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Background: Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birth cohort analysis, aimed to determine if repeated exposure to anticholinergic medications was associated with greater decline, and whether decline was reversed with medication reduction. Methods: From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified by the Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantified by the Word Learning Test [WLT], and processing speed quantified by the Timed Letter Search Task [TLST]) at three time points (age 53, 60–64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms. Results: Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60–64 (mean difference − 2.34, 95% confidence interval [CI] − 3.51 to − 1.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure − 0.90, 95% CI − 1.63 to − 0.17; mean difference with lagged exposure − 1.53, 95% CI − 2.43 to − 0.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure −1.78, 95% CI −2.85 to − 0.71; mean difference with lagged exposure − 2.23, 95% CI − 3.33 to − 1.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference − 13.14, 95% CI − 19.04 to − 7.23; p < 0.01). Conclusions: Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study. [ABSTRACT FROM AUTHOR]

Importance: Associations between affective symptoms and mortality have been evaluated, but studies have not examined timing or cumulative exposure to affective symptoms over the life course.Objectives: To examine how lifetime accumulation and timing of affective symptoms are associated with mortality and identify potential explanatory factors.Design, Setting, and Participants: Data were obtained from the MRC National Survey of Health and Development (1946 British birth cohort), a socially stratified, population-based sample originally consisting of 5362 singleton births in England, Wales, and Scotland during March 1946. The cohort has been followed up 24 times, most recently in 2014-2015. Eligible participants included those flagged for mortality with affective symptom data available at a minimum of 3 time points (n = 3001). Data analysis was conducted from July 2016 to January 2019.Exposures: Affective symptoms were assessed at ages 13 to 15 years (teacher-rated questionnaire), 36 years (Present State Examination clinical semistructured interview), 43 years (Psychiatric Symptom Frequency questionnaire), and 53 years (General Health Questionnaire-28). Case-level affective symptoms were determined by those scoring in the top 16th percentile (ie, suggestive of a clinical diagnosis).Main Outcomes and Measures: Mortality data were obtained from the UK National Health Service Central Register from age 53 to 68 years.Results: Of 3001 study members (1509 [50.3%] female, 1492 [49.7%] male), 235 individuals (7.8%) died over a 15-year follow-up. After adjustment for sex, those who experienced case-level affective symptoms 1, 2, and 3 to 4 times had 76%, 87%, and 134% higher rates of premature mortality, respectively, compared with those who never experienced case-level symptoms. Case-level symptoms in adolescence only (ages 13-15 years) were associated with a 94% increased rate of mortality, which was unexplained after full adjustment for covariates (hazard ratio, 1.73; 95% CI, 1.10-2.72). Associations between participants with case-level symptoms multiple (2-4) times and mortality were predominately explained by adult health indicators and behaviors. For example, associations for those with case-level symptoms 3 to 4 times were most strongly attenuated by number of health conditions (32.1%), anxiolytic use (28.4%), lung function (24.6%), physical activity (23.9%), smoking (24.6%), antidepressant use (20.1%), diet (16.4%), pulse rate (12.7%), and adult social class (11.2%).Conclusions and Relevance: Lifetime accumulation of affective symptoms may be associated with an increased rate of mortality, with explanatory pathways dependent on the duration and timing of symptoms. Future research into causal pathways and potential points of intervention should consider affective symptom history. [ABSTRACT FROM AUTHOR]

Background: Childhood IQ has been related to mortality in later life in four studies. Cognitive ability may be a mediator between early disadvantage and mortality, a marker of the efficiency of information processing in the central nervous system, or predict entry to safe adult environments or healthy behaviours. We examined mortality in relation to cognitive ability at age 8 years in a birth cohort and investigated these possible reasons., Methods: Cox's proportional hazards models were used to investigate the effect of early cognitive ability on all-cause mortality in 2057 women and 2192 men born in England, Scotland, and Wales in March 1946 and followed until age 54 years. We tested whether the relationship was accounted for by childhood socioeconomic conditions or serious illness, education, adult socioeconomic conditions, or smoking., Results: Cognitive ability was related to mortality in men but not women. The excess mortality rate in men was concentrated in the bottom quarter of the cognitive score (hazard ratio [HR] for bottom versus top quarter 1.8, 95% CI: 1.0, 3.0) and there was no gradient across the range of ability. Adjustment for childhood socioeconomic conditions and serious illness had a small effect on the HR for deaths between 9 and 54 years while adjustment for education or early adult socioeconomic conditions halved the HR for deaths from age 26 years. Smoking was not a mediator of the effect of early ability on adult mortality., Conclusions: Greater cumulative exposure to poor lifetime socioeconomic conditions is the most likely explanation for the observed relationship between low cognitive ability in childhood and mortality. This relationship may therefore be elucidated further by studying the causes of lifelong socioeconomic inequalities in health.