Healthy cognitive ageing in the Lothian Birth Cohort studies: marginal gains not magic bullet

Abstract

In the face of shifting demographics and an increase in human longevity, it is important to examine carefully what is known about cognitive ageing, and to identify and promote possibly malleable lifestyle and health-related factors that might mitigate age-associated cognitive decline. The Lothian Birth Cohorts of 1921 (LBC1921, n = 550) and 1936 (LBC1936, n = 1091) are longitudinal studies of cognitive and brain ageing based in Scotland. Childhood IQ data are available for these participants, who were recruited in later life and then followed up regularly. This overview summarises some of the main LBC findings to date, illustrating the possible genetic and environmental contributions to cognitive function (level and change) and brain imaging biomarkers in later life. Key associations include genetic variation, health and fitness, psychosocial and lifestyle factors, and aspects of the brain's structure. It addresses some key methodological issues such as confounding by early-life intelligence and social factors and emphasises areas requiring further investigation. Overall, the findings that have emerged from the LBC studies highlight that there are multiple correlates of cognitive ability level in later life, many of which have small effects, that there are as yet few reliable predictors of cognitive change, and that not all of the correlates have independent additive associations. The concept of marginal gains, whereby there might be a cumulative effect of small incremental improvements across a wide range of lifestyle and health-related factors, may offer a useful way to think about and promote a multivariate recipe for healthy cognitive and brain ageing.

Cohort Profile Update: The Lothian Birth Cohorts of 1921 and 1936

“…Since the original cohort profile, 4 the studies have continued to produce new findings in the fields of cognitive ageing and epidemiology. A narrative overview of key cognitive and brain ageing results from almost 20 years of research on the LBC studies is available elsewhere 23 . Here we give an update on some results published since the 2012 profile, mainly stemming from new data types or resulting from new longitudinal analyses.…”

Assessing amyloid-β, tau, and glial features in Lothian Birth Cohort 1936 participants post-mortem

“…These individuals were first tested at 11 years of age in 1947 using a general intelligence test and since the age of 70 have been cognitively re-evaluated every 3 years. In addition to this longitudinal data on cognition, the LBC1936 study has accumulated an extensive database on genetics, biomedical, social and lifestyle factors, and longitudinal brain imaging, resulting in a highly characterised cohort [6] [7] [8] [9]. Post-mortem brains have been donated by 9 nondemented individuals, and to date, there is pre-mortem authorisation for brain donation from 173 individuals.…”

Influence of young adult cognitive ability and additional education on later-life cognition

“…They are also frequently used as indices of cognitive reserve (7); for example, higher education is associated with greater resistance to Alzheimer's disease (AD) pathology (4,8). However, such putative protective effects for promoting or maintaining brain and cognitive function could indicate reverse causation, that is, people with higher intellectual capacity attaining higher levels of education and occupational complexity and engaging more frequently in intellectually stimulating activities (9)(10)(11). Reverse causation is also consistent with the substantial genetic association between education and general cognitive ability (GCA), and the relationship of education to midlife and later-life cognitive function is largely mediated by genetic influences on GCA (12,13).…”