Trajectories of self‐rated concerns in individuals developing cognitive decline

Background Subjective perception of cognitive decline is identified as an important marker related to the risk of progression to Alzheimer's disease. However, loss of awareness has also been observed in predementia stages, potentially reducing the validity of the subjective experience. The aim of this study was to characterize the trajectories of complaints in cognitively normal (CN) individuals who later developed cognitive decline, as well as investigate differences in demographics, brain pathology and clinical progression between individuals aware and unaware of these changes. Method We included participants (CN at baseline) from the Harvard Aging Brain Study. Linear Mixed effect models were used to compute individual longitudinal changes of memory complaints (7 questions questionnaire) and cognition (Preclinical Alzheimer’s Cognitive Composite, PACC5). Participants who demonstrated a statistically significant PACC5 decline over time were divided into two groups: an Unaware (N=36) group defined as individuals with statistically significantly decreasing or displaying low (<2.5/7) complaints, and a Heightened (N=14) group defined as individuals with significantly increasing or displaying high (>2.5/7) complaints (Fig 1). Participants who did not decline in memory were assigned to the Stable group (N=248). Kaplan‐Meier survival analysis was performed to determine the rate of progression from CN to clinically impaired (MCI or dementia diagnosis) across groups. Result No group differences were found for gender, education, depressive symptoms or Apolipoprotein E4‐carrier status (Tab 1). Unaware participants were significantly older than the Stable group (p<0.001). The Heightened and Unaware groups demonstrated equivalent amyloid burden, which was significantly greater than the Stable group (p<0.01). The survival analysis revealed significant differences between all groups (p<0.001,Fig 2). Heightened participants had the fastest rate of clinical progression, followed by the Unaware group. Conclusion Participants with heightened awareness demonstrated the fastest rate of progression from cognitively normal to MCI or dementia. Importantly, among the individuals with a subsequent cognitive decline, a number of individuals (72%) were unaware of their decline. These individuals had the same demographic profile and amyloid burden as the individuals with heightened awareness. Future research will investigate the mechanisms of self‐awareness and potential dysfunction of systems underlying the loss of awareness, as it can be essential for the preservation of individual autonomy.