Abstract
Alzheimer’s disease (AD) is a disease of a heterogeneous nature, which can be disentangled by exploring the characteristics of each AD subtype in the brain structure, neuropathology, and cognition. In this study, a total of 192 AD and 228 cognitively normal (CN) subjects were obtained from the Alzheimer’s disease Neuroimaging Initiative database. Based on the cortical thickness patterns, the mixture of experts method (MOE) was applied to the implicit model spectrum of transforms lined with each AD subtype, then their neuropsychological and neuropathological characteristics were analyzed. Furthermore, the piecewise linear classifiers composed of each AD subtype and CN were resolved, and each subtype was comprehensively explained. The following four distinct AD subtypes were discovered: bilateral parietal, frontal, and temporal atrophy AD subtype (occipital sparing AD subtype (OSAD), 29.2%), left temporal dominant atrophy AD subtype (LTAD, 22.4%), minimal atrophy AD subtype (MAD, 16.1%), and diffuse atrophy AD subtype (DAD, 32.3%). These four subtypes display their own characteristics in atrophy pattern, cognition, and neuropathology. Compared with the previous studies, our study found that some AD subjects showed obvious asymmetrical atrophy in left lateral temporal-parietal cortex, OSAD presented the worst cerebrospinal fluid levels, and MAD had the highest proportions of APOE ε4 and APOE ε2. The subtype characteristics were further revealed from the aspect of the model, making it easier for clinicians to understand. The results offer an effective support for individual diagnosis and prognosis.
Highlights
Alzheimer’s disease (AD) is a heterogeneous disease
The AD subjects were divided into 4 subtypes using the mixture of experts (MOE) method
The atrophy patterns of gray matter from structural magnetic resonance imaging (sMRI) were input into MOE to simulate the heterogeneous cerebral cortex change process from cognitively normal (CN) to AD
Summary
Alzheimer’s disease (AD) is a heterogeneous disease. Memory impairment is a common characteristic among AD patients; some, suffer from other obvious cognitive deficits, such as executive function impairment or language impairment [1]. A postmortem study pointed out that the tau protein tangles showed different development rules among about 25% of AD subjects, and these samples were classified into two subtypes: hippocampal-sparing AD (HSAD) and limbic-predominant AD (LPAD) [2]. The atrophy features of gray matter were extracted via structural magnetic resonance imaging (sMRI), the subtypes similar to those by Murray et al and obtained the subtypes presented different neuropathological and neuropsychological characteristics [3]. The cortical atrophy features acquired from sMRI have been applied to the research on early-stage AD subtypes [4]. The subtypes have been identified via visual rating scales [8,9]. These methods, which belong to priori hypothesis, need to preset the subtypes and their corresponding
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