Study design and methods: U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER).

INTRODUCTION: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans. METHODS: U.S. POINTER was planned as a 2-year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well-established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER. RESULTS: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and every 6 months. Both interventions focus on exercise, diet, cognitive/social stimulation, and cardiovascular health, but differ in intensity and accountability. The study partners with a worldwide network of similar trials for harmonization of methods and data sharing. DISCUSSION: U.S. POINTER is testing a potentially sustainable intervention to support brain health and Alzheimer's prevention for Americans. Impact is strengthened by the targeted participant diversity and expanded scientific scope through ancillary studies.

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.).

Adherence to MIND Diet, Genetic Susceptibility, and Incident Dementia in Three US Cohorts.

Adherence to Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) may lower the risk of dementia by impacting immunity and cholesterol, which are pathways also implicated by genome-wide association studies of Alzheimer's Dementia (AD). We examined whether adherence to the MIND diet could modify the association of genetic risk for AD with incident dementia. We used three ongoing US cohorts: Chicago Health and Aging Project (CHAP, n = 2449), Rush Memory and Aging Project (MAP, n = 725), and Women's Health Initiative Memory Study (WHIMS, n = 5308). Diagnosis of dementia was based on clinical neurological examination and standardized criteria. Repeated measures of global cognitive function were available in MAP and CHAP. Self-reported adherence to MIND was estimated using food-frequency questionnaires. Global and pathway-specific genetic scores (GS) for AD were derived. Cox proportional hazard, logistic regression, and mixed models were used to examine associations of MIND, GS, and GS-MIND interactions with incident dementia and cognitive decline. Higher adherence to MIND and lower GS were associated with a lower risk of dementia in MAP and WHIMS and a slower rate of cognitive decline in MAP (p < 0.05). MIND or GS were not associated with incident dementia or cognitive decline in CHAP. No gene−diet interaction was replicated across cohorts. Genetic risk and MIND adherence are independently associated with dementia among older US men and women.

Caffeine Consumption and Dementia: Are Lewy Bodies the Link?

OBJECTIVE: The objective of this study was to examine the association between caffeine intake and cognitive impairment. Caffeine-neuropathology correlations and interactions with lifestyle and genetic factors impacting caffeine metabolism and response were also tested. METHODS: We included 888 participants aged 59+ years from the Rush Memory and Aging Project (MAP) and 303,887 participants aged 55+ years from the UK Biobank (UKB). MAP participants took part in annual cognitive testing. Diagnosis of dementia was based on clinical neurological examination and standardized criteria. A subset provided postmortem tissue for neuropathologic evaluation for common age-related diseases (eg, Alzheimer's disease [AD], Lewy bodies, and vascular). For UKB, dementia was determined by linked hospital and death records. Self-reported caffeine intake was estimated using food-frequency questionnaires in both cohorts. Cox proportional hazard ratio (HR), regression, and mixed models were used to examine associations of caffeine intake with incident dementia, cognitive decline, and neuropathology. RESULTS: In MAP, compared to ≤100 mg/day, caffeine intake >100 mg/day was associated with a significantly higher HR (95% confidence interval [CI]) of all-cause (HR = 1.35, 95% CI = 1.03-1.76) and AD (HR = 1.41, 95% CI = 1.07-1.85) dementia. Caffeine intake was not associated with cognitive decline. In UKB, compared to ≤100 mg/day, the HRs (95% CI) of all-cause dementia for consuming 100 ≤ 200, 200 ≤ 300, 300 ≤ 400, and > 400 mg/day were 0.83 (95% CI = 0.72-0.94), 0.74 (95% CI = 0.64-0.85), 0.74 (95% CI = 0.64-0.85), and 0.92 (95% CI = 0.79-1.08), respectively. Similar results were observed for Alzheimer's dementia. In MAP, caffeine intake was inversely associated with postmortem Lewy bodies but no other age-related pathologies. Caffeine intake >100 mg/day was associated with lower neocortical type Lewy bodies (odds ratio (95%CI): 0.40 (95% CI = 0.21-0.75). INTERPRETATION: Caffeine intake was inconsistently associated with clinical dementia; potentially explained by cohort differences in underlying dementia etiology. Lewy bodies may link caffeine to lower risk in some persons. ANN NEUROL 2022;91:834-846.

Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) study: Rationale, design and baseline characteristics of a randomized control trial of the MIND diet on cognitive decline.

Alzheimer's dementia (AD) is the sixth leading cause of death in the U.S., with an estimated $305 billion cost of care in 2020. Currently there are no cures or therapies to ameliorate the disease progression and symptoms. Growing evidence links a diet characterized by high antioxidant components with benefits to cognitive function, which is indicative of the preventative potential of dietary inteventions. The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) study is a 3-year, multicenter, randomized controlled trial to test the effects of the MIND diet on cognitive function in 604 individuals at risk for AD. Men and women ages 65 to 84 years were recruited. Eligible participants were randomized to either the MIND diet with mild caloric restriction or their usual diet with mild caloric restriction. Cognitive assessments, medical history, blood pressure, anthropometric measurements, and blood and urine sample collections will be taken at baseline and follow-up visits. MRI scans will be completed on approximately half of the enrolled participants at the start and end of the study. Unique features of the MIND study include: 1) a dietary pattern, rather than single nutrient or food, tested in an at-risk population; 2) foods featured as key components of the MIND diet (i.e. extra-virgin olive oil, blueberries, and nuts) provided for participants; and 3) MRI scans of brain structure and volume that may provide potential mechanistic evidence on the effects of the diet. Results from the study will be crucial to the development of dietary guidelines for the prevention of AD.

Regional brain iron associated with deterioration in Alzheimer's disease: A large cohort study and theoretical significance.

OBJECTIVE: This paper is a proposal for an update of the iron hypothesis of Alzheimer's disease (AD), based on large-scale emerging evidence. BACKGROUND: Iron featured historically early in AD research efforts for its involvement in the amyloid and tau proteinopathies, APP processing, genetics, and one clinical trial, yet iron neurochemistry remains peripheral in mainstream AD research. Much of the effort investigating iron in AD has focused on the potential for iron to provoke the onset of disease, by promoting proteinopathy though increased protein expression, phosphorylation, and aggregation. NEW/UPDATED HYPOTHESIS: We provide new evidence from a large post mortem cohort that brain iron levels within the normal range were associated with accelerated ante mortem disease progression in cases with underlying proteinopathic neuropathology. These results corroborate recent findings that argue for an additional downstream role for iron as an effector of neurodegeneration, acting independently of tau or amyloid pathologies. We hypothesize that the level of tissue iron is a trait that dictates the probability of neurodegeneration in AD by ferroptosis, a regulated cell death pathway that is initiated by signals such as glutathione depletion and lipid peroxidation. MAJOR CHALLENGES FOR THE HYPOTHESIS: While clinical biomarkers of ferroptosis are still in discovery, the demonstration of additional ferroptotic correlates (genetic or biomarker derived) of disease progression is required to test this hypothesis. The genes implicated in familial AD are not known to influence ferroptosis, although recent reports on APP mutations and apolipoprotein E allele (APOE) have shown impact on cellular iron retention. Familial AD mutations will need to be tested for their impact on ferroptotic vulnerability. Ultimately, this hypothesis will be substantiated, or otherwise, by a clinical trial of an anti-ferroptotic/iron compound in AD patients. LINKAGE TO OTHER MAJOR THEORIES: Iron has historically been linked to the amyloid and tau proteinopathies of AD. Tau, APP, and apoE have been implicated in physiological iron homeostasis in the brain. Iron is biochemically the origin of most chemical radicals generated in biochemistry and thus closely associated with the oxidative stress theory of AD. Iron accumulation is also a well-established consequence of aging and inflammation, which are major theories of disease pathogenesis.

