Lu, Kirsty; (2019) Characterising cognition in later life and its relationship with biomarkers of Alzheimer's disease: a study of members of the National Survey of Health and Development (the British 1946 birth cohort). Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Alzheimer’s disease (AD) has a long preclinical stage characterised by the accumulation of brain pathology, which is estimated to begin several decades before the onset of symptoms. A significant proportion of older adults harbour such pathology, although many of them may not develop dementia during their lifetimes. Growing evidence suggests that subtle cognitive decline occurs during this preclinical period, but many unanswered questions remain about the nature and timing of changes in different cognitive domains, and associations with life-course predictors. This thesis is based on data from Insight 46, a neuroimaging sub-study of the MRC National Survey of Health and Development (the British 1946 birth cohort). In this population-based sample of 502 adults aged ~70 years, cognitive performance was assessed using standard and novel tests, and associations were investigated between cognition, life-course predictors, genetic risk factors for AD and brain pathologies, with a particular focus on β-amyloid. The key finding was that participants with elevated levels of β-amyloid showed poorer performance across a range of cognitive domains – some of which have received little attention in previous studies – including non-verbal reasoning, intra-individual variability in reaction time, visuomotor integration and memory. Other important results include: independent effects of childhood cognitive ability, educational attainment and adult socioeconomic position on later-life cognition; an association between white matter pathology and slower processing speed; associations between larger whole brain volume and faster performance on several diverse timed measures; and evidence that APOE-ε4 carriers may be advantaged on tests of short-term memory after accounting for the detrimental effect of β-amyloid. These results have implications for the interpretation of cognitive data measured in later life, and for the use of cognitive assessments to detect and track subtle cognitive decline in clinical trials that seek to delay or prevent the onset of AD dementia.

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