A quarter-century study tracking cognitive abilities from childhood through to older age has provided unprecedented insights into brain ageing, challenging long-held assumptions about cognitive decline and revealing remarkable variations in how individuals’ brains age across the lifespan. A paper published 7 November 2024 in Genomic Psychiatry [1] looks at lessons learned from this study.
Lifetime stability of intelligence
One of the most striking findings from the Lothian Birth Cohorts (LBC) studies is that approximately half of the variance in intelligence test scores measured in older age can be traced back to childhood cognitive ability. The research, which followed Scottish individuals born in 1921 and 1936, found correlations of about 0.7 between cognitive test scores at age 11 and those same tests taken in participants’ 70s and 80s.
This remarkable stability in cognitive differences across most of the human life course provides important insights into both the persistence of early-life cognitive capabilities and the factors that might influence cognitive change over time. The researchers note that this correlation represents a lower-bound estimate, as it doesn’t account for measurement error or the restriction of range in these samples compared with their background populations.
Brain structure and ageing patterns
The research team’s detailed brain imaging studies revealed substantial variations in brain health among people of the same chronological age. Using magnetic resonance imaging (MRI) of participants at age 73, they documented striking differences in both brain atrophy and white matter health, even among individuals born in the same year.
The researchers found that the health of brain white matter – the connecting tissues between different brain regions – showed consistent patterns. “People’s differences in brain white matter health were modestly associated with cognitive functioning,” the authors note in their paper. “Moreover, these two variables change together in a synchronized fashion over time: on average, those with steeper ageing of their brain white matter pathways are those whose general cognitive functioning declines more steeply.”
Survival and cognitive ability
A particularly significant finding from the research relates to the relationship between early-life cognitive ability and longevity. The study found that higher intelligence test scores at age 11 were associated with a better chance of survival to older age and lower risk of death from many major causes of mortality.
The researchers found that a one-standard deviation advantage in childhood cognitive test scores was associated with approximately 20% to 25% lower chance of dying from most major causes of death up to the late 70s. This association remained significant even after accounting for various socioeconomic factors, suggesting a robust link between early cognitive ability and later health outcomes.
Genetic influences across the lifespan
The study revealed intriguing findings about genetic influences on intelligence. The researchers discovered that genetic factors affecting cognitive ability are not identical in childhood and older age. Their work with the APOE gene, known for its association with Alzheimer’s risk, showed that while it had no association with cognitive test scores at age 11, it significantly influenced cognitive performance at age 79.
The team’s genome-wide association studies revealed that hundreds of tiny individual genetic associations contribute to intelligence differences, with genetic factors accounting for about two-thirds of the stability in intelligence from childhood to older age but only about a quarter of the changes in intelligence rankings across the same period.
DNA methylation and ageing
The research team made significant discoveries regarding epigenetic markers of ageing. They found that DNA methylation patterns – chemical modifications to DNA that can affect gene expression – could predict mortality risk. This finding suggests that biological ageing processes may be more accurately measured through molecular markers than chronological age alone.
The study also revealed that these epigenetic patterns were associated with various lifestyle factors, including smoking and body mass index, which in turn showed relationships with brain and cognitive differences. This provides evidence for potential biological mechanisms linking lifestyle choices to cognitive ageing.
Reverse causation challenges
One of the most thought-provoking findings challenges conventional wisdom about factors affecting cognitive ageing. The researchers discovered that some variables previously thought to be causes of cognitive differences in later life were actually outcomes of early-life cognitive ability.
For example, factors such as physical fitness, social engagement, and certain health markers in older age were found to be partially predicted by childhood intelligence. This suggests a complex relationship between early cognitive ability and later life choices or circumstances that influence brain health.
The power of longitudinal data
The study’s unique strength derives from its use of the Scottish Mental Surveys of 1932 and 1947, which tested almost every child born in 1921 and 1936 in Scotland. This comprehensive baseline allowed researchers to track cognitive changes across entire lifespans with unprecedented accuracy.
The value of this longitudinal approach became particularly evident when examining factors affecting cognitive decline. The researchers found that cross-sectional associations between various lifestyle factors and cognitive ability often disappeared when accounting for childhood cognitive ability, highlighting the importance of having early-life data for accurate interpretation.
Methodological insights
The research team emphasises that the effect sizes in cognitive ageing studies are typically small. Individual factors like fitness, genetic variants, or lifestyle choices usually contribute about 1% of the variance to cognitive capability in older age, after accounting for youth cognitive ability.
This finding has important implications for both research methodology and public health interventions. It suggests that rather than seeking single large effects, researchers and clinicians should consider the cumulative impact of multiple small influences on cognitive health.
Future research directions
Looking ahead, the research team continues to follow the surviving members of the 1936 cohort, who are now in their late 80s. This ongoing work promises to provide even more insights into the factors that influence cognitive health in advanced age.
The researchers have also established a brain tissue bank, with some participants consenting to donate their brains after death. This resource will enable future studies to examine the cellular and molecular basis of cognitive ageing, potentially revealing new therapeutic targets for age-related cognitive decline.
Practical implications
The findings suggest that maintaining cognitive health in later life likely requires a multifaceted approach. While some factors affecting cognitive ageing are fixed (such as genetics and early-life cognitive ability), others are potentially modifiable through lifestyle choices and environmental factors.
The researchers advocate for a “marginal gains” approach to cognitive health, where individuals focus on making multiple small positive changes rather than seeking a single solution. This could include maintaining physical activity, engaging in social and intellectual activities, and managing cardiovascular health.
Reference:
- Deary I. J., & Cox, S. R. Lessons we learned from the Lothian Birth Cohorts of 1921 and 1936. Genomic Psychiatry, 1-14. (7 November 2024). https://doi.org/10.61373/gp024i.0076
