Association of Egg Intake With Alzheimer's Dementia Risk in Older Adults: The Rush Memory and Aging Project.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder with increasing prevalence due to population aging. Eggs provide many nutrients important for brain health, including choline, omega-3 fatty acids, and lutein. Emerging evidence suggests that frequent egg consumption may improve cognitive performance on verbal tests, but whether consumption influences the risk of Alzheimer's dementia and AD is unknown. OBJECTIVES: To examine the association of egg consumption with Alzheimer's dementia risk among the Rush Memory and Aging Project cohort. METHODS: Dietary assessment was collected using a modified Harvard semiquantitative food frequency questionnaire. Participants' first food frequency questionnaire was used as the baseline measure of egg consumption. Multivariable adjusted Cox proportional hazards regression models were used to investigate the associations of baseline egg consumption amount with Alzheimer's dementia risk, adjusting for potential confounding factors. Subgroup analyses using Cox and logistic regression models were performed to investigate the associations with AD pathology in the brain. Mediation analysis was conducted to examine the mediation effect of dietary choline in the relationship between egg intake and incident Alzheimer's dementia. RESULTS: This study included 1024 older adults {mean [±standard deviation (SD)] age = 81.38 ± 7.20 y}. Over a mean (±SD) follow-up of 6.7 ± 4.8 y, 280 participants (27.3%) were clinically diagnosed with Alzheimer's dementia. Weekly consumption of >1 egg/wk (hazard ratio [HR]: 0.53; 95% confidence interval [CI]: 0.34, 0.83) and ≥2 eggs/wk (HR: 0.53; 95% CI: 0.35, 0.81) was associated with a decreased risk of Alzheimer's dementia. Subgroup analysis of brain autopsies from 578 deceased participants showed that intakes of >1 egg/wk (HR: 0.51; 95% CI: 0.35, 0.76) and ≥2 eggs/wk (HR: 0.62; 95% CI: 0.44, 0.90) were associated with a lower risk of AD pathology in the brain. Mediation analysis showed that 39% of the total effect of egg intake on incident Alzheimer's dementia was mediated through dietary choline. CONCLUSIONS: These findings suggest that frequent egg consumption is associated with a lower risk of Alzheimer's dementia and AD pathology, and the association with Alzheimer's dementia is partially mediated through dietary choline.

MYB4, a member of R2R3-subfamily of MYB transcription factor functions as a repressor of key genes involved in flavonoid biosynthesis and repair of UV-B induced DNA double strand breaks in Arabidopsis.

Plants accumulate flavonoids as part of UV-B acclimation, while a high level of UV-B irradiation induces DNA damage and leads to genome instability. Here, we show that MYB4, a member of the R2R3-subfamily of MYB transcription factor plays important role in regulating plant response to UV-B exposure through the direct repression of the key genes involved in flavonoids biosynthesis and repair of DNA double-strand breaks (DSBs). Our results demonstrate that MYB4 inhibits seed germination and seedling establishment in Arabidopsis following UV-B exposure. Phenotype analyses of atmyb4-1 single mutant line along with uvr8-6/atmyb4-1, cop1-6/atmyb4-1, and hy5-215/atmyb4-1 double mutants indicate that MYB4 functions downstream of UVR8 mediated signaling pathway and negatively affects UV-B acclimation and cotyledon expansion. Our results indicate that MYB4 acts as transcriptional repressor of two key flavonoid biosynthesis genes, including 4CL and FLS, via directly binding to their promoter, thus reducing flavonoid accumulation. On the other hand, AtMYB4 overexpression leads to higher accumulation level of DSBs along with repressed expression of several key DSB repair genes, including AtATM, AtKU70, AtLIG4, AtXRCC4, AtBRCA1, AtSOG1, AtRAD51, and AtRAD54, respectively. Our results further suggest that MYB4 protein represses the expression of two crucial DSB repair genes, AtKU70 and AtXRCC4 through direct binding with their promoters. Together, our results indicate that MYB4 functions as an important coordinator to regulate plant response to UV-B through transcriptional regulation of key genes involved in flavonoids biosynthesis and repair of UV-B induced DNA damage.

Healthy Lifestyle and Cognition in Older Adults With Common Neuropathologies of Dementia.

