Steady-state cerebral autoregulation in older adults with amnestic mild cognitive impairment: linear mixed model analysis

Li Zhang, Evan P. Pasha, Jie Liu, Chang Yang Xing, Danilo Cardim, Takashi Tarumi Ph.D., Kyle Womack, Linda S Hynan, C Munro Cullum, Rong Zhang

Research output: Contribution to journalArticle

Abstract

We examined whether the efficacy of steady-state cerebral autoregulation (CA) is reduced in older adults with amnestic mild cognitive impairment (aMCI), a prodromal stage of clinical Alzheimer disease (AD). Forty-two patients with aMCI and 24 cognitively normal older adults (NC) of similar age, sex, and education underwent stepwise decreases and increases in mean arterial pressure (MAP) induced by intravenous infusion of sodium nitroprusside and phenylephrine, respectively. Changes in cerebral blood flow (CBF) were measured repeatedly in the internal carotid and vertebral artery. Linear mixed modeling, including random effects of both individual intercept and regression slope, was used to quantify the MAP-CBF relationship accounting for nonindependent, repeated CBF measures. Changes in end-tidal CO2 (EtCO2) associated with changes in MAP were also included in the model to account for their effects on CBF. Marginal mean values of MAP were reduced by 13-14 mmHg during sodium nitroprusside and increased by 20-24 mmHg during phenylephrine infusion in both groups with similar doses of drug infusion. A steeper slope of changes in CBF in response to changes in MAP was observed in aMCI relative to NC, indicating reduced efficacy of CA (MAP × Group, P = 0.040). These findings suggest that cerebrovascular dysfunction may occur early in the development of AD.NEW & NOTEWORTHY Cerebral autoregulation is a fundamental regulatory mechanism to protect brain perfusion against changes in blood pressure that, if impaired, may contribute to the development of Alzheimer's disease. Using a linear mixed model, we demonstrated that the efficacy of cerebral autoregulation, assessed during stepwise changes in arterial pressure, was reduced in individuals with amnestic mild cognitive impairment, a prodromal stage of Alzheimer's disease. These findings support the hypothesis that cerebrovascular dysfunction may be an important underlying pathophysiological mechanism for the development of clinical Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)377-385
Number of pages9
JournalJournal of applied physiology (Bethesda, Md. : 1985)
Volume129
Issue number2
DOIs
StatePublished - Aug 1 2020

Keywords

  • Alzheimer disease
  • cerebral autoregulation
  • cerebral blood flow
  • linear mixed model
  • mild cognitive impairment

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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