Objectives
To investigate longitudinal associations between polypharmacy and cognitive and physical capability and to determine whether these associations differ with cumulative exposure to ...polypharmacy.
Design
Prospective birth cohort study.
Setting
England, Scotland, and Wales.
Participants
An eligible sample of men and women from the Medical Research Council National Survey of Health and Development with medication data at age 69 (N=2,122, 79%).
Measurements
Cognitive capability was assessed using a word learning test, visual search speed task, and the Addenbrooke's Cognitive Examination, Third Edition (ACE‐III). Physical capability was measured using chair rise speed, standing balance time, walking speed, and grip strength.
Results
Polypharmacy (5–8 prescribed medications) was present in 18.2% of participants at age 69 and excessive polypharmacy (≥9 prescribed medications) in 4.7%. Both were associated with poorer cognitive and physical capability in models adjusted for sex, education, and disease burden. Stronger associations were found for excessive polypharmacy (e.g., difference in mean ACE‐III scores comparing polypharmacy=−2.0, 95% CI=−2.8 to −1.1 and excessive polypharmacy=−2.9, 95% CI=−4.4 to −1.4 with no polypharmacy). Participants with polypharmacy at age 60 to 64 and at age 69 showed stronger Negative associations with cognitive and physical capability were stronger still in participants with polypharmacy at both age 60 to 64 and at age 69 (e.g. difference in mean chair rise speed, comparing polypharmacy with no polypharmacy at both ages=−3.9, 95% CI=−5.2 to −2.6 and at age 60–64 only=−2.5, 95% CI=−4.1 to −0.9).
Conclusion
Polypharmacy at age 60 to 64 and age 69 was associated with poorer physical and cognitive capability, even after adjusting for disease burden. Stronger negative associations were seen in participants with longstanding polypharmacy, suggesting a cumulative, dose‐dependent relationship (where dose is the number of prescribed medications). Future research aiming to improve cognitive and physical capability should consider interventions to reduce the duration and level of polypharmacy at younger ages, in addition to optimizing disease control with appropriate medications.
Abstract
Background
The objective of this study was to examine the association between education and incidence of accelerated cognitive decline.
Methods
Secondary analyses of data from the Health and ...Retirement Study (HRS), a nationally representative prospective cohort study of U.S. residents were conducted (N = 28,417). Cox proportional hazards survival models were layered on longitudinal mixed-effects modeling to jointly examine healthy cognitive aging and incidence of accelerated cognitive decline consistent with patterns seen in preclinical Alzheimer’s disease and related dementias (ADRD). Replication analyses were completed on a database including 62,485 additional respondents from HRS sister studies. Life expectancy ratios (LER) and 95% confidence intervals (CIs) were reported.
Results
This study replicated research showing that education was positively associated with cognition at baseline. Model fit improved using the survival method compared to random-slopes models alone. Analyses of HRS data revealed that higher education was associated with delayed onset of accelerated cognitive decline (LER = 1.031 95% CI = 1.013–1.015, p < 1E-06). Replication analyses using data from 14 countries identified similar results.
Conclusions
These results are consistent with cognitive reserve theory, suggesting that education reduces risk of ADRD-pattern cognitive decline. Follow-up work should seek to differentiate specific dementia types involved and consider potential mechanisms.
Midlife hypertension confers increased risk for cognitive impairment in late life. The sensitive period for risk exposure and extent that risk is mediated through amyloid or vascular-related ...mechanisms are poorly understood. We aimed to identify if, and when, blood pressure or change in blood pressure during adulthood were associated with late-life brain structure, pathology, and cognition.
Participants were from Insight 46, a neuroscience substudy of the ongoing longitudinal Medical Research Council National Survey of Health and Development, a birth cohort that initially comprised 5362 individuals born throughout mainland Britain in one week in 1946. Participants aged 69–71 years received T1 and FLAIR volumetric MRI, florbetapir amyloid-PET imaging, and cognitive assessment at University College London (London, UK); all participants were dementia-free. Blood pressure measurements had been collected at ages 36, 43, 53, 60–64, and 69 years. We also calculated blood pressure change variables between ages. Primary outcome measures were white matter hyperintensity volume (WMHV) quantified from multimodal MRI using an automated method, amyloid-β positivity or negativity using a standardised uptake value ratio approach, whole-brain and hippocampal volumes quantified from 3D-T1 MRI, and a composite cognitive score—the Preclinical Alzheimer Cognitive Composite (PACC). We investigated associations between blood pressure and blood pressure changes at and between 36, 43, 53, 60–64, and 69 years of age with WMHV using generalised linear models with a gamma distribution and log link function, amyloid-β status using logistic regression, whole-brain volume and hippocampal volumes using linear regression, and PACC score using linear regression, with adjustment for potential confounders.
