (Aβ) aggregation, the key pathological marker of Alzheimer's disease. Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis. Compared to currently approved drugs prescribed for the treatment of Alzheimer's disease, THC is a considerably superior inhibitor of Aβ aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.
Source : Mol Pharm.
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Green tea extract enhances parieto-frontal connectivity during working memory processing
André Schmidt1, 2, Felix Hammann3, Bettina Wölnerhanssen3, Anne Christin Meyer-Gerspach3, Jürgen Drewe3, Christoph Beglinger3 and Stefan Borgwardt1, 2, 4
(1)Department of Psychiatry (UPK), University of Basel, Wilhelm Klein Str. 27, 4012 Basel, Switzerland
(2)Medical Image Analysis Center, Schanzenstrasse 55, 4031 Basel, Switzerland
(3)Department of Gastroenterology, University Hospital Basel, 4031 Basel, Switzerland
(4)Department of Psychosis Studies, Institute of Psychiatry, King’s College London, London, UK
It has been proposed that green tea extract may have a beneficial impact on cognitive functioning, suggesting promising clinical implications. However, the neural mechanisms underlying this putative cognitive enhancing effect of green tea extract still remain unknown.
Objectives This study investigates whether the intake of green tea extract modulates effective brain connectivity during working memory processing and whether connectivity parameters are related to task performance.
Material and methods Using a double-blind, counterbalanced, within-subject design, 12 healthy volunteers received a milk whey-based soft drink containing 27.5 g of green tea extract or a milk whey-based soft drink without green tea as control substance while undergoing functional magnetic resonance imaging. Working memory effect on effective connectivity between frontal and parietal brain regions was evaluated using dynamic causal modeling.
Results Green tea extract increased the working memory induced modulation of connectivity from the right superior parietal lobule to the middle frontal gyrus. Notably, the magnitude of green tea induced increase in parieto-frontal connectivity positively correlated with improvement in task performance.
Conclusions Our findings provide first evidence for the putative beneficial effect of green tea on cognitive functioning, in particular, on working memory processing at the neural system level by suggesting changes in short-term plasticity of parieto-frontal brain connections. Modeling effective connectivity among frontal and parietal brain regions during working memory processing might help to assess the efficacy of green tea for the treatment of cognitive impairments in psychiatric disorders such as dementia
Source : Psychopharmacology
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Protective effect of curcumin (Curcuma longa), against aluminium toxicity: Possible behavioral and biochemical alterations in rats.
Kumar A1, Dogra S, Prakash A.
Aluminium is a potent neurotoxin and has been associated with Alzheimer's disease (AD) causality for decades. Prolonged aluminium exposure induces oxidative stress and increases amyloid beta levels in vivo. Current treatment modalities for AD provide only symptomatic relief thus necessitating the development of new drugs with fewer side effects. The aim of the study was to demonstrate the protective effect of chronic curcumin administration against aluminium-induced cognitive dysfunction and oxidative damage in rats. Aluminium chloride (100 mg/kg, p.o.) was administered to rats daily for 6 weeks. Rats were concomitantly treated with curcumin (per se; 30 and 60 mg/kg, p.o.) daily for a period of 6 weeks. On the 21st and 42nd day of the study behavioral studies to evaluate memory (Morris water maze and elevated plus maze task paradigms) and locomotion (photoactometer) were done. The rats were sacrificed on 43rd day following the last behavioral test and various biochemical tests were performed to assess the extent of oxidative damage. Chronic aluminium chloride administration resulted in poor retention of memory in Morris water maze, elevated plus maze task paradigms and caused marked oxidative damage. It also caused a significant increase in the acetylcholinesterase activity and aluminium concentration in aluminium treated rats. Chronic administration of curcumin significantly improved memory retention in both tasks, attenuated oxidative damage, acetylcholinesterase activity and aluminium concentration in aluminium treated rats (P<0.05). Curcumin has neuroprotective effects against aluminium-induced cognitive dysfunction and oxidative damage.
Source : Journal Behav Brain Res.
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New Treatment for Alzheimer’s Disease, Kamikihito, Reverses Amyloid- -Induced Progression of Tau Phosphorylation and Axonal Atrophy
Hidetoshi Watari,1,2 Yutaka Shimada,2 and Chihiro Tohda1
1Division of Neuromedical Science, Department of Bioscience, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
2Department of Japanese Oriental Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
We previously reported that kamikihito (KKT), a traditional Japanese medicine, improved memory impairment and reversed the degeneration of axons in the 5XFAD mouse model of Alzheimer’s disease (AD). However, the mechanism underlying the effects of KKT remained unknown. The aim of the present study was to investigate the mechanism by which KKT reverses the progression of axonal degeneration.
Methods. Primary cultured cortical neurons were treated with amyloid beta (Aβ) fragment comprising amino acid residues (25–35) (10 μM) in an in vitro AD model. KKT (10 μg/mL) was administered to the cells before or after Aβ treatment. The effects of KKT on Aβ-induced tau phosphorylation, axonal atrophy, and protein phosphatase 2A (PP2A) activity were investigated. We also performed an in vivo assay in which KKT (500 mg/kg/day) was administered to 5XFAD mice once a day for 15 days. Cerebral cortex homogenates were used to measure PP2A activity.
Results. KKT improved Aβ-induced tau phosphorylation and axonal atrophy after they had already progressed. In addition, KKT increased PP2A activity in vitro and in vivo.
Conclusions. KKT reversed the progression of Aβ-induced axonal degeneration. KKT reversed axonal degeneration at least in part through its role as an exogenous PP2A stimulator.
Source : Evidence Based Complementary and Alternative Medicine
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Natural plant compound prevents Alzheimer's disease in mice
A chemical that's found in fruits and vegetables from strawberries to cucumbers appears to stop memory loss that accompanies Alzheimer's disease in mice, scientists have discovered. In experiments on mice that normally develop Alzheimer's symptoms less than a year after birth, a daily dose of the compound -- a flavonol called fisetin -- prevented the progressive memory and learning impairments. The drug, however, did not alter the formation of amyloid plaques in the brain, accumulations of proteins which are commonly blamed for Alzheimer's Disease. The new finding suggests a way to treat Alzheimer's symptoms independently of targeting amyloid plaques.
"We had already shown that in normal animals, fisetin can improve memory," says Pamela Maher, a senior staff scientist in Salk's Cellular Neurobiology Laboratory who led the new study. "What we showed here is that it also can have an effect on animals prone to Alzheimer's."
More than a decade ago, Maher discovered that fisetin helps protect neurons in the brain from the effects of aging. She and her colleagues have since -- -in both isolated cell cultures and mouse studies -- -probed how the compound has both antioxidant and anti-inflammatory effects on cells in the brain. Most recently, they found that fisetin turns on a cellular pathway known to be involved in memory.
"What we realized is that fisetin has a number of properties that we thought might be beneficial when it comes to Alzheimer's," says Maher.
