Associations Between Cognitive Complaints, Memory Performance, Mood, and Amyloid-beta Accumulation in Healthy Amyloid Negative Late-Midlife Individuals

Background: Cognitive complaints are gaining more attention as they may represent an early marker of increased risk for AD in individuals without objective decline at standard neuropsychological examination. Objective: Our aim was to assess whether cognitive complaints in late middle-aged individuals not seeking medical help are related to objective cognitive outcomes known as early markers for AD risk, concomitant affective state, and amyloid-beta (A beta) burden. Methods: Eighty-seven community-based cognitively normal individuals aged 50-69 years underwent neuropsychological assessment for global cognition, using Preclinical Alzheimer's Cognitive Composite 5 (PACC5) score, and a more specific episodic memory measure. Affective state was based on self-assessment questionnaires for depression and anxiety. A beta PET burden was assessed via [F-18]Flutemetamol (N=84) and [F-18]Florbetapir (N=3) uptake. Cognitive complaints were evaluated using Cognitive Difficulties Scale. Results: Higher cognitive complaints were significantly associated with lower episodic memory performance and worse affective state. Moreover, higher level of cognitive complaints was related to higher (but still sub-clinical) global A beta accumulation (at uncorrected significance level). Importantly, all three aspects remained significant when taken together in the same statistical model, indicating that they explained distinct parts of variance. Conclusion: In healthy A beta negative late middle-aged individuals, a higher degree of cognitive complaints is associated with lower episodic memory efficiency, more anxiety and depression, as well as, potentially, with higher A beta burden, suggesting that complaints might signal subtle decline. Future studies should untangle how cognitive complaints in healthy aging populations are related to longitudinal changes in objective cognition and AD biomarker correlates.

Automated summary

In healthy late middle-aged individuals without Aβ burden, increased cognitive complaints are associated with lower episodic memory efficiency, higher anxiety and depression, and potentially higher Aβ burden, indicating possible subtle cognitive decline. Future studies should explore the longitudinal relationship between cognitive complaints and objective cognition and AD biomarkers in healthy aging populations.