Sex-specific relationships among risk factors in those with Mild Cognitive Impairment or Alzheimer’s disease and healthy controls

Motivation: The increasing global incidence of dementia, particularly among females, necessitates a deeper understanding of risk factors (RF) to inform healthcare interventions. Goal(s): This study aims to identify both non-modifiable and modifiable RF for cognitive decline (CD), emphasizing sex-specific differences in these factors and their interrelationships. Approach: A network analysis of 353 participants from the Sunnybrook Dementia Study and Ontario Neurodegenerative Research Initiative, comparing RF in healthy controls and those with CD, including cerebral structural MRI imaging. Results: Our findings revealed distinct network patterns of RF, highlighting greater interconnectedness among RF in CD individuals, with notable sex differences, underscoring the need for sex-specific analyses. Impact: This study identifies sex-specific risk factor networks in cognitive decline, suggesting tailored intervention points. By pinpointing unique biomarkers and relationships, particularly among modifiable factors, these findings advance the path toward precision medicine in dementia care.