So Maher -- -who works with Dave Schubert, the head of the Cellular Neurobiology Lab -- -turned to a strain of mice that have mutations in two genes linked to Alzheimer's disease. The researchers took a subset of these mice and, when they were only three months old, began adding fisetin to their food. As the mice aged, the researchers tested their memory and learning skills with water mazes. By nine months of age, mice that hadn't received fisetin began performing more poorly in the mazes. Mice that had gotten a daily dose of the compound, however, performed as well as normal mice, at both nine months and a year old.
"Even as the disease would have been progressing, the fisetin was able to continue preventing symptoms," Maher says.
In collaboration with scientists at the University of California, San Diego, Maher's team next tested the levels of different molecules in the brains of mice that had received doses of fisetin and those that hadn't. In mice with Alzheimer's symptoms, they found, pathways involved in cellular inflammation were turned on. In the animals that had taken fisetin, those pathways were dampened and anti-inflammatory molecules were present instead. One protein in particular -- -known as p35 -- -was blocked from being cleaved into a shorter version when fisetin was taken. The shortened version of p35 is known to turn on and off many other molecular pathways. The results were published December 17, 2013, in the journal Aging Cell.
Studies on isolated tissue had hinted that fisetin might also decrease the number of amyloid plaques in Alzheimer's affected brains. However, that observation didn't hold up in the mice studies. "Fisetin didn't affect the plaques," says Maher. "It seems to act on other pathways that haven't been seriously investigated in the past as therapeutic targets."
Next, Maher's team hopes to understand more of the molecular details on how fisetin affects memory, including whether there are targets other than p35.
"It may be that compounds like this that have more than one target are most effective at treating Alzheimer's disease," says Maher, "because it's a complex disease where there are a lot of things going wrong."
They also aim to develop new studies to look at how the timing of fisetin doses affect its influence on Alzheimer's.
"The model that we used here was a preventive model," explains Maher. "We started the mice on the drugs before they had any memory loss. But obviously human patients don't go to the doctor until they are already having memory problems." So the next step in moving the discovery toward the clinic, she says, is to test whether fisetin can reverse declines in memory once they have already appeared.
- Antonio Currais, Marguerite Prior, Richard Dargusch, Aaron Armando, Jennifer Ehren, David Schubert, Oswald Quehenberger, Pamela Maher. Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer's disease transgenic mice. Aging Cell, 2013; DOI: 10.1111/acel.12185
Source : Science Daily
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Cocoa Improves Cognitive Functioning in Older Adults with Neurovascular Compromise
Sorond FA, Hurwitz S, Salat DH, Greve DN, Fisher NDL.
Neurovascular coupling, cerebral white matter integrity, and response to cocoa in older people. Neurology. 2013;81(10):904-909.
Neurovascular coupling is the relationship between neuronal activity and cerebral blood flow; an increase in neuronal activity increases the demand for glucose and oxygen, so cerebral blood flow increases. The relationship between neurovascular coupling and cognition and aging is unknown. Cocoa (Theobroma cacao), which is rich in flavanols, may improve endothelial and cognitive function. The purpose of this randomized, double-blind, placebo-controlled study was to determine whether neurovascular coupling is associated with lower cognitive function, whether impaired coupling is associated with cerebral white matter disease, and whether cocoa can modify coupling.
Subjects (n = 60, aged > 65 years) were recruited from local advertisements near Boston, Massachusetts. Included subjects had hypertension (systolic blood pressure [SBP] > 140 mmHg or diastolic blood pressure [DBP] > 90 mmHg on repeated occasions, or treatment with antihypertensive medication) and/or well-controlled type 2 diabetes mellitus. Excluded subjects had absent temporal acoustic windows; intracranial stenosis; history of stroke, chest pain, or heart attack in the last 6 months; stage 2 high blood pressure not controlled by medication (> 160/100 mmHg); serum creatinine > 2 mg/dL; or diagnosis of dementia. Subjects received cocoa powder (Mars, Inc.; McLean, Virginia) in packets to be mixed with water and were instructed to consume 2 cups of cocoa daily either as flavanol-rich cocoa (609 mg flavanols/serving) or flavanol-poor cocoa (13 mg flavanols/serving) for 30 days.
Subjects continued with regular medications and were instructed to eliminate 100 kcal from the diet to prevent weight gain or worsening of diabetes. They were told to refrain from eating chocolate and not to consume caffeine on the study days. Cerebral blood flow velocity was measured at the middle cerebral artery via transcranial Doppler ultrasonography at baseline and after 30 days of treatment at rest, in response to cognitive tasks (N-back tasks), and before and after cocoa consumption. Magnetic resonance imaging (MRI) was conducted on 24 subjects to determine volumes of normal and abnormal brain white matter.
Subjects with intact neurovascular coupling had significantly better scores on the Trails B Cognitive test (P = 0.002) and the 2-Back Task (P = 0.02). There was no significant association between neurovascular coupling and the mini-mental state examination score. On MRI, abnormal white matter appears as hyperintensities, and tissue microstructure is measured with fractional anisotropy and mean diffusivity. As would be expected, greater neurovascular coupling occurred in subjects with less white matter macro- and microstructure damage (smaller volume of hyperintensities and higher fractional anisotropy, P = 0.02).
After both 24 hours and 30 days of cocoa consumption, cerebral blood flow and blood pressure did not significantly differ between high- and low-flavanol treatment groups, so both groups were combined for analysis. Blood pressure significantly decreased after 1 day of cocoa compared with baseline (SBP: 3.2 ± 13.4 mmHg, P = 0.07; DBP: 3.0 ± 9.6 mmHg, P = 0.02); however, at 30 days there was no significant effect on blood pressure. At rest, there was no significant difference between treatment groups for neurovascular coupling. During cognitive testing, 89% of subjects with impaired coupling at baseline had a significant improvement in coupling after 30 days of cocoa compared with 36% of those with intact baseline coupling (P = 0.0002). In those subjects with impaired baseline coupling, cocoa consumption was associated with 10.6% (P = 0.0001) and 8.3% (P < 0.0001) increases in coupling at 24 hours and 30 days, respectively. Cocoa resulted in very little change in coupling in subjects with intact coupling at baseline. Also, Trails B performance significantly improved in response to 30 days of cocoa consumption in those with impaired coupling at baseline (P < 0.007).
The authors conclude that neurovascular coupling is related to cognitive performance and cerebral white matter structural integrity in elderly subjects with vascular risk factors. In addition, they conclude that neurovascular coupling can be modified by cocoa. Cocoa had an effect irrespective of the amount of flavanols, indicating that there is something else in cocoa that is producing the benefit or that coupling is so sensitive to flavanols that even the small amount in the flavanol-poor group was enough to produce a benefit. It should be noted that this study population had vascular disease, so the effect of cocoa on healthy populations may be different. The authors do not discuss other forms of cocoa, for example, a chocolate bar, which may be preferable to drinking daily hot cocoa especially in warmer months.
