Association of Whole Grain Consumption and Cognitive Decline: An Investigation From a Community-Based Biracial Cohort of Older Adults.

BACKGROUND AND OBJECTIVES: To examine the association of whole grain consumption and longitudinal change in global cognition, perceptual speed, and episodic memory by different race/ethnicity. METHODS: We included 3,326 participants from the Chicago Health and Aging Project who responded to a Food Frequency Questionnaire (FFQ), with 2 or more cognitive assessments. Global cognition was assessed using a composite score of episodic memory, perceptual speed, and the Mini Mental State Examination (MMSE). Diet was assessed by a 144-item FFQ. Linear mixed-effects models were used to estimate the association of intakes of whole grains and cognitive decline. RESULTS: This study involved 3,326 participants (60.1% African American [AA], 63.7% female) with a mean age of 75 years at baseline and a mean follow-up of 6.1 years. Higher consumption of whole grains was associated with a slower rate of global cognitive decline. Among AA participants, those in the highest quintile of whole grain consumption had a slower rate of decline in global cognition (ß = 0.024, 95% CI [0.008-0.039], p = 0.004), perceptual speed (ß = 0.023, 95% CI [0.007-0.040], p = 0.005), and episodic memory (ß = 0.028, 95% CI [0.005-0.050], p = 0.01) compared with those on the lowest quintile. Regarding the amount consumed, in AA participants, those who consumed >3 servings/d vs those who consumed <1 serving/d had a slower rate of decline in global cognition (ß = 0.021, 95% CI [0.005-0.036], p = 0.0093). In White participants, with >3 servings/d, we found a suggestive association of whole grains with global cognitive decline when compared with those who consumed <1 serving/d (ß = 0.025, 95% CI [-0.003 to 0.053], p = 0.08). DISCUSSION: Among AA participants, individuals with higher consumption of whole grains and more frequent consumption of whole grain had slower decline in global cognition, perceptual speed, and episodic memory. We did not see a similar trend in White adults.

Dietary Sugar Intake Associated with a Higher Risk of Dementia in Community-Dwelling Older Adults.

BACKGROUND: We have limited evidence for the relationship of high sugar intake with dementia risk. OBJECTIVE: To determine whether high sugar intake is associated with an increased risk of dementia in community-dwelling older adultsMethods:This study included 789 participants of the Rush Memory and Aging Project (community-based longitudinal cohort study of older adults free of known dementia at enrollment), with annual clinical assessments and complete nutrient data (obtained by validated food frequency questionnaire). Clinical diagnosis of dementia is based on the criteria of the joint working group of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. We used Cox proportional hazard models. RESULTS: 118 participants developed dementia during 7.3±3.8 years of follow-up. Those in the highest quintile of total sugar intake were twice as likely to develop dementia than those in the lowest quintile (Q5 versus Q1:HR=2.10 (95% CI: 1.05, 4.19) when adjusted for age, sex, education, APOEɛ4 allele, calories from sources other than sugar, physical activity, and diet score. Higher percent calories from sugar were positively associated with dementia risk (ß=0.042, p = 0.0009). In exploratory analyses, the highest versus lowest quintile of fructose and sucrose in the diet had higher dementia risk by 2.8 (95% CI: 1.38, 5.67) and 1.93 (95% CI: 1.05, 3.54) times, respectively. CONCLUSIONS: A higher intake of total sugar or total calories from sugar is associated with increased dementia risk in older adults. Among simple sugars, fructose (e.g., sweetened beverages, snacks, packaged desserts) and sucrose (table sugar in juices, desserts, candies, and commercial cereals) are associated with higher dementia risk.

Cardiovascular health and cognitive outcomes: Findings from a biracial population-based study in the United States.

INTRODUCTION: The aim of this study was to evaluate the association of cardiovascular health (CVH) with cognitive outcomes, including incident Alzheimer's dementia, rate of cognitive decline, and measures of brain injury and structure. METHODS: This study consisted of 1702 Black or African American and White participants living in the south side of Chicago, Illinois, and enrolled in the Chicago Health and Aging Project, a population-based cohort since 1993. CVH was based on seven risk factors, including diet, physical activity, body mass index, smoking, dyslipidemia, hypertension, and diabetes. RESULTS: In a multivariable-adjusted model, CVH was associated with a lower risk of Alzheimer's dementia. The hazard ratio per 1 additional point in CVH score was 0.84 (95% CI 0.76, 0.94). CVH was also associated with a slower rate of cognitive decline and less volume (injury) in white matter hyperintensities. DISCUSSION: Promoting CVH in communities with Black residents may lower the future risk of Alzheimer's dementia.

