Abstract
BackgroundWe examined in cognitively intact older adults the relative weight of cognitive, genetic, structural and amyloid brain imaging variables for predicting cognitive change over a 4-year time course.MethodsOne hundred-eighty community-recruited cognitively intact older adults (mean age 68 years, range 52–80 years, 81 women) belonging to the Flemish Prevent Alzheimer’s Disease Cohort KU Leuven (F-PACK) longitudinal observational cohort underwent a baseline evaluation consisting of detailed cognitive assessment, structural MRI and 18F-flutemetamol PET. At inclusion, subjects were stratified based on Apolipoprotein E (APOE) ε4 and Brain-Derived Neurotrophic Factor (BDNF) val66met polymorphism according to a factorial design. At inclusion, 15% were amyloid-PET positive (Centiloid >23.4). All subjects underwent 2-yearly follow-up of cognitive performance for a 4-year time period. Baseline cognitive scores were analysed using factor analysis. The slope of cognitive change over time was modelled using latent growth curve analysis. Using correlation analysis, hierarchical regression and mediation analysis, we examined the effect of demographic (age, sex, education) and genetic variables, baseline cognition, MRI volumetric (both voxelwise and region-based) as well as amyloid imaging measures on the longitudinal slope of cognitive change.ResultsA base model of age and sex explained 18.5% of variance in episodic memory decline. This increased to 41.6% by adding baseline episodic memory scores. Adding amyloid load or volumetric measures explained only a negligible additional amount of variance (increase to 42.2%). A mediation analysis indicated that the effect of age on episodic memory scores was partly direct and partly mediated via hippocampal volume. Amyloid load did not play a significant role as mediator between age, hippocampal volume and episodic memory decline.ConclusionIn cognitively intact older adults, the strongest baseline predictor of subsequent episodic memory decline was the baseline episodic memory score. When this score was included, only very limited explanatory power was added by brain volume or amyloid load measures. The data warn against classifications that are purely biomarker-based and highlight the value of baseline cognitive performance levels in predictive models.
Highlights
There has been a longstanding interest in the brain mechanisms underlying cognitive ageing
Participants who dropped out were significantly older at baseline, had lower Mini Mental State Examination (MMSE), lower Auditory Verbal Learning Test (AVLT) TL scores and lower Raven’s Progressive Matrices (RPM) scores than retainees
Other baseline variables such as amyloid load or genetic polymorphisms did not differ between drop-outs and continuers
Summary
There has been a longstanding interest in the brain mechanisms underlying cognitive ageing. One of the key characteristics of cognitive ageing [1] is decline in episodic memory performance [2]. This decline starts around the third decade [3]. Increased amyloid load in cognitively intact healthy older adults is associated with slightly lower baseline cognitive scores and a higher risk of cognitive decline over the subsequent years [9,10,11,12,13,14]. We examined in cognitively intact older adults the relative weight of cognitive, genetic, structural and amyloid brain imaging variables for predicting cognitive change over a 4-year time course
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