Cognitive aging is not created equally: differentiating unique cognitive phenotypes in "normal" adults

Abstract

Age-related cognitive decline is a public health problem but highly diverse and difficult to predict. We captured nonoverlapping cognitive phenotypes in high-functioning adults and identified baseline factors differentiating trajectories. Three hundred fourteen functionally normal adults (M = 69 y) completed 2+ visits. Participants with sample-based longitudinal slopes in memory or processing speed less than -1 SD were classified as "declining" on that measure; 29 and 50 individuals had slopes less than -1 SD on processing speed or memory, respectively; 2.5% met criteria for both, who were excluded. At baseline, speed decliners demonstrated greater age, inflammation, and cognitive complaints compared with speed-stable adults; memory decliners were more likely to be male and had lower depressive symptoms, gray matter volumes, and white matter hyperintensities compared with memory-stable adults. Baseline speed, TNFα, and cognitive complaints accurately classified 96.3% of future speed decliners; baseline memory, sex, precuneal volume, and white matter hyperintensities accurately classified 88.5% of future memory decliners. There are discrete cognitive aging phenotypes reflecting nonoverlapping vulnerabilities in high-functioning adults. Early markers can predict cognition even within the "normal" spectrum and underscore therapeutic targets.

Keywords: Alzheimer's disease; Cytokines; Episodic memory; Mood; Neuroimaging; Processing speed.

Figure 1.

Baseline characteristics uniquely discriminated older adults who developed a declining processing speed or episodic memory phenotype. Note. Bars reflect decliners minus stable individuals such that higher effect sizes indicate that decliners have more of the trait; Bolded bars = p<0.05; All values reflect full model adjustments described in text.