INTRODUCTION: Maintenance of cerebral blood flow during orthostasis is impaired with aging and associated with cognitive decline, but the effect of Apolipoprotein ɛ4-allele (APOE4) is unknown. METHODS: Older adults (n=108) (APOE4 carriers, n=47; noncarriers, n=61) diagnosed as cognitively-normal (NC), MCI, or AD participated. Middle cerebral artery blood velocity (MCAv), assessed using Transcranial Doppler ultrasound, and beat-to-beat mean arterial blood pressure (MAP) were continuously recorded during a sit-to-stand transition. Anticipatory and orthostatic-induced MCAv and MAP responses were compared between genotypes and across disease progression. RESULTS: Cognitively-normal APOE4 carriers showed greater anticipatory MCAv increase, greater MCAv decrease with orthostasis, and shorter latency of peripheral MAP responses to orthostasis compared to noncarriers. MCAv and MAP responses were delayed and attenuated across the APOE4 disease progression, with no differences between genotypes in MCI and AD. DISCUSSION: APOE4 carriers and noncarriers present with distinct phenotypes of cerebral vascular dysfunction during hemodynamic orthostatic challenge. Unique cerebral and peripheral vascular compensation observed in APOE4 carriers may be lost as AD progresses.

The authors have declared no competing interest.

This work was supported by the National Institute on Aging of the National Institutes of Health [K99AG075255 (JP)] and [P30 AG072973 (SB)], the National Heart, Lung and Blood Institute [T32HL134643 (AWH)] the Cardiovascular Centers A.O. Smith Fellowship Scholars Program, and the Georgia Holland Endowment Fund. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or any other funding agency. The funding sources had no involvement in the collection, analysis, or interpretation of the presented data.

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