Longitudinal basal forebrain atrophy in association with amyloid‐β positivity and dementia severity

Background Dysfunction of the cholinergic basal forebrain (BF) system and deposition of amyloid‐β (Aβ) are early pathological features in Alzheimer’s disease (AD). Degeneration of the BF in association with Aβ burden and cognitive decline has not been well studied, particularly in AD prior to dementia. We assessed the longitudinal trajectory patterns of the global BF volume, and the relationship to Aβ levels and clinical disease severity in older adults. The hippocampal volume (HV) trajectories were also assessed for reference. Method Volumetric measures of the BF and HV were quantified from the MRIs of 521 participants (age = 72.6±5.9, 52.8% female, CDR range 0‐1) from the Australian Imaging, Biomarker and Lifestyle (AIBL) study, who had Aβ‐PET imaging and longitudinal structural MRI (follow‐up over 4.3±2.6 years). Aβ load was quantified using CapAIBL and Aβ+ was defined for centiloid values >20. Participants were classified at baseline based on their being cognitively unimpaired (CU, CDR = 0) or symptomatic (CDR = 0.5‐1) and Aβ status, which were CU Aβ‐, CU Aβ+ (preclinical AD), symptomatic Aβ‐ and symptomatic Aβ+ (prodromal AD and AD) (Table 1). BF and HV volumes were standardized using the mean and standard deviation of the relevant measures in the CU Aβ‐ group at baseline. Linear mixed effect models were used to compare the changes over time (slope) of BF and HV in different clinical groups. The magnitude of the difference in slopes between groups was assessed using Cohen’s d (summarised in Table 2). Result In CU Aβ‐, age‐related atrophy was greater in the BF compared to the HV (Cohen’s d = 0.811). Compared to the CU Aβ‐ group, the rate of atrophy was significantly faster for BF and HV in the preclinical AD group, and this decline was even greater in the prodromal AD and AD group (Figure 1 and Table 2). The symptomatic Aβ‐ group showed greater rate of BF atrophy than the CU Aβ‐ group, while there was no difference in the rate of HV atrophy. Conclusion These findings provided prospective evidence confirming early vulnerability of the BF in aging as well as differentiated BF degeneration that was associated with baseline Aβ positivity and dementia severity.