Trial of the MIND Diet for Prevention of Cognitive Decline in Older Persons.

BACKGROUND: Findings from observational studies suggest that dietary patterns may offer protective benefits against cognitive decline, but data from clinical trials are limited. The Mediterranean-DASH Intervention for Neurodegenerative Delay, known as the MIND diet, is a hybrid of the Mediterranean diet and the DASH (Dietary Approaches to Stop Hypertension) diet, with modifications to include foods that have been putatively associated with a decreased risk of dementia. METHODS: We performed a two-site, randomized, controlled trial involving older adults without cognitive impairment but with a family history of dementia, a body-mass index (the weight in kilograms divided by the square of the height in meters) greater than 25, and a suboptimal diet, as determined by means of a 14-item questionnaire, to test the cognitive effects of the MIND diet with mild caloric restriction as compared with a control diet with mild caloric restriction. We assigned the participants in a 1:1 ratio to follow the intervention or the control diet for 3 years. All the participants received counseling regarding adherence to their assigned diet plus support to promote weight loss. The primary end point was the change from baseline in a global cognition score and four cognitive domain scores, all of which were derived from a 12-test battery. The raw scores from each test were converted to z scores, which were averaged across all tests to create the global cognition score and across component tests to create the four domain scores; higher scores indicate better cognitive performance. The secondary outcome was the change from baseline in magnetic resonance imaging (MRI)-derived measures of brain characteristics in a nonrandom sample of participants. RESULTS: A total of 1929 persons underwent screening, and 604 were enrolled; 301 were assigned to the MIND-diet group and 303 to the control-diet group. The trial was completed by 93.4% of the participants. From baseline to year 3, improvements in global cognition scores were observed in both groups, with increases of 0.205 standardized units in the MIND-diet group and 0.170 standardized units in the control-diet group (mean difference, 0.035 standardized units; 95% confidence interval, -0.022 to 0.092; P = 0.23). Changes in white-matter hyperintensities, hippocampal volumes, and total gray- and white-matter volumes on MRI were similar in the two groups. CONCLUSIONS: Among cognitively unimpaired participants with a family history of dementia, changes in cognition and brain MRI outcomes from baseline to year 3 did not differ significantly between those who followed the MIND diet and those who followed the control diet with mild caloric restriction. (Funded by the National Institute on Aging; ClinicalTrials.gov number, NCT02817074.).

Brain vitamin D forms, cognitive decline, and neuropathology in community-dwelling older adults.

INTRODUCTION: Vitamin D purportedly protects against cognitive decline and dementia based on observational data using circulating 25-hydroxyvitamin D (25(OH)D). Little is known about vitamin D in the human brain and the association with dementia or neuropathology. METHODS: Decedents of the Rush Memory and Aging Project (n = 290) had vitamin D concentrations measured in four brain regions. Associations with cognitive and neuropathological outcomes were estimated using linear and logistic regression. RESULTS: The main form of vitamin D in all brain regions measured was 25(OH)D3 . Higher brain 25(OH)D3 concentrations were associated with a 25% to 33% lower odds of dementia or mild cognitive impairment (MCI) at the last visit before death (all P ≤ .031). However, brain 25(OH)D concentrations were not associated with any post-mortem neuropathology outcome studied. DISCUSSION: Higher brain 25(OH)D3 concentrations were associated with better cognitive function prior to death. Additional research is needed to clarify the specific mechanisms underlying this potentially protective relationship.

Lifestyle and Cognitive Decline in Community-Dwelling Stroke Survivors.

