Classification of Clinically Diagnosed Alzheimer’s Disease Associated with Diabetes Based on Amyloid and Tau PET Results

Article type: Research Article

Authors: Takenoshita, Naoto^a | Shimizu, Soichiro^a | Kanetaka, Hidekazu^a | Sakurai, Hirofumi^a | Suzuki, Ryo^b | Miwa, Takashi^b | Odawara, Masato^b | Ishii, Kenji^c | Shimada, Hitoshi^d | Higuchi, Makoto^d | Suhara, Tetsuya^d | Hanyu, Haruo^{a; *}

Affiliations: [a] Department of Geriatric Medicine, Tokyo Medical University, Tokyo, Japan | [b] Department of Diabetes, Endocrinology and Metabolism, Tokyo Medical University, Tokyo, Japan | [c] Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan | [d] Department of Functional Brain Imaging Research, Clinical Research Cluster, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba-shi, Chiba, Japan

Correspondence: [*] Correspondence to: Haruo Hanyu, MD, PhD, Department of Geriatric Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Tel.: +81 3 3342 6111; Fax: +81 3 3342 2305; E-mail: h-hanyu@tokyo-med.ac.jp.

Abstract: Background/Objective:Although type 2 diabetes mellitus (DM) is a risk factor for the development of dementia, the underlying brain pathologies and mechanisms vary among patients. In this study, we classified patients with clinically diagnosed Alzheimer’s disease (AD) associated with DM into subgroups based on their amyloid and tau accumulation patterns on positron emission tomography (PET), and analyzed the differences in clinical features and brain imaging findings between the subgroups. Methods:Sixty-four patients with probable or possible AD associated with DM were classified using PiB (detects amyloid, A) and PBB3 (detects tau, T) PET studies. Patients were classified into the A+/T+ group (n = 35, AD pathology), the A– /T+ group (n = 19, tauopathy), and the A– /T– group (n = 10, non-amyloid/non-tau neuronal damage). Results:Compared with the A+/T+ group, the A– /T+ group showed less-well controlled glycemia, longer duration of diabetes, more glucose variability, higher frequency of insulin therapy and biochemical hypoglycemia, and greater impairment of frontal lobe function, slower progression of cognitive decline, fewer APOE4 carriers, less severe medial temporal lobe atrophy, and lower frequency of posterior cerebral hypoperfusion. This subgroup showed different clinical and radiological features from AD. Conclusion:Among patients with clinically diagnosed AD with DM, there are subgroups with neuronal damage independent of AD pathology. A subgroup of dementia patients suspected of having tauopathy is strongly associated with DM-related metabolic abnormalities. This study highlights the identification of a novel dementia subgroup (diabetes-related dementia), which is important for considering appropriate therapies and care in clinical practice.

Keywords: Alzheimer’s disease, amyloid, diabetes mellitus, diabetes-related dementia, positron emission tomography, tau

DOI: 10.3233/JAD-190620

Journal: Journal of Alzheimer's Disease, vol. 71, no. 1, pp. 261-271, 2019