Superior Memory Reduces 8-year Risk of Mild Cognitive Impairment and Dementia But Not Amyloid β-Associated Cognitive Decline in Older Adults

Abstract

Objective To prospectively examine 8-year risk of clinical disease progression to mild cognitive impairment (MCI)/dementia in older adults ≥60 with superior episodic memory (SuperAgers) compared to those cognitively normal for their age (CNFA). Additionally, to determine the extent to which SuperAgers were resilient to the negative effects of elevated amyloid-beta (Aβ+) on cognition. Method Participants were classified as SuperAgers based on episodic memory performance consistent with younger adults aged 30–44 and no impairment on non-memory tests (n = 179), and were matched with CNFA on age, sex, education, and follow-up time (n = 179). Subdistribution hazard models examined risk of clinical progression to MCI/dementia. Linear mixed models assessed the effect of Aβ on cognition over time. Results Prevalence of Aβ+ and APOE ε4 was equivalent between SuperAgers and CNFA. SuperAgers had 69%–73% reduced risk of clinical progression to MCI/dementia compared to CNFA (HR: 0.27–0.31, 95% CI: 0.11–0.73, p < .001). Aβ+ was associated with cognitive decline in verbal memory and executive function, regardless of SuperAger/CNFA classification. In the absence of Aβ+, equivalent age-related changes in cognition were observed between SuperAgers and CNFA. Conclusions SuperAgers displayed resilience against clinical progression to MCI/dementia compared to CNFA despite equivalent risk for Alzheimer’s disease (AD); however, SuperAgers had no greater protection from Aβ+ than CNFA. The deleterious effects of Aβ on cognition persist regardless of baseline cognitive ability. Thus, superior cognitive performance does not reflect resistance against the neuropathological processes associated with AD, and the observed resilience for SuperAgers may instead reflect neuropsychological criteria for cognitive impairment.

Rates of age‐ and amyloid β‐associated cortical atrophy in older adults with superior memory performance

“…Compared to the Aβ− group, the Aβ+ group had higher prevalence of APOE ε4 carriage (odds ratio: 4.08, 95% confidence interval [CI]: 2.47‐6.73; P < .0005) and were 2 years older on average [F(1,343) = 10.84, P = .001; d = 0.36)]. As previously reported for this sample, SuperAgers were less likely to progress to mild cognitive impairment/dementia compared to CNFA (24 CNFA and 5 SuperAgers; odds ratio: 0.19, 95% CI: 0.07‐0.50; P < .0005) [3].…”

“…Individuals were classified as SuperAgers at baseline using neuropsychological criteria adapted from the Northwestern SuperAging Study criteria as described previously [3]. A greater number of nonmemory tests were included in the classification criteria for this study compared to that used in the Northwestern SuperAging Study [12] to increase classification specificity.…”

“…Individuals were classified as SuperAgers at baseline using neuropsychological criteria adapted from the Northwestern SuperAging Study criteria as described previously [3]. A greater number of nonmemory tests were included AIBL CN at baseline (n=1171)…”

“…Although cognitive decline is considered characteristic of aging [1,2], the existence of older adults with superior cognitive ability for their age suggests that cognitive decline is not inevitable [3]. Studies describe such individuals as successful agers [4][5][6][7], optimal memory performers [8], supernormals [9][10][11], or SuperAgers [12,13].…”

Comments about SuperAging and SuperAgers

“…This study and an equally important and complementary study published by this group in 2018 tell a consistent story [4]. To recapitulate, that paper, utilizing a group of SuperAgers defined psychometrically and a group of otherwise cognitively intact individuals from Australian Imaging, Biomarkers and Lifestyle study (identical to the 2019 groups), studied memory performance over a 9‐year period.…”