Understanding factors associated with the trajectory of subjective cognitive complaints in groups with similar objective cognitive trajectories

Abstract

Background: Cognitive complaints are often regarded as an early sign of Alzheimer's disease (AD) but may also occur in several other conditions and contexts. This study examines the correlates of cognitive complaint trajectories over a 5-year period in individuals who shared similar objective cognitive trajectories.

Methods: We analyzed a subsample (n = 1748) of the MEMENTO cohort, consisting of individuals with subjective cognitive decline or mild cognitive impairment at baseline. Participants were stratified based on their latent MMSE trajectory over a 5-year period: "high and increasing," "subtle decline," and "steep decline." Within each of the three strata, we used a latent-class longitudinal approach to identify distinct trajectories of cognitive complaints. We then used multiple logistic regressions to examine the association between these complaint trajectories and several factors, including AD biomarkers (blood pTau/Aβ42 ratio, cortical thickness, APOE genotype), anxiety, depression, social relationships, a comorbidity-polypharmacy score, and demographic characteristics.

Results: Among participants with high and increasing MMSE scores, greater baseline comorbidity-polypharmacy scores (odds ratio (OR) = 1.30, adjusted p = 0.03) were associated with higher odds of moderate and increasing cognitive complaints (as opposed to mild and decreasing complaints). Baseline depression and social relationships also showed significant associations with the complaint pattern but did not survive correction for multiple comparisons. Among participants with subtle decline in MMSE scores, greater baseline depression (OR = 1.76, adjusted p = 0.02) was associated with higher odds of moderate and increasing cognitive complaints (versus mild and decreasing). Similarly, baseline comorbidity-polypharmacy scores and pTau/Aβ₄₂ ratio exhibited significant associations, but they did not survive correction. Among participants with a steep decline in MMSE scores, greater baseline comorbidity-polypharmacy scores increased the odds of moderate complaints (versus mild, OR = 1.38, unadjusted p = 0.03, adjusted p = 0.32), but this effect did not survive correction for multiple comparisons.

Conclusions: Despite similar objective cognitive trajectory, there is heterogeneity in the subjective perception of these cognitive changes. This perception was explained by both AD-related and, more robustly, non-AD-related factors. These findings deepen our understanding of the multifaceted nature of subjective cognitive complaints in individuals at risk for dementia and underscore the importance of considering a range of factors when interpreting cognitive complaints.

Keywords: Alzheimer’s disease; Blood-based AD biomarkers; Cognitive complaints; Cohort study; Comorbidity-polypharmacy; Dementia risk; Depression; Latent class mixed model; Loneliness; Longitudinal study; Objective cognitive trajectories.

Fig. 1

Flow diagram illustrating participant selection from the MEMENTO cohort

Fig. 2

Trajectories of the MMSE in our subsample of MEMENTO study participants. Note. The trajectories of the MMSE were estimated using a longitudinal latent class approach

Fig. 3

Trajectories of subjective cognitive complaints stratified by objective cognitive trajectory, in our subsample of MEMENTO study participants. Note. In each stratum, the trajectories of cognitive complaints were estimated using a longitudinal latent class approach

Fig. 4

Results from multivariable logistic regression modeling the association between subjective complaint trajectory and the variables of interest, stratified by objective cognitive trajectory, in our subsample of MEMENTO study participants. Note. The dependent variable is the cognitive complaint trajectory. The reference category is the “mild and decreasing complaint” trajectory for Strata #1 and #2, and the “mild complaint” trajectory for Stratum #3. *Statistically significant before FDR correction (i.e., p < 0.05). **Statistically significant after FDR correction (i.e., p < 0.05)