Identification of Successful Cognitive Aging in the Alzheimer’s Disease Neuroimaging Initiative Study

Abstract

The present prospective observational study aimed to identify the existence of successful cognitive agers among a group of well-defined cognitively healthy older adults (n = 354, mean age = 75 years), and to examine baseline individual-level predictors and associated health outcomes over time. Episodic memory (EM) and executive function (EF) composite scores and multiple health outcomes were obtained annually over 5 years. Potential individual-level predictors that were related to Alzheimer's pathology or genetic risk, neurodegeneration, and vascular risks were collected at baseline. Three latent classes with matched age and education were identified using growth mixture modeling: a group of participants who exhibited high, stable EM and EF (40.7% of the sample, “successful agers”); a group who had initial high cognitive performance that declined over time (21.2%, “declining agers”); and a group who had normal (EM) or poor (EF) but stable cognitive performance over time (38.1%, “low stable agers”). The group classification predicted significant differences in the incidence of global cognitive impairment, the development of at least one depressive symptom, and everyday functional impairment. Sex, Apolipoprotein E allele 4, beta-amyloid1-42, and t-tau significantly contributed to the difference in cognitive trajectories between the successful agers and the other two groups. Characterizing successful cognitive agers who are relatively resistant to both tau and amyloid pathology provides potential pathways for promoting successful cognitive aging and preventing cognitive decline.

Distinct Cognitive Trajectories in Late Life and Associated Predictors and Outcomes: A Systematic Review

“…Inclusion of individuals with low cognitive function at baseline indicates that individuals were not sufficiently screened at study entry and may have also had symptoms of severe impairment or dementia. It is worth mentioning that the 'rapid-decline' and 'stable-low' class was found to be predicted and prospectively associated with physical limitation/disability, suggesting that decline in cognitive and physical function is most likely to occur concurrently [25,30,40,42,51,57,58]. Together, these findings outline several main phenotypes of cognitive aging in the general population and highlight the importance of studying cognitive function as trajectories which takes both the baseline and longitudinal changes into account.…”

“…The strongest evidence for this 'stable-high' class was for a measure of general cognitive function, but this was also because most studies focused on this cognitive assessment. However, the 'stable-high' class was also observed in terms of some other cognitive domains such as memory, processing speed, and executive function [23,34,43,45,[49][50][51]. Of note, these are cognitive domains that are thought to decline more rapidly than others during the 'normal' aging process [2].…”

“…The other classes identified across a number of studies include the rapid-decliners, which could be viewed as individuals with 'pathological cognitive aging', and possibly even reaching criteria for mild cognitive impairment or dementia [ 19, 20, 24, 25, 32, 50, 51, 53-56]. In four studies, an atypical 'stable-low' class was identified which also had a higher prevalence of risk factors for cognitive decline and poorer health outcomes compared to other classes [30][31][32]51]. It remains unclear if the stability of cognitive function in this class resulted from floor effects in terms of the cognitive tests or large intra-individual variability of the slope [51].…”

“…In four studies, an atypical 'stable-low' class was identified which also had a higher prevalence of risk factors for cognitive decline and poorer health outcomes compared to other classes [30][31][32]51]. It remains unclear if the stability of cognitive function in this class resulted from floor effects in terms of the cognitive tests or large intra-individual variability of the slope [51]. Inclusion of individuals with low cognitive function at baseline indicates that individuals were not sufficiently screened at study entry and may have also had symptoms of severe impairment or dementia.…”

“…For example, memory loss, as one of the most common cognitive complaints from older adults, is a core early symptom of dementia [2,61]. Therefore, it is reasonable that studies focusing on episodic memory generally reported fewer participants in the 'stable-high' class compared to those of general cognitive function [33,43,45,[49][50][51]. However, the trajectory profiles were still highly heterogeneous among the 15 studies that used a common assessment of general cognitive function, the MMSE.…”