Slowed Temporal and Parietal Cerebrovascular Response in Patients with Alzheimer's Disease

Kenneth R. Holmes; David Tang-Wai; Kevin Sam; Larissa Mcketton; Julien Poublanc; Adrian P. Crawley; Olivia Sobczyk; Melanie Cohn; James Duffin; Maria Carmela Tartaglia; Sandra E. Black; Joseph A. Fisher; Bruce Wasserman; David J. Mikulis

doi:10.1017/cjn.2020.30

Slowed Temporal and Parietal Cerebrovascular Response in Patients with Alzheimer's Disease

Kenneth R. Holmes, David Tang-Wai, Kevin Sam, Larissa Mcketton, Julien Poublanc, Adrian P. Crawley, Olivia Sobczyk, Melanie Cohn, James Duffin, Maria Carmela Tartaglia, Sandra E. Black, Joseph A. Fisher, Bruce Wasserman, David J. Mikulis

School of Medicine

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Background: Recent investigations now suggest that cerebrovascular reactivity (CVR) is impaired in Alzheimer's disease (AD) and may underpin part of the disease's neurovascular component. However, our understanding of the relationship between the magnitude of CVR, the speed of cerebrovascular response, and the progression of AD is still limited. This is especially true in patients with mild cognitive impairment (MCI), which is recognized as an intermediate stage between normal aging and dementia. The purpose of this study was to investigate AD and MCI patients by mapping repeatable and accurate measures of cerebrovascular function, namely the magnitude and speed of cerebrovascular response (τ) to a vasoactive stimulus in key predilection sites for vascular dysfunction in AD.Methods: Thirty-three subjects (age range: 52-83 years, 20 males) were prospectively recruited. CVR and τ were assessed using blood oxygen level-dependent MRI during a standardized carbon dioxide stimulus. Temporal and parietal cortical regions of interest (ROIs) were generated from anatomical images using the FreeSurfer image analysis suite.Results: Of 33 subjects recruited, 3 individuals were excluded, leaving 30 subjects for analysis, consisting of 6 individuals with early AD, 11 individuals with MCI, and 13 older healthy controls (HCs). τ was found to be significantly higher in the AD group compared to the HC group in both the temporal (p = 0.03) and parietal cortex (p = 0.01) following a one-way ANCOVA correcting for age and microangiopathy scoring and a Bonferroni post-hoc correction.Conclusion: The study findings suggest that AD is associated with a slowing of the cerebrovascular response in the temporal and parietal cortices.

Original language	English (US)
Pages (from-to)	366-373
Number of pages	8
Journal	Canadian Journal of Neurological Sciences
Volume	47
Issue number	3
DOIs	https://doi.org/10.1017/cjn.2020.30
State	Published - May 1 2020

Keywords

Alzheimer's disease
Cerebral blood flow regulation
Cerebrovascular reactivity
Magnetic resonance imaging

ASJC Scopus subject areas

Clinical Neurology
Neurology

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10.1017/cjn.2020.30

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Holmes, K. R., Tang-Wai, D., Sam, K., Mcketton, L., Poublanc, J., Crawley, A. P., Sobczyk, O., Cohