Brain atrophy rates in first degree relatives at risk for Alzheimer's.
A positive family history (FH) raises the risk for late-onset Alzheimer's disease though, other than the known risk conferred by apolipoprotein ε4 (ApoE4), much of the genetic variance remains unexplained. We examined the effect of family history on longitudinal regional brain atrophy rates in 184 subjects (42% FH+, mean age 79.9) with mild cognitive impairment (MCI) enrolled in a national biomarker study. An automated image analysis method was applied to T1-weighted MR images to measure atrophy rates for 20 cortical and subcortical regions. Mixed-effects linear regression models incorporating repeated-measures to control for within-subject variation over multiple time points tested the effect of FH over a follow-up of up to 48 months. Most of the 20 regions showed significant atrophy over time. Adjusting for age and gender, subjects with a positive FH had greater atrophy of the amygdala (p < 0.01), entorhinal cortex (p < 0.01), hippocampus (p < 0.053) and cortical gray matter (p < 0.009). However, when E4 genotype was added as a covariate, none of the FH effects remained significant. Analyses by ApoE genotype showed that the effect of FH on amygdala atrophy rates was numerically greater in ε3 homozygotes than in E4 carriers, but this difference was not significant. FH+ subjects had numerically greater 4-year cognitive decline and conversion rates than FH- subjects but the difference was not statistically significant after adjusting for ApoE and other variables. We conclude that a positive family history of AD may influence cortical and temporal lobe atrophy in subjects with mild cognitive impairment, but it does not have a significant additional effect beyond the known effect of the E4 genotype.
Department of Psychiatry, Duke University Medical Center, Durham, NC, USA.
Erika J
EJ
Lampert
Department of Radiology, Duke University Medical Center, Durham, NC, USA.
Kingshuk
K
Roy Choudhury
Department of Radiology, Duke University Medical Center, Durham, NC, USA.
Christopher A
CA
Hostage
Department of Psychiatry, Duke University Medical Center, Durham, NC, USA.
Bharath
B
Rathakrishnan
Department of Psychiatry, University of California, San Francisco and San Francisco VA Medical Center, San Francisco, USA ; Department of Radiology, University of California, San Francisco and San Francisco VA Medical Center, San Francisco, USA.
Michael
M
Weiner
Department of Radiology, Duke University Medical Center, Durham, NC, USA.
Jeffrey R
JR
Petrella
Department of Psychiatry, Duke University Medical Center, Durham, NC, USA ; Institute for Brain Sciences, Duke University Medical Center, Durham, NC, USA.
P Murali
PM
Doraiswamy
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D053327:Apolipoprotein E4 / Q000235:genetics; D001284:Atrophy; D015415:Biomarkers; D001921:Brain / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000235:genetics / Q000473:pathology*; D005190:Family; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012307:Risk Factors
D053327:Apolipoprotein E4; D015415:Biomarkers
Amygdala; Dementia; Entorhinal cortex; Family history; Hippocampus; Memory