—Heather S. Oliff, PhD
Source : ABC
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Chinese Herbs for Memory Disorders: A Review and Systematic Analysis of Classical Herbal Literature
Brian H. May, Chuanjian Lu, Yubo Lu, Anthony L. Zhang, Charlie C.L. Xue
Text mining and other literature-based investigations can assist in identifying natural products for experimental and clinical research. This article details a method for systematically analyzing data derived from the classical Chinese medical literature. We present the results of electronic searches of Zhong Hua Yi Dian (“Encyclopaedia of Traditional Chinese Medicine”), a CD of 1000 premodern (before 1950) medical books, for single herbs, and other natural products used for dementia, memory disorders, and memory improvement. This review explores how the terminology for these disorders has changed over time and which herbs have been used more or less frequently, and compares the results from the premodern literature with the herbs indexed for memory disorders in a modern pharmacopoeia. The searches located 731 citations deriving from 127 different books written between ca. 188 ad and ca. 1920. Of the 110 different natural products identified, those most frequently cited for forgetfulness were yuan zhi (Polygala tenuifolia), fu shen (Poria cocos), and chang pu (Acorus spp.), all of which have been cited repeatedly over the past 1800 years and appear among the 31 herbs indexed in a modern pharmacopoeia. By providing a complete, hierarchically organized list of herbs for a specific disorder, this approach can assist researchers in selecting herbs for research.
Source : Journal of Acupuncture and Meridian Studies
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Association of vitamin E and C supplement use with cognitive function and dementia in elderly men
- K.H. Masaki, MD,
- K.G. Losonczy, MA,
- G. Izmirlian, PhD,
- D.J. Foley, MS,
- G.W. Ross, MD,
- H. Petrovitch, MD,
- R. Havlik, MD and
- L.R. White, MD
Objective: To determine whether use of vitamin E and C supplements protects against subsequent development of dementia and poor cognitive functioning.
Methods: The Honolulu–Asia Aging Study is a longitudinal study of Japanese-American men living in Hawaii. Data for this study were obtained from a subsample of the cohort interviewed in 1982, and from the entire cohort from a mailed questionnaire in 1988 and the dementia prevalence survey in 1991 to 1993. The subjects included 3,385 men, age 71 to 93 years, whose use of vitamin E and C supplements had been ascertained previously. Cognitive performance was assessed with the Cognitive Abilities Screening Instrument, and subjects were stratified into four groups: low, low normal, mid normal, and high normal. For the dementia analyses, subjects were divided into five mutually exclusive groups: AD (n = 47), vascular dementia (n = 35), mixed/other types of dementia (n = 50), low cognitive test scorers without diagnosed dementia (n = 254), and cognitively intact (n = 2,999; reference).
Results: In a multivariate model controlling for other factors, a significant protective effect was found for vascular dementia in men who had reported taking both vitamin E and C supplements in 1988 (odds ratio [OR], 0.12; 95% CI, 0.02 to 0.88). They were also protected against mixed/other dementia (OR, 0.31; 95% CI, 0.11 to 0.89). No protective effect was found for Alzheimer’s dementia (OR, 1.81; 95% CI, 0.91 to 3.62). Among those without dementia, use of either vitamin E or C supplements alone in 1988 was associated significantly with better cognitive test performance at the 1991 to 1993 examination (OR, 1.25; 95% CI, 1.04 to 1.50), and use of both vitamin E and C together had borderline significance (OR, 1.18; 95% CI, 0.995 to 1.39).
Conclusions: These results suggest that vitamin E and C supplements may protect against vascular dementia and may improve cognitive function in late life.
Source : Journal Neurology
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Can Certain Herbs Stave Off Alzheimer's Disease
ST. LOUIS -- Enhanced extracts made from special antioxidants in spearmint and rosemary improve learning and memory, a study in an animal model at Saint Louis University found.
"We found that these proprietary compounds reduce deficits caused by mild cognitive impairment, which can be a precursor to Alzheimer's disease," said Susan Farr, Ph.D., research professor geriatrics at Saint Louis University School of Medicine.
Farr added, "This probably means eating spearmint and rosemary is good for you. However, our experiments were in an animal model and I don't know how much -- or if any amount -- of these herbs people would have to consume for learning and memory to improve. In other words, I'm not suggesting that people chew more gum at this point."
Farr presented the early findings at Neuroscience 2013, a meeting of 32,000 on Monday, Nov. 11. She tested a novel antioxidant-based ingredient made from spearmint extract and two different doses of a similar antioxidant made from rosemary extract on mice that have age-related cognitive decline.
She found that the higher dose rosemary extract compound was the most powerful in improving memory and learning in three tested behaviors. The lower dose rosemary extract improved memory in two of the behavioral tests, as did the compound made from spearmint extract.
Further, there were signs of reduced oxidative stress, which is considered a hallmark of age-related decline, in the part of the brain that controls learning and memory.
"Our research suggests these extracts made from herbs might have beneficial effects on altering the course of age-associated cognitive decline," Farr said. "It's worth additional study."
The research, which was supported by the VA Medical Center in St. Louis, was conducted in conjunction with Kemin Industries, which manufactures specialty ingredients for vitamin/dietary supplements or that can be added to food to enhance its nutritional and health benefits.
Established in 1836, the School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: infectious disease, liver disease, aging and brain disease, cancer and heart/lung disease.
Source : St. Louis University
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Two Exciting Alzheimer’s Advances: A Novel Early Detection Test Using Peanut Butter, and a Study Evaluating Coconut Oil
At present, some 5.4 million Americans have Alzheimer’s disease, according to the Alzheimer's Association's 2011 Alzheimer's Disease Facts and Figures.1
By 2050, this is expected to jump to 16 million, and in the next 20 years it is projected that Alzheimer's will affect one in four Americans, rivaling the current prevalence of obesity and diabetes.
Since treatments are few and rarely effective, early diagnosis and prevention become all the more important.
Interestingly, simple tools like a tablespoon of peanut butter and a ruler could potentially be used to confirm a diagnosis of the disease in its early stages. As reported by Medical News Today:2
“Jennifer Stamps, a graduate student in the University of Florida (UF) McKnight Brain Institute Center for Smell and Taste, and her colleagues reported the findings of a small pilot study in the Journal of the Neurological Sciences.3
Stamps came up with the idea of using peanut butter to test for smell sensitivity while she was working with Dr. Kenneth Heilman, one of the world's best known behavioral neurologists, from the UF College of Medicine's department of neurology.
...The ability to smell is associated with the first cranial nerve and is often one of the first things to be affected in cognitive decline... She thought of peanut butter because, she said, it is a 'pure odorant' that is only detected by the olfactory nerve and is easy to access.”
The pilot study tested the ability to smell of 24 patients diagnosed with mild cognitive impairment. To perform the test, the patient was asked to close their eyes and mouth, and hold one nostril closed while breathing normally through the other.
Using a ruler, the clinician measured the distance between the open nostril and the peanut butter, marking the distance at which the patient was able to detect the distinct odor. After a 90 second delay, the procedure was repeated with the other nostril.
They discovered that those diagnosed with early stage Alzheimer’s (which was done through other clinical testing) experienced a significant difference in their ability to detect the odor between the two nostrils. According to the featured report:
“[T]he left nostril was impaired and did not detect the smell until it was an average of 10 cm closer to the nose than the right nostril had made the detection in patients with Alzheimer's disease.
