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.

A Longitudinal Study of Acculturation in Context and Cardiovascular Health and Their Effects on Cognition Among Older Latino Adults.

Background We previously outlined the importance of considering acculturation within the context of older Latino adults' lived experience (ie, acculturation in context) to better capture contributors to cognitive aging. We now examine this conceptual framework as related to level of and change in cardiovascular health, and whether cardiovascular health modifies previously documented associations of acculturation in context with cognition. Methods and Results Acculturation in context data from 192 Latino participants without dementia at baseline (age ~70 years) were compiled into 3 separate composite scores: acculturation-related (nativity, language-, and social-based preferences), contextually related socioenvironmental (experiences of discrimination, social isolation, social networks), and familism-related (Latino-centric family ethos). A modified American Heart Association's Life's Simple 7 (mLS7; ie, smoking, physical activity, body mass index, blood pressure, total cholesterol, blood glucose) was used to measure cardiovascular health. Mixed effects regressions simultaneously tested the association of all 3 composite scores with total mLS7 adjusting for confounders. Separate models tested whether mLS7 modified associations of the 3 composite scores and cognition. The contextually related socioenvironmental composite score reflecting higher discrimination, higher social isolation, and smaller social networks (estimate=0.22, SE=0.10, P=0.02) and the familism score (estimate=0.16, SE=0.07, P=0.02) both significantly associated with change in total mLS7. The acculturation-related composite was not significantly associated with change in mLS7. No composite was significantly associated with level of mLS7. Total mLS7, however, significantly modified associations between the acculturation-related composite and change in working memory (estimate=-0.02, SE=0.01, P=0.043). Conclusions Acculturation within the context of older Latino adults' lived experience is important for maintaining cardiovascular health, relationships that also affect domain-specific cognitive decline.

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.

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.

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.

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.

Higher circulating α-carotene was associated with better cognitive function: an evaluation among the MIND trial participants.

There is emerging evidence linking fruit and vegetable consumption and cognitive function. However, studies focusing on the nutrients underlying this relationship are lacking. We aim to examine the association between plasma nutrients and cognition in a population at risk for cognitive decline with a suboptimal diet. The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) trial is a randomized controlled intervention that examines the effects of the MIND diet to prevent cognitive decline. The primary outcome is global cognition. A multivariate linear model was used to investigate the association between blood nutrients and global and/or domain-specific cognition. The model was adjusted for age, sex, education, study site, smoking status, cognitive activities and physical activities. High plasma α-carotene was associated with better global cognition. Participants in the highest tertile of plasma α-carotene had a higher global cognition z score of 0⋅17 when compared with individuals in the lowest tertile (P 0⋅002). Circulating α-carotene levels were also associated with higher semantic memory scores (P for trend 0⋅007). Lutein and zeaxanthin (combined) was positively associated with higher semantic memory scores (P for trend 0⋅009). Our study demonstrated that higher α-carotene levels in blood were associated with higher global cognition scores in a US population at risk for cognitive decline. The higher α-carotene levels in blood reflected greater intakes of fruits, other types of vegetables and lesser intakes of butter and margarine and meat. The higher circulating levels of lutein plus zeaxanthin reflected a dietary pattern with high intakes of fruits, green leafy, other vegetables and cheese, and low consumption of fried foods. Objective nutrient markers in the blood can better characterize dietary intake, which may facilitate the implementation of a tailored dietary intervention for the prevention of cognitive decline.

Trajectories of Multiple Behavioral Risk Factors and Their Associations With Cognitive Function Trajectories Among Older African Americans and White Americans.

Objectives: This study examined the joint trajectories of behavioral risk factors (smoking, alcohol drinking, and body mass index) and their associations with cognitive function trajectories among older African Americans and white Americans. Methods: Data from the Health and Retirement Study (1998-2014) were used. Group-based mixture modeling and multinomial logistic regression analysis were performed. Results: Three joint trajectories of behavioral risk factors (overweight, smoking and drinking, and drinking and overweight) and three cognitive function trajectories (low, moderate, and high) were identified. A significantly higher percentage of African Americans were in the "overweight," "smoking and drinking," and "low" cognitive functioning groups as measured by the total cognition composite score compared to white Americans. After accounting for covariates, the "drinking and overweight" group was associated with the "moderate" or "high" cognitive functioning group. Discussion: Future interventions targeting the combinations of behavioral risk factors are needed to promote healthy aging among high-risk populations.

