medRxiv · Jan 28, 2026

Subjective cognition trajectories, Alzheimer biomarkers, and incident mild cognitive impairment

By Kuhn E, Kleinedam L, Stark M et al.

BACKGROUND: Subjective cognitive decline (SCD) is common in older adults and may precede mild cognitive impairment (MCI). Whether longitudinal changes in self- or study partner (SP)-reported SCD improve early identification of individuals at risk for clinical progression, particularly along the Alzheimer's disease (AD) biological continuum, remains unclear. METHODS: We pooled data from two longitudinal observational cohorts (DELCODE and ADNI). Cognitively unimpaired (CU) participants were recruited through public advertisement or memory clinics and included if baseline amyloid status, ≥2 SCD assessments, and clinical follow-up were available. SCD was assessed using the Everyday Cognition questionnaire (self- and SP-report). Linear mixed-effects models examined longitudinal associations between SCD trajectories, baseline AD biomarkers, and progression to incident MCI. Multivariable Cox proportional hazards models tested whether one-year changes in SCD predicted subsequent progression. FINDINGS: Among 770 participants (median age 69·9years [IQR 66·0-74·6]; 52·6% women; median follow-up 5·0years [4·0-7·0]), amyloid-positive individuals and those who progressed to MCI showed steeper longitudinal increases in both SCD reports. In amyloid-positive participants, only increases in SP-reported SCD differentiated progressors from non-progressors. One-year increases in SP-reported SCD predicted a higher risk of subsequent MCI compared with unchanged scores (hazard ratio 3·24 [95%CI 1·73-6·07]), with effects confined to amyloid-positive participants. INTERPRETATION: Longitudinal increases in SP-reported cognitive difficulties, particularly over short intervals, are associated with near-term progression to MCI in amyloid-positive CU older adults. SP-based longitudinal monitoring may represent a low-burden approach to support earlier clinical surveillance in aging populations. FUNDING: German Center for Neurodegenerative Diseases, US National Institutes of Health.

doi.org/10.64898/2026.01.27.26344715 Open access PubMed 41646752 Biomarkers