AMYLOID-β IS ASSOCIATED WITH THINNER CORTEX IN COGNITIVELY NORMAL OLDEST-OLD INDIVIDUALS

Abstract

Background: Previous autopsy studies have demonstrated a high prevalence of widespread Alzheimer s disease (AD) pathology in individuals without dementia at high ages (>85y), which has raised doubts on the relationship of amyloid-β (Aβ) with dementia. In younger elderly (60-80y) without cognitive impairment, Aβ accumulation has been associated with subtle cognitive changes and cortical thinning. However, it remains unclear whether Aβ accumulation in oldest-old individuals with normal cognition is associated with changes in brain structure and cognitive functioning. We studied this using data from the EMIF-AD 90+ study. Methods: We selected 61 cognitively normal (CN) individuals from the EMIF-AD 90+ study, with available amyloid positron emission tomography (PET), and structural magnetic resonance imaging (MRI). Visual rating of the amyloid PET scan was used to classify the subjects as CN Aβ- (n=34) or CN Aβ+ (n=27). Cognitive performance on the Logical Delayed Memory test and MMSE were compared between groups. Subcortical volumes and cortical thickness measures in each ROI of FreeSurfer s Desikan-Killany atlas were calculated from 3T 3D-T1 images, and compared between groups using general linear models with Bonferroni correction and adjusted for age, and sex. Results: The individuals had a mean age of 93 years (range 88-102y), and 44% were rated as Aβ+. CN Aβ+ individuals had lower, but non-significant, memory scores and worse MMSE scores compared to the Aβ- group (Table1). Moreover, compared to the Aβ- group, CN individuals with Aβ+ showed thinner parahippocampal, rostral anterior cingulate, medial orbitofrontal, fusiform, superior temporal cortex, and smaller amygdala volume (pBonferroni