Publication:
Differential patterns of gray matter volumes and associated gene expression profiles in cognitively-defined Alzheimer's disease subgroups.

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Date

2021-04-03

Authors

Groot, Colin
Grothe, Michel J
Mukherjee, Shubhabrata
Jelistratova, Irina
Jansen, Iris
van Loenhoud, Anna Catharina
Risacher, Shannon L
Saykin, Andrew J
Mac Donald, Christine L
Mez, Jesse

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Abstract

The clinical presentation of Alzheimer's disease (AD) varies widely across individuals but the neurobiological mechanisms underlying this heterogeneity are largely unknown. Here, we compared regional gray matter (GM) volumes and associated gene expression profiles between cognitively-defined subgroups of amyloid-β positive individuals clinically diagnosed with AD dementia (age: 66 ± 7, 47% male, MMSE: 21 ± 5). All participants underwent neuropsychological assessment with tests covering memory, executive-functioning, language and visuospatial-functioning domains. Subgroup classification was achieved using a psychometric framework that assesses which cognitive domain shows substantial relative impairment compared to the intra-individual average across domains, which yielded the following subgroups in our sample; AD-Memory (n = 41), AD-Executive (n = 117), AD-Language (n = 33), AD-Visuospatial (n = 171). We performed voxel-wise contrasts of GM volumes derived from 3Tesla structural MRI between subgroups and controls (n = 127, age 58 ± 9, 42% male, MMSE 29 ± 1), and observed that differences in regional GM volumes compared to controls closely matched the respective cognitive profiles. Specifically, we detected lower medial temporal lobe GM volumes in AD-Memory, lower fronto-parietal GM volumes in AD-Executive, asymmetric GM volumes in the temporal lobe (left 

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MeSH Terms

Aged
Alzheimer Disease
Amyloid beta-Peptides
Brain
Female
Gray Matter
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Neuropsychological Tests
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Keywords

Alzheimer’s disease, Gene expression, Gray matter volumes, Heterogeneity, Psychometrics

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