Family history of Alzheimer's disease and hippocampal structure in healthy people.
OBJECTIVE
Structural brain changes appear years before the onset of Alzheimer's disease, the leading cause of dementia late in life. Determining risk factors for such presymptomatic brain changes may assist in identifying candidates for future prevention treatment trials. In addition to the e4 allele of the apolipoprotein E gene (APOE-4), the major known genetic risk factor, a family history of Alzheimer's disease also increases the risk to develop the disease, reflecting yet unidentified genetic and, perhaps, nongenetic risks. The authors investigated the influence of APOE-4 genotype and family history risks on cortical thickness in medial temporal lobe subregions among volunteers without cognitive impairment.


METHODS
High-resolution magnetic resonance imaging (MRI) and a cortical unfolding method were performed on 26 subjects (APOE-4 carriers: N=13; noncarriers: N=13) with at least one first-degree relative with Alzheimer's disease and 25 subjects (APOE-4 carriers: N=12; noncarriers: N=13) without this risk factor. All subjects (mean age: 62.3 years [SD=10.7]; range=38-86 years) were cognitively healthy.


RESULTS
Family history of Alzheimer's disease and APOE-4 status were associated with a thinner cortex in the entorhinal region, subiculum, and adjacent medial temporal lobe subfields. Although these associations were additive, family history of Alzheimer's disease explained a greater proportion of the unique variance in cortical thickness than APOE-4 carrier status.


CONCLUSIONS
APOE-4 carrier status and family history of Alzheimer's disease are independently associated with and contribute additively to hippocampal cortical thinning.
Donix
Markus
M
Center for Cognitive Neurosciences, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California Los Angeles, Semel Institute, Los Angeles, CA 90095, USA.
Burggren
Alison C
AC
Suthana
Nanthia A
NA
Siddarth
Prabha
P
Ekstrom
Arne D
AD
Krupa
Allison K
AK
Jones
Michael
M
Martin-Harris
Laurel
L
Ercoli
Linda M
LM
Miller
Karen J
KJ
Small
Gary W
GW
Bookheimer
Susan Y
SY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D053327:Apolipoprotein E4 / Q000235:genetics*; D002540:Cerebral Cortex / Q000473:pathology*; D018728:Entorhinal Cortex / Q000473:pathology; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012307:Risk Factors; D013702:Temporal Lobe / Q000473:pathology
D053327:Apolipoprotein E4