Age-associated cognitive changes in community dwelling adults

在巴尔的摩老龄化纵向研究中，一项对美国社区成年人的前瞻性队列研究，我们检查了载脂蛋白E (ApoE) epsilon4携带状态、性别和时间依赖性认知状态与死亡风险的关系，并调查了这些关联对所有心血管和非心血管原因导致的死亡时间的联合影响。在3047名首次就诊时年龄在17至98岁之间的BLSA参与者（60.1%为男性）中，纳入了1704名具有完整ApoE基因型数据的参与者，其中1461名年龄在50岁及以上且有一次或多次就诊的参与者符合条件。ApoE - epsilon4携带者的生存几率较低，尤其是老年人。全因死亡率的Cox比例风险模型得出ApoE ε 4携带者与非携带者的风险比（HR）为1.31（95%可信区间(CI) = 1.02-1.68）。心血管疾病死亡率也发现了这种关联。时间依赖性全因痴呆（HR = 1.73, 95% CI = 1.33-2.26）和轻度认知障碍（HR = 1.95, 95% CI = 1.42-2.67）增加了全因死亡风险，并与非心血管疾病死亡率相关。当个体没有认知障碍时，发现epsilon4等位基因与全因死亡率呈剂量-反应关系（1个epsilon4的HR = 1.40, 95% CI = 0.94-2.07； 2个epsilon4的HR = 2.61, 95% CI = 1.12-6.07）。阿尔茨海默病（AD）发病后，仅携带一个epsilon4等位基因的患者的全因死亡率比非携带者高约77%。ApoE epsilon4携带者增加了男性全因死亡风险，并与时间依赖性AD相互作用，增加了该结果的风险（相互作用导致的相对超额风险= 2.15,95% CI = 1.22-3.07）。ApoE epsilon4携带状态增加了全因死亡率和心血管死亡率风险，并与性别和时间依赖性AD状态相互作用，影响全因死亡率。

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.