Longitudinal Amyloid-β PET in Atypical Alzheimer's Disease and Frontotemporal Lobar Degeneration

Background: Rates of amyloid-beta (A beta) accumulation have been characterized across the cognitively normal to typical Alzheimer's dementia spectrum, but little is known about A beta accumulation in atypical Alzheimer's disease (AD) and other neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD). Objective: We aimed to characterize longitudinal A beta accumulation and determine the influence of age, apolipoprotein E (APOE) genotype, disease duration, and sex in atypical AD and FTLD. Methods: 322 patients (138 atypical AD, 184 FTLD) underwent Pittsburgh compound B PET scanning, with 73 having serial PiB-PET scans (42 atypical AD, 31 FTLD). Global A beta standard uptake value ratios were calculated for every scan. Mixed effects models were used to assess the effect of age, APOE genotype, disease duration, and sex on baseline and change measures of A beta. Results: Atypical AD showed higher baseline A beta than FTLD. Rate of A beta accumulation was not associated with baseline A beta in either group. Older age was associated with greater baseline A beta and faster rates of accumulation in FTLD. In patients under age 70, atypical AD showed faster rates of accumulation than FTLD. APOE epsilon 4 genotype was associated with greater baseline A beta in FTLD but did not influence rates of accumulation. Rates of A beta accumulation were faster in FTLD patents with time from onset-to-PET <= 4 years. Female sex was associated with faster rates of accumulation in atypical AD. Conclusion: Accumulation of A beta is observed in atypical AD and FTLD, although different demographic factors influence accumulation in these diseases providing insight into potentially different biological mechanisms of A beta deposition.