Definitions and characteristics of successful cognitive aging

Abstract

AbstractBackgroundDifferent approaches have been used to define successful agers (SA), but there is currently no consensus on either the definition of SA or the underlying neural mechanisms. The aim of this study was to compare new and existing definitions, to understand whether SA are resistant to atrophy and Alzheimer’s disease pathology or resilient to their effects, and whether this varies by SA definition.MethodMachine learning algorithms were used to predict age from neuropsychological tests in 184 cognitively normal adults over the age of 70. Differences between cognitive‐predicted age and chronological age (cognitive age gap, CAG) were used as a novel measure of SA, defined as below the 20th percentile (SA‐CAG, n = 37). In the same sample, SA were also defined as individuals performing in the top 20% on composite scores for episodic memory (SA‐EM, n = 37) and non‐memory cognition (SA‐NM, n = 37), and participants with performance comparable to individuals aged 18‐32 years on the California Verbal Learning Test long delay free recall (SA‐CVLT, n = 31). The four definitions were used to compare SA to typical agers (TA, n = 109) in hippocampal volume, anterior cingulate cortex (ACC) thickness, APOE genotype, PET‐measured amyloid (11C‐Pittsburgh compound‐B, PiB) and, in a subsample (n = 114), PET‐measured tau (18F‐Flortaucipir, FTP). All analyses were age and sex adjusted.ResultSA‐CAG definition showed moderate agreement with SA‐EM (Cohen’s κ = 0.46), SA‐NM (κ = 0.49), but only fair agreement with SA‐CVLT (κ = 0.24). Fair agreement was found between the other definitions (Figure 1). Compared to TA, greater hippocampal volume was found in SA‐CAG (p = 0.005), SA‐EM (p = 0.02), and SA‐CVLT (p = 0.02). Greater ACC thickness was found in SA‐CAG (p = 0.01), SA‐EM (p = 0.02), and SA‐NM (p = 0.004). Lower entorhinal FTP uptake was found in SA‐CAG (p = 0.04), SA‐EM (p = 0.007), and SA‐NM (p = 0.008) (Figure 2). No between‐group differences were detected in the proportion of APOE ε4 carriers and PiB+ participants.ConclusionDespite imperfect overlap in SA groups identified by different definitions, common brain features were found in SA‐CAG, SA‐EM, and SA‐NM compared to TA. Greater hippocampal volume, greater ACC thickness and lower entorhinal tau deposition suggests that SA, regardless of its exact definition, may be resistant to tau pathology and its downstream effects.