Impact of the Apolipoprotein E ε4 Allele on the Relationship Between Healthy Lifestyle and Cognitive Decline: A Population-Based Study.

Adherence to a healthy lifestyle-characterized by abstaining from smoking, being physically and cognitively active, having a high-quality diet, and limiting alcohol use-is associated with slower cognitive decline in older adults, but whether this relationship extends to persons with a genetic predisposition (e.g., carriers of the ε4 allele of the apolipoprotein E gene (APOE*E4)) remains uncertain. Using data from a population-based study, the Chicago Health and Aging Project (Chicago, Illinois), we followed 3,886 individuals who underwent regular clinical and cognitive assessments from 1993 to 2012. Of 3,886 older adults, 1,269 (32.7%) were APOE*E4 carriers. Compared with noncarriers, APOE*E4 carriers had faster cognitive decline (ß = -0.027 units/year, 95% confidence interval (CI): -0.032, -0.023). In contrast, persons with 2-3 and 4-5 healthy lifestyle factors had slower cognitive decline (ß = 0.008 units/year (95% CI: 0.002, 0.014) and ß = 0.019 units/year (95% CI: 0.011, 0.026), respectively) compared with those with 0-1 factor. In analyses stratified by APOE*E4 status, adherence to a healthy lifestyle (e.g., 4-5 factors vs. 0-1 factors) was associated with a slower rate of cognitive decline in both APOE*E4 carriers (ß = 0.029, 95% CI: 0.013, 0.045) and noncarriers (ß = 0.013, 95% CI: 0.005, 0.022). These results underscore the impact of a healthy lifestyle on cognition, particularly among persons with a genetic predisposition, who are more vulnerable to cognitive decline as they age.

A study protocol for MindMoves: A lifestyle physical activity and cognitive training intervention to prevent cognitive impairment in older women with cardiovascular disease.

INTRODUCTION: Cognitive impairment (CI) and cardiovascular disease (CVD) disproportionately affect women compared to men, and CVD increases risk of CI. Physical activity and cognitive training can improve cognition in older adults and may have additive or synergistic effects. However, no combined intervention has targeted women with CVD or utilized a sustainable lifestyle approach. The purpose of the trial is to evaluate efficacy of MindMoves, a 24-week multimodal physical activity and cognitive training intervention, on cognition and serum biomarkers in older women with CVD. Three serum biomarkers (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor [VEGF], and insulin-like growth factor 1 [IGF-1]) were selected as a priori hypothesized indicators of the effects of physical activity and/or cognitive training on cognition. METHODS: The study design is a randomized controlled trial with a 2 × 2 factorial design, to determine independent and combined efficacies of Mind (tablet-based cognitive training) and Move (lifestyle physical activity with goal-setting and group meetings) on change in cognition (primary outcome) and serum biomarkers (secondary outcomes). We will recruit 254 women aged ≥65 years with CVD and without CI from cardiology clinics. Women will be randomized to one of four conditions: (1) Mind, (2) Move, (3) MindMoves, or (4) usual care. Data will be obtained from participants at baseline, 24, 48, and 72 weeks. DISCUSSION: This study will test efficacy of a lifestyle-focused intervention to prevent or delay cognitive impairment in older women with CVD and may identify relevant serum biomarkers that could be used as early indicators of intervention response.

Sex-specific genetic predictors of Alzheimer's disease biomarkers.

Cerebrospinal fluid (CSF) levels of amyloid-ß 42 (Aß42) and tau have been evaluated as endophenotypes in Alzheimer's disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes. We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. Data came from a previous genome-wide association study (GWAS) of CSF Aß42 and tau (1527 males, 1509 females). We evaluated sex interactions at previous loci, performed sex-stratified GWAS to identify sex-specific associations, and evaluated sex interactions at sex-specific GWAS loci. We then evaluated sex-specific associations between prefrontal cortex (PFC) gene expression at relevant loci and autopsy measures of plaques and tangles using data from the Religious Orders Study and Rush Memory and Aging Project. In Aß42, we observed sex interactions at one previous and one novel locus: rs316341 within SERPINB1 (p = 0.04) and rs13115400 near LINC00290 (p = 0.002). These loci showed stronger associations among females (ß = - 0.03, p = 4.25 × 10-8; ß = 0.03, p = 3.97 × 10-8) than males (ß = - 0.02, p = 0.009; ß = 0.01, p = 0.20). Higher levels of expression of SERPINB1, SERPINB6, and SERPINB9 in PFC was associated with higher levels of amyloidosis among females (corrected p values < 0.02) but not males (p > 0.38). In total tau, we observed a sex interaction at a previous locus, rs1393060 proximal to GMNC (p = 0.004), driven by a stronger association among females (ß = 0.05, p = 4.57 × 10-10) compared to males (ß = 0.02, p = 0.03). There was also a sex-specific association between rs1393060 and tangle density at autopsy (pfemale = 0.047; pmale = 0.96), and higher levels of expression of two genes within this locus were associated with lower tangle density among females (OSTN p = 0.006; CLDN16 p = 0.002) but not males (p ≥ 0.32). Results suggest a female-specific role for SERPINB1 in amyloidosis and for OSTN and CLDN16 in tau pathology. Sex-specific genetic analyses may improve understanding of AD's genetic architecture.