BACKGROUND: Patients with stroke are at a higher risk of cognitive impairment and Alzheimer's disease dementia. OBJECTIVE: To quantify the role of lifestyle pre-stroke, post-stroke, and changes in lifestyle before and after stroke with cognitive decline in community-dwelling stroke survivors. METHODS: Utilizing data from the Chicago Health and Aging Project, a population-based cohort study, we studied 1,078 individuals with stroke (662 incident and 416 prevalent) who underwent cognitive testing during the study period. A healthy lifestyle score was defined by scoring four behaviors: non-smoking, exercising, being cognitively active, and having a high-quality diet. The global cognitive score was derived from a comprehensive battery of 4 standardized tests. RESULTS: The mean age at incident stroke was 78.2 years, and 60.1% were women. A healthy lifestyle pre-incident stroke was associated with a slower rate of cognitive decline after stroke. Participants with 3-4 healthy lifestyle factors pre-incident stroke had a slower cognitive decline after stroke by 0.046 units/year (95% CI 0.010, 0.083), or 47.7% slower, than participants with 0-1 healthy lifestyle factor. Lifestyle score post-prevalent stroke was not associated with cognitive decline. Changes in lifestyle behaviors from pre- to post-incident stroke were related to cognitive decline after stroke. Individuals who deteriorated their lifestyle quality after stroke had a faster cognitive decline by 0.051 units/year (ß -0.051, 95% CI -0.090, -0.012) than participants with no change in lifestyle score. CONCLUSION: A healthy lifestyle pre-stroke was associated with a slower rate of cognitive decline in stroke survivors, highlighting the importance of primary prevention. After the stroke, changes in lifestyle behaviors may influence the cognitive abilities of older adults as they age.

A healthy plant-based diet was associated with slower cognitive decline in African American older adults: a biracial community-based cohort.

BACKGROUND: African American (AA) adults have about twice the risk of developing dementia compared with white adults. However, evidence on dietary modification in preventing cognitive decline from diverse populations focusing on AA adults is minimal. OBJECTIVES: We aimed to evaluate the association between a plant-based diet and the rate of cognitive decline in a population-based sample of AA and white adults. METHODS: This study consisted of 3337 participants from the Chicago Health and Aging Project (60% AA participants, 64% female). Plant-based diet quality was evaluated by the overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI). Global cognition was assessed using a composite score of 4 individual tests of cognition. We used mixed models to examine the associations of PDI, hPDI, and uPDI with the rates of decline in global cognition, perceptual speed, and episodic memory. Models were adjusted for age, sex, presence of apoE e4 allele, lifestyle factors including education, cognitive activities, smoking status, calorie intake, risk factors for cardiovascular disease, time, and the interaction terms of time × each covariate. RESULTS: AA and white participants had various dietary patterns. Higher hPDI was associated with a slower rate of decline in global cognition, perceptual speed, and episodic memory in AA participants but not white participants. AA study participants in the highest quintile of hPDI had significantly slower rates of global cognitive decline (ß: 0.0183 ± 0.0086; P = 0.032), perceptual speed (ß: 0.0179 ± 0.0088; P = 0.04), and episodic memory (ß: 0.0163 ± 0.0118; P = 0.04) than individuals in the lowest quintile of hPDI. There were no associations of either PDI or uPDI with the rate of cognitive decline in either racial group. CONCLUSIONS: A healthy plant-based diet was associated with a slower rate of decline in global cognition, perceptual speed, and episodic memory in AA adults.

Pelargonidin and Berry Intake Association with Alzheimer's Disease Neuropathology: A Community-Based Study.

BACKGROUND: An anthocyanidin, pelargonidin, primarily found in berries, has antioxidant and anti-inflammatory properties, and is associated with better cognition and reduced Alzheimer's dementia risk. OBJECTIVE: This study investigated if pelargonidin or berry intake is associated with Alzheimer's disease (AD) neuropathology in human brains. METHODS: The study was conducted among 575 deceased participants (age at death = 91.3±6.1 years; 70% females) of the Rush Memory and Aging Project, with dietary data (assessed using a food frequency questionnaire) and neuropathological evaluations. Calorie-adjusted pelargonidin intake was modeled in quartiles and berry intake as continuous (servings/week). Mean amyloid-beta load and phosphorylated tau neuronal neurofibrillary tangle density across multiple cortical regions were assessed using immunohistochemistry. Global AD pathology burden, a quantitative summary score of neurofibrillary tangles, and diffuse and neuritic plaques using Bielschowsky silver stains in multiple brain regions, was also assessed. RESULTS: In a linear regression model adjusted for age at death, sex, education, APOE ɛ4 status, vitamin E, and vitamin C, participants in the highest quartile of pelargonidin intake when compared to those in the lowest quartile, had less amyloid-ß load (ß (SE) = -0.293 (0.14), p = 0.038), and fewer phosphorylated tau tangles (ß (SE) = -0.310, p = 0.051). Among APOE ɛ4 non-carriers, higher strawberry (ß (SE) = -0.227 (0.11), p = 0.037) and pelargonidin (Q4 versus Q1: ß (SE) = -0.401 (0.16), p = 0.011; p trend = 0.010) intake was associated with less phosphorylated tau tangles, no association was observed in APOE ɛ4 carriers. Berry intake was not associated with AD pathology. However, excluding participants with dementia or mild cognitive impairment at baseline, strawberry (p = 0.004) and pelargonidin (ptrend = 0.007) intake were associated with fewer phosphorylated tau tangles. CONCLUSION: Higher intake of pelargonidin, a bioactive present in strawberries, is associated with less AD neuropathology, primarily phosphorylated tau tangles.

