Impact of APOE-ɛ4 and family history of dementia on gray matter atrophy in cognitively healthy middle-aged adults

Mara ten Kate, Ernesto J. Sanz-Arigita, Betty M. Tijms, Alle Meije Wink, Montserrat Clerigue, Maite Garcia-Sebastian, Andrea Izagirre, Miriam Ecay-Torres, Ainara Estanga, Jorge Villanua, Hugo Vrenken, Pieter Jelle Visser, Pablo Martinez-Lage, Frederik Barkhof
Neurobiology of Aging. 2016-02-01; 38: 14-20
DOI: 10.1016/j.neurobiolaging.2015.10.018

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1. Neurobiol Aging. 2016 Feb;38:14-20. doi: 10.1016/j.neurobiolaging.2015.10.018.
Epub 2015 Nov 10.

Impact of APOE-ɛ4 and family history of dementia on gray matter atrophy in
cognitively healthy middle-aged adults.

Ten Kate M(1), Sanz-Arigita EJ(2), Tijms BM(3), Wink AM(4), Clerigue M(5),
Garcia-Sebastian M(2), Izagirre A(5), Ecay-Torres M(5), Estanga A(5), Villanua
J(6), Vrenken H(4), Visser PJ(7), Martinez-Lage P(5), Barkhof F(4).

Author information:
(1)Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam,
VU University Medical Center, Amsterdam, the Netherlands. Electronic address:
.
(2)Neuroimaging Department, CITA-Alzheimer Foundation, San Sebastian, Spain.
(3)Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam,
VU University Medical Center, Amsterdam, the Netherlands.
(4)Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam,
VU University Medical Center, Amsterdam, the Netherlands.
(5)Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain.
(6)Neuroimaging Department, CITA-Alzheimer Foundation, San Sebastian, Spain;
Donostia Unit, Osatek SA, Donostia Univeristy Hospital, San Sebastian, Spain.
(7)Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam,
VU University Medical Center, Amsterdam, the Netherlands; Department of
Psychiatry and Neuropsychology, School for Mental Health and Neuroscience,
Maastricht University, Maastricht, the Netherlands.

The apolipoprotein E ε4 allele (APOE4) and family history of dementia (FH) are
well-known risk factors for the development of sporadic Alzheimer’s disease. We
assessed the effects of these risk factors on gray matter (GM) volume in 295
cognitively healthy middle-aged community-dwelling subjects. Voxel-based
morphometry was used to study GM volume differences between high- and low-risk
subjects, based on APOE4 carriership (n = 74), first-degree FH (n = 228), or both
(n = 62). No significant results were found using a corrected p value. Using a
more lenient threshold (p < 0.001 and minimum cluster size of 100 voxels), APOE4 carriers had reduced GM in the striatum compared to noncarriers. Subjects with FH had reduced GM in right precuneus compared to subjects without FH. Maternal and paternal FH provided similar atrophy patterns. APOE4 carriers with FH had GM reductions in bilateral insula compared to subjects with neither APOE4 nor FH. We conclude that a family history of dementia and APOE4 carriership are both associated with regional GM decreases in cognitively healthy middle-aged subjects, with differential effects on brain regions typically affected in Alzheimer's disease. Copyright © 2016 Elsevier Inc. All rights reserved. DOI: 10.1016/j.neurobiolaging.2015.10.018 PMID: 26827639 [Indexed for MEDLINE]

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