Abstract

Background:Episodic memory decline is a hallmark of Alzheimer’s disease (AD). Subjective memory complaints (SMCs) may represent one of the earliest signs of impending cognitive decline. The degree to which self- or partner-reported SMCs predict cognitive change remains unclear.Objective:We aimed to evaluate the relationship between self- and partner-reported SMCs, objective cognitive performance, AD biomarkers, and risk of future decline in a well-characterized longitudinal memory center cohort. We also evaluated whether study partner characteristics influence reports of SMCs.Methods:758 participants and 690 study partners were recruited from the Penn Alzheimer’s Disease Research Center Clinical Core. Participants included those with Normal Cognition, Mild Cognitive Impairment, and AD. SMCs were measured using the Prospective and Retrospective Memory Questionnaire (PRMQ), and were evaluated for their association with cognition, genetic, plasma, and neuroimaging biomarkers of AD, cognitive and functional decline, and diagnostic progression over an average of four years.Results:We found that partner-reported SMCs were more consistent with cognitive test performance and increasing symptom severity than self-reported SMCs. Partner-reported SMCs showed stronger correlations with AD-associated brain atrophy, plasma biomarkers of neurodegeneration, and longitudinal cognitive and functional decline. A 10-point increase on baseline PRMQ increased the annual risk of diagnostic progression by approximately 70%. Study partner demographics and relationship to participants influenced reports of SMCs in AD participants only.Conclusion:Partner-reported SMCs, using the PRMQ, have a stronger relationship with the neuroanatomic and cognitive changes associated with AD than patient-reported SMCs. Further work is needed to evaluate whether SMCs could be used to screen for future decline.

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