Between May 28, 2015, and Jan 10, 2018, 502 individuals were assessed as part of Insight 46. 465 participants (238 51% men; mean age 70·7 years SD 0·7; 83 18% amyloid-β-positive) were included in imaging analyses. Higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) at age 53 years and greater increases in SBP and DBP between 43 and 53 years were positively associated with WMHV at 69–71 years of age (increase in mean WMHV per 10 mm Hg greater SBP 7%, 95% CI 1–14, p=0·024; increase in mean WMHV per 10 mm Hg greater DBP 15%, 4–27, p=0·0057; increase in mean WMHV per one SD change in SBP 15%, 3–29, p=0·012; increase in mean WMHV per 1 SD change in DBP 15%, 3–30, p=0·017). Higher DBP at 43 years of age was associated with smaller whole-brain volume at 69–71 years of age (−6·9 mL per 10 mm Hg greater DBP, −11·9 to −1·9, p=0·0068), as were greater increases in DBP between 36 and 43 years of age (−6·5 mL per 1 SD change, −11·1 to −1·9, p=0·0054). Greater increases in SBP between 36 and 43 years of age were associated with smaller hippocampal volumes at 69–71 years of age (−0·03 mL per 1 SD change, −0·06 to −0·001, p=0·043). Neither absolute blood pressure nor change in blood pressure predicted amyloid-β status or PACC score at 69–71 years of age.
High and increasing blood pressure from early adulthood into midlife seems to be associated with increased WMHV and smaller brain volumes at 69–71 years of age. We found no evidence that blood pressure affected cognition or cerebral amyloid-β load at this age. Blood pressure monitoring and interventions might need to start around 40 years of age to maximise late-life brain health.
Alzheimer's Research UK, Medical Research Council, Dementias Platform UK, Wellcome Trust, Brain Research UK, Wolfson Foundation, Weston Brain Institute, Avid Radiopharmaceuticals.
Low social participation is a potentially modifiable risk factor for cognitive deterioration in the general population and related to lower quality of life (QoL). We aimed to find out whether social ...participation is linked to cognitive deterioration and QoL for people with borderline intellectual functioning and mild intellectual disability.
We used data from the National Child Development Study, consisting of people born during one week in 1958, to compare midlife social participation in people with mild intellectual disability, borderline intellectual functioning, and without intellectual impairment. We defined social participation as 1. confiding/emotional support from the closest person and social network contact frequency at age 44, and 2. confiding relationships with anyone at age 50. We then assessed the extent to which social participation mediated the association between childhood intellectual functioning and cognition and QoL at age 50.
14,094 participants completed cognitive tests at age 11. People with borderline intellectual functioning and mild intellectual disability had more social contact with relatives and confiding/emotional support from their closest person, but fewer social contacts with friends and confiding relationships with anyone than those without intellectual disability. Having a confiding relationship partially mediated the association at age 50 between IQ and cognition (6.4%) and QoL (27.4%) for people with borderline intellectual functioning.
We found adults with intellectual disability have positive family relationships but fewer other relationships. Even at the age of 50, confiding relationships may protect cognition for people with borderline intellectual functioning and are important for QoL.
We tested the association between APOE-ε4 and processing speed and memory between ages 43 and 69 in a population-based birth cohort. Analyses of processing speed (using a timed letter search task) ...and episodic memory (a 15-item word learning test) were conducted at ages 43, 53, 60-64 and 69 years using linear and multivariable regression, adjusting for gender and childhood cognition. Linear mixed models, with random intercepts and slopes, were conducted to test the association between APOE and the rate of decline in these cognitive scores from age 43 to 69. Model fit was assessed with the Bayesian Information Criterion. A cross-sectional association between APOE-ε4 and memory scores was detected at age 69 for both heterozygotes and homozygotes (β = -0.68 and β = -1.38, respectively, p = 0.03) with stronger associations in homozygotes; no associations were observed before this age. Homozygous carriers of APOE-ε4 had a faster rate of decline in memory between ages 43 and 69, when compared to non-carriers, after adjusting for gender and childhood cognition (β = -0.05, p = 0.04). There were no cross-sectional or longitudinal associations between APOE-ε4 and processing speed. We conclude that APOE-ε4 is associated with a subtly faster rate of memory decline from midlife to early old age; this may be due to effects of APOE-ε4 becoming manifest around the latter stage of life. Continuing follow-up will determine what proportion of this increase will become clinically significant.