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.

DASH and Mediterranean-Dash Intervention for Neurodegenerative Delay (MIND) Diets Are Associated With Fewer Depressive Symptoms Over Time.

BACKGROUND: Depression is common in older adults and more prevalent in those with cognitive impairment, vascular risk factors, or stroke. Nonpharmacologic strategies to reduce depression, such as diet, may be effective; however, few studies have investigated the relation. METHODS: A total of 709 participants (23.3% men, mean age 80.4), from an observational prospective cohort study were assessed annually for an average of 6.53 years of follow-up. Participants with missing or invalid baseline dietary evaluations or fewer than two depression assessments were excluded. Depressive symptoms were assessed with a 10-item version of the Center for Epidemiologic Studies Depression scale. High burden of depressive symptoms was defined as the presence of four or more depressive symptoms. Diet scores were computed using a validated food frequency questionnaire for the Dietary Approaches to Stop Hypertension (DASH) diet, Mediterranean diet, Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, and Western diets. Diet scores were modeled in tertiles. A generalized estimating equation (GEE) model was performed for the longitudinal analysis of depression as a binary outcome. RESULTS: Participants in the highest tertile of the DASH (ß = -0.10, confidence interval [CI]: -0.20, -0.0064) and MIND (ß = -0.12, CI: -0.23, -0.0092) diet scores had lower rates of depressive symptoms over time when compared to those in the respective lowest tertiles. The Western diet was positively associated with depressive symptoms over time (ß = 0.093, p-trend = .05). CONCLUSIONS: Diet may be effective in reducing depressive symptoms in older adults. A diet intervention trial may be needed to determine the optimal nutritional components for prevention of late onset depression.

Toward a theory-based specification of non-pharmacological treatments in aging and dementia: Focused reviews and methodological recommendations.

INTRODUCTION: Non-pharmacological treatments (NPTs) have the potential to improve meaningful outcomes for older people at risk of, or living with dementia, but research often lacks methodological rigor and continues to produce mixed results. METHODS: In the current position paper, experts in NPT research have specified treatment targets, aims, and ingredients using an umbrella framework, the Rehabilitation Treatment Specification System. RESULTS: Experts provided a snapshot and an authoritative summary of the evidence for different NPTs based on the best synthesis efforts, identified main gaps in knowledge and relevant barriers, and provided directions for future research. Experts in trial methodology provide best practice principles and recommendations for those working in this area, underscoring the importance of prespecified protocols. DISCUSSION: We conclude that the evidence strongly supports various NPTs in relation to their primary targets, and discuss opportunities and challenges associated with a unifying theoretical framework to guide future efforts in this area.

Dietary carotenoids related to risk of incident Alzheimer dementia (AD) and brain AD neuropathology: a community-based cohort of older adults.

BACKGROUND: Studies have reported a protective relation to cognitive decline with long-term intake of total and individual dietary carotenoids. However, the underlying mechanisms have not yet been clearly established in humans. OBJECTIVES: To evaluate the prospective association between intakes of total and individual carotenoids and risk of incident Alzheimer dementia (AD) and explore the underlying neuropathological basis. METHODS: Among 927 participants from the Rush Memory and Aging Project who were free from AD at baseline and were followed up for a mean of 7 y, we estimated HRs for AD using Cox proportional hazards models by intakes of energy-adjusted carotenoids. Brain AD neuropathology was assessed in postmortem brain autopsies among 508 deceased participants. We used linear regression to assess the association of carotenoid intake with AD-related neuropathology. RESULTS: Higher intake of total carotenoids was associated with substantially lower hazard of AD after controlling for age, sex, education, ApoE-ε4, participation in cognitively stimulating activities, and physical activity level. Comparing the top and bottom quintiles (median intake: 24.8 compared with 6.7 mg/d) of total carotenoids, the multivariate HR (95% CI) was 0.52 (0.33, 0.81), P-trend < 0.01. A similar association was observed for lutein-zeaxanthin, a weaker linear inverse association was observed for ß-carotene, and a marginally significant linear inverse association was found for ß-cryptoxanthin. Among the deceased participants, consumers of higher total carotenoids (top compared with bottom tertile, 18.2 compared with 8.2 mg/d) had less global AD pathology (b: -0.10; SE = 0.04; P-trend = 0.01). For individual carotenoids, lutein-zeaxanthin and lycopene were inversely associated with brain global pathology, whereas lutein-zeaxanthin showed additional inverse associations with AD diagnostic score, neuritic plaque severity, and neurofibrillary tangle density and severity. CONCLUSIONS: Our findings support a beneficial role of total carotenoid consumption, in particular lutein/zeaxanthin, on AD incidence that may be related to the inhibition of brain ß-amyloid deposition and fibril formation.

