Journal
ALZHEIMERS & DEMENTIA
Volume 16, Issue 2, Pages 335-344Publisher
WILEY
DOI: 10.1016/j.jalz.2019.08.201
Keywords
Alzheimer's disease; Atrophy; Cognition; Dementia; Subtypes; Tau; Thickness
Categories
Funding
- European Research Council
- Swedish Research Council
- Marianne and MarcusWallenberg Foundation
- Knut and AliceWallenberg Foundation
- Strategic Research Area MultiPark
- SwedishBrain Foundation
- Swedish Alzheimer Foundation
- Parkinson Foundation of Sweden
- Parkinson Research Foundation
- Skfine University Hospital Foundation
- Swedish federal government
- National Institute on Aging [R01-AG045611, P50-AG023501, P01-AG19724, R01-AG038791, U54-NS092089]
- GEHealthcare
- Alzheimer's Association [AARF-16443577]
- Tau Consortium
- Michael J Fox foundation
- National Research Foundation of Korea [MSIP, 2015R1C1A2A01054507]
- Ministry of Science, ICT and Future Planning [2017R1A2B2006694]
- Alzheimer's Society [AS-JF-17-011]
- National Research Foundation of Korea [2017R1A2B2006694] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Introduction: Differential 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. Methods: The four subtypes were replicated using a clustering method on MRI data in 260 amyloid-beta-positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [F-18]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline. Results: Voxel-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. Discussion: Our data suggest that structural MRI can be used to identify biologically and clinically meaningful subtypes of AD.
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