Five-Year Longitudinal Brain Volume Change in Healthy Elders at Genetic Risk for Alzheimer's Disease.
Neuropathological changes associated with Alzheimer's disease (AD) precede symptom onset by more than a decade. Possession of an apolipoprotein E (APOE) ɛ4 allele is the strongest genetic risk factor for late onset AD. Cross-sectional studies of cognitively intact elders have noted smaller hippocampal/medial temporal volumes in ɛ4 carriers (ɛ4+) compared to ɛ4 non-carriers (ɛ4-). Few studies, however, have examined long-term, longitudinal, anatomical brain changes comparing healthy ɛ4+ and ɛ4- individuals. The current five-year study examined global and regional volumes of cortical and subcortical grey and white matter and ventricular size in 42 ɛ4+ and 30 ɛ4- individuals. Cognitively intact participants, ages 65-85 at study entry, underwent repeat anatomical MRI scans on three occasions: baseline, 1.5, and 4.75 years. Results indicated no between-group volumetric differences at baseline. Over the follow-up interval, the ɛ4+ group experienced a greater rate of volume loss in total grey matter, bilateral hippocampi, right hippocampal subfields, bilateral lingual gyri, bilateral parahippocampal gyri, and right lateral orbitofrontal cortex compared to the ɛ4- group. Greater loss in grey matter volumes in ɛ4+ participants were accompanied by greater increases in lateral, third, and fourth ventricular volumes. Rate of change in white matter volumes did not differentiate the groups. The current results indicate that longitudinal measurements of brain atrophy can serve as a sensitive biomarker for identifying neuropathological changes in persons at genetic risk for AD and potentially, for assessing the efficacy of treatments designed to slow or prevent disease progression during the preclinical stage of AD.
Department of Psychology, Marquette University, Milwaukee, WI, USA.
Katherine
K
Reiter
Department of Psychology, Marquette University, Milwaukee, WI, USA.|Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA.
Kristy A
KA
Nielson
Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA.
Sally
S
Durgerian
Department of Psychology, Wayne State University, Detroit, MI, USA.
John L
JL
Woodard
Department of Kinesiology, School of Public Health, University of Maryland, College Park, MD, USA.
J Carson
JC
Smith
Department of Psychology, Rosalind Franklin University, North Chicago, IL, USA.
Michael
M
Seidenberg
Department of Psychology, Rosalind Franklin University, North Chicago, IL, USA.
Dana A
DA
Kelly
Schey Center for Cognitive Neuroimaging, Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
Stephen M
SM
Rao
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D020547:Lateral Ventricles / Q000000981:diagnostic imaging / Q000473:pathology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D013223:Statistics as Topic
D053327:Apolipoprotein E4
Alzheimer’s disease; ApoE4; MRI scans; longitudinal studies