Neopterin is associated with hippocampal subfield volumes and cognition in HIV.

OBJECTIVE: HIV infection sets off an immediate immune response and inflammatory cascade that can lead to neuronal injury and cognitive impairment, but the relationship between immune markers, regional brain volumes, and cognition remains understudied in HIV-infected adults. METHODS: Cross-sectional associations were examined between serum immune markers of activation (neopterin) and inflammation (interleukin [IL]-1ß, IL-6, tumor necrosis factor alpha, and C-reactive protein) with regional brain volumes (cortical, subcortical, total gray matter, hippocampus, and subfields) and cognition in 66 HIV-infected, virally suppressed, adults who underwent 3.0-T MRI as part of the Research Core of the Rush Center of Excellence on Disparities in HIV and Aging. Immune markers were assayed from frozen plasma, values were entered into linear regression models as predictors of regional brain volumes, and interactive effects of immune response and regional brain volumes on cognition were examined. RESULTS: No inflammatory marker was associated with any regional brain volume. Higher neopterin level was associated with lower total hippocampal, presubiculum, and cornu ammonis (CA) subfield volumes. Higher neopterin level and lower total hippocampal volume were independently associated with lower episodic memory, and neopterin level fully mediated the effect of hippocampal atrophy on episodic memory. Higher neopterin levels were associated with lower presubiculum, CA1, and CA4/dentate volumes and lower semantic memory, working memory, and global cognition. CONCLUSION: Immune activation in response to HIV infection, measured by neopterin, has a deleterious and targeted effect on regional brain structure, which can be visualized with clinically available MRI measures of hippocampus and its subfields, and this effect is associated with lower cognitive function.

Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau.

Importance: The strongest genetic risk factor for Alzheimer disease (AD), the apolipoprotein E (APOE) gene, has a stronger association among women compared with men. Yet limited work has evaluated the association between APOE alleles and markers of AD neuropathology in a sex-specific manner. Objective: To evaluate sex differences in the association between APOE and markers of AD neuropathology measured in cerebrospinal fluid (CSF) during life or in brain tissue at autopsy. Design, Setting, and Participants: This multicohort study selected data from 10 longitudinal cohort studies of normal aging and AD. Cohorts had variable recruitment criteria and follow-up intervals and included population-based and clinic-based samples. Inclusion in our analysis required APOE genotype data and either CSF data available for analysis. Analyses began on November 6, 2017, and were completed on December 20, 2017. Main Outcomes and Measures: Biomarker analyses included levels of ß-amyloid 42, total tau, and phosphorylated tau measured in CSF. Autopsy analyses included Consortium to Establish a Registry for Alzheimer's Disease staging for neuritic plaques and Braak staging for neurofibrillary tangles. Results: Of the 1798 patients in the CSF biomarker cohort, 862 were women, 226 had AD, 1690 were white, and the mean (SD) age was 70 [9] years. Of the 5109 patients in the autopsy cohort, 2813 were women, 4953 were white, and the mean (SD) age was 84 (9) years. After correcting for multiple comparisons using the Bonferroni procedure, we observed a statistically significant interaction between APOE-ε4 and sex on CSF total tau (ß = 0.41; 95% CI, 0.27-0.55; P < .001) and phosphorylated tau (ß = 0.24; 95% CI, 0.09-0.38; P = .001), whereby APOE showed a stronger association among women compared with men. Post hoc analyses suggested this sex difference was present in amyloid-positive individuals (ß = 0.41; 95% CI, 0.20-0.62; P < .001) but not among amyloid-negative individuals (ß = 0.06; 95% CI, -0.18 to 0.31; P = .62). We did not observe sex differences in the association between APOE and ß-amyloid 42, neuritic plaque burden, or neurofibrillary tangle burden. Conclusions and Relevance: We provide robust evidence of a stronger association between APOE-ε4 and CSF tau levels among women compared with men across multiple independent data sets. Interestingly, APOE-ε4 is not differentially associated with autopsy measures of neurofibrillary tangles. Together, the sex difference in the association between APOE and CSF measures of tau and the lack of a sex difference in the association with neurofibrillary tangles at autopsy suggest that APOE may modulate risk for neurodegeneration in a sex-specific manner, particularly in the presence of amyloidosis.