This was not the case in patients with other kinds of dementia; instead, these patients had either no differences in odor detection between nostrils or the right nostril was worse at detecting odor than the left one.”
Of course, it’s too early to tell whether this test might be reliable enough to become widely used. More research needs to be done. But according to Stamps, the test can be used to confirm a diagnosis. The team is planning to study patients with mild cognitive impairment next, to assess whether it might help predict a future diagnosis of Alzheimer’s.
Benefits of Coconut Oil Make Headlines Again In related news, Florida researchers are also looking into whether coconut oil might be of benefit against Alzheimer’s. Three years ago, I published Dr. Mary Newport’s theory that ketone bodies, an alternative fuel for your brain that your body makes when digesting coconut oil, might offer profound benefits in the fight against Alzheimer's disease.
At the time I said that, should her theory turn out to be accurate, it could be one of the greatest natural health discoveries in a long time. Now, Dr. Newport's research is being used to launch one of the first clinical trials of its kind to test her theory. The research is being done at the USF Health Byrd Alzheimer’s Institute.
Sixty-five patients diagnosed with mild to moderate Alzheimer’s have been enrolled to evaluate the effects of coconut oil on the disease, compared to a placebo. Dr. Newport hopes to have the results within a year.
This issue strikes close to home for Dr. Newport, whose husband has been battling the disease for years. As reported by CTV News:4
“While there is currently no clinical data showing the benefits of coconut oil on the prevention and treatment of dementia, Newport -- whose husband Steve was diagnosed with Alzheimer’s at age 51 -- said she began to see improvements after starting him on four teaspoons of coconut oil per day.
‘Before the coconut oil, he could not tie his shoes. His weird slow gait… That improved. He walked normally and he was able to start running again.
He was able to start reading again, his conversation improved dramatically and then over several months we saw improvements in his memory,’ Newport said. Prior to starting him on coconut oil, Newport said none of the existing medications were working.”
Coconut Oil Appears to Be an Ideal Brain Food There are only two types of fuel your body can convert into energy: carbs/sugar, or fat. Again, ketones are what your body produces when it converts fat (as opposed to glucose) into energy. And a primary source of ketone bodies are the medium-chain triglycerides (MCT) found in coconut oil. In fact, coconut oil contains about 66 percent MCTs.
Medium-chain triglycerides (MCT) are fats that are not processed by your body in the same manner as long-chain triglycerides. Normally, a fat taken into your body must be mixed with bile released from your gallbladder before it can be broken down in your digestive system.
But medium-chain triglycerides go directly to your liver, which naturally converts the oil into ketones, bypassing the bile entirely. Your liver then immediately releases the ketones into your bloodstream where they are transported to your brain to be readily used as fuel.
While your brain is quite happy running on glucose, there’s evidence suggesting that ketone bodies may actually help restore and renew neurons and nerve function in your brain, even after damage has set in. Interestingly, the mechanism of this MCT-ketone metabolism appears to be that your body treats MCTs as a carbohydrate and not a fat. This allows the ketone energy to hit your bloodstream without the normal insulin spike associated with carbohydrates entering your bloodstream. So in effect, coconut oil is a fat that acts like a carbohydrate when it comes to brain fuel.
How Much Coconut Oil Might You Need? Therapeutic levels of MCTs have been studied at 20 grams per day. According to Dr. Newport's calculations,5 just over two tablespoons of coconut oil (about 35 ml or seven level teaspoons) would supply you with the equivalent of 20 grams of MCT, which is indicated as either a preventative measure against degenerative neurological diseases, or as a treatment for an already established case.
While more research certainly needs to be done in this area as well, I see no reason not to incorporate coconut oil in your diet, or the diet of a loved one who is exhibiting symptoms of brain degeneration. Coconut oil has so many profound health benefits; it’s not going to do any harm.
It’s worth noting that people tolerate coconut oil differently, and you may have to start slowly and build up to these therapeutic levels. My recommendation is to start with one teaspoon, taken with food in the mornings. Gradually add more coconut oil every few days until you are able to tolerate about four tablespoons. It’s best to take it with food, to avoid upsetting your stomach.
Low-Fat Craze Has Likely Contributed to Dramatic Rise in Alzheimer’s A number of seriously flawed nutritional guidelines have contributed to more than a few health problems in the US, and the low-fat craze (aimed at preventing heart disease) is toward the top of that list. Not only does avoiding healthful fat promote heart disease, it also promotes brain diseases like Alzheimer’s.
According to neurologist Dr. David Perlmutter, fat avoidance and carbohydrate overconsumption are at the heart of the Alzheimer’s epidemic—which is an entirely preventable disease, driven by lifestyle factors such as diet. Dr. Perlmutter’s book, Grain Brain, provides a powerful argument for eliminating grains from your diet to protect your brain health. Another major factor is the development and increased consumption of genetically engineered (GE) grains, which are now pervasive in most processed foods sold in the US. Unfortunately, despite dire need, there’s little money available for research into treatments using regular food items. As Amanda Smith, Medical Director at University of South Florida (USF) Health Byrd Alzheimer's Institute told CTV News:
“The pharmaceutical industry is in this -- of course to make money for their companies, and of course they want to help people theoretically -- but at the end of the day it is about dollars and cents, and so money gets invested in things that are new or patentable rather than things that are sitting on the shelf already.”
Intermittent Fasting Can Also Increase Ketone Production There are two additional ways to increase ketone production: restricting carbohydrates, and intermittent fasting. Personally, I believe all three of these strategies are best applied together, as you need to replace the lost carbs with high quality fat (and coconut oil certainly fits that bill), and intermittent fasting will help your body shift to burning fat as its primary fuel. It takes about six to eight hours for your body to metabolize your glycogen stores, after which you start to shift to burning stored fat, and hence producing ketone bodies.
Contrary to more stringent and challenging fasts, intermittent fasting simply involves timing your meals to allow your body to enter the fat-burning “window.” To be effective, the length of your fast must be at least 16 hours. For example, this would mean eating only between the hours of 11am until 7pm, or noon until 8pm. You can restrict it even further — down to six, four, or even two hours if you want, but you can still reap many of the health benefits associated with intermittent fasting by limiting your eating to an eight-hour window each day.
I recommend easing yourself into this type of eating schedule. Start by not eating anything for three hours prior to bed, and then gradually extend the time before you eat breakfast each day to the point that you have skipped breakfast and have your first meal at lunch. This typically takes a few weeks to a few months. Also, this is not something that needs to be done continuously once your body has shifted to fat burning mode. However, your desire to eat will be dramatically reduced so you won’t feel the need to eat like you did before shifting your body’s primary fuel burning preference.
Tips for Maintaining Healthy Brain Function and Avoiding Alzheimer's Disease Knowing that Alzheimer’s is a preventable disease, predicated on your lifestyle choices, puts the power into your hands. Diet is paramount, and the beauty of following my optimized nutrition plan is that it helps prevent and treat virtually ALL chronic degenerative diseases, including Alzheimer’s disease.
