The dynamic interplay between longitudinal subjective and objective cognitive decline along the early AD spectrum in the Harvard Aging Brain Study: Featured research and focused topic sessions: The transitional stage 2 of Alzheimer's disease — Clinical features, biomarkers and longitudinal course. (7th December 2020)

• Record Type: Journal Article
• Authors: Amariglio, Rebecca; Chou, Hsiang‐Chin Lori; Buckley, Rachel F.; Papp, Kathryn V.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 6
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.040260
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Applying a biomarker‐based definition of Alzheimer's disease (AD) (Jack et al., 2018) affords characterization of early, disease‐specific symptoms that are subtle, yet dynamic. Our previous work comparing cognitively‐unimpaired individuals with elevated amyloid (Ab+) to non‐elevated (Ab‐), shows increasing subjective cognitive decline, while neuropsychological performance decreases longitudinally. Here, we sought to directly examine longitudinal associations between subjective and objective cognitive decline along the early AD trajectory. Method: 224 cognitively‐unimpaired individuals at baseline from the Harvard Aging Brain Study, a community‐based sample, were followed up to 9 years with annual neuropsychological assessment (PACC) and a participant reported cognitive complaint questionnaire (STIDA). A second cognitive complaint questionnaire (CFI) was introduced several years into the study (mean=3.23 (1.65) years) and was administered to both the participant and a study partner annually thereafter. Ab‐PET using Pittsburgh Compound B was collected closest to the time of CFI. Previously established cut‐offs were used to determine Ab+/‐. Longitudinal trajectories of STIDA, PACC, and CFI (participant and study partner) were examined by Ab status. Result: Piecewise linear mixed models revealed initially increasing STIDA (0‐3.5years, t=2.17, p = 0.03) that plateaued in the remaining years (3.6‐9.1 years, t = 0.26, p = 0.80) in Ab+. Likewise, increasing STIDA corresponded with decreasing PACC in the first 3 years (r = ‐0.36, p = 0.001), but not in subsequent years (r = 0.11, p = 0.33). When examining cross‐sectional CFI (first collection of CFI) with retrospective PACC (mean= 3.23 years), higher participant CFI (r = ‐0.26, p = 0.03) and study partner CFI (r = ‐0.32, p = 0.006) were associated with steeper PACC decline in Ab+. Finally, comparison of concurrent slopes between longitudinal participant and study partner CFI, revealed a significant divergent pattern (t=‐2.50, p = 0.01), such that study partner CFI increases relative to slightly decreasing participant CFI over time. Conclusion: Among Ab+ individuals, participant report initially increases and tracks with objective decline. Over time, however, participant report begins to diminish as study partner report continues to increase. Our findings highlight the dynamic nature of subjective report in early AD, which has significant implications for clinically meaningful outcome measures in secondary prevention trials.