- Joint subjective-objective cognitive profiles reflect biologically meaningful heterogeneity linked to neurodegeneration and brain ageing.
- Profiles differed on plasma NfL and brain-predicted age difference, indicating neurodegeneration and accelerated brain ageing associations.
- Concordant lower functioning profile showed higher NfL and lower volumetric AD signature; p-tau217 and GFAP did not vary across profiles.
Alzheimers Dement. 2026 Aug;22(8):e71743. doi: 10.1002/alz.71743.
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.
PMID:42576170 | DOI:10.1002/alz.71743
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