Measurement of Dimensions of Self-awareness of Memory Function and Their Association With Clinical Progression in Cognitively Normal Older Adults.

Importance: The ability to separately explore 2 dimensions of self-awareness of memory function-increased and decreased awareness-in cognitively normal older adults provides an important opportunity to understand subtle changes in either direction in relation to risk of Alzheimer disease. Objective: To investigate the association of a novel measure for self-awareness of memory function with future clinical progression in individuals who were cognitively normal at baseline. Design, Setting, and Participants: This cohort study used data from the Alzheimer's Disease Neuroimaging Initiative, a multicenter study. Participants were older adults who were cognitively normal (ie, Clinical Dementia Rating [CDR] global score of 0) at baseline and had at least 2 years of follow-up. Data were collected from June 2010 to December 2021 and pulled from the University of Southern California Laboratory of Neuro Imaging database on January 18, 2022. Clinical progression was defined as the first instance of 2 consecutive follow-up CDR scale global scores of 0.5 or greater. Main Outcomes and Measures: A traditional awareness score was measured by calculating the mean discrepancy between the participant and their study partner's scores on the Everyday Cognition questionnaire. An unawareness or heightened awareness subscore was generated by capping item-level positive or negative differences at zero before averaging. The main outcome-risk of future clinical progression-was analyzed for each baseline awareness measure using Cox regression analysis. Longitudinal trajectories of each measure were additionally compared using linear mixed-effects models. Results: The 436-person sample included 232 (53.2%) female participants, with a mean (SD) age of 74.5 (6.7) years; 25 participants (5.7%) were Black, 14 (3.2%) Hispanic, and 398 (91.3%) White; and 91 participants (20.9%) clinically progressed over their period of observation. Survival analyses showed that a 1-point improvement on the unawareness subscore was associated with an 84% reduction in progression hazard (hazard ratio, 0.16 [95% CI, 0.07-0.35]; P < .001), or equivalently, a 1-point decrease was associated with a 540% increase in progression hazard (95% CI, 183% to 1347%), with no significant results for the heightened awareness or traditional scores. Conclusions and Relevance: In this cohort study of 436 cognitively normal older adults, unawareness, rather than heightened awareness, of memory decline was strongly associated with future clinical progression, providing further support that discordant self- and informant-reported cognitive decline may provide important information to practitioners.