Examining the relationship between brain activation and proxies of disease severity using quantile regression in individuals at risk of Alzheimer's disease.

Previous studies have reported a pattern of hyperactivation in the pre-dementia phase of Alzheimer's disease (AD), followed by hypoactivation in later stages of the disease. This pattern was modeled as an inverse U-shape function between activation and markers of disease severity. In this study, we used quantile regression to model the association between task-related brain activation in AD signature regions and three markers of disease severity (hippocampal volume, cortical thickness, and associative memory). This approach offers distinct advantages over standard regression models as it analyzes the relationship between brain activation and disease severity across various levels of brain activation. Participants were 54 older adults with subjective cognitive decline+ (SCD+) or mild cognitive impairment (MCI) from the CIMA-Q cohort. The analysis revealed an inverse U-shape quadratic function depicting the relationship between disease severity markers and the activation of the left superior parietal region, while a linear relationship was observed for activation of the hippocampal and temporal regions. Quantile differences were observed for temporal and parietal activation, with more pronounced effects observed in the higher quantiles of activation. When comparing quantiles, we found that higher quantile of activation featured a greater number of individuals with SCD+ compared to mild cognitive impairment (MCI). Results are globally consistent with the presence of an inverse-U shape function of activation in relation to disease severity. They study also underscores the utility of employing quantile regression modeling as the modeling approach revealed the presence of non-homogeneous effects across various quantiles.

Sex differences in patterns of associative memory-related activation in individuals at risk of Alzheimer's disease.

The risk of developing Alzheimer's disease dementia is higher in females compared to males and is greater in individuals with subjective cognitive decline and mild cognitive impairment than in healthy controls. We used a multivariate behavioral partial least square correlation analysis to examine how relationships between memory-related activation and associative memory performance vary as a function of sex and clinical status. This was assessed in 182 participants from the Consortium for the Early Identification of Alzheimer's Disease-Quebec cohort, which were stratified according to sex (Male, Female) and clinical status (healthy controls, subjective cognitive decline, mild cognitive impairment). We found 6 significant latent variables mainly expressing: (1) overall sex differences; (2) between-sex differences according to clinical status; and (3) within-sex differences according to clinical status in relationships between whole-brain memory-related activation and memory performance. These patterns of activation mostly involved the default mode and fronto-parietal networks. Our results have implication in understanding the macro-scale functional processes possibly contributing to the higher risk of cognitive decline in females compared to males in the context of aging and early Alzheimer's disease.