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Article type: Research Article
Authors: Tomoto, Tsubasaa; b | Tarumi, Takashia; b; c | Chen, Jasona | Pasha, Evan P.a; b | Cullum, C. Munrob; d; e | Zhang, Ronga; b; f; *
Affiliations: [a] Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, TX, USA | [b] Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA | [c] Human Informatics Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan | [d] Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA | [e] Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA | [f] Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
Correspondence: [*] Correspondence to: Rong Zhang, PhD, 7232 Greenville Ave, Dallas, TX 75231, USA. Tel.: +1 214 345 4670; Fax: +1 214 345 4618; E-mail: RongZhang@TexasHealth.org.
Abstract: Background:Cerebral blood flow (CBF) is sensitive to changes in arterial CO2, referred to as cerebral vasomotor reactivity (CVMR). Whether CVMR is altered in patients with amnestic mild cognitive impairment (aMCI), a prodromal stage of Alzheimer disease (AD), is unclear. Objective:To determine whether CVMR is altered in aMCI and is associated with cognitive performance. Methods:Fifty-three aMCI patients aged 55 to 80 and 22 cognitively normal subjects (CN) of similar age, sex, and education underwent measurements of CBF velocity (CBFV) with transcranial Doppler and end-tidal CO2 (EtCO2) with capnography during hypocapnia (hyperventilation) and hypercapnia (rebreathing). Arterial pressure (BP) was measured to calculate cerebrovascular conductance (CVCi) to normalize the effect of changes in BP on CVMR assessment. Cognitive function was assessed with Mini-Mental State Examination (MMSE) and neuropsychological tests focused on memory (Logical Memory, California Verbal Learning Test) and executive function (Delis-Kaplan Executive Function Scale; DKEFS). Results:At rest, CBFV and MMSE did not differ between groups. CVMR was reduced by 13% in CBFV% and 21% in CVCi% during hypocapnia and increased by 22% in CBFV% and 20% in CVCi% during hypercapnia in aMCI when compared to CN (all p < 0.05). Logical Memory recall scores were positively correlated with hypocapnia (r = 0.283, r = 0.322, p < 0.05) and negatively correlated with hypercapnic CVMR measured in CVCi% (r = –0.347, r = –0.446, p < 0.01). Similar correlations were observed in D-KEFS Trail Making scores. Conclusion:Altered CVMR in aMCI and its associations with cognitive performance suggests the presence of cerebrovascular dysfunction in older adults who have high risks for AD.
Keywords: Cerebral blood flow, cerebral vasomotor reactivity, hypercapnia, hypocapnia, mild cognitive impairment, transcranial Doppler
DOI: 10.3233/JAD-200194
Journal: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 191-202, 2020
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