Longitudinal basal forebrain atrophy is related to changes in functional connectivity in older adults at risk for Alzheimer's disease

Poster Session C - Sunday, April 14, 2024, 5:00 – 7:00 pm EDT, Sheraton Hall ABC

Miriam Taza¹, Giulia Baracchini¹, Colleen Hughes¹, Jennifer Tremblay-Mercier¹, Judes Poirier¹, Sylvia Villeneuve¹, Gary R. Turner², R. Nathan Spreng¹; ¹McGill University, ²York University

The basal forebrain (BF) is one of the earliest brain regions affected in Alzheimer’s disease (AD). The BF compromises large cholinergic projection neurons that densely innervate the entire cortical mantle and serves as the primary source of acetylcholine. This neurotransmitter plays a vital role in cortical processes, especially cognitive functions involving attention. Recent cross-sectional studies have found that the BF exhibits broad connectivity with key hub regions of functional networks, which is disrupted in mild cognitive impairment and AD. However, longitudinal changes of the BF structure and functional connectivity and their consequence on cognition in presymptomatic AD are not understood. Longitudinal anatomical and resting-state multi-echo functional MRIs were analyzed in a sample of 150 healthy older adults (mean age at baseline = 67.75 years, SD = 4.89) at risk of AD. BF volume significantly atrophied between timepoints (~32 months, F(1, 163.90) = 16.18, p <.001) after accounting for sex, age, education, intracranial volume, and brain volume. Using multivariate partial least squares analysis, longitudinal atrophy was significantly associated with annualized percent change in BF-cortical resting-state functional connectivity (p <.05). Greater BF atrophy was associated with reduced BF connectivity to lateral temporal cortex, motor cortex, and middle cingulum. These results provide novel evidence for longitudinal structure-function changes with advancing age to the cholinergic system.

Topic Area: OTHER