Association of vitamin K with cognitive decline and neuropathology in community-dwelling older persons.

Higher vitamin K intakes have been associated with better cognitive function, suggestive of a vitamin K mechanistic effect or simply reflective of a healthy diet. To test the hypothesis that brain vitamin K is linked to cognitive decline and dementia, vitamin K concentrations were measured in four brain regions, and their associations with cognitive and neuropathological outcomes were estimated in 325 decedents of the Rush Memory and Aging Project. Menaquinone-4 (MK4) was the main vitamin K form in the brain regions evaluated. Higher brain MK4 concentrations were associated with a 17% to 20% lower odds of dementia or mild cognitive impairment (MCI) (P-value < .014), with a 14% to 16% lower odds of Braak stage ≥IV (P-value < 0.045), with lower Alzheimer's disease global pathology scores and fewer neuronal neurofibrillary tangles (P-value < 0.012). These findings provide new and compelling evidence implicating vitamin K in neuropathology underlying cognitive decline and dementia.

Healthy lifestyle and life expectancy with and without Alzheimer's dementia: population based cohort study.

OBJECTIVE: To determine the impact of lifestyle factors on life expectancy lived with and without Alzheimer's dementia. DESIGN: Prospective cohort study. SETTING: The Chicago Health and Aging Project, a population based cohort study in the United States. PARTICIPANTS: 2449 men and women aged 65 years and older. MAIN EXPOSURE: A healthy lifestyle score was developed based on five modifiable lifestyle factors: a diet for brain health (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay-MIND diet score in upper 40% of cohort distribution), late life cognitive activities (composite score in upper 40%), moderate or vigorous physical activity (≥150 min/week), no smoking, and light to moderate alcohol consumption (women 1-15 g/day; men 1-30 g/day). MAIN OUTCOME: Life expectancy with and without Alzheimer's dementia in women and men. RESULTS: Women aged 65 with four or five healthy factors had a life expectancy of 24.2 years (95% confidence interval 22.8 to 25.5) and lived 3.1 years longer than women aged 65 with zero or one healthy factor (life expectancy 21.1 years, 19.5 to 22.4). Of the total life expectancy at age 65, women with four or five healthy factors spent 10.8% (2.6 years, 2.0 to 3.3) of their remaining years with Alzheimer's dementia, whereas women with zero or one healthy factor spent 19.3% (4.1 years, 3.2 to 5.1) with the disease. Life expectancy for women aged 65 without Alzheimer's dementia and four or five healthy factors was 21.5 years (20.0 to 22.7), and for those with zero or one healthy factor it was 17.0 years (15.5 to 18.3). Men aged 65 with four or five healthy factors had a total life expectancy of 23.1 years (21.4 to 25.6), which is 5.7 years longer than men aged 65 with zero or one healthy factor (life expectancy 17.4 years, 15.8 to 20.1). Of the total life expectancy at age 65, men with four or five healthy factors spent 6.1% (1.4 years, 0.3 to 2.0) of their remaining years with Alzheimer's dementia, and those with zero or one healthy factor spent 12.0% (2.1 years, 0.2 to 3.0) with the disease. Life expectancy for men aged 65 without Alzheimer's dementia and four or five healthy factors was 21.7 years (19.7 to 24.9), and for those with zero or one healthy factor life expectancy was 15.3 years (13.4 to 19.1). CONCLUSION: A healthy lifestyle was associated with a longer life expectancy among men and women, and they lived a larger proportion of their remaining years without Alzheimer's dementia. The life expectancy estimates might help health professionals, policy makers, and stakeholders to plan future healthcare services, costs, and needs.

Primary prevention recommendations to reduce the risk of cognitive decline.