Brain tocopherol levels are associated with lower activated microglia density in elderly human cortex.

INTRODUCTION: Higher brain tocopherol levels have been associated with lower levels of Alzheimer's disease (AD) neuropathology; however, the underlying mechanisms are unclear. METHODS: We studied the relations of α- and γ-tocopherol brain levels to microglia density in 113 deceased participants from the Memory and Aging Project. We used linear regression analyses to examine associations between tocopherol levels and microglia densities in a basic model adjusted for age, sex, education, apolipoprotein E (APOE)ε4 genotype (any ε4 allele vs. none) , and post-mortem time interval, and a second model additionally adjusted for total amyloid load and neurofibrillary tangle severity. RESULTS: Higher α- and γ-tocopherol levels were associated with lower total and activated microglia density in cortical but not in subcortical brain regions. The association between cortical α-tocopherol and total microglia density remained statistically significant after adjusting for AD neuropathology. DISCUSSION: These results suggest that the relation between tocopherols and AD might be partly explained by the alleviating effects of tocopherols on microglia activation.

Brain γ-Tocopherol Levels Are Associated with Presynaptic Protein Levels in Elderly Human Midfrontal Cortex.

BACKGROUND: Higher vitamin E intake has been widely related to lower risks of cognitive decline and dementia. Animal models suggest that this relationship might be (partially) explained by the protection of vitamin E against presynaptic protein oxidation. OBJECTIVE: In this cross-sectional study, we aimed to examine the associations between brain tocopherols and presynaptic protein levels in elderly humans. METHODS: We examined associations of α- and γ-tocopherol brain levels with presynaptic protein levels in 113 deceased participants (age 88.5±6.0 years, 45 (40%) female) from the prospective Memory and Aging project. Three distinct presynaptic proteins, a SNARE protein composite, a synaptotagmin synaptophysin composite and the protein-protein interaction between synaptosomal-associated protein 25 (SNAP-25), and syntaxin were measured in two cortical brain regions. Linear regression models assessed associations of brain tocopherols with presynaptic protein levels. RESULTS: Higher brain γ-tocopherol levels were associated with higher levels of the SNARE protein composite, complexin-I, complexin-II, the synaptotagmin synaptophysin composite, and septin-5 in the midfrontal cortex (B(SE) = 0.272 to 0.412 (0.084 to 0.091), p < 0.001 to 0.003). When additionally adjusted for global Alzheimer's disease pathology, cerebral infarcts, and Lewy body disease pathology, these associations remained largely similar. No associations were found between α-tocopherol and presynaptic protein levels. CONCLUSION: In this cross-sectional study, we found higher brain γ-tocopherol levels were associated with presynaptic protein levels in the midfrontal cortex. These results are consistent with a proposed role of vitamin E to maintain presynaptic protein levels.

Recent Caffeine Drinking Associates with Cognitive Function in the UK Biobank.

