Cognitive impairment, including dementia, is a major health concern with the increasing aging population. Preventive measures to delay cognitive decline are of utmost importance. Alzheimer's disease (AD) is the most frequent cause of dementia, increasing in prevalence from <1% below the age of 60 years to >40% above 85 years of age. We systematically reviewed selected modifiable factors such as education, smoking, alcohol, physical activity, caffeine, antioxidants, homocysteine (Hcy), n-3 fatty acids that were studied in relation to various cognitive health outcomes, including incident AD. We searched MEDLINE for published literature (January 1990 through October 2012), including cross-sectional and cohort studies (sample sizes > 300). Analyses compared study finding consistency across factors, study designs and study-level characteristics. Selecting studies of incident AD, our meta-analysis estimated pooled risk ratios (RR), population attributable risk percent (PAR%) and assessed publication bias. 247 studies were retrieved for systematic review. Consistency analysis for each risk factor suggested positive findings ranging from 38.9% for caffeine to 89% for physical activity. Education also had a significantly higher propensity for a positive finding compared to caffeine, smoking and antioxidant-related studies. Meta-analysis of 31 studies with incident AD yielded pooled RR for low education (RR = 1.99; 95%CI: 1.30-3.04), high Hcy (RR = 1.93; 95%CI: 1.50-2.49), and current or ever smoking status (RR = 1.37; 95%CI: 1.23-1.52) while indicating protective effects of higher physical activity and n-3 fatty acids. Estimated PAR% were particularly high for physical activity (PAR% = 31.9; 95%CI: 22.7-41.2) and smoking (PAR%-31.0%; 95%CI: 17.9-44.3). Overall, no significant publication bias was found. Higher Hcy levels, lower educational attainment, and decreased physical activity were particularly strong predictors of incident AD. Among modifiable lifestyle factors, diet may affect cognitive health. Cross-sectional and longitudinal associations may exist between dietary exposures e.g., caffeine (mg/d), alcohol (g/d), and nutrient adequacy and cognitive performance and change over time. Data were drawn from a prospective cohort study (n = 628-1305 persons depending on the cognitive outcome; approximately 2 visits/person). Outcomes included 10 cognitive scores, spanning various domains of cognition. Caffeine and alcohol intakes and a nutrient adequacy score (NAS) were estimated from 7-d food diaries. Among key findings, caffeine intake was associated with better baseline global cognition among participants with a baseline age (Agebase) of &#8805;70y. A higher NAS was associated with better baseline global cognition performance (overall, women, Agebase <70y), better baseline verbal memory (immediate and delayed recall, Agebase &#8805;70y), and slower rate of decline or faster improvement in the attention domain (women). For an Agebase of <70y, alcohol consumption was associated with slower improvement on letter fluency and global cognition over time. Conversely, for an Agebase of &#8805;70 y and among women, alcohol intake was related to better baseline attention and working memory. In sum, patterns of diet and cognition associations indicate stratum-specific associations by sex and baseline age. The general observed trend was that of putative beneficial effects of caffeine intake and nutrient adequacy on domains of global cognition, verbal memory, and attention, and mixed effects of alcohol on domains of letter fluency, attention, and working memory. Growing evidence suggests that self-reported physical activity accounts for variability in cognitive function among older adults, and aerobic intervention may improve cognitive function in this population. However, much less is known about the longitudinal association between direct measures of cardiorespiratory fitness and cognitive function across the life span. We examined the prospective association between symptom-limited maximal oxygen consumption (VO2max) and longitudinal performance on a comprehensive neuropsychological battery. Up to 1,400 participants aged 19-94 years underwent initial VO2max assessment and completed subsequent tests of memory, attention, perceptuomotor speed, language, and executive function, in addition to cognitive screening measures, on up to six occasions (mean, M = 2; standard deviation, SD = 1) for up to 18 years (M = 7, SD = 3). Mixed-effects regression models were adjusted for demographic, biomedical, and behavioral confounders. We found significant longitudinal associations between baseline VO2max and trajectory of performance on multiple measures of verbal and visual memory, as well as on a cognitive screening test (all ps < .05). Individuals with lower VO2max had accelerated trajectories of cognitive decline over time. Baseline cardiorespiratory fitness is related to longitudinal neuropsychological performance, and memory appears to be a particularly vulnerable domain. Evidence that aerobic fitness is associated with accelerated cognitive decline emphasizes the possible importance of behavioral interventions to optimize cognitive aging over time. The literature thus far is equivocal about longitudinal associations between total cholesterol and cognitive decline. We examined prospective nonlinear relations of coincident trajectories of total cholesterol and cognitive function among persons free of stroke, dementia, and other neurological disease. Up to 1,601 participants from prospective cohort study (aged 19-93, 51% male, 75% White) underwent fasting cholesterol measurement and neuropsychological assessment on up to 12 occasions (M = 3.2, SD = 2.1) over up to 19 years (M = 6.4, SD = 5.3) of follow-up. Mixed-effects regression analyses were adjusted for age, sex, race, education, systolic blood pressure, body mass index, cardiovascular disease, lipid-lowering medication use, smoking, alcohol use, and depressive symptoms. Analyses revealed significant longitudinal associations between quadratic total cholesterol and performance on measures of global mental status, verbal learning, executive function, and language (all ps < .05). In general, higher total cholesterol was associated with poorer middle-aged or young-old (60-69 years) cognitive performance, but better old-old (80-89 years) cognitive performance. Linear models also revealed an association between lower total cholesterol and accelerated decline in visual memory performance. Overall, results indicate nonlinear longitudinal relations of total cholesterol to cognitive decline. Evidence that depressive symptoms are inversely related to n-3 (omega-3) fatty acids is growing among United States adults. We assessed whether self-reported depressive symptoms were inversely associated with n-3 fatty acid intakes by using a cross-sectional study in 1746 adults (aged 30-65 y) in Baltimore City, MD (2004-2009). The 20-item Center for Epidemiologic Studies-Depression Scale (CES-D) was used, with a CES-D score &#8805;16 suggestive of elevated depressive symptoms (EDS). N-3 highly unsaturated fatty acids (HUFAs; &#8805;20 carbons), n-3 polyunsaturated fatty acids (PUFAs; >/=18 carbons), and plausible ratios with n-6 (omega6) fatty acids were estimated. EDS prevalence was 18.1% among men and 25.6% among women. In women, the uppermost tertile (tertile 3) of n-3 PUFAs (compared with tertile 1) was associated with reduced odds of EDS by 49%, with a substantial sex differential. The n-3 PUFA:n-6:PUFA ratio was inversely related to EDS among women (tertile 2 vs. tertile 1, OR: 0.74; 95% CI: 0.41, 1.32; tertile 3 vs. tertile 1, OR: 0.47; 95% CI: 0.27, 0.83). A similar pattern was noted for n-3 HUFA:n-6 HUFA among women.