Importance: A healthy lifestyle is associated with better cognitive functioning in older adults, but whether this association is independent of the accumulation of dementia-related pathologies in the brain is uncertain. Objective: To determine the role of postmortem brain pathology, including ß-amyloid load, phosphorylated tau tangles, cerebrovascular pathology, and other brain pathologies, in the association between lifestyle and cognition proximate to death. Design, Setting, and Participants: This cohort study used data from the Rush Memory and Aging Project, a longitudinal clinical-pathologic study with autopsy data from 1997 to 2022 and up to 24 years of follow-up. Participants included 754 deceased individuals with data on lifestyle factors, cognitive testing proximate to death, and a complete neuropathologic evaluation at the time of these analyses. Data were analyzed from January 2023 to June 2023. Exposures: A healthy lifestyle score was developed based on self-reported factors, including noncurrent smoking, at least 150 minutes of physical activity per week, limiting alcohol consumption, a Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet score higher than 7.5, and a late-life cognitive activity score higher than 3.2. The lifestyle score ranges from 0 to 5, with higher scores reflecting a healthier lifestyle. Main Outcomes and Measures: The global cognitive score was derived from a battery of nineteen standardized tests. Brain pathology measures included ß-amyloid load, phosphorylated tau tangles, global Alzheimer disease pathology, vascular brain pathologies, Lewy body, hippocampal sclerosis, and TAR DNA-binding protein 43. Results: Of 586 included decedents, 415 (70.8%) were female, 171 (29.2%) were male, and the mean (SD) age at death was 90.9 (6.0) years. Higher lifestyle score was associated with better global cognitive functioning proximate to death. In the multivariable-adjusted model, a 1-point increase in lifestyle score was associated with 0.216 (SE = 0.036, P < .001) units higher in global cognitive scores. Neither the strength nor the significance of the association changed substantially when common dementia-related brain pathologies were included in the multivariable-adjusted models. The ß estimate after controlling for the ß-amyloid load was 0.191 (SE = 0.035; P < .001). A higher lifestyle score was associated with lower ß-amyloid load in the brain (ß = -0.120; SE = 0.041; P = .003), and 11.6% of the lifestyle-cognition association was estimated through ß-amyloid load. Conclusions and Relevance: This study found that in older adults, a healthy lifestyle may provide a cognitive reserve to maintain cognitive abilities independently of common neuropathologies of dementia.

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.

The MIND diet, brain transcriptomic alterations, and dementia.

Identifying novel mechanisms underlying dementia is critical to improving prevention and treatment. As an approach to mechanistic discovery, we investigated whether MIND diet (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay), a consistent risk factor for dementia, is correlated with a specific profile of cortical gene expression, and whether such a transcriptomic profile is associated with dementia, in the Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP). RNA sequencing (RNA-Seq) was conducted in postmortem dorsolateral prefrontal cortex tissue from 1,204 deceased participants; neuropsychological assessments were performed annually prior to death. In a subset of 482 participants, diet was assessed ~6 years before death using a validated food-frequency questionnaire; in these participants, using elastic net regression, we identified a transcriptomic profile, consisting of 50 genes, significantly correlated with MIND diet score (P=0.001). In multivariable analysis of the remaining 722 individuals, higher transcriptomic score of MIND diet was associated with slower annual rate of decline in global cognition (ß=0.011 per standard deviation increment in transcriptomic profile score, P=0.003) and lower odds of dementia (odds ratio [OR] =0.76, P=0.0002). Cortical expression of several genes appeared to mediate the association between MIND diet and dementia, including TCIM, whose expression in inhibitory neurons and oligodendrocytes was associated with dementia in a subset of 424 individuals with single-nuclei RNA-seq data. In a secondary Mendelian randomization analysis, genetically predicted transcriptomic profile score was associated with dementia (OR=0.93, P=0.04). Our study suggests that associations between diet and cognitive health may involve brain molecular alterations at the transcriptomic level. Investigating brain molecular alterations related to diet may inform the identification of novel pathways underlying 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.).

Association of Mediterranean-DASH Intervention for Neurodegenerative Delay and Mediterranean Diets With Alzheimer Disease Pathology.

