Abstract
INTRODUCTION
Subjective cognitive concerns frequently diverge from objective cognitive performance in cognitively unimpaired (CU) older adults, yet the neurobiological basis of this mismatch remains unclear.
METHODS
In 648 participants from the Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE), we defined four profiles by integrating subjective and objective cognitive status. We examined associations with plasma neurofilament light chain (NfL), phosphorylated tau 217 (p-tau217), glial fibrillary acidic protein (GFAP), a magnetic resonance imaging–based volumetric Alzheimer’s disease (AD) signature reflecting atrophy, and brain-predicted age difference (brain-PAD).
RESULTS
Joint profiles were differentially associated with NfL (P = 0.0427) and brain-PAD (P = 0.0296). Follow-up contrasts further indicated higher NfL and lower volumetric AD signature in the concordant lower functioning profile, and higher brain-PAD in discordant profiles. p-tau217 and GFAP did not differ across profiles.
DISCUSSION
Joint subjective–objective cognitive profiles may capture biologically meaningful heterogeneity relevant to neurodegeneration and brain aging in older adults.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT02875301
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This post is Copyright: | August 10, 2026
Neuro-Dementia