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

BackgroundSubjective 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 Alzheimers disease (AD) biological continuum, remains unclear. MethodsWe 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. FindingsAmong 770 participants (median age 69{middle dot}9years [IQR 66{middle dot}0-74{middle dot}6]; 52{middle dot}6% women; median follow-up 5{middle dot}0years [4{middle dot}0-7{middle dot}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{middle dot}24 [95%CI 1{middle dot}73-6{middle dot}07]), with effects confined to amyloid-positive participants. InterpretationLongitudinal 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. FundingGerman Center for Neurodegenerative Diseases, US National Institutes of Health.