BACKGROUND AND OBJECTIVES: Diet may reduce Alzheimer dementia risk and slow cognitive decline, but the understanding of the relevant neuropathologic mechanisms remains limited. The association of dietary patterns with Alzheimer disease (AD) pathology has been suggested using neuroimaging biomarkers. This study examined the association of Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) and Mediterranean dietary patterns with ß-amyloid load, phosphorylated tau tangles, and global AD pathology in postmortem brain tissue of older adults. METHODS: Autopsied participants of the Rush Memory and Aging Project with complete dietary information (collected through a validated food frequency questionnaire) and AD pathology data (ß-amyloid load, phosphorylated tau tangles, and global AD pathology [summarized neurofibrillary tangles and neuritic and diffuse plaques]) were included in this study. Linear regression models controlled for age at death, sex, education, APOE-ε4 status, and total calories were used to investigate the dietary patterns (MIND and Mediterranean diets) and dietary components associated with AD pathology. Further effect modification was tested for APOE-ε4 status and sex. RESULTS: Among our study participants (N = 581, age at death: 91.0 ± 6.3 years; mean age at first dietary assessment: 84.2 ± 5.8 years; 73% female; 6.8 ± 3.9 years of follow-up), dietary patterns were associated with lower global AD pathology (MIND: ß = -0.022, p = 0.034, standardized ß = -2.0; Mediterranean: ß = -0.007, p = 0.039, standardized ß = -2.3) and specifically less ß-amyloid load (MIND: ß = -0.068, p = 0.050, standardized ß = -2.0; Mediterranean: ß = -0.040, p = 0.004, standardized ß = -2.9). The findings persisted when further adjusted for physical activity, smoking, and vascular disease burden. The associations were also retained when participants with mild cognitive impairment or dementia at the baseline dietary assessment were excluded. Those in the highest tertile of green leafy vegetables intake had less global AD pathology when compared with those in the lowest tertile (tertile 3 vs tertile 1: ß = -0.115, p = 0.0038). DISCUSSION: The MIND and Mediterranean diets are associated with less postmortem AD pathology, primarily ß-amyloid load. Among dietary components, higher green leafy vegetable intake was associated with less AD pathology.

The association of MIND diet with cognitive resilience to neuropathologies.

INTRODUCTION: Cognitive resilience (CR) can be defined as the continuum of better through worse than expected cognition, given the degree of neuropathology. The relation of healthy diet patterns to CR remains to be elucidated. METHODS: Using longitudinal cognitive data and post mortem neuropathology from 578 deceased older adults, we examined associations between the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet at baseline and two standardized CR measures reflecting higher cognitive levels over time (CR Level ¯ $_{\overline {{\rm{Level}}}} $ ), and slower decline (CRSlope ), than expected given neuropathology. RESULTS: Compared to individuals in the lowest tertile of MIND score, those in the top tertile had higher CR Level ¯ $_{\overline {{\rm{Level}}}} $ (mean difference [MD] = 0.34; 95% confidence interval [CI] = 0.14, 0.55) and CRSlope (MD = 0.27; 95% CI = 0.05, 0.48), after multivariable adjustment. Overall MIND score was more strongly related to CR than the individual food components. DISCUSSION: The MIND diet is associated with both higher cognition and slower rates of cognitive decline, after controlling for neuropathology, indicating the MIND diet may be important to cognitive resilience.

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.

Association of Dietary Intake of Flavonols With Changes in Global Cognition and Several Cognitive Abilities.

BACKGROUND AND OBJECTIVES: Previous research has examined the association between cognition and flavonoids: bioactives found in foods, known to possess anti-inflammatory and antioxidant properties. We extend this research by investigating associations of dietary intakes of total flavonols and constituents (kaempferol, quercetin, myricetin, and isorhamnetin) on the change in cognitive performance in global cognition, episodic memory, semantic memory, visuospatial ability, perceptual speed, and working memory. METHODS: The study was conducted using 961 participants (aged 60-100 years) of the Rush Memory and Aging Project, a prospective cohort of community-dwelling Chicagoans who were followed for an average of 6.9 years. Diet was assessed using a validated semiquantitative food frequency questionnaire. Cognitive performance was assessed annually with a battery of 19 standardized tests. Flavonol intake was analyzed as a continuous variable using linear mixed-effects models. Cognitive domain scores were regressed on baseline calorie-adjusted flavonol variables. RESULTS: Higher dietary intakes of total flavonols and flavonol constituents were associated with a slower rate of decline in global cognition and multiple cognitive domains. In continuous models adjusted for age, sex, education, APOE ɛ4, late-life cognitive activity, physical activity, and smoking, total flavonol intake was associated with slower decline in global cognition ß estimate = 0.004 (95% CI 0.001-0.006), episodic memory ß = 0.004 (95% CI 0.002-0.006), semantic memory ß = 0.003 (95% CI 0.001-0.007), perceptual speed ß = 0.003 (95% CI 0.001-0.004), and working memory ß = 0.003 (95% CI 0.001-0.005) and marginally associated with visuospatial ability ß = 0.001 (95% CI -0.001 to 0.003). Analyses of individual flavonol constituents demonstrated that intakes of kaempferol and quercetin were associated with slower global cognitive decline (ß = 0.01 [95% CI 0.006-0.02] and ß = 0.004 [95% CI 0.0005-0.007]), respectively. Myricetin and isorhamnetin were not associated with global cognition. DISCUSSION: Results suggest that dietary intakes of total flavonols and several flavonol constituents may be associated with slower decline in global cognition and multiple cognitive abilities with older age.

