¹⁸F-Flortaucipir PET Associations with Cerebrospinal Fluid, Cognition, and Neuroimaging in Mild Cognitive Impairment due to Alzheimer’s Disease

Article type: Research Article

Authors: Okafor, Maureen^a | Nye, Jonathon A.^b | Shokouhi, Mahsa^a | Shaw, Leslie M.^c | Goldstein, Felicia^a | Hajjar, Ihab^{a; d; *}

Affiliations: [a] Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA | [b] Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, USA | [c] Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA | [d] Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

Correspondence: [*] Correspondence to: Ihab Hajjar, Department of Neurology, Emory University, Goizueta Alzheimer’s Disease Research Center, 6 Executive Park Dr NE, 2nd Floor, Atlanta, GA 30329, USA. Tel.: +1 404 712 1763; Fax: +1 404 712 5446; E-mail: [email protected].

Abstract: Background:Tau positron emission tomography (PET) imaging is used in research, but its relation to cerebrospinal fluid (CSF) tau and other Alzheimer’s disease (AD)-related clinical measures is unclear in mild cognitive impairment with AD biomarkers (MCI-AD). Objective:To determine associations between 18F-flortaucipir PET and CSF AD biomarkers, cognitive functioning, and neuroimaging measures in MCI-AD. Methods:In 29 participants 50 years or older with MCI-AD, 18F-flortaucipir PET, CSF total tau (T-tau), phosphorylated tau181p (P-tau), amyloid-β (Aβ), structural MRI, and neuropsychological testing were collected as baseline assessments of an ongoing clinical trial. 11C-Pittsburgh compound B PET was simultaneously conducted in 20 participants. Associations between 18F-flortaucipir PET and these measures were assessed by multiple linear regression adjusted for potential confounders and using global, lobar, and voxel-wise standardized uptake value ratio (SUVr). Results:Whole brain 18F-flortaucipir SUVr was significantly associated with CSF T-tau (r = 0.68, p < 0.001) and P-tau (r = 0.42, p = 0.04) after adjusting for age, sex, race, and education, with strongest associations in the temporal region (T-tau: r = 0.69, p < 0.001; P-tau: r = 0.49, p = 0.02). Voxel-wise analysis confirmed these regional associations. 18F-flortaucipir PET was also associated with CSF Aβ (r = –0.45, p = 0.03), episodic memory (r = –0.61, p = 0.001), visuospatial working memory (r = –0.46, p = 0.02), and brain cortical thickness (r = –0.44, p = 0.03) but not hippocampal volume. In the amyloid PET subset, although 11C-PiB PET associated strongly with 18F-flortaucipir (r = 0.79, p≤0.001), associations were stronger between 11C-PiB and key outcomes, compared to 18F-flortaucipir. Conclusion:18F-flortaucipir PET is moderately associated with CSF AD biomarkers and other AD-related phenotypes. The associations in this MCI-AD sample are stronger than previously described in other populations.

Keywords: Alzheimer’s disease, cerebrospinal fluid biomarkers, cognitive function, cortical thickness, flortaucipir, mild cognitive impairment, positron emission tomography, tau PET

DOI: 10.3233/JAD-191330

Journal: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 589-601, 2020