Clinical evidence points to the premise that caffeine may benefit cognition, but whether these findings extend to real life settings and amidst factors that impact caffeine metabolism is unclear. The aim of this study was to investigate the impact of recent caffeine drinking on cognitive ability while additionally accounting for lifestyle and genetic factors that impact caffeine metabolism. We included up to 434,900 UK Biobank participants aged 37-73 years, recruited in 2006-2010, who provided biological samples and completed touchscreen questionnaires regarding sociodemographic factors, medical history, lifestyle, and diet. Recent caffeine drinking (yes/no in the last hour) was recorded during a physical assessment. Participants completed at least one of four self-administered cognitive function tests using the touchscreen system: prospective memory (PM), pairs matching (Pairs), fluid intelligence (FI), and reaction time (RT). Multivariable regressions were used to examine the association between recent caffeine drinking and cognition test scores. We also tested interactions between recent caffeine drinking and a genetic caffeine-metabolism score (CMS) on cognitive function. Among white participants, recent caffeine drinking was associated with higher performance on RT but lower performance on FI, Pairs, and PM (p ≤ 0.004). Similar directions of associations for FI (p = 0.09), Pairs (p = 0.03), and PM (p = 0.34) were observed among non-white participants. No significant and consistent effect modification by age, sex, smoking, test time, habitual caffeine intake, or CMS was observed. Caffeine consumed shortly before tasks requiring shorter reaction times may improve task performance. Potential impairments in memory and reasoning tasks with recent caffeine drinking warrant further study.

Caffeinated Coffee and Tea Consumption, Genetic Variation and Cognitive Function in the UK Biobank.

BACKGROUND: Coffee and tea are the major contributors of caffeine in the diet. Evidence points to the premise that caffeine may benefit cognition. OBJECTIVE: We examined the associations of habitual regular coffee or tea and caffeine intake with cognitive function whilst additionally accounting for genetic variation in caffeine metabolism. METHODS: We included white participants aged 37-73 y from the UK Biobank who provided biological samples and completed touchscreen questionnaires regarding sociodemographic factors, medical history, lifestyle, and diet. Habitual caffeine-containing coffee and tea intake was self-reported in cups/day and used to estimate caffeine intake. Between 97,369 and 445,786 participants with data also completed ≥1 of 7 self-administered cognitive functioning tests using a touchscreen system (2006-2010) or on home computers (2014). Multivariable regressions were used to examine the association between coffee, tea, or caffeine intake and cognition test scores. We also tested interactions between coffee, tea, or caffeine intake and a genetic-based caffeine-metabolism score (CMS) on cognitive function. RESULTS: After multivariable adjustment, reaction time, Pairs Matching, Trail Making test B, and symbol digit substitution, performance significantly decreased with consumption of 1 or more cups of coffee (all tests P-trend < 0.0001). Tea consumption was associated with poor performance on all tests (P-trend < 0.0001). No statistically significant CMS × tea, CMS × coffee, or CMS × caffeine interactions were observed. CONCLUSIONS: Our findings, based on the participants of the UK Biobank, provide little support for habitual consumption of regular coffee or tea and caffeine in improving cognitive function. On the contrary, we observed decrements in performance with intakes of these beverages which may be a result of confounding. Whether habitual caffeine intake affects cognitive function therefore remains to be tested.

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.

Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology.

Cortical iron has been shown to be elevated in Alzheimer's disease (AD), but the impact of the directly measured iron on the clinical syndrome has not been assessed. We investigated the association between post-mortem iron levels with the clinical and pathological diagnosis of AD, its severity, and the rate of cognitive decline in the 12 years prior to death in subjects from the Memory and Aging Project (n = 209). Iron was elevated (ß [SE] = 9.7 [2.6]; P = 3.0 × 10-4) in the inferior temporal cortex only in subjects who were diagnosed with clinical AD during life and had a diagnosis of AD confirmed post-mortem by standardized criteria. Although iron was weakly associated with the extent of proteinopathy in tissue with AD neuropathology, it was strongly associated with the rate of cognitive decline (e.g., global cognition: ß [SE] = -0.040 [0.005], P = 1.6 × 10-14). Thus, cortical iron might act to propel cognitive deterioration upon the underlying proteinopathy of AD, possibly by inducing oxidative stress or ferroptotic cell death, or may be related to an inflammatory response.

