Regional amyloid accumulation, post-traumatic distress, and intrusive symptoms in cognitively unimpaired older adults at risk for Alzheimer's

Introduction: In preclinical Alzheimer's disease (AD), early pathology may heighten vulnerability to psychiatric symptoms. We examined whether Aβ accumulation in cognitive-emotional regions was associated with post-pandemic psychiatric symptoms.

Methods: This prospective cohort study included 115 cognitively unimpaired ALzheimer's and FAmilies participants (69 [60%] women, mean [SD] age 64.9 [4.8] years). Amyloid beta (Aβ) change was examined in anterior cingulate, posterior cingulate, superior parietal, medial orbitofrontal gyri, and insula using two [18F]flutemetamol positron emission tomography (PET) scans. Outcomes were pandemic-related post-traumatic distress (Impact of Events Scale Revised [IES-R]; total, intrusive, avoidance, and hyperarousal symptoms) and anxious-depressive symptoms (Hospital Anxiety and Depression Scale [HADS]; mean follow-up: 3.62 years [SD = 0.68]). Linear regression and voxel-wise analyses were performed.

Results: Aβ accumulation across anterior cingulate (β = 40.29, p = 0.036), posterior cingulate (β = 29.52, p = 0.012), superior parietal (β = 35.58, p = 0.036), and medial orbitofrontal gyri (β = 35.08, p = 0.036) was associated with post-pandemic intrusive symptoms only, independent of baseline anxious-depressive symptoms.

Discussion: Aβ accumulation in cognitive-emotional regions may increase vulnerability to intrusive symptoms, highlighting their potential as early clinical markers in AD.