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

Article type: Research Article

Authors: Whitwell, Jennifer L.^{a; *} | Tosakulwong, Nirubol^b | Weigand, Stephen D.^b | Graff-Radford, Jonathan^c | Duffy, Joseph R.^d | Clark, Heather M.^d | Machulda, Mary M.^e | Botha, Hugo^c | Utianski, Rene L.^d | Schwarz, Christopher G.^a | Senjem, Matthew L.^{a; f} | Strand, Edythe A.^d | Ertekin-Taner, Nilufer^g | Jack Jr, Clifford R.^a | Lowe, Val J.^a | Josephs, Keith A.^c

Affiliations: [a] Department of Radiology, Mayo Clinic, Rochester, MN, USA | [b] Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA | [c] Department of Neurology, Division of Behavioral Neurology, Mayo Clinic, Rochester, MN, USA | [d] Department of Neurology, Division of Speech Pathology, Mayo Clinic, Rochester, MN, USA | [e] Department of Psychology and Psychiatry, Mayo Clinic, Rochester, MN, USA | [f] Department of Information Technology, Mayo Clinic, Rochester, MN, USA | [g] Department of Neuroscience and Neurology, Mayo Clinic, Jacksonville, FL, USA

Correspondence: [*] Correspondence to: Jennifer L. Whitwell, PhD, Professor of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN, USA. Tel.: +1 507 284 5576; Fax: +1 507 284 9778; E-mail: whitwell.jennifer@mayo.edu.

Abstract: Background:Rates of amyloid-β (Aβ) accumulation have been characterized across the cognitively normal to typical Alzheimer’s dementia spectrum, but little is known about Aβ accumulation in atypical Alzheimer’s disease (AD) and other neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD). Objective:We aimed tocharacterize longitudinal Aβ accumulation anddetermine the influence of age, apolipoprotein E (APOE) genotype, disease duration, and sexin atypical AD and FTLD. Methods:322 patients (138 atypical AD, 184 FTLD) underwent Pittsburgh compound B PET scanning, with 73 having serialPiB-PET scans (42 atypical AD, 31 FTLD). Global Aβ 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 Aβ. Results:Atypical AD showed higher baseline Aβ than FTLD. Rate of Aβ accumulation was not associated with baseline Aβ in either group. Older age was associated with greater baseline Aβ and faster rates of accumulation in FTLD. In patients under age 70, atypical AD showed faster rates of accumulation than FTLD. APOE ɛ4 genotype was associated with greater baseline Aβ in FTLD but did not influence rates of accumulation. Rates of Aβ 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 Aβ is observed in atypical AD and FTLD, although different demographic factors influence accumulation in these diseases providing insight into potentially different biological mechanisms of Aβ deposition.

Keywords: Alzheimer’s disease, amyloid plaques, frontotemporal lobar degeneration, positron emission tomography

DOI: 10.3233/JAD-190699

Journal: Journal of Alzheimer's Disease, vol. 74, no. 1, pp. 377-389, 2020