Abstract
Prospective studies suggest that memory deficits are detectable decades before clinical symptoms of dementia emerge. However, individual differences in long-term memory trajectories prior to diagnosis need to be further elucidated. The aim of the current study was to investigate long-term dementia and mortality risk for individuals with different memory trajectory profiles in a well-characterized population-based sample. 1062 adults (aged 45-80 years) who were non-demented at baseline were followed over 23-28 years. Dementia and mortality risk were studied for three previously classified episodic memory trajectory groups: maintained high performance (Maintainers; 26%), average decline (Averages; 64%), and accelerated decline (Decliners; 12%), using multistate modeling to characterize individuals' transitions from an initial non-demented state, possibly to a state of dementia and/or death. The memory groups showed considerable intergroup variability in memory profiles, starting 10-15 years prior to dementia diagnosis, and prior to death. A strong relationship between memory trajectory group and dementia risk was found. Specifically, Decliners had more than a fourfold risk of developing dementia compared to Averages. In contrast, Maintainers had a 2.6 times decreased dementia risk compared to Averages, and in addition showed no detectable memory decline prior to dementia diagnosis. A similar pattern of association was found for the memory groups and mortality risk, although only among non-demented. There was a strong relationship between accelerated memory decline and dementia, further supporting the prognostic value of memory decline. The intergroup differences, however, suggest that mechanisms involved in successful memory aging may delay symptom onset.
Highlights
Several prospective studies suggest that memory deficits are detectable decades before clinical symptoms of dementia emerge (Boraxbekk et al, 2015; Elias et al, 2000; Rajan et al, 2015)
There was no significant difference in proportions of Maintainers, Averages, and Decliners between Alzheimer’s disease (AD) and vascular dementia (VaD) ( p = 0.725), and no significant differences for the memory groups in age at onset between AD and VaD
Having a more beneficial memory trajectory was consistently associated with better outcomes in terms of older age at disease onset or death
Summary
Several prospective studies suggest that memory deficits are detectable decades before clinical symptoms of dementia emerge (Boraxbekk et al, 2015; Elias et al, 2000; Rajan et al, 2015). Some studies have observed accelerated decline in multiple cognitive functions in the prodromal phase, starting 3–6 years before clinical symptoms (Albert et al, 2014; Amieva et al, 2004; Cloutier et al, 2015; Li et al, 2017; Wilson et al, 2011). These studies have followed initially cognitively normal individuals longitudinally and examined if an accelerated cognitive rate of change precedes clinical diagnosis. In older populations, mortality is a competing event
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