Regional Tau Correlates of Instrumental Activities of Daily Living and Apathy in Mild Cognitive Impairment and Alzheimer’s Disease Dementia

Article type: Research Article

Authors: Marshall, Gad A.^{a; b; d; *} | Gatchel, Jennifer R.^{e; g} | Donovan, Nancy J.^{a; b; c; e} | Muniz, Martha C.^{a; b} | Schultz, Aaron P.^d | Becker, J. Alex^f | Chhatwal, Jasmeer P.^d | Hanseeuw, Bernard J.^{d; f; h} | Papp, Kathryn V.^{a; b; c; d} | Amariglio, Rebecca E.^{a; b; c; d} | Rentz, Dorene M.^{a; b; c; d} | Sperling, Reisa A.^{a; b; d} | Johnson, Keith A.^{a; b; e}

Affiliations: [a] Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA | [b] Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA | [c] Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA | [d] Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [e] Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [f] Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [g] Division of Geriatric Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, USA | [h] Department of Neurology, Cliniques Universitaires Saint-Luc, Institute of Neurosciences, Université Catholique de Louvain, Brussels, Belgium

Correspondence: [*] Correspondence to: Gad A. Marshall, MD, Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital, 60 Fenwood Road, 9016P, Boston, MA 02115, USA. Tel.: +1 617 732 8085; Fax: +1 617 264 6831; E-mail: [email protected].

Abstract: Background:Instrumental activities of daily living (IADL) impairment and apathy occur in early-stage Alzheimer’s disease (AD) and are associated with regional atrophy and hypometabolism in vivo and greater tau burden at autopsy. Objective:To explore the association between IADL impairment, apathy, and in vivo regional tau in mild cognitive impairment (MCI) and AD dementia. Methods:Forty participants (24 MCI, 16 AD dementia) underwent assessments of IADL (Functional Activities Questionnaire, FAQ) and apathy (Apathy Evaluation Scale Informant report, AES-I). Regional tau was assessed using flortaucipir positron emission tomography (PET) and amyloid using Pittsburgh Compound B PET. Regions with unadjusted associations of p≤0.01 were entered into regression models assessing the relationship between tau and FAQ or AES-I, adjusting for age, sex, and cognition, with/without a tau by amyloid interaction. Results:Unadjusted IADL impairment but not apathy was associated with greater tau in multiple regions. After adjusting for covariates, for medial orbitofrontal and entorhinal cortex the interaction between tau and amyloid was associated with IADL impairment and for anterior cingulate it was not but independent associations with both tau and amyloid were retained. With whole brain analyses, similar results were seen for IADL, while for apathy tau in small clusters within the right anterior cingulate and dorsolateral prefrontal cortices were seen, which were more pronounced in individuals with greater amyloid. Conclusions:This exploratory study suggests that IADL impairment in AD is associated with medial temporal and frontal tau, especially in individuals with elevated amyloid, while apathy may be associated with right frontal tau.

Keywords: Alzheimer’s disease, amyloid, apathy, instrumental activities of daily living, mild cognitive impairment, positron emission tomography, tau.

DOI: 10.3233/JAD-170578

Journal: Journal of Alzheimer's Disease, vol. 67, no. 2, pp. 757-768, 2019