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Updated: Jun 13, 2026

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Cardiovascular risk and hippocampal-cognitive coupling in Alzheimer's disease
Sofia Fernandez-Lozano1,2, Sylvia Villeneuve1,3,4, D Louis Collins1,2,5
1Montreal Neurological Institute, McConnell Brain Imaging Centre, Montreal, Quebec, Canada.
Introduction:
The Framingham Risk Score (FRS) indexes cardiovascular risk (CVR), but age-weighting may confound associations with brain and cognitive outcomes.
Methods:
In 923 amyloid-positive ADNI participants, we compared FRS against a Multiple Indicators Multiple Causes (MIMIC)-derived age-adjusted measure (CVRmimic) using sex-stratified linear mixed-effects (LME) and latent growth curve mediation (LGCM) models of hippocampal-to-ventricle ratio (HVR)-cognitive coupling.
Results:
FRS predicted hippocampal atrophy in all six LGCM models; CVRmimic in none of the six. HVR-cognitive coupling held in four of six FRS and four of six CVRmimic models. Indirect effects reached significance in four of six FRS and none of the six CVRmimic models. LME 3-way interactions (years × risk × HVR) survived FDR correction in all six FRS versus none of the six CVRmimic models.
Discussion:
FRS "effects" on hippocampal-cognitive decline largely reflect age-related variance. Age-adjusted measures complement FRS by isolating cardiovascular effects from aging.
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