Adolescent mental health difficulties are increasing over time. However, it is not known whether their adulthood health and socio-economic sequelae are changing over time.
Participants (
= 31 349) ...are from two prospective national birth cohort studies: 1958 National Child Development Study (
= 16 091) and the 1970 British Cohort Study (
= 15 258). Adolescent mental health was operationalised both as traditional internalising and externalising factors and a hierarchical bi-factor. Associations between adolescent psychopathology and age 42 health and wellbeing (mental health, general health, life satisfaction), social (cohabitation, voting behaviour) and economic (education and employment) outcomes are estimated using linear and logistic multivariable regressions across cohorts, controlling for a wide range of early life potential confounding factors.
The prevalence of adolescent mental health difficulties increased and their associations with midlife health, wellbeing, social and economic outcomes became more severe or remained similar between those born in 1958 and 1970. For instance, a stronger association with adolescent mental health difficulties was found for those born in 1970 for midlife psychological distress odds ratio (OR) 1970 = 1.82 (1.65-1.99), OR 1958 = 1.60 (1.43-1.79), cohabitation OR 1970 = 0.64 (0.59-0.70), OR 1958 = 0.79 (0.72-0.87), and professional occupations OR 1970 = 0.75 (0.67-0.84), OR 1958 = 1.05 (0.88-1.24). The associations of externalising symptoms with later outcomes were mainly explained by their shared variance with internalising symptoms.
The widening of mental health-based inequalities in midlife outcomes further supports the need to recognise that secular increases in adolescent mental health symptoms is a public health challenge with measurable negative consequences through the life-course. Increased public health efforts to minimise adverse outcomes are needed.
Abstract Purpose Social isolation is associated with suicidal ideation (SI) and self-harm (SH) among adolescents. However, the association between preference for solitude (PfS), SI, and SH is ...unknown. The prevalence of adolescents who have both of PfS and social isolation and the risks for SI and SH among them are also unknown. Methods Information on PfS, social isolation, SI, and SH was collected in a large-scale school-based survey on adolescents, using a self-report questionnaire. Associations between PfS, SI, and SH were examined by logistic regression analysis. The interactions between PfS and social isolation on SI and SH were also investigated. The odds of SI and SH were examined for groups defined by presence of PfS and social isolation. Results Responses from 17,437 students (89.3% of relevant classes) were available. After adjusting for demographic characteristics and social isolation, PfS was associated with increased odds of SI (odds ratio OR = 3.1) and SH (OR = 1.9). There was no interaction between PfS and social isolation on SI and SH. After adjusting for demographic characteristics, the odds for SI (OR = 8.6) and SH (OR = 3.8) were highest among adolescents with both PfS and social isolation (8.4% of all respondents). Conclusions PfS was associated with increased odds of SI and SH in adolescents. No interaction effect between PfS and social isolation on SI and SH was found, but adolescents with PfS and social isolation had the highest risk for SI and SH. Parents and professionals should pay attention to suicide risk in adolescents with PfS.
We examined the relationship between childhood and adult socioeconomic position (SEP) and objectively assessed, later-life functioning.
We used the Medical Research Council's National Survey of ...Health and Development data to examine performance at 60 to 64 years (obtained in 2006-2011) for a representative UK sample. We compared 9 physical and cognitive performance measures (forced expiratory volume, forced vital capacity, handgrip strength, chair rise time, standing balance time, timed get up and go speed, verbal memory score, processing speed, and simple reaction time) over the SEP distribution.
Each performance measure was socially graded. Those at the top of the childhood SEP distribution had between 7% and 20% better performance than those at the bottom. Inequalities generally persisted after adjustment for adult SEP. When we combined the 9 performance measures, the relative difference was 66% (95% confidence interval = 53%, 78%).
Public health practice should monitor and target inequalities in functional performance, as well as risk of disease and death. Effective strategies will need to affect the social determinants of health in early life to influence inequalities into old age.
The concept of reserve in neuroscience maintains that there are aspects of brain structure and function that can buffer the effects of neuropathology such that the greater the reserve, the more ...severe the pathology must be to cause functional impairment. This article provides a concise overview of structural and functional approaches to reserve and shows how reserve may be conceived as the sum of its lifetime input. In this context, reserve therefore provides an empirical yet general model of cognitive aging and development. Ann Neurol 2005;58:617–622
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