Memory Fidelity in Healthy Ageing and Risk for Cognitive Decline

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Memory decline is characteristic of cognitive ageing and it has been suggested that one important factor underpinning the magnitude of age deficits is a reduction in the fidelity or quality of perceptual and mnemonic representations. This thesis examined cognitive and neural underpinnings of individual differences in representational quality in healthy ageing and individuals at increased risk for cognitive decline to evaluate the potential of fidelity metrics for the early detection of memory impairment. Chapters 2 and 3 demonstrate that the ability to discriminate targets from highly similar lures in memory generally declines with age and in non-clinical older adults at risk for mild cognitive impairment. Importantly, the contribution of executive functions and the quality of perceptual representations to individual differences in mnemonic discrimination depends on the degree to which tasks provide retrieval support. Even when familiarity-based responding can be relied upon, memory deficits remain in both cognitively normal and at-risk older adults, suggesting that demands on complex stimulus representations are a key determinant of age-dependent memory deficits. Structural markers of medial temporal lobe regions contributed little to individual differences in mnemonic discrimination and complex perception. Chapter 4 shows that age-related declines are already present in midlife provided a task requires complex, precise stimulus representations. In contrast, ageing may spare the accessibility of coarse-grained representations, suggesting that memory decline was not due to forgetting but due to a decline in the availability of stimulus details. These age-related declines in high-quality representations were ubiquitous across tasks of perception, short- term and long-term memory. Chapters 5 and 6 tested whether tasks of mnemonic discrimination of highly similar objects and precision for object-location relational binding are sensitive to risk for Alzheimer’s disease and resilience against memory decline. Neither family history nor genetic risk for late-onset Alzheimer’s disease were associated with a decline in representational fidelity among cognitively unimpaired middle-aged and older adults. Cognitive reserve as measured based on a socially engaged and cognitively active lifestyle was associated with better long- term memory regardless of demands on representational quality. These findings demonstrate that ageing is associated with cognitive decline in any task that indexes the fidelity of complex stimulus representations. This reduction in representational quality is already present at midlife. The results also underscore the utility of representational fidelity measures for future investigations into individual differences in memory decline in both healthy and at-risk ageing.

Simons, Jon
memory, ageing, medial temporal lobe, neuroimaging, cognitive decline, cognitive reserve
Doctor of Philosophy (PhD)
Awarding Institution
University of Cambridge
Medical Research Council (1941893)
Medical Research Council; Pinsent Darwin Award; Biotechnology and Biological Sciences Research Council; James S. McDonnell Foundation
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