People who experience very little decline in their cognitive function up until their deaths have been found (post-mortem) to be free of brain lesions, showing that it's entirely possible to prevent the damage from occurring in the first place… and one of the best ways to do this is by leading a healthy lifestyle. The following guidelines will help you protect your brain health well into old age:
- Avoid sugar and refined fructose. Ideally, you’ll want to keep your sugar levels to a minimum and your total fructose below 25 grams per day, or as low as 15 grams per day if you have insulin resistance or any related disorders.
- Avoid gluten (primarily wheat). Research shows that your blood-brain barrier, the barrier that keeps things out of your brain where they don’t belong, is negatively affected by gluten. Gluten also makes your gut more permeable, which allows proteins to get into your bloodstream, where they don’t belong. That then sensitizes your immune system and promotes inflammation and autoimmunity, both of which play a role in the development of Alzheimer’s.
- Optimize your gut flora by regularly eating fermented foods or taking a high-potency and high quality probiotic supplement.
- Increase consumption of all healthful fats, including animal-based omega-3. Beneficial health-promoting fats that your brain needs for optimal function include organic butter from raw milk, clarified butter called organic grass-fed raw butter, olives, organic virgin olive oil and coconut oil, nuts like pecans and macadamia, free-range eggs, wild Alaskan salmon, and avocado.
- Contrary to popular belief, the ideal fuel for your brain is not glucose but ketones. Ketones are what your body produces when it converts fat (as opposed to glucose) into energy. The medium-chain triglycerides (MCT) found in coconut oil are GREAT source of ketone bodies, because coconut oil is about 66 percent MCTs. In fact, ketones appear to be the preferred source of brain food in patients affected by diabetes or Alzheimer's.
Also make sure you’re getting enough animal-based omega-3 fats, such as krill oil. (I recommend avoiding most fish because, although fish is naturally high in omega-3, most fish are now severely contaminated with mercury.) High intake of the omega-3 fats EPA and DHA help by preventing cell damage caused by Alzheimer's disease, thereby slowing down its progression, and lowering your risk of developing the disorder.
- Reduce your overall calorie consumption, and/or intermittently fast. As mentioned above, ketones are mobilized when you replace carbs with coconut oil and other sources of healthy fats. A one-day fast can help your body to “reset” itself, and start to burn fat instead of sugar.
- As part of a healthy lifestyle, I prefer an intermittent fasting schedule that simply calls for limiting your eating to a narrower window of time each day. By restricting your eating to a 6-8 hour window, you effectively fast 16-18 hours each day. To learn more, please see this previous article.
- Improve your magnesium levels. There is some exciting preliminary research strongly suggesting a decrease in Alzheimer symptoms with increased levels of magnesium in the brain. Unfortunately, most magnesium supplements do not pass the blood brain levels, but a new one, magnesium threonate, appears to and holds some promise for the future for treating this condition and may be superior to other forms.
- Optimize your vitamin D levels with safe sun exposure. Strong links between low levels of vitamin D in Alzheimer's patients and poor outcomes on cognitive tests have been revealed. Researchers believe that optimal vitamin D levels may enhance the amount of important chemicals in your brain and protect brain cells by increasing the effectiveness of the glial cells in nursing damaged neurons back to health.
- Vitamin D may also exert some of its beneficial effects on Alzheimer's through its anti-inflammatory and immune-boosting properties. Sufficient vitamin D is imperative for proper functioning of your immune system to combat inflammation that is also associated with Alzheimer's.
- Keep your fasting insulin levels below 3. This is indirectly related to fructose, as it will clearly lead to insulin resistance. However, other sugars (sucrose is 50 percent fructose by weight), grains and lack of exercise are also important factors. Lowering insulin will also help lower leptin levels which is another factor for Alzheimer’s.
- Eat a nutritious diet, rich in folate, such as the one described in my nutrition plan. Vegetables, without question, are your best form of folate, and we should all eat plenty of fresh raw veggies every day.
- Avoid and eliminate mercury from your body. Dental amalgam fillings, which are 50 percent mercury by weight, are one of the major sources of heavy metal toxicity, however you should be healthy prior to having them removed. Once you have adjusted to following the diet described in my optimized nutrition plan, you can follow the mercury detox protocol and then find a biological dentist to have your amalgams removed.
- Avoid aluminum, such as antiperspirants, non-stick cookware, vaccine adjuvants, etc.
- Exercise regularly. It's been suggested that exercise can trigger a change in the way the amyloid precursor protein is metabolized,6 thus, slowing down the onset and progression of Alzheimer's. Exercise also increases levels of the protein PGC-1alpha. Research has also shown that people with Alzheimer's have less PGC-1alpha in their brains7 and cells that contain more of the protein produce less of the toxic amyloid protein associated with Alzheimer's. I would strongly recommend reviewing the Peak Fitness Technique for my specific recommendations.
- Avoid flu vaccinations as most contain mercury, a well-known neurotoxic and immunotoxic agent.
- Eat blueberries. Wild blueberries, which have high anthocyanin and antioxidant content, are known to guard against Alzheimer's and other neurological diseases. Like any fruit though, avoid excesses here.
- Challenge your mind daily. Mental stimulation, especially learning something new, such as learning to play an instrument or a new language, is associated with a decreased risk of Alzheimer's. Researchers suspect that mental challenge helps to build up your brain, making it less susceptible to the lesions associated with Alzheimer's disease.
- Avoid anticholinergics and statin drugs. Drugs that block acetylcholine, a nervous system neurotransmitter, have been shown to increase your risk of dementia. These drugs include certain nighttime pain relievers, antihistamines, sleep aids, certain antidepressants, medications to control incontinence, and certain narcotic pain relievers.
- Statin drugs are particularly problematic because they suppress the synthesis of cholesterol, deplete your brain of coenzyme Q10 and neurotransmitter precursors, and prevent adequate delivery of essential fatty acids and fat-soluble antioxidants to your brain by inhibiting the production of the indispensable carrier biomolecule known as low-density lipoprotein.
- Astaxanthin is a natural pigment with unique properties and many clinical benefits, including some of the most potent antioxidant activity currently known. As a fat-soluble nutrient, astaxanthin readily crosses your blood-brain barrier. One study8 found it may help prevent neurodegeneration associated with oxidative stress, as well as make a potent natural "brain food."
- The molecules of astaxanthin neutralize free radicals and other oxidants without being destroyed or becoming pro-oxidants themselves in the process. It's is a unique molecule whose shape allows it to precisely fit into a cell membrane and span its entire width. In this position, astaxanthin can intercept potentially damaging molecules before they can damage your cells.
You can get some astaxanthin by taking krill oil, which is a fantastic omega-3 fat supplement. But you can boost your astaxanthin even MORE by adding a pure astaxanthin supplement to your nutritional regimen. For optimal absorption, make sure to take krill oil and/or astaxanthin with a fat-containing meal, since both are fat-soluble.
- Gingko biloba: Many scientific studies have found that Gingko biloba has positive effects for dementia. Gingko, which is derived from a tree native to Asia, has long been used medicinally in China and other countries. A 1997 study from JAMA showed clear evidence that Gingko improves cognitive performance and social functioning for those suffering from dementia. Research since then has been equally promising. One study in 2006 found Gingko as effective as the dementia drug Aricept (donepezil) for treating mild to moderate Alzheimer's type dementia. A 2010 meta-analysis found Gingko biloba to be effective for a variety of types of dementia.