INTRODUCTION: Few resources address steps clinicians can take to help patients reduce their risk of dementia, despite growing recognition that brain health can be optimized and that risk reduction for cognitive decline can be accomplished by lifestyle modifications. METHODS: To address this gap, UsAgainstAlzheimer's convened a risk reduction workgroup (RRWG) to review existing evidence and develop recommendations for primary care clinicians discussing cognitive decline and risk reduction with their patients.  RESULTS: The RRWG produced 11 consensus-based recommendations and implementation strategies across six topics: neurovascular risk management, physical activity, sleep, nutrition, social isolation, and cognitive stimulation.  DISCUSSION: These recommendations are a first step for clinicians to address brain health with patients and potentially help them prevent cognitive decline. To ensure there is routine care for brain health, proper incentives and policies must be instituted and more education for consumers should be provided.

Dietary antioxidants associated with slower progression of parkinsonian signs in older adults.

Background and Objective: Progressive loss of motor function including parkinsonian signs is common in older adults. As diet may contribute to the motor decline, we tested the hypothesis that dietary intake of antioxidant nutrients (carotenoids, vitamin E and vitamin C) is related to the progression of parkinsonian signs in older adults.Research Design and Methods: A total of 682 participants without a clinical diagnosis of Parkinson's Disease from the Rush Memory and Aging Project, were assessed annually over an average of 5.7 (±3.0) years using a 26-item modified version of the United Parkinson's Disease Rating Scale. The scale assesses the severity of four parkinsonian signs (bradykinesia, gait, tremors, and rigidity) that were averaged to construct a global parkinsonian sign score. Nutrient intakes were assessed at baseline using a validated food frequency questionnaire. The associations between quintiles of antioxidant nutrient intakes and progression of parkinsonian signs were assessed using mixed effects models adjusted for age, sex, education, smoking.Results: In separate adjusted models, a slower rate of progressive parkinsonian signs was observed among those in the highest intake quintiles of total carotenoids (ß= -0.06, 95%CI: -0.10 to -0.02,), beta-carotene from foods (ß= -0.04, 95% CI:-0.08 to -0.0021), lutein-zeaxanthin (ß= -0.05, 95%CI:-0.09 to -0.02), vitamin E from foods (ß= -0.04, 95%CI:-0.08 to -0.01,) and vitamin C from foods (ß= -0.06, 95%CI:-0.10 to -0.02), when compared to those in the lowest quintiles of intake.Conclusion: A higher level of dietary antioxidant nutrients may slow the rate of parkinsonian sign progression in older adults.

Genetic risk, adherence to a healthy lifestyle, and cognitive decline in African Americans and European Americans.

INTRODUCTION: We investigated the role of genetic risk and adherence to lifestyle factors on cognitive decline in African Americans and European Americans. METHODS: Using data from the Chicago Health and Aging Project (1993-2012; n = 3874), we defined the genetic risk based on presence of apolipoprotein E (APOE) ε4$\varepsilon 4$ allele and determined a healthy lifestyle using a scoring of five factors: non-smoking, exercising, being cognitively active, having a high-quality diet, and limiting alcohol use. We used linear mixed-effects models to estimate cognitive decline by genetic risk and lifestyle score. RESULTS: APOE  ε4$\varepsilon 4$ allele was associated with faster cognitive decline in both races. However, within APOE  ε4$\varepsilon 4$ carriers, adherence to a healthy lifestyle (eg., 4 to 5 healthy factors) was associated with a slower cognitive decline by 0.023 (95% confidence interval [CI] 0.004, 0.042) units/year in African Americans and 0.044 (95% CI 0.008, 0.080) units/year in European Americans. DISCUSSION: A healthy lifestyle was associated with a slower cognitive decline in African and European Americans.

MIND Dietary Pattern and Its Association with Cognition and Incident Dementia in the UK Biobank.

A high adherence to the Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurodegenerative Delay (MIND) has been associated with better cognition and a lower risk of dementia in some but not all studies. We measured adherence to MIND and its association with cognitive health in the UK Biobank (UKB). A MIND score was derived from 24 h diet recall questionnaires for 120,661 participants who completed at least one of seven self-administered cognitive function tests. In a subset of 78,663 participants aged 55+, diagnosis of dementia was determined by linked hospital and death records. Multivariable regression and Cox proportional hazard ratio (HR) models were used to examine associations of MIND with cognitive ability and incident dementia. Higher adherence to MIND was associated with a small but significant worsening in performance on five of seven cognitive tests (p < 0.002). Associations were strongest among highly educated participants (p < 0.002 for MIND × education interaction). After a mean follow-up time of 10.5 years, 842 participants developed dementia. Overall, MIND adherence was not associated with incident dementia. An inverse association was observed among females (HR = 0.87 per score standard deviation (SD), p = 0.008) but not males (HR = 1.09, p = 0.11) (p = 0.008 for MIND × sex interaction). Similar associations with cognitive ability and dementia were observed for the Alternative Healthy Eating Index-2010 (AHEI-2010) dietary pattern. Associations were not modified by genetic susceptibility. In UKB, the MIND diet was not associated with better cognitive test scores and only with lower dementia risk in women.

