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The long arm of childhood intelligence on terminal decline: Evidence from the Lothian Birth Cohort 1921.

ABSTRACT: The current study investigates the heterogeneity of cognitive trajectories at the end of life by assigning individuals into groups according to their cognitive trajectories prior to death. It also examines the role of childhood intelligence and education on these trajectories and group membership. Participants were drawn from the Lothian Birth Cohort of 1921 (LBC1921), a longitudinal study of individuals with a mean age of 79 years at study entry, and observed up to a maximum of five times to their early 90s. Growth mixture modeling was employed to identify groups of individuals with similar trajectories of global cognitive function measured with the Mini-Mental State Examination (MMSE) in relation to time to death, accounting for childhood intelligence, education, the time to death from study entry, and health conditions (hypertension, diabetes, and cardiovascular disease). Two distinct groups of individuals (classes) were identified: a smaller class (18% of the sample) of individuals whose MMSE scores dropped linearly with about 0.5 MMSE points per year closer to death and a larger group (82% of the sample) with stable MMSE across the study period. Only childhood intelligence was found to be associated with an increased probability of belonging to the stable class of cognitive functioning prior to death (odds ratio = 1.08, standard error = 0.02, p ≤ .001). These findings support a protective role of childhood intelligence, a marker of cognitive reserve, against the loss of cognitive function prior to death. Our results also suggest that terminal decline is not necessarily a normative process. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

SUBMITTER: Cadar D

PROVIDER: S-EPMC8352070 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPrevious studies have demonstrated that individual measures of fitness - such as reduced pulmonary function, slow walking speed and weak handgrip - are associated with an increased risk of dementia. Only a minority of participants included in these studies were aged over 80. The aim of this study was therefore to investigate the association between physical fitness and dementia in the oldest old.MethodsSubjects (n = 488) were enrolled in the Lothian Birth Cohort 1921 and aged 79 at baseline. Dementia cases arising after enrolment were determined using data from death certificates, electronic patient records and clinical reviews. Fitness measures included grip strength, forced expiratory volume in 1 s (FEV1) and walking speed over 6 m, measured at 79 years. Dementia risk associated with each fitness variable was initially determined by logistic regression analysis, followed by Cox regression analysis, where death was considered as a competing risk. APOE ε4 status, age, sex, height, childhood IQ, smoking, history of cardiovascular or cerebrovascular disease, hypertension and diabetes were included as additional variables. Cumulative incidence graphs were calculated using Aalen-Johansen Estimator.ResultsAlthough initial results indicated that greater FEV1 was associated with an increased risk of dementia (OR (odds ratio per unit increase) 1.93, p = 0.03, n = 416), taking into account the competing risk of mortality, none of the fitness measures were found to be associated with dementia; FEV1 (HR (hazard ratio per unit increase) 1.30, p = 0.37, n = 416), grip strength (HR 0.98, p = 0.35, n = 416), walking speed (HR 0.99, p = 0.90, n = 416). The presence of an APOE ɛ4 allele was however an important predictor for dementia (HR 2.85, p < 0.001, n = 416). Cumulative incidence graphs supported these findings, with an increased risk of dementia for APOE ɛ4 carriers compared with non-carriers. While increased FEV1 was associated with reduced risk of death, there was no reduction in risk for dementia.ConclusionsIn contrast to previous studies, this study found that lower fitness beyond age 79 was not a risk factor for subsequent dementia. This finding is not explained by those with poorer physical fitness, who would have been more likely to develop dementia, having died before onset of dementia symptoms.

Project description:BackgroundDNA methylation outlier burden has been suggested as a potential marker of biological age. An outlier is typically defined as DNA methylation levels at any one CpG site that are three times beyond the inter-quartile range from the 25th or 75th percentiles compared to the rest of the population. DNA methylation outlier burden (the number of such outlier sites per individual) increases exponentially with age. However, these findings have been observed in small samples.ResultsHere, we showed an association between age and log10-transformed DNA methylation outlier burden in a large cross-sectional cohort, the Generation Scotland Family Health Study (N = 7010, β = 0.0091, p < 2 × 10-16), and in two longitudinal cohort studies, the Lothian Birth Cohorts of 1921 (N = 430, β = 0.033, p = 7.9 × 10-4) and 1936 (N = 898, β = 0.0079, p = 0.074). Significant confounders of both cross-sectional and longitudinal associations between outlier burden and age included white blood cell proportions, body mass index (BMI), smoking, and batch effects. In Generation Scotland, the increase in epigenetic outlier burden with age was not purely an artefact of an increase in DNA methylation level variability with age (epigenetic drift). Log10-transformed DNA methylation outlier burden in Generation Scotland was not related to self-reported, or family history of, age-related diseases, and it was not heritable (SNP-based heritability of 4.4%, p = 0.18). Finally, DNA methylation outlier burden was not significantly related to survival in either of the Lothian Birth Cohorts individually or in the meta-analysis after correction for multiple testing (HRmeta = 1.12; 95% CImeta = [1.02; 1.21]; pmeta = 0.021).ConclusionsThese findings suggest that, while it does not associate with ageing-related health outcomes, DNA methylation outlier burden does track chronological ageing and may also relate to survival. DNA methylation outlier burden may thus be useful as a marker of biological ageing.

Project description:BackgroundWith increasing numbers of people surviving beyond eighty years, this section of the population demands attention to reduce the impact of dementia. In order to develop effective preventative strategies, it is essential to understand age-specific risk factor profiles for dementia: do risk factors for dementia in those in their sixties and seventies persist into oldest age? The aims of this study were to determine incident dementia and to investigate the risk profile for dementia from age 79 to 95 years in a well-characterised cohort.MethodsParticipants underwent intelligence testing at age 11 and were followed-up from at 79 years of age. Variables included: age, sex, age 11 IQ, APOE ɛ4, education, diabetes, hypertension, statin use, physical activity at leisure and in occupation, symptoms of depression, height, number of teeth, body mass index, blood pressure, cholesterol and HbA1c. Dementia cases were ascertained from death certificates, electronic patient records and clinical reviews. Logistic regression analysis determined the degree of risk for dementia associated with each variable. Analyses were completed both with and without the physical activity variables due to the significant number of missing data for these variables.ResultsOf the eligible cohort, n = 410 participants remained dementia-free and n = 110 had developed probable dementia. When logistic regression analyses contained all variables, complete data was available for n = 234 (n = 48 with dementia). Results demonstrated that positive APOE ɛ4 carrier status (OR: 2.15, 95% CI: 1.04, 4.42) and greater lifetime physical activity (OR: 1.14, 95% CI: 1.02, 1.28) increased the risk for dementia. A reduction in risk for dementia was seen for hypertension (OR: 0.47, 95% CI: 0.23, 0.98). When physical activity variables were excluded, the number with complete data increased to n = 377 (n = 80 with dementia). APOE ɛ4 remained significant (OR: 2.37; 95% CI: 1.37, 4.07), as did hypertension (OR: 0.55; 95% CI: 0.32, 0.93).ConclusionsDementia incidence was consistent with expected rates. The risk profile for dementia in this cohort of participants aged 79-95 confirmed previous findings that risk factors differ for those over 79 years. Further evidence is recommended in order that the risk profile for this age group can be accurately determined.

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The long arm of childhood intelligence on terminal decline: Evidence from the Lothian Birth Cohort 1921.

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