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Clinical phenotype,...
Clinical phenotype, atrophy, and small vessel disease in APOEε2 carriers with Alzheimer disease
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- Groot, Colin (author)
- Amsterdam UMC - Vrije Universiteit Amsterdam
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- Sudre, Carole H. (author)
- University College London
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- Barkhof, Frederik (author)
- University College London,Amsterdam UMC - Vrije Universiteit Amsterdam
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- Teunissen, Charlotte E. (author)
- Amsterdam UMC - Vrije Universiteit Amsterdam
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van Berckel, Bart N.M. (author)
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- Seo, Sang Won (author)
- Sungkyunkwan University
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- Ourselin, Sébastien (author)
- University College London
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- Scheltens, Philip (author)
- Amsterdam UMC - Vrije Universiteit Amsterdam
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- Cardoso, M. Jorge (author)
- University College London
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- van der Flier, Wiesje M. (author)
- Amsterdam UMC - Vrije Universiteit Amsterdam
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- Ossenkoppele, Rik (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Amsterdam UMC - Vrije Universiteit Amsterdam
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(creator_code:org_t)
- 2018
- 2018
- English.
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In: Neurology. - 1526-632X. ; 91:20, s. 1851-1859
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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- OBJECTIVE: To examine the clinical phenotype, gray matter atrophy patterns, and small vessel disease in patients who developed prodromal or probable Alzheimer disease dementia, despite carrying the protective APOEε2 allele. METHODS: We included 36 β-amyloid-positive (by CSF or PET) APOEε2 carriers (all ε2/ε3) with mild cognitive impairment or dementia due to Alzheimer disease who were matched for age and diagnosis (ratio 1:2) to APOEε3 homozygotes and APOEε4 carriers (70% ε3/ε4 and 30% ε4/ε4). We assessed neuropsychological performance across 4 cognitive domains (memory, attention, executive, and language functions), performed voxelwise and region of interest analyses of gray matter atrophy on T1-weighted MRI, used fluid-attenuated inversion recovery images to automatically quantify white matter hyperintensity volumes, and assessed T2*-weighted images to identify microbleeds. Differences in cognitive domain scores, atrophy, and white matter hyperintensities between ε2 carriers, ε3 homozygotes, and ε4 carriers were assessed using analysis of variance analyses, and Pearson χ2 tests were used to examine differences in prevalence of microbleeds. RESULTS: We found that ε2 carriers performed worse on nonmemory domains compared to both ε3 homozygotes and ε4 carriers but better on memory compared to ε4 carriers. Voxelwise T1-weighted MRI analyses showed asymmetric (left > right) temporoparietal-predominant atrophy with subtly less involvement of medial-temporal structures in ε2 carriers compared to ε4 carriers. Finally, ε2 carriers had larger total white matter hyperintensity volumes compared to ε4 carriers (mean 10.4 vs 7.3 mL) and a higher prevalence of microbleeds compared to ε3 homozygotes (37.5% vs 18.3%). CONCLUSION: APOEε2 carriers who develop Alzheimer disease despite carrying the protective allele display a nonamnestic clinical phenotype with more severe small vessel disease.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
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- art (subject category)
- ref (subject category)
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Neurology
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- By the author/editor
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Groot, Colin
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Sudre, Carole H.
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Barkhof, Frederi ...
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Teunissen, Charl ...
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van Berckel, Bar ...
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Seo, Sang Won
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Ourselin, Sébast ...
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Scheltens, Phili ...
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Cardoso, M. Jorg ...
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van der Flier, W ...
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Ossenkoppele, Ri ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
- Articles in the publication
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Neurology
- By the university
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Lund University