Abstract
Background: Gray matter (GM) density and cortical thickness (CT) obtained from structural magnetic resonance imaging are representative GM morphological measures that have been commonly used in Alzheimer’s disease (AD) subtype research. However, how the two measures affect the definition of AD subtypes remains unclear. Methods: A total of 180 AD patients from the ADNI database were used to identify AD subgroups. The subtypes were identified via a data-driven strategy based on the density features and CT features, respectively. Then, the similarity between the two features in AD subtype definition was analyzed. Results: Four distinct subtypes were discovered by both density and CT features: diffuse atrophy AD, minimal atrophy AD (MAD), left temporal dominant atrophy AD (LTAD), and occipital sparing AD. The matched subtypes exhibited relatively high similarity in atrophy patterns and neuropsychological and neuropathological characteristics. They differed only in MAD and LTAD regarding the carrying of apolipoprotein E ε2. Conclusions: The results verified that different representative morphological GM measurement methods could produce similar AD subtypes. Meanwhile, the influences of apolipoprotein E genotype, asymmetric disease progression, and their interactions should be considered and included in the AD subtype definition. This study provides a valuable reference for selecting features in future studies of AD subtypes.
Highlights
Published: 30 January 2022It is generally accepted that the neurofibrillary tangles (NFTs) of Alzheimer’s disease (AD) derive from the entorhinal cortex, spread subsequently to the association cortex via the hippocampus, and invade the primary cortex [1]
Given the high-dimensionality of structural magnetic resonance imaging, automated region-based analyses have been conducted in the studies of AD subtypes by parcellating the brain into anatomically defined regions
The first phase (ADNI-1) lasted from 2004 to 2010, during which time the plan was to recruit a total of 800 individuals aged 50–90, including AD: 200, cognitive normal (CN): 200, and mild cognitive impairment (MCI): 400
Summary
Published: 30 January 2022It is generally accepted that the neurofibrillary tangles (NFTs) of Alzheimer’s disease (AD) derive from the entorhinal cortex, spread subsequently to the association cortex via the hippocampus, and invade the primary cortex [1]. GM atrophy pattern-based morphometric measures have received increasing attention in the studies of biologically defined AD subtypes [5,6]. GM density and cortical thickness (CT) obtained from sMRI are two widely used morphometric features. Gray matter (GM) density and cortical thickness (CT) obtained from structural magnetic resonance imaging are representative GM morphological measures that have been commonly used in Alzheimer’s disease (AD) subtype research. The matched subtypes exhibited relatively high similarity in atrophy patterns and neuropsychological and neuropathological characteristics. They differed only in MAD and LTAD regarding the carrying of apolipoprotein E ε2. Conclusions: The results verified that different representative morphological GM measurement methods could produce similar AD subtypes. The influences of apolipoprotein E genotype, asymmetric disease progression, and their interactions should be considered and included in the AD subtype definition
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