Vitamin D intake and cognitive decline in Blacks and Whites: The role of diet and supplements.

INTRODUCTION: To determine the role of vitamin D intake on cognitive decline among Blacks and Whites. METHODS: Using data from the population-based Chicago Health and Aging Project, we studied 2061 Blacks and 1329 Whites with dietary vitamin D data and cognitive testing over 12 years of follow-up. Multivariable linear mixed-effects models were used to determine the association of vitamin D intake with cognitive decline. RESULTS: Vitamin D intake, particularly dietary vitamin D, was associated with a slower rate of decline in cognitive function among Blacks. In Blacks, comparing individuals in the lowest tertile of dietary intake, those in the highest tertile had a slower cognitive decline of 0.017 units/year (95% confidence interval 0.006, 0.027), independently of supplementation use. In Whites, vitamin D intake was not associated with cognitive decline. DISCUSSION: Dietary vitamin D may help to slow the decline in cognitive abilities among Blacks as they age.

Brain copper may protect from cognitive decline and Alzheimer's disease pathology: a community-based study.

Copper is an essential micronutrient for brain health and dyshomeostasis of copper could have a pathophysiological role in Alzheimer's disease (AD), however, there are limited data from community-based samples. In this study, we investigate the association of brain copper (assessed using ICP-MS in four regions -inferior temporal, mid-frontal, anterior cingulate, and cerebellum) and dietary copper with cognitive decline and AD pathology burden (a quantitative summary of neurofibrillary tangles, diffuse and neuritic plaques in multiple brain regions) at autopsy examination among deceased participants (N = 657; age of death: 90.2(±6.2)years, 70% women, 25% APOE-ɛ4 carriers) in the Rush Memory and Aging Project. During annual visits, these participants completed cognitive assessments using a 19-test battery and dietary assessments (using a food frequency questionnaire). Regression, linear mixed-effects, and logistic models adjusted for age at death, sex, education, and APOE-ε4 status were used. Higher composite brain copper levels were associated with slower cognitive decline (ß(SE) = 0.028(0.01), p = 0.001) and less global AD pathology (ß(SE) = -0.069(0.02), p = 0.0004). Participants in the middle and highest tertile of dietary copper had slower cognitive decline (T2vs.T1: ß = 0.038, p = 0.0008; T3vs.T1: ß = 0.028, p = 0.01) than those in the lowest tertile. Dietary copper intake was not associated with brain copper levels or AD pathology. Associations of higher brain copper levels with slower cognitive decline and with less AD pathology support a role for copper dyshomeostasis in AD pathogenesis and suggest that lower brain copper may exacerbate or indicate disease severity. Dietary and brain copper are unrelated but dietary copper is associated with slower cognitive decline via an unknown mechanism.

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.

Greater intake of the MEDI diet is associated with better cognitive trajectory in older adults with type 2 diabetes.

AIMS: To determine associations of three dietary patterns (Mediterranean (MEDI) diet, the Dietary Approaches to Stop Hypertension (DASH) diet and the Mediterranean- DASH Intervention for Neurodegenerative Delay (MIND) diet) with cognitive decline in older adults with type 2 diabetes mellitus (T2D). METHODS: This is a longitudinal observational study. Participants (N = 960) from the Israel Diabetes and Cognitive Decline (IDCD) study were included in this study. A multivariable-adjusted model including all three dietary patterns concurrently was developed to investigate their independent effect on cognitive decline. RESULTS: The mean follow up was 4.1 ± 2.1 years. While high adherence to both the MIND and the MEDI diet was associated with a slower decline, in the multivariable model only the associations of higher MEDI diet intake with greater decline in global cognition and in executive functions remained significant (ß = 0.013, SE = 0.006; P = 0.042; ß = 0.001, SE = 0.008, Pv = 0.023 respectively). CONCLUSIONS: In older adults with T2D, adherence to the MEDI is related to better cognitive trajectory. Diet is a meaningful factor in the path linking T2D and cognition.

