Lower cerebral oxygen utilization is associated with Alzheimer's disease-related neurodegeneration and poorer cognitive performance among apolipoprotein E ε4 carriers.

Autor: Robb WH; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA., Khan OA; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Biostatistics, 12328Vanderbilt University Medical Center, Vanderbilt University Medical Center, Nashville, TN, USA., Ahmed HA; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA., Li J; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA., Moore EE; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA., Cambronero FE; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA., Pechman KR; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA., Liu D; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Biostatistics, 12328Vanderbilt University Medical Center, Vanderbilt University Medical Center, Nashville, TN, USA., Gifford KA; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Neurology, 12328Vanderbilt University Medical Center, Vanderbilt University Medical Center, Nashville, TN, USA., Landman BA; Department of Neurology, 12328Vanderbilt University Medical Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Biomedical Engineering, 5718Vanderbilt University, Vanderbilt University, Nashville, TN, USA.; Department of Electrical Engineering and Computer Science, 5718Vanderbilt University, Vanderbilt University, Nashville, TN, USA.; Department of Radiology and Radiological Sciences, 12328Vanderbilt University Medical Center, Vanderbilt University Medical Center, Nashville, TN, USA., Donahue MJ; Department of Neurology, 12328Vanderbilt University Medical Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Radiology and Radiological Sciences, 12328Vanderbilt University Medical Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA., Hohman TJ; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Neurology, 12328Vanderbilt University Medical Center, Vanderbilt University Medical Center, Nashville, TN, USA., Jefferson AL; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Neurology, 12328Vanderbilt University Medical Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Medicine, 12328Vanderbilt University Medical Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Jazyk: angličtina
Zdroj: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism [J Cereb Blood Flow Metab] 2022 Apr; Vol. 42 (4), pp. 642-655. Date of Electronic Publication: 2021 Nov 07.
DOI: 10.1177/0271678X211056393
Abstrakt: Oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) 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 CMRO 2 to cognitive performance and structural neuroimaging variables among older adults (n = 246, 74 ± 7 years, 37% female) and tested whether apolipoprotein E ( APOE )-ε4 status modified these associations. Main effects of OEF and CMRO 2 were null (p-values >0.06), and OEF interactions with APOE -ε4 status on cognitive and structural imaging outcomes were null (p-values >0.06). However, CMRO 2 interacted with APOE- ε4 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- ε4 carriers only. Associations between CMRO 2 and cognitive performance were primarily driven by APOE- ε4 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 -ε4 may interact with cerebral oxygen metabolism in the pathogenesis of Alzheimer's disease and related neurodegeneration.
Databáze: MEDLINE