Unhealthy foods may attenuate the beneficial relation of a Mediterranean diet to cognitive decline.

INTRODUCTION: It is unclear whether eating Western diet food components offsets the Mediterranean diet's (MedDiet) potential benefits on cognitive decline. METHODS: The study includes 5001 Chicago Health and Aging Project participants (63% African American, 36% males, 74 ± 6.0 years old), with food frequency questionnaires and ≥ two cognitive assessments over 6.3 ± 2.8 years of follow-up. Mixed-effects models were adjusted for age, sex, education, race, cognitive activities, physical activity, and total calories. RESULTS: Stratified analysis showed a significant effect of higher MedDiet on cognitive decline only with a low Western diet score (highest vs lowest MedDiet tertile: ß = 0.020, P = .002; p trend = 0.002) and not with a high Western diet score (highest vs lowest MedDiet tertile: ß = 0.010, P = .11; p trend = 0.09). CONCLUSION: This prospective study found that high consumption of Western diet components attenuates benefits of the MedDiet on cognition.

Vitamin D and Vitamin K Concentrations in Human Brain Tissue Are Influenced by Freezer Storage Time: The Memory and Aging Project.

BACKGROUND: Vitamins D and K, which are present in human brain, may have a role in neurodegenerative disease. OBJECTIVES: Given the interest in measuring nutrient concentrations in archived brain samples, it is important to evaluate whether freezer storage time affects these concentrations. Therefore, we evaluated differences in vitamin D and vitamin K concentrations in human brain samples stored for various lengths of time. METHODS: Postmortem brain samples were obtained from 499 participants in the Rush Memory and Aging Project (mean age 92 y, 72% female). Concentrations of vitamins D and K and their metabolites were measured in 4 regions (midtemporal cortex, midfrontal cortex, cerebellum, anterior watershed white matter) using LC-MS/MS and HPLC, respectively. The predominant forms were 25-hydroxycholecalciferol [25(OH)D3] and menaquinone-4 (MK4). ANOVA was used to determine if concentrations differed according to storage time. RESULTS: The geometric mean of the mean 25(OH)D3 concentration (across 4 regions) in brains stored for 1.1 to 6.0 y did not differ from that in brains stored ≤1.0 y (all P ≥ 0.37), whereas 25(OH)D3 in brains stored >6.0 y was 31-40% lower (P ≤ 0.003). MK4 had similar results, with the geometric mean MK4 concentration in the brains stored ≥9.0 y being 48-52% lower than those in brains stored ≤1.0 y (P ≤ 0.012). The 25(OH)D3 and MK4 concentrations were positively correlated across all 4 regions (all Spearman ρ ≥ 0.79, P < 0.001). CONCLUSIONS: 25(OH)D3 and MK4 appear to be stable in brain tissue from older adults stored at -80°C for up to 6 and 9 y, respectively, but not longer. Freezer storage time should be considered in the design and interpretation of studies using archived brain tissue.

Dietary flavonols and risk of Alzheimer dementia.

OBJECTIVE: To determine whether dietary intake of flavonols is associated with Alzheimer dementia. METHODS: The study was conducted among 921 participants of the Rush Memory and Aging Project (MAP), an ongoing community-based, prospective cohort. Participants completed annual neurologic evaluations and dietary assessments using a validated food frequency questionnaire. RESULTS: Among 921 MAP participants who initially had no dementia in the analyzed sample, 220 developed Alzheimer dementia. The mean age of the sample was 81.2 years (SD 7.2), with the majority (n = 691, 75%) being female. Participants with the highest intake of total flavonols had higher levels of education and more participation in physical and cognitive activities. In Cox proportional hazards models, dietary intakes of flavonols were inversely associated with incident Alzheimer dementia in models adjusted for age, sex, education, APOE ɛ4, and participation in cognitive and physical activities. Hazard ratios (HRs) for the fifth vs first quintiles of intake were as follows: for total flavonol, 0.52 (95% confidence interval [CI], 0.33-0.84); for kaempferol, 0.49 (95% CI, 0.31-0.77); for myricetin, 0.62 (95% CI, 0.4-0.97); and for isorhamnetin, 0.62 (95% CI, 0.39-0.98). Quercetin was not associated with Alzheimer dementia (HR, 0.69; 95% CI, 0.43-1.09). CONCLUSION: Higher dietary intakes of flavonols may be associated with reduced risk of developing Alzheimer dementia.

