Objective: Diet may reduce Alzheimer’s dementia risk and slow cognitive decline, but the understanding of the relevant neuropathologic mechanisms remains limited. The association of dietary patterns with Alzheimer’s disease (AD) pathology has been suggested using neuroimaging biomarkers. This study examined the association of MIND and Mediterranean dietary patterns with beta-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 (beta-amyloid load, phosphorylated tau tangles, and global AD pathology [summarized neurofibrillary tangles, neuritic and diffuse plaques]) were included in this study. Linear regression models controlled for age at death, sex, education, APO-ε4 status, and total calories were used to investigate the dietary patterns (MIND and Mediterranean diet) and dietary components associated with AD pathology. Further effect modification was tested for APO-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; 73% female; 6.8 ± 3.9 years of follow-up) dietary patterns were associated with lower global AD pathology (MIND: β= -0.022, p=0.034, standardized β=-2.0; Mediterranean: β=-0.007, p=0.039, standardized β=-2.3) and specifically less beta-amyloid load (MIND: β=-0.068, p=0.050, standardized β=-2.0; Mediterranean: β=-0.040, p=0.004, standardized β=-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 to those in the lowest tertile (Tertile-3 vs. Tertile-1: β= -0.115, p=0.0038). Conclusion: The MIND and Mediterranean diets are associated with less postmortem AD pathology, primarily beta-amyloid load. Among dietary components, green leafy vegetables inversely correlate with AD pathology.

Background In old age, motor impairments including parkinsonian signs are common, but treatment is lacking for many older adults. In this study, we examined the association of a diet specifically developed to promote brain health, called MIND (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay), to the incidence and progression of parkinsonism in older adults. Methods A total of 706 Memory and Aging Project participants aged 59–97 years and without parkinsonism at baseline were assessed annually for the presence of four parkinsonian signs using a 26-item modified version of the United Parkinson’s Disease Rating Scale. Incident parkinsonism was defined as the first occurrence over 4.6 years of follow-up of two or more parkinsonian signs. The progression of parkinsonism was assessed by change in a global parkinsonian score (range: 0-100). MIND, Mediterranean, and DASH diet pattern scores were computed based on a validated food frequency questionnaire including 144 food items. We employed Cox-Proportional Hazard models and linear mixed models, to examine the associations of baseline diet scores with incident parkinsonism and the annual rate of change in global parkinsonian score, respectively. Results In models adjusted for age, sex, smoking, total energy intake, BMI and depressive symptoms, higher MIND diet scores were associated with a decreased risk of parkinsonism [(HR=0.89, 95% CI 0.83-0.96)]; and a slower rate of parkinsonism progression [(β= -0.008; SE=0.0037; p=0.04)]. The Mediterranean diet was marginally associated with reduced parkinsonism progression (β= -0.002; SE=0.0014; p=0.06). The DASH diet, by contrast, was not associated with either outcome. Conclusion The MIND diet created for brain health may be a associated with decreased risk and slower progression of parkinsonism in older adults.

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.

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.

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 β estimate = 0.004 (95% CI 0.001–0.006), episodic memory β = 0.004 (95% CI 0.002–0.006), semantic memory β = 0.003 (95% CI 0.001–0.007), perceptual speed β = 0.003 (95% CI 0.001–0.004), and working memory β = 0.003 (95% CI 0.001–0.005) and marginally associated with visuospatial ability β = 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 (β = 0.01 [95% CI 0.006–0.02] and β = 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.

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.