HAI Book 2025 - Flipbook - Page 313
Javanray, Mohammadali
63
Higher time varying brain functional connectivity is associated with
slower tau accumulation at the preclinical stage of Alzheimer9s disease
Mohammadali Javanray1,3, Frédéric St-Onge1,3, Pierre Bellec4, Bratislav Misic1,2,5, Jean-Paul
Soucy1,2,5, Sylvia Villenueve1,3
1
McGill University, Montreal, QC, CA
Montreal Neurological Institute and Hospital, Montreal, QC, CA
3
Douglas Mental Health Research Centre, Montreal, QC, CA
4
Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal (CRIUGM), Montreal, QC, CA
5
McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, CA
2
Background: Amyloid beta (A´) and tau accumulations in the brain begin years before clinical symptoms of
Alzheimer's disease (AD) emerge, indicating the preclinical stage of AD. The level and accumulation patterns of A´
and tau have been linked to brain functional connectivity (FC). However, at the AD preclinical stage, studies exhibit
inconsistent findings, with both increases and decreases in the FC of resting-state functional networks relative to
pathology levels. Given the time-varying nature of FC and its significance for cognition and behavior, Time Varying
FC (TVFC) is a candidate for a more sensitive measure of early A´ and tau accumulation. Accordingly, the
relationship of TVFC with A´ and tau burden and their accumulation at the preclinical phase of AD was assessed.
Methods: Our study focused on 240 cognitively unimpaired individuals at risk of developing AD dementia from the
PREVENT-AD cohort with both resting state functional magnetic resonance imaging (rsfMRI) and positron
emission tomography (PET). A´ (NAV4694) and tau (18F-flortaucipir) accumulation were quantified as the average
Standardized Uptake Value Ratio (SUVR) within a global ROI and temporal meta-ROI, respectively. TVFC of the
Default Mode Network (DMN), limbic and whole brain networks were computed (fig 1), and the relationship of TVFC
with cross-sectional levels and longitudinal accumulation rates of A´ and tau was further assessed.
Results: Higher DMN and whole brain TVFC were associated with slower annual rates of tau accumulation, while
no association was observed with A´ accumulation rate (fig 2). Cross-sectionally, no relationship was observed
between A´ or tau level with TVFC (fig 3).
Conclusion: Our findings highlight the role of time-varying brain FC in relation to A´ and tau accumulation during
the preclinical stage of AD. Greater variability in whole-brain and DMN FC may help slow tau accumulation,
emphasizing the significance of TVFC in early AD pathological process.
HAI2025 - 313
