title: Impact of APOE-ɛ4 and family history of dementia on gray matter atrophy in cognitively healthy middle-aged adults.
abstract: 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.
authors.affiliation: Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands. Electronic address: m.tenkate1@vumc.nl.
authors.forename: Mara
authors.initials: M
authors.lastname: Ten Kate
authors.affiliation: Neuroimaging Department, CITA-Alzheimer Foundation, San Sebastian, Spain.
authors.forename: Ernesto J
authors.initials: EJ
authors.lastname: Sanz-Arigita
authors.affiliation: Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Betty M
authors.initials: BM
authors.lastname: Tijms
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Alle Meije
authors.initials: AM
authors.lastname: Wink
authors.affiliation: Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Clerigue
authors.affiliation: Neuroimaging Department, CITA-Alzheimer Foundation, San Sebastian, Spain.
authors.forename: Maite
authors.initials: M
authors.lastname: Garcia-Sebastian
authors.affiliation: Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Izagirre
authors.affiliation: Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Ecay-Torres
authors.affiliation: Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain.
authors.forename: Ainara
authors.initials: A
authors.lastname: Estanga
authors.affiliation: Neuroimaging Department, CITA-Alzheimer Foundation, San Sebastian, Spain; Donostia Unit, Osatek SA, Donostia Univeristy Hospital, San Sebastian, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Villanua
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Hugo
authors.initials: H
authors.lastname: Vrenken
authors.affiliation: 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.
authors.forename: Pieter Jelle
authors.initials: PJ
authors.lastname: Visser
authors.affiliation: Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Martinez-Lage
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000209:etiology; D053327:Apolipoprotein E4 / Q000235:genetics*; D001284:Atrophy; D003704:Dementia / Q000235:genetics*; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4
keywords: Alzheimer's disease; Apolipoprotein E; Dementia; Family history; MRI; Voxel-based morphometry