APOE epsilon 4 Genotype and Longitudinal Changes in Cerebral Blood Flow in Normal Aging

作者：Thambisetty Madhav^*; Beason Held Lori; An Yang; Kraut Michael A; Resnick Susan M

来源：Archives of Neurology, 2010, 67(1): 93-98.

DOI：10.1001/archneurol.2009.913

Objective: To study differences in longitudinal changes in regional cerebral blood flow (rCBF) between apolipoprotein E (APOE) epsilon 4 carriers and noncarriers in non-demented older adults from the Baltimore Longitudinal Study of Aging using positron emission tomography in order to determine whether there are regionally specific longitudinal changes in rCBF in APOE epsilon 4 carriers that might be related to its well-established role as a genetic risk factor for Alzheimer disease.
Design, Setting, and Participants: Using oxygen 15 ([(15)O])-labeled water positron emission tomography and voxel-based analysis, we compared changes in rCBF over an 8-year period between 29 nondemented APOE epsilon 4 carriers and 65 noncarriers older than 55 years. Serial neuropsychological data were collected for all participants.
Results: Widespread differences were observed in longitudinal change in rCBF between epsilon 4 carriers and noncarriers. The predominant pattern was greater rCBF decline in epsilon 4 carriers. These differences were observed in the frontal, parietal, and temporal cortices. The affected brain regions were those especially vulnerable to pathological changes in Alzheimer disease. Both epsilon 4 carriers and noncarriers remained free of clinical diagnoses of dementia or mild cognitive impairment during the course of the study.
Conclusions: Our findings suggest that APOE epsilon 4-mediated risk for Alzheimer disease is associated with widespread decline in rCBF over time that precedes the onset of dementia. Accelerated rates of decline in brain function in APOE epsilon 4 carriers may contribute to an increased risk for Alzheimer disease and a younger age at onset.

• 出版日期2010-1