- Alpha lipoic acid (ALA): ALA can stabilize cognitive functions among Alzheimer's patients and may slow the progression of the disease.
- Vitamin B12: A small Finnish study published in the journal Neurology9 found that people who consume foods rich in B12 may reduce their risk of Alzheimer's in their later years. For each unit increase in the marker of vitamin B12, the risk of developing Alzheimer's was reduced by two percent. Remember, sublingual methylcobalamin may be your best bet here.
Source : Dr. Mercola
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Study on Protection Against b-Amyloid Peptide Toxicity With Oral Administration of Medicinal Herbs
Songhee Jeon, PhD1 , Jae-Hyun Kang, PhD, OMD2, Sok Cheon Pak, PhD3 , and Byung-Soo Koo, PhD, OMD2
Seonghyangjeongkisan has been used as a therapeutic agent for cerebral disease in Korea, but its effectiveness in Alzheimer’s
disease is not well known. In this study, we examined whether Seonghyangjeongkisan could protect against amyloid
b–induced cytotoxicity in neuroblastoma cells and the brain. Seonghyangjeongkisan rescued amyloid b–induced cytotoxicity dose dependently and reduced amyloid b–induced apoptosis and reactive oxygen species. Injection of mice with amyloid b impaired per-
formance on the passive avoidance task, but Seonghyangjeongkisan markedly improved memory impairment in mice, with it being
more effective than tacrine treatment in mice. Moreover, the activation of stress-related kinases such as extracellular signal-
regulated kinase, c-Jun NH2 -terminal kinase, and p38 was suppressed, and the phosphorylation of t protein, which is known
as a marker of Alzheimer’s disease, was also suppressed by Seonghyangjeongkisan treatment in the hippocampus. These results
demonstrate that Seonghyangjeongkisan reduces amyloid b-induced toxicity in the brain, suggesting that it may be a useful com-
plementary therapy against Alzheimer’s disease.
Source: Journal of Evidence Based Complementary and Alternative Medicine
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An Ethanolic Extract of Bacopa Safely Enhances Attention, Working Memory, Cognitive Processing, and Cholinergic Function in Healthy, Elderly Subjects
Peth-Nui T, Wattanathorn J, Muchimapura S, et al.
Effects of 12-week Bacopa monnieri consumption on attention, cognitive processing, working memory, and functions of both cholinergic and monoaminergic systems in healthy elderly volunteers. Evid Based Complement Alternat Med. 2012;2012:606424. doi: 10.1155/2012/606424.
Bacopa (Bacopa monnieri) has been used as a nerve tonic and to treat neurological and neuropsychiatric disorders in Ayurvedic medicine for centuries. The authors hypothesize that bacopa may alter the cholinergic system. This would enhance attention and cognitive processing and ultimately enhance working memory. Attention and cognitive processing can be evaluated by characterizing event-related potentials (ERPs). One component of ERP is called N100. Its amplitude is modulated by selective attention. Another component is called P300. Its amplitude reflects attention and memory operations. The latencies of both components increase with aging, and the amplitudes are decreased with aging. The purpose of this randomized, double-blind, placebo-controlled pilot study was to evaluate the effect of bacopa on attention, cognitive processing, working memory, and cholinergic and monoaminergic function in elderly people.
Healthy subjects (n = 60; mean age = 62.6 years) participated in this study that was conducted at Khon Kaen University; Khon Kaen, Thailand. Included subjects were said to be free of any herbal or prescribed medication that might interfere with nervous system function. The study excluded habitual smokers consuming > 10 cigarettes/day and any subjects who would have difficulty abstaining from smoking during the study. Subjects were instructed to abstain from caffeine and alcohol for ≥ 12 hours prior to the test session. Subjects were given tablets of either placebo, 300 mg/day of bacopa extract, or 600 mg/day of bacopa extract for 12 weeks. The ethanolic extract of bacopa used in this study was said to be a "proprietary extract" prepared by the Faculty of Pharmaceutical Sciences at Naresuan University in Phitsanulok, and it was said to contain 5% saponins, including unreported amounts of bacoside A3, bacopaside I and II, bacopaside X, and bacopasaponin C. The placebo tablet was said to have the same odor and color as the active tablet. It is unclear how this was accomplished. The battery of cognitive tests included working memory (word presentation, picture presentation, simple reaction time, digit vigilance task, choice reaction time, spatial working memory, and numeric working memory) and ERP assessment. There was an assessment of acetylcholinesterase (AChE) and monoamine oxidase (MAO) activity via tests on venous blood after 8-hour fasts. There were no control groups reported for the assays, so findings must be accepted at face value. Subjects were assessed at baseline, 4 weeks, 8 weeks, and 12 weeks, and also 4 weeks after treatment.
There were no significant differences in mean age, education, or body mass index between groups. Table 1 shows the effect of bacopa on parameters of working memory compared with placebo. The 300 mg/day dose had a more robust effect than the 600 mg/day dose.
Table 1: Significant Effects of Bacopa on Working Memory Compared with Placebo (click on full article)
Bacopa had no effect compared with placebo on N100 amplitude and P300 amplitude. N100 latency was significantly decreased compared with placebo at week 12 in both the 300 mg/day group (P < 0.001) and the 600 mg/day group (P < 0.05). P300 latency was significantly decreased compared with placebo at weeks 8 and 12 in the 300 mg/day group (P < 0.05 and P < 0.01, respectively) and at week 12 in the 600 mg/day group (P < 0.05). No significant changes were observed 4 weeks after the cessation of bacopa.
The 300 mg/day group had a significant reduction of AChE activity at week 4 through week 12 compared to placebo (P < 0.01-0.001). The 600 mg/day group only had a significant reduction of AChE activity at week 12 compared to placebo (P < 0.01). The significant changes in both groups persisted 4 weeks after the cessation of bacopa (P < 0.01, compared to placebo). There were no significant changes in MAO activity.
There were no serious adverse effects, no changes in hematological and biochemical values that would indicate toxicity, and no electrocardiogram (ECG) recordings outside normal limits. No subjects dropped out of the study.
The authors conclude that bacopa enhanced attention, cognitive processing, working memory, and cholinergic function. Bacopa may suppress the function of AChE in the brain, leading to increased levels of acetylcholine which can enhance attention and memory. Since mild cognitive impairment and early Alzheimer's disease are due in part to a decline in acetylcholine, bacopa may benefit these patients, but additional research is needed to evaluate bacopa's benefits for patients with these conditions.
Source : American Botanical Council
Link to Full Article
Combinatorial Treatment of Tart Cherry Extract and Essential Fatty Acids Reduces Cognitive Impairments and Inflammation in the mu-p75 Saporin-Induced Mouse Model of Alzheimer's Disease
Jessica J. Matchynski,1,2,3 Steven A. Lowrance,1,2 Colleen Pappas,1,2 Julien Rossignol,1,2,4 Nicole Puckett,1,2 Michael Sandstrom,2,5 and Gary L. Dunbar1,2,4,5,6
1Field Neurosciences Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, Michigan, USA
.2Program in Neuroscience, Central Michigan University, Mt. Pleasant, Michigan, USA.