Accelerating the Search for Interventions Aimed at Expanding the Health Span in Humans: The Role of Epidemiology.

BACKGROUND: Extensive work in basic and clinical science suggests that biological mechanisms of aging are causally related to the development of disease and disability in late life. Modulation of the biological mechanisms of aging can extend both life span and health span in animal models, but translation to humans has been slow. METHODS: Summary of workshop proceedings from the 2018-2019 Epidemiology of Aging Workshop hosted by the Intramural Research Program at the National Institute on Aging. RESULTS: Epidemiologic studies play a vital role to progress in this field, particularly in evaluating new risk factors and measures of biologic aging that may influence health span, as well as developing relevant outcome measures that are robust and relevant for older individuals. CONCLUSIONS: Appropriately designed epidemiological studies are needed to identify targets for intervention and to inform study design and sample size estimates for future clinical trials designed to promote health span.

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.

Olive Oil Intake Associated with Increased Attention Scores in Women Living with HIV: Findings from the Chicago Women's Interagency HIV Study.

Women aging with human immunodeficiency virus (HIV) are particularly vulnerable to cognitive decline. Recent studies have highlighted the potential protective effects of olive oil on cognition in persons living without HIV. We sought to evaluate the association between olive oil consumption and domain-specific cognitive performance (dCog) t-scores (adjusted for age, race, education, reading level, practice effects) in women living with HIV (WLWH) and sociodemographically similar women living without HIV. A total of 166 women (113 WLWH and 53 women living without HIV) participating in the Cook County Women's Interagency HIV Study (WIHS) completed cognitive testing and a Block 2014 Food Frequency Questionnaire within 18 months. Use of olive oil was associated with a 4.2 point higher attention/concentration (p = 0.02), 4.0 point higher for verbal learning (p = 0.02), and 1.91 point higher for verbal memory (p = 0.05). Associations between using olive oil and attention/concentration cognitive domain were seen in WLWH but not in women living without HIV. Associations between olive oil and verbal learning and memory were only seen in women without HIV. Our data suggest that using olive oil as a primary cooking oil may contribute to differential effects in attention/concentration, verbal learning, and verbal memory between women living with and without HIV.

Age and cognitive decline in the UK Biobank.

OBJECTIVES: Age-related cognitive decline is a well-known phenomenon after age 65 but little is known about earlier changes and prior studies are based on relatively small samples. We investigated the impact of age on cognitive decline in the largest population sample to date including young to old adults. METHOD: Between 100,352 and 468,534 participants aged 38-73 years from UK Biobank completed at least one of seven self-administered cognitive functioning tests: prospective memory (PM), pairs matching (Pairs), fluid intelligence (FI), reaction time (RT), symbol digit substitution, trail making A and B. Up to 26,005 participants completed at least one of two follow-up assessments of PM, Pairs, FI and RT. Multivariable regression models examined the association between age (<45[reference], 45-49, 50-54, 55-59, 60-64, 65+) and cognition scores at baseline. Mixed models estimated the impact of age on cognitive decline over follow-up (~5.1 years). RESULTS: FI was higher between ages 50 and 64 and lower at 65+ compared to <45 at baseline. Performance on all other baseline tests was lower with older age: with increasing age category, difference in test scores ranged from 2.5 to 7.8%(P<0.0001). Compared to <45 at baseline, RT and Pairs performance declined faster across all older age cohorts (3.0 and 1.2% change, respectively, with increasing age category, P<0.0001). Cross-sectional results yielded 8 to 12-fold higher differences in RT and Pairs with age compared to longitudinal results. CONCLUSIONS: Our findings suggest that declines in cognitive abilities <65 are small. The cross-sectional differences in cognition scores for middle to older adult years may be due in part to age cohort effects.