In the Baltimore Longitudinal Study of Aging, a prospective cohort study of community-dwelling U.S. adults, we examined associations of apolipoprotein E (ApoE) epsilon4 carrier status, sex, and time-dependent cognitive status with mortality risk and investigated these joint effects of these associations on time to death from all, cardiovascular, and noncardiovascular causes. Of 3,047 BLSA participants aged 17 to 98 at first visit (60.1% male), 1,704 with complete ApoE genotype data were included, of whom 1,461 aged 50 and older with one or more visits were eligible. Probability of survival was lower for ApoE epsilon4 carriers, particularly those who were older. A Cox proportional hazards model for all-cause mortality yielded a hazard ratio (HR) for ApoE epsilon4 carrier versus noncarriers of 1.31 (95% confidence interval (CI) = 1.02-1.68). This association was also found for cardiovascular mortality. Time-dependent all-cause dementia (HR = 1.73, 95% CI = 1.33-2.26) and mild cognitive impairment (HR = 1.95, 95% CI = 1.42-2.67) increased all-cause mortality risk, associations that were also detected for noncardiovascular mortality. When individuals were free of cognitive impairment, a dose-response relationship with epsilon4 alleles was found for all-cause mortality (HR = 1.40, 95% CI = 0.94-2.07 for 1 epsilon4;HR = 2.61, 95% CI = 1.12-6.07 for 2 epsilon4). After onset of Alzheimer's disease (AD), carrying only one epsilon4 allele resulted in an approximately 77% greater all-cause mortality risk than in noncarriers. ApoE epsilon4 carrier status increased all-cause mortality risk in men and interacted with time-dependent AD to increase the risk of this outcome (relative excess risk due to interaction = 2.15, 95% CI = 1.22-3.07). ApoE epsilon4 carrier status was found to increase all-cause and cardiovascular mortality risks and interacted with sex and time-dependent AD status to affect all-cause mortality. Recent evidence indicates that thyroid hormones may be closely linked to cognition among adults. We investigated associations between thyroid hormones and cognitive performance, while testing effect modification by sex, race and elevated depressive symptoms (EDS). In this cross-sectional study used extensive data from the HANDLS study, performed in Baltimore City, MD in 2004-2009 on adult participants aged 30-64y. Sample sizes ranged from 1,275 to 1,346. Outcomes included thirteen cognitive test scores spanning domains of learning/memory, language/verbal, attention, visuo-spatial/visuo-construction, psychomotor speed, executive function, and mental status.. We found that within reference ranges, and after Bonferroni correction, elevated free thyroxine (fT4) was associated with better performance on tests of visuo-spatial/visuo-construction ability (overall, women and African-Americans), learning/memory (women and African-Americans);whereas a higher total thyroxine (tT4) level was associated with better performance in the domain of psychomotor speed (individuals without EDS) and a higher level of both fT4 and tT4 was linked to better language/verbal test performance among men. In contrast, higher T3(%uptake) was related to better performance on tests of visuo-spatial/visuo-construction ability and psychomotor speed among Whites. When comparing above reference range to within in the overall population, and after Bonferroni correction, within reference range fT4 was linked to better performance on visuo-spatial/visuo-constrution ability and psychomotor speed, while being below the normal range thyroid stimulating hormone (TSH) level (compared to the reference range) was linked to better performance in domains of psychomotor speed and attention. These results suggest that thyroid hormones and cognition are closely linked, differentially by sex, race and EDS status. Helicobacter pylori seropositivity is a potential risk for poor cognition among US adults. In cross-sectional data from the National Health and Nutrition Examination Survey III, Phase 1 (1988-1991), we examined age group-specific neuropsychological test batteries and two measures of H. pylori seropositivity (immunoglobulin G IgG and IgG CagA) (20-59 years old: n = 2090-2,248;60-90 years old: n = 2123-2388). We explored sex- and race-specific associations. Using multiple ordinary least square and zero-inflated Poisson regression models, we detected a poorer performance among those 60-90 years old with H. pylori IgG+ versus IgG- on a verbal memory test (story recall, correct items), overall (beta = -0.04 0.01, p = .010). Non-Hispanic (NH) blacks and women (20-59 years old) performed worse on the serial digits learning total errors (SDL-TE) when H. pylori IgG+ (versus IgG-), another verbal memory test (beta = +0.94 0.40;p = .029 and beta = +1.19 0.44;p = .012, respectively;p<.10 for interaction by sex and race). More trials to completion on this test (SDL-TTC) were also required among H. pylori IgG+ overall (20-59 years old;beta = +0.30 0.13, p = .033). Other race-specific associations without significant interaction by race were detected in the same direction of worse performance with seropositivity in all three major race groups and for both age categories, covering several domains of cognition. These data suggest that H. pylori seropositivity markers were associated with poor cognition among US adults. Longitudinal research is needed to extrapolote those findings to cognitive decline, incident dementia, and Alzheimer's disease. We examined the relationship between erythrocyte mean corpuscular volume (MCV) and cognitive performance over time in longitudinal data from the Baltimore Longitudinal Study of Aging (BLSA). Eight hundred twenty-seven participants (mean age 67, range 50-96) had measures of mean corpuscular volume and several other blood indices were measured, including hemoglobin, iron, ferritin, vitamin B12, folate, white blood cell count, albumin, and erythrocyte sedimentation rate. Cognitive performance was examined using neuropsychological measures of visual memory, verbal memory, language, attention, executive function, and global mental status. High MCV levels were significantly associated with lower global mental status even after adjusting for potential confounders. High MCV levels were also significantly associated with high rates of decline on tasks of global mental status, long delay memory, and attention, even after adjusting for potential confounders. The findings confirm a previous observation that larger erythrocytes in older adults are associated with poorer cognitive function. Anemia and inflammation do not appear to explain the relationship between MCV and cognition. Further research is needed to clarify the mechanisms behind this association.

National Institute of Health (NIH)
National Institute on Aging (NIA)
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Wendell, Carrington R; Zonderman, Alan B; Katzel, Leslie I et al. (2016) Nonlinear associations between plasma cholesterol levels and neuropsychological function. Neuropsychology 30:980-987
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