3Department of Psychology and Behavioral Sciences, Rochester College, Rochester, Michigan, USA.
4College of Medicine, Central Michigan University, Mt. Pleasant, Michigan, USA.
5Department of Psychology, Central Michigan University, Mt. Pleasant, Michigan, USA.6Field Neurosciences Institute, Saginaw, Michigan, USA.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects more than five million Americans and is characterized by a progressive loss of memory, loss of cholinergic neurons in the basal forebrain, formation of amyloid plaques and neurofibrillary tangles, and an increase in oxidative stress. Recent studies indicate that dietary supplements of antioxidants and omega-3 and omega-6 fatty acids may reduce the cognitive deficits in AD patients. The current study tested a combinatorial treatment of antioxidants from tart cherry extract and essential fatty acids from Nordic fish and emu oils for reducing cognitive deficits in the mu-p75 saporin (SAP)–induced mouse model of AD. Mice were given daily gavage treatments of Cerise® Total-Body-Rhythm™ (TBR; containing tart cherry extract, Nordic fish oil, and refined emu oil) or vehicle (methylcellulose) for 2 weeks before intracerebroventricular injections of the cholinergic toxin, mu-p75 SAP, or phosphate-buffered saline. The TBR treatments continued for an additional 17 days, when the mice were tested on a battery of cognitive and motor tasks. Results indicate that TBR decreased the SAP-induced cognitive deficits assessed by the object-recognition, place-recognition, and Morris-water-maze tasks. Histological examination of the brain tissue indicated that TBR protected against SAP-induced inflammatory response and loss of cholinergic neurons in the area around the medial septum. These findings indicate that TBR has the potential to serve as an adjunctive treatment which may help reduce the severity of cognitive deficits in disorders involving cholinergic deficits, such as AD.
Source Journal of Medicinal Food
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BP Control May Help Slow Alzheimer's
Genetics and high blood pressure appear to interact to increase deposits in the brain of a protein involved in the pathology of Alzheimer's disease, researchers reported.
In a cross-sectional study of cognitively normal older adults, brain levels of beta-amyloid were highest in volunteers with both hypertension and the ε4 variant of the apolipoprotein E gene, according to Karen Rodrigue, PhD, of the University of Texas at Dallas, and colleagues.
But people with just one of those factors were not significantly different in terms of beta-amyloid deposition in the brain from volunteers with neither, Rodrigue and colleagues reported online in JAMA Neurology.
And within the group with the genetic risk factor, unmedicated hypertension was associated with the greatest risk for accumulating beta-amyloid, while participants with controlled hypertension had significantly less amyloid burden than the unmedicated group and just slightly more than those without hypertension.
Since hypertension is highly responsive to treatment, the researchers argued, medication or lifestyle modifications "may be able to prevent, or at least slow, pathological aging."
Current theories suggest that deposition of beta-amyloid in the brain is one of the earliest signs of Alzheimer's, Rodrigue and colleagues noted, and determining what factors affect that process might help with early detection and treatment.
The E4 allele of the apolipoprotein E (ApoE) gene is associated with increased risk for Alzheimer's – up to 12-fold higher for people with two copies of the variant, compared with those with two copies of the E3 allele, Rodrigue and colleagues noted.
As well, epidemiological studies have linked vascular disease with an increased risk for Alzheimer's, so the researchers hypothesized that hypertension and the ApoE4 allele might have a synergistic effect on beta-amyloid deposition.
To find out, they studied 147 cognitively normal adults – ages 30 to 89 -- who had cognitive testing, magnetic resonance imaging, and fluorine 18–labeled florbetapir positron emission tomography imaging (to determine beta-amyloid levels in the brain) as part of the Dallas Lifespan Brain study.
The participants also had blood drawn to determine their ApoE genotype and had seven blood pressure measurements during study visits.
All told, 75 volunteers had normal blood pressure, but the normotensive and hypertensive groups were significantly different in age, so Rodrigue and colleagues excluded normotensive volunteers younger than 47 – the youngest age in the hypertensive group.
In the reduced cohort of 118 people, 69 had high blood pressure, including 54 who were medicated for the condition. If they carried at least one E4 allele, participants were classified as having genetic risk; 18.6% had one allele and 4.2% had two.
Analysis showed that hypertension and genetic risk had a significant interaction at P<0.05, the researchers reported.
Among those with normal blood pressure, the presence of the E4 allele made no difference in uptake of beta-amyloid, they found, but in the participants with high blood pressure, having the E4 allele meant a significant increase in beta-amyloid deposition (P=0.05).
When participants were stratified by genetic risk, there was no significant difference in amyloid burden by blood pressure among those without the E4 allele.
On the other hand, among those with the allele, normal blood pressure was associated with amyloid burden similar to the non-E4 group. Those with high blood pressure controlled by medication had a higher burden, but not significantly so.
But participants with unmedicated hypertension and the E4 allele had significantly higher levels of amyloid burden than all other groups (P=0.02), Rodrigue and colleagues reported.
Although more study is needed, "these initial findings suggest that individuals with an ApoE4 allele may be able to attenuate their likelihood for amyloid accumulation through proper control of blood pressure," the researchers argued.
Rodrigue and colleagues cautioned that the study was snapshot and can't say anything about cause and effect. As well, the study population is highly screened for a study of healthy aging, so the results may not apply more widely.
Source: MedPage Today via JAMA Neurology reference: Rodrigue KM, et al "Risk factors for β-amyloid deposition in healthy aging: Vascular and genetic effects" JAMA Neurol 2013; DOI: 10.1001/jamaneurol.2013.1342.
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Green tea holds promise against Alzheimer's
Researchers at the University of Michigan have found that a molecule in green tea can prevent misfolding of specific proteins in the brain, which is associated with amyloid plaques in Alzheimer's disease.
The aggregation of these proteins, called metal-associated amyloids, is also associated with other neurodegenerative conditions.
U-M Life Sciences Institute faculty member Mi Hee Lim and an interdisciplinary team of researchers used green tea extract to control the generation of metal-associated amyloid-beta aggregates associated with Alzheimer's disease in the lab.
The specific molecule in green tea, epigallocatechin-3-gallate, also known as EGCG, prevented aggregate formation and broke down existing aggregate structures in the proteins that contained metalsâ€”specifically copper, iron and zinc.
"A lot of people are very excited about this molecule," said Lim, noting that the EGCG and other flavonoids in natural products have long been established as powerful antioxidants.
"We used a multidisciplinary approach. This is the first example of structure-centric, multidisciplinary investigations by three principal investigators with three different areas of expertise," the researcher added.
The research team included chemists, biochemists and biophysicists.
While many researchers are investigating small molecules and metal-associated amyloids, most are looking from a limited perspective, said Lim, assistant professor of chemistry and research assistant professor at the Life Sciences Institute, where her lab is located and her research is conducted.
"But we believe you have to have a lot of approaches working together, because the brain is very complex," she said.