Effects of Fish Oil on HIV-Related Inflammation and Markers of Immunosenescence: A Randomized Clinical Trial.

OBJECTIVE: To explore the safety and efficacy of fish oil to modulate parameters of inflammation and immunosenescence in HIV-infected older adults. DESIGN: This study uses a randomized, controlled, double-blind clinical trial. SETTING: The study was conducted in an outpatient HIV/AIDS clinic in a large urban Midwestern city in the United States. SUBJECTS: A total of 37 clinically stable HIV-infected adults between the ages of 40 and 70 years of age participated. INTERVENTIONS: Fish oil 1.6 g/day was administered for 12 weeks or placebo. OUTCOME MEASURES: Inflammatory cytokine production, surface markers of immunosenescence, and adverse events were measured. RESULTS: After 12 weeks of supplementation, there were no significant differences between the treatment and control groups on any measures of inflammation or immunosenescence in both CD4+ and CD8+ T lymphocytes. More participants in the treatment group reported adverse gastrointestinal events compared with the control group. CONCLUSIONS: A 12-week supplementation regimen of 1.6 g/day of fish oil did not favorably modulate parameters of inflammation or immune senescence in HIV-infected adults. Future studies should test agents that directly target mechanisms that underlie HIV-related inflammation to determine whether reducing inflammation can reverse immunosenescence.

Nutrients and bioactives in green leafy vegetables and cognitive decline: Prospective study.

OBJECTIVE: To increase understanding of the biological mechanisms underlying the association, we investigated the individual relations to cognitive decline of the primary nutrients and bioactives in green leafy vegetables, including vitamin K (phylloquinone), lutein, ß-carotene, nitrate, folate, kaempferol, and α-tocopherol. METHODS: This was a prospective study of 960 participants of the Memory and Aging Project, ages 58-99 years, who completed a food frequency questionnaire and had ≥2 cognitive assessments over a mean 4.7 years. RESULTS: In a linear mixed model adjusted for age, sex, education, participation in cognitive activities, physical activities, smoking, and seafood and alcohol consumption, consumption of green leafy vegetables was associated with slower cognitive decline; the decline rate for those in the highest quintile of intake (median 1.3 servings/d) was slower by ß = 0.05 standardized units (p = 0.0001) or the equivalent of being 11 years younger in age. Higher intakes of each of the nutrients and bioactives except ß-carotene were individually associated with slower cognitive decline. In the adjusted models, the rates for the highest vs the lowest quintiles of intake were ß = 0.02, p = 0.002 for phylloquinone; ß = 0.04, p = 0.002 for lutein; ß = 0.05, p < 0.001 for folate; ß = 0.03, p = 0.02 for α-tocopherol; ß = 0.04, p = 0.002 for nitrate; ß = 0.04, p = 0.003 for kaempferol; and ß = 0.02, p = 0.08 for ß-carotene. CONCLUSIONS: Consumption of approximately 1 serving per day of green leafy vegetables and foods rich in phylloquinone, lutein, nitrate, folate, α-tocopherol, and kaempferol may help to slow cognitive decline with aging.

Personality Predicts Mortality Risk: An Integrative Data Analysis of 15 International Longitudinal Studies.

This study examined the Big Five personality traits as predictors of mortality risk, and smoking as a mediator of that association. Replication was built into the fabric of our design: we used a Coordinated Analysis with 15 international datasets, representing 44,094 participants. We found that high neuroticism and low conscientiousness, extraversion, and agreeableness were consistent predictors of mortality across studies. Smoking had a small mediating effect for neuroticism. Country and baseline age explained variation in effects: studies with older baseline age showed a pattern of protective effects (HR<1.00) for openness, and U.S. studies showed a pattern of protective effects for extraversion. This study demonstrated coordinated analysis as a powerful approach to enhance replicability and reproducibility, especially for aging-related longitudinal research.

Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans.

