Distinct tau PET patterns in atrophy‐defined subtypes of Alzheimer's disease

• DOI: 10.1016/j.jalz.2019.08.201
• Publication Date: 2019-10-28T13:29:13Z
• Authors: Rik Ossenkoppele; Chul Hyoung Lyoo; Carole H. Sudre; Danielle van Westen; Hanna Cho; Young Hoon Ryu; Jae Yong Choi; Ruben Smith; Olof Strandberg; Sebastian Palmqvist; Eric Westman; Richard Tsai; Joel Kramer; Adam L. Boxer; Maria L. Gorno‐Te...; Renaud La Joie; Bruce L. Miller; Gil D. Rabinovici; Oskar Hansson
• Keywords: Aging; Image Processing; Biological Psychology; Clinical sciences; Neurodegenerative; Alzheimer's Disease; Hippocampus; Computer-Assisted; Cognition; 0302 clinical medicine; Image Processing, Computer-Assisted; Psychology; 2.1 Biological and endogenous factors; Alzheimer's Disease Related Dementias (ADRD); Subtypes; Alzheimer's disease; Middle Aged; Magnetic Resonance Imaging; White Matter; 3. Good health; Neurological; Biomedical Imaging; Female; Thickness; Clinical Sciences; 610; tau Proteins; Article; 03 medical and health sciences; Clinical Research; Alzheimer Disease; 616; Behavioral and Social Science; Acquired Cognitive Impairment; Humans; Cognitive Dysfunction; Aged; Neurosciences; Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD); Brain Disorders; 4.1 Discovery and preclinical testing of markers and technologies; Geriatrics; Positron-Emission Tomography; Biological psychology; Dementia; Tau; Atrophy; Carbolines

AbstractIntroductionDifferential patterns of brain atrophy on structural magnetic resonance imaging (MRI) revealed four reproducible subtypes of Alzheimer's disease (AD): (1) “typical”, (2) “limbic‐predominant”, (3) “hippocampal‐sparing”, and (4) “mild atrophy”. We examined the neurobiological characteristics and clinical progression of these atrophy‐defined subtypes.MethodsThe four subtypes were replicated using a clustering method on MRI data in 260 amyloid‐β‐positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [18F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline.ResultsVoxel‐wise and region‐of‐interest analyses revealed the greatest neocortical tau load in hippocampal‐sparing (frontoparietal‐predominant) and typical (temporal‐predominant) patients, while limbic‐predominant patients showed particularly high entorhinal tau. Typical patients with AD had the most pronounced white matter hyperintensity load, and hippocampal‐sparing patients showed the most rapid global cognitive decline.DiscussionOur data suggest that structural MRI can be used to identify biologically and clinically meaningful subtypes of AD.