Association of Strawberries and Anthocyanidin Intake with Alzheimer's Dementia Risk.

BACKGROUND: Strawberries have been identified to have antioxidant and anti-inflammatory properties that improve neuronal function and cognition, mostly in animal studies. It is unknown if the consumption of strawberries or related bioactives may reduce the risk of Alzheimer's dementia risk. MATERIAL AND METHODS: The study was conducted in 925 participants, aged 58-98 years of the Rush Memory and Aging Project. Participants were dementia-free at baseline, completed a food frequency questionnaire, and had at least two annual neurological evaluations. The diagnosis of Alzheimer's dementia was based on structured clinical neurological examination and standardized diagnostic criteria. The association of strawberry intake and incident Alzheimer's dementia was analyzed using proportional hazard models adjusted for age, sex, education, physical activity, participation in cognitive activities, APOE-ɛ4 genotype, dietary intake of other fruits, and total calorie intake. RESULTS: A total of 245 participants developed Alzheimer's dementia over the mean follow-up of 6.7 (±3.6) years. Higher strawberry intake was associated with reduced risk of Alzheimer's dementia (HR = 0.76, 95% CI: 0.60-0.96). In separate adjusted models, highest vs. lowest quartile intakes of Vitamin C (HR = 0.64, 95% CI: 0.45, 0.92), Pelargonidin (0.63, 95% CI: 0.43, 0.92), total anthocyanidins (0.69, 95% CI: 0.48, 0.99), and total flavonoids (0.67, 95% CI: 0.46, 0.98) were each associated with lower Alzheimer's dementia risk. These associations remained after further adjustment for cardiovascular conditions. CONCLUSION: Consumption of strawberries and foods rich in vitamin C, pelargonidin, anthocyanidins, and total flavonoids may reduce the risk of Alzheimer's dementia.

Determination of Vitamin D and Its Metabolites in Human Brain Using an Ultra-Pressure LC-Tandem Mass Spectra Method.

BACKGROUND: Low serum total 25-hydroxyvitamin D3 [25(OH)D3] concentrations have been associated with cognitive impairment. However, it is unclear if serum 25(OH)D3 concentrations are a valid indicator of the concentrations of vitamin D and its metabolites in human brain. OBJECTIVES: The aim of this study was to develop and validate a method to quantify vitamin D3, 25(OH)D3, and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in human brain. METHODS: The assay developments were performed using porcine brains. Liquid extraction was used in homogenized samples (∼0.1 g each) prior to analysis by LC-MS/MS with electrospray ionization following derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione. This method was then applied to the determination of vitamin D and its metabolites in a whole human brain obtained from the National Development and Research Institutes. RESULTS: The method showed good linearity of vitamin D3, 25(OH)D3, and 1,25(OH)2D3 over the physiological range (R 2 = 0.9995, 0.9968, and 0.9970, respectively). The lowest detection limit for vitamin D3, 25(OH)D3, and 1,25(OH)2D3 in porcine brain was 25, 50 and 25 pg/g, respectively. The method was successfully applied to the determination of vitamin D3 and its metabolites in the prefrontal cortex, middle frontal cortex, middle temporal cortex, cerebellum, corpus callosum, medulla, and pons of a human brain. All analyzed human brain regions contained 25(OH)D3, with corpus callosum containing 334 pg/g compared with 158 pg/g in cerebellum. 1,25(OH)2D3 was only detected in prefrontal and middle frontal cortices at a very low level. No vitamin D3 was detected in any examined areas of this single human brain. CONCLUSIONS: To the best of our knowledge, this study is the first report of the measurement of concentrations of vitamin D metabolites in human brain. This validated method can be applied to postmortem studies to obtain accurate information about the presence and role of vitamin D and its metabolites in human brain and neurodegenerative diseases.