HAI Book 2025 - Flipbook - Page 210
Garrone, Aurélie
44
Assessing the relationship between neuropsychiatric symptoms,
amyloid and tau pathology, and white matter hyperintensity volume across
sexes in preclinical Alzheimer9s disease
Aurélie Garrone1, Yara Yakoub1,2, Alfonso Fajardo-Valdez1,2, Ting Qiu1,2, Valentin Ourry1,2, Sylvia
Villeneuve1,2,3
1
Douglas Mental Health University Institute, Montreal, QC, CA
Integrated Program in Neuroscience, Faculty of medicine, McGill University, Montreal, QC, CA
3
Department of Psychiatry, Faculty of medicine, McGill University, Montreal, QC, CA
2
Introduction: Neuropsychiatric symptoms (NPS) are highly prevalent in Alzheimer9s disease (AD) and may
constitute both risk factors and early signs of the disease. Cross-sectional and longitudinal studies have shown
that NPS are associated with increased Ab and tau burden in preclinical AD populations. The amygdala, a brain
region involved in emotion modulation and processing, is among the most vulnerable regions to exhibit early tau
deposition. Further, white matter hyperintensity (WMH) volume, another neurological correlate of AD, has been
linked to worsening NPS, especially in frontotemporal regions. Interestingly, sex may also affect the incidence
and prevalence of NPS in AD. We assessed the associations between NPS and 1) A´, 2) amygdala tau and 3) frontal
WMH burden in cognitively unimpaired older adults.
Methods: 208 participants from the longitudinal PREVENT-AD cohort received amyloid (18F-NAV4694) and tau (18FFlortaucipir) PET-scans. We conducted linear regressions using sex as an interaction term to assess the effect of
NPS (apathy, anxiety, depression, stress, perseverative thinking and neuroticism) on global A´-PET standard
uptake values ratio (SUVr), tau-PET SUVr in the amygdala, and WMH volume in the frontal lobe. These associations
were also examined separately in males and females. All models were corrected for age.
Results: Despite females having slightly more NPS than males, the associations between depression and amyloid
and between WMH volume and neuroticism were stronger in males as compared to females. Several other
associations, particularly with WMH volume, were found in males but not in females.
Conclusions: We found associations between NPS and both MRI and PET markers of AD in cognitively unimpaired
individuals at risk of AD. Some of these associations were stronger in males, despite females being at increased
risk of AD and known to exhibit a higher prevalence of NPS. These findings will need to be replicated in an
independent cohort.
HAI2025 - 210
