Longitudinal trajectories of remote assessment of self‐ and study partner‐rated cognitive concerns, mood and Alzheimer’s disease biomarkers
Authors: Munro Catherine E , Buckley Rachel F. , Vannini Patrizia , Sperling Reisa A. , Rentz Dorene M. , Johnson Keith A. , Gatchel Jennifer R , Amariglio Rebecca E. 
Published: December 2021

Background

Previous work has shown discordance between participant‐ and study‐partner‐reported cognitive concerns across symptomatic stages of Alzheimer’s Disease (AD). Longitudinal trajectories of participant and study‐partner report in preclinical AD have not been fully elucidated. This study sought to capture longitudinal trajectories of participant‐ and study‐partner‐reported concerns along with potential modifying factors: participant amyloid‐biomarker burden and depressive symptoms

Method

Participants came from the Harvard Aging Brain Study, a longitudinal observational cohort of cognitively unimpaired individuals at baseline who received PIB‐PET imaging (high‐amyloid>1.185DVR;all participants and study‐partners blinded to amyloid status). In this sub‐study (n=74,mean age=77.29,56% female), every 3 months participants and study‐partners completed a modified Cognitive Function Index (CFI) measuring current concerns (median sessions completed=6) and participants also completed the Geriatric Depression Scale (GDS). Additionally, participants and study‐partners were asked about any change in cognitive functioning over the last year during an in‐clinic visit (median months=10). Linear mixed effects models were used to investigate the interaction between in‐clinic CFI and amyloid burden on longitudinal remote‐CFI, for both study‐partners and participants. Remote‐CFI slopes for participant and study‐partner were extracted from ordinary least‐squares regression models and compared to remote GDS slopes (stratified by participant amyloid status) using linear regression models. All models controlled for age, sex, and education.

Result

Participant remote‐CFI did not change over time (slope=0.94,SE=0.66,p=0.15), unlike the modestly‐increasing study‐partner remote‐CFI (slope=1.52,SE=0.66,p=0.02). Participant remote‐CFI slope was not significantly related to in‐clinic CFI. A significant interaction was seen with participant amyloid burden in study‐partners, whereby increasing study‐partner remote‐CFI was associated with higher in‐clinic CFI for participants with greater amyloid burden (estimate=‐1.21(0.6),p=0.04). In participants with high‐amyloid, however, concurrent change was seen in participant‐rated remote‐CFI and GDS, but not with study‐partner‐rated remote‐CFI.

Conclusion

Increasing concerns over months are associated with an overall perception of change over the last year from study‐partners of higher‐amyloid participants. Conversely, in high‐amyloid participants, increasing cognitive concerns were associated with increasing depressive symptoms suggesting greater alignment between cognitive complaints and mood symptoms among those with high‐amyloid. These data suggest that frequent assessment offers rapid insight into emerging divergent patterns of cognitive concerns between participant and study‐partner during preclinical AD.