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.

Western diet associated with increased post-stroke depressive symptoms.

The present study examines the association of diet with depressive symptoms among stroke survivors from a community cohort of older adults. Depression is common after stroke. A healthy diet has previously been associated with fewer depressive symptoms in older individuals, but it is unknown if this effect is also seen in stroke survivors. Eighty-six participants from the Memory and Aging Project with a history of stroke at their study baseline enrolment, complete dietary data and two or more assessments for depression were included in this observational prospective cohort analysis. Depressive symptoms were assessed annually with a 10-item version of the Center for Epidemiologic Studies Depression scale. Diet was assessed using a validated food-frequency questionnaire administered at baseline. Diet scores were based on analysis of participants' reported intakes of 144 food items. A generalised estimating equation (GEE) model was applied to examine the association of diet score with depressive symptoms. The study participants had a mean age of 82 ± 7⋅17 years and 14⋅42 ± 2⋅61 years of education, and 82⋅56 % were female. Western diet score was positively associated with depressive symptoms over time (diet score tertile 3 v. tertile 1: ß = 0⋅22, se = 0⋅09, P = 0⋅02; P for trend = 0⋅022). Interaction with sex suggested a stronger effect in females. A Western diet was associated with more post-stroke depressive symptoms, suggesting nutrition is important not only for reducing cerebrovascular risk, but for protecting post-stoke mental health as well.

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.

Apolipoprotein E potently inhibits ferroptosis by blocking ferritinophagy.

Allelic variation to the APOE gene confers the greatest genetic risk for sporadic Alzheimer's disease (AD). Independent of genotype, low abundance of apolipoprotein E (apoE), is characteristic of AD CSF, and predicts cognitive decline. The mechanisms underlying the genotype and apoE level risks are uncertain. Recent fluid and imaging biomarker studies have revealed an unexpected link between apoE and brain iron, which also forecasts disease progression, possibly through ferroptosis, an iron-dependent regulated cell death pathway. Here, we report that apoE is a potent inhibitor of ferroptosis (EC50 ≈ 10 nM; N27 neurons). We demonstrate that apoE signals to activate the PI3K/AKT pathway that then inhibits the autophagic degradation of ferritin (ferritinophagy), thus averting iron-dependent lipid peroxidation. Using postmortem inferior temporal brain cortex tissue from deceased subjects from the Rush Memory and Aging Project (MAP) (N = 608), we found that the association of iron with pathologically confirmed clinical Alzheimer's disease was stronger among those with the adverse APOE-ε4 allele. While protection against ferroptosis did not differ between apoE isoforms in vitro, other features of ε4 carriers, such as low abundance of apoE protein and higher levels of polyunsaturated fatty acids (which fuel ferroptosis) could mediate the ε4 allele's heighted risk of AD. These data support ferroptosis as a putative pathway to explain the major genetic risk associated with late onset AD.

Consideration of sex and gender in Alzheimer's disease and related disorders from a global perspective.

Sex or gender differences in the risk of Alzheimer's disease and related dementias (ADRD) differ by world region, suggesting that there are potentially modifiable risk factors for intervention. However, few epidemiological or clinical ADRD studies examine sex differences; even fewer evaluate gender in the context of ADRD risk. The goals of this perspective are to: (1) provide definitions of gender, biologic sex, and sexual orientation. and the limitations of examining these as binary variables; (2) provide an overview of what is known with regard to sex and gender differences in the risk, prevention, and diagnosis of ADRD; and (3) discuss these sex and gender differences from a global, worldwide perspective. Identifying drivers of sex and gender differences in ADRD throughout the world is a first step in developing interventions unique to each geographical and sociocultural area to reduce these inequities and to ultimately reduce global ADRD risk. HIGHLIGHTS: The burden of dementia is unevenly distributed geographically and by sex and gender. Scientific advances in genetics and biomarkers challenge beliefs that sex is binary. Discrimination against women and sex and gender minority (SGM) populations contributes to cognitive decline. Sociocultural factors lead to gender inequities in Alzheimer's disease and related dementias (ADRD) worldwide.