INTRODUCTION: African Americans' (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power. METHODS: We conducted a genome-wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome-wide set of single-nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs. RESULTS: Two SNPs at novel loci, rs112404845 (P = 3.8 × 10-8), upstream of COBL, and rs16961023 (P = 4.6 × 10-8), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability. DISCUSSION: An informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS.

APOE ε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline.

OBJECTIVE: To examine the association between consumption of seafood and long-chain n-3 fatty acids with change in 5 cognitive domains over an average of 4.9 years. METHODS: From an ongoing longitudinal, community-based epidemiologic study of aging and dementia (the Rush Memory and Aging Project), we included 915 participants (age 81.4 ± 7.2 years, 25% men) who had completed at least one follow-up cognitive assessment and dietary data. Diet was assessed by semiquantitative food frequency questionnaire. Scores for global cognitive function and 5 cognitive domains (episodic, semantic, and working memory, perceptual speed, and visuospatial ability) were assessed using 19 cognitive tests. Mixed models adjusted for multiple risk factors of cognitive change were used to assess the associations. RESULTS: Consumption of seafood was associated with slower decline in semantic memory (ß = 0.024; p = 0.03) and perceptual speed (ß = 0.020; p = 0.05) in separate models adjusted for age, sex, education, participation in cognitive activities, physical activity, alcohol consumption, smoking, and total energy intake. In secondary analyses, APOE ε4 carriers demonstrated slower rates of decline in global cognition and in multiple cognitive domains with weekly seafood consumption and with moderate to high long-chain n-3 fatty acid intake from food. These associations were not present in APOE ε4 noncarriers. Higher intake levels of α-linolenic acid were associated with slower global cognitive decline, but also only in APOE ε4 carriers. CONCLUSIONS: These results suggest protective relations of one meal per week of seafood and long-chain n-3 fatty acids against decline in multiple cognitive domains. The role of APOE ε4 in this association needs further study.

Change in Cognitive Abilities in Older Latinos.

The aim of this study was to compare patterns of cognitive decline in older Latinos and non-Latinos. At annual intervals for a mean of 5.7 years, older Latino (n=104) and non-Latino (n=104) persons of equivalent age, education, and race completed a battery of 17 cognitive tests from which previously established composite measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability were derived. In analyses adjusted for age, sex, and education, performance declined over time in each cognitive domain, but there were no ethnic group differences in initial level of function or annual rate of decline. There was evidence of retest learning following the baseline evaluation, but neither the magnitude nor duration of the effect was related to Latino ethnicity, and eliminating the first two evaluations, during which much of retest learning occurred, did not affect ethnic group comparisons. Compared to the non-Latino group, the Latino group had more diabetes (38.5% vs. 25.0; χ2[1]=4.4; p=.037), fewer histories of smoking (24.0% vs. 39.4%, χ2[1]=5.7; p=.017), and lower childhood household socioeconomic level (-0.410 vs. -0.045, t[185.0]=3.1; p=.002), but controlling for these factors did not affect results. Trajectories of cognitive aging in different abilities are similar in Latino and non-Latino individuals of equivalent age, education, and race. (JINS, 2016, 22, 58-65).

Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women.

OBJECTIVE: To determine the association between age at surgical menopause and both cognitive decline and Alzheimer disease (AD) pathology in 2 longitudinal cohorts. METHODS: Female subjects from 2 longitudinal studies of cognitive decline (Religious Orders Study and Rush Memory and Aging Project) were included (total n = 1,884). The primary analysis examined the association between age at surgical menopause and decline in a global cognition score. Secondary analyses examined additional outcomes: 1) decline in 5 cognitive subdomains and 2) a global measure of the burden of AD pathology. In exploratory analyses, we examined the effect of hormone replacement therapy (HRT). We adjusted all models for age, education, smoking, and cohort and stratified by surgical vs natural menopause. RESULTS: For the 32% of subjects with surgical menopause, earlier age at menopause was associated with faster decline in global cognition (p = 0.0007), specifically episodic memory (p = 0.0003) and semantic memory (p = 0.002). Earlier age at menopause was also associated with increased AD neuropathology (p = 0.038), in particular neuritic plaques (p = 0.013). HRT use for at least 10 years, when administered within a 5-year perimenopausal window, was associated with decreased decline in global cognition. No associations were seen in women who had natural menopause. CONCLUSIONS: Early age at surgical menopause was associated with cognitive decline and AD neuropathology. Ongoing studies should clarify the potential effect of HRT on this relationship.