期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 42, 期 4, 页码 642-655出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X211056393
关键词
Apolipoprotein E4; Alzheimer disease; cognition; metabolism; neuroimaging
资金
- Alzheimer's Association [IIRG-08-88733, R01AG034962, R01-NS100980, K24-AG046373, R01-AG056534]
- Paul B. Beeson Career Development Award in Aging [K23-AG045966, T32-AG058524, F30-AG064847, T32GM007447, K01-AG049164]
- Vanderbilt Clinical Translational Science Award [UL1-TR000445, UL1-TR002243]
- Vanderbilt's High-Performance Computer Cluster for Biomedical Research [S10-OD023680]
- Vanderbilt Alzheimer's Disease Research Center [P20-AG068082]
- Vanderbilt Memory and Alzheimer's Center
The study found interactions between CMRO2 and APOE-ε4 status in cognitive performance and neuroimaging variables among older adults, suggesting that low oxygen metabolism is associated with certain cognitive impairments, particularly in APOE-ε4 carriers.
Oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) are markers of cerebral oxygen homeostasis and metabolism that may offer insights into abnormal changes in brain aging. The present study cross-sectionally related OEF and CMRO2 to cognitive performance and structural neuroimaging variables among older adults (n = 246, 74 +/- 7 years, 37% female) and tested whether apolipoprotein E (APOE)-epsilon 4 status modified these associations. Main effects of OEF and CMRO2 were null (p-values >0.06), and OEF interactions with APOE-epsilon 4 status on cognitive and structural imaging outcomes were null (p-values >0.06). However, CMRO2 interacted with APOE-epsilon 4 status on language (p = 0.002), executive function (p = 0.03), visuospatial (p = 0.005), and episodic memory performances (p = 0.03), and on hippocampal (p = 0.006) and inferior lateral ventricle volumes (p = 0.02). In stratified analyses, lower oxygen metabolism related to worse language (p = 0.02) and episodic memory performance (p = 0.03) among APOE-epsilon 4 carriers only. Associations between CMRO2 and cognitive performance were primarily driven by APOE-epsilon 4 carriers with existing cognitive impairment. Congruence across language and episodic memory results as well as hippocampal and inferior lateral ventricle volume findings suggest that APOE-epsilon 4 may interact with cerebral oxygen metabolism in the pathogenesis of Alzheimer's disease and related neurodegeneration.
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