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-β-positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [¹⁸ F]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.