Lim and her team's next step is to "tweak" the molecule and then test its ability to interfere with plaque formation in fruit flies.
"We want to modify them for the brain, specifically to interfere with the plaques associated with Alzheimer's," she said.
The study was published recently in the Proceedings of the National Academy of Sciences.
Source : The Times of India
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Tea, wine extracts disable Alzheimer’s ‘clumps’
Chemicals from green tea and red wine may disrupt a key step in the progression of Alzheimer’s disease, a new study shows.
In early-stage laboratory experiments, the researchers identified the process that allows harmful clumps of protein to latch on to brain cells, causing them to die. They were able to interrupt this pathway using the purified extracts of EGCG from green tea and resveratrol from red wine.
The findings, published in the Journal of Biological Chemistry, offer potential new targets for developing drugs to treat Alzheimer’s disease, which affects some 800,000 people in the UK alone, and for which there is currently no cure.
“This is an important step in increasing our understanding of the cause and progression of Alzheimer’s disease,” says lead researcher Professor Nigel Hooper of the University of Leeds. “It’s a misconception that Alzheimer’s is a natural part of aging; it’s a disease that we believe can ultimately be cured through finding new opportunities for drug targets like this.”
Alzheimer’s disease is characterized by a distinct build-up of amyloid protein in the brain, which clumps together to form toxic, sticky balls of varying shapes. These amyloid balls latch onto the surface of nerve cells in the brain by attaching to proteins on the cell surface called prions, causing the nerve cells to malfunction and eventually die.
“We wanted to investigate whether the precise shape of the amyloid balls is essential for them to attach to the prion receptors, like the way a baseball fits snugly into its glove,” says co-author Jo Rushworth. “And if so, we wanted to see if we could prevent the amyloid balls binding to prion by altering their shape, as this would stop the cells from dying.”
The team formed amyloid balls in a test tube and added them to human and animal brain cells. “When we added the extracts from red wine and green tea, which recent research has shown to re-shape amyloid proteins, the amyloid balls no longer harmed the nerve cells,” says Hooper. “We saw that this was because their shape was distorted, so they could no longer bind to prion and disrupt cell function.
“We also showed, for the first time, that when amyloid balls stick to prion, it triggers the production of even more amyloid, in a deadly vicious cycle,” he adds.
Hooper says that the team’s next steps are to understand exactly how the amyloid-prion interaction kills off neurons. “I’m certain that this will increase our understanding of Alzheimer’s disease even further, with the potential to reveal yet more drug targets,” he says.
“Understanding the causes of Alzheimer’s is vital if we are to find a way of stopping the disease in its tracks,” says Simon Ridley, head of research at Alzheimer’s Research UK, the UK’s leading dementia research charity, which partly funded the study.
“While these early-stage results should not be a signal for people to stock up on green tea and red wine, they could provide an important new lead in the search for new and effective treatments. With half a million people affected by Alzheimer’s in the UK, we urgently need treatments that can halt the disease—that means it’s crucial to invest in research to take results like these from the lab bench to the clinic.”
The Wellcome Trust, Alzheimer’s Research UK, and the Medical Research Council funded the study.
Source : Futurity via Leeds University
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High cholesterol linked to dementia with stroke
Having high serum levels may increase risk of dementia with stroke in elderly people, according to a study in the Journal of American Medical Association.
The study led by Joan T. Moroney, MD, MRCPI and colleagues found levels of low density lipoprotein (LDL) cholesterol were significantly correlated with an increased risk of dementia with stroke.
For the study, Moroney et al. followed a total of 1,111 nondemented participants with a mean age of 75 years for an average 2.1 years. Total srum cholesterol, low-density lipoprotein cholesterol, high density lipoportein cholesterol, lipoproteins(a) and apolipoprotein E genotype were determined at baseline.
During the follow-up, 286 participants developed dementia, 61 were diagnosed with dementia with stroke, and 225 with probable Alzheimer's disease.
Participants in the highest quartile of LDL cholesterol were found to be three times as likely as those in the lowest quartile of LDL cholesterol to be diagnosed with dementia with stroke after adjustment for vascular risk factors and demographic factors.
And serum levels of LDL corrected for lipoprotein(a) were even more significantly associated with risk of dementia with stroke. Participants in the highest quartile of lipoprotein(a)–corrected LDL cholesterol were four times as likely as those in the lowest quartile to develop dementia with stroke after adjustment for confounders.
Serum levels of lipid or lipoprotein levels were not associated with the development of Alzheimer disease in the study population.
The researchers concluded "Elevated levels of LDL cholesterol were associated with the risk of dementia with stroke in elderly patients. Further study is needed to determine whether treatment of elevated LDL cholesterol levels will reduce the risk of dementia with stroke."
Statins can lower cholesterol, but can also cause side effects. Red yeast rice is a safe alternative, which is as effectively as statins at lowering cholesterol.
Source : Food Consumer
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Simple Tests May Flag Dementia, Stroke Risk.
Walking speed and hand-grip strength during middle age correlated with cognitive function and stroke risk in older adults, suggesting simple tests might aid diagnosis of the two conditions, according to data from a large cohort study.
During 11 years of follow-up, slower walking speed at baseline was associated with a 50% rise in the hazard for dementia. Brain volume and performance on a variety of tests of cognitive function also were significantly lower in slower walkers.
Grip strength did not influence stroke risk in the overall cohort, but a higher baseline grip strength was associated with a 42% reduction in stroke risk among individuals 65 and older, as will be reported here in April at the American Academy of Neurology meeting.
"These are basic office tests [that] can provide insight into the risk of dementia and stroke and can be easily performed by a neurologist or general practitioner," Erica C. Camargo, MD, PhD, of Boston Medical Center, said in a statement.
"While frailty and lower physical performance in elderly people have been associated with an increased risk of dementia, we weren't sure until now how it impacted people of middle age," she added.
The findings came from an analysis of data from the Framingham Offspring Cohort, children of the original participants in the long-running study of the natural history of cardiovascular disease.
Camargo and colleagues analyzed data for 2,410 participants in the offspring cohort study, mean age 62, all of whom were stroke- and dementia-free at baseline. The initial workup included assessments of walking speed, grip strength, and cognitive function, as well as MRI scans of the brain.
The investigators statistically related age-standardized grip strength and walking speed with baseline cerebral volume estimated by MRI, with age- and education-standardized cognitive function and with stroke and dementia incidence.
During follow-up, 34 participants developed dementia, and 79 had strokes or transient ischemic attacks (TIAs). Slower walking speed had a significant correlation with:
- Increased stroke risk (HR 1.50, P=0.020)
- Lower total cerebral volume (P=0.007)
- Poorer performance on tests of various aspects of memory (visual reproduction, P=0.009; paired associate learning, P<0.001; executive function, P=0.004; visuo-perceptual function, P=0.002; and language, P=0.006)
Increasing grip strength also was associated with:
- Total cerebral brain volume (P<0.001)
- Visual reproduction (P<0.001)
- Executive function (P=0.009)
- Visuo-perceptional function (P<0.001)
- Language (P=0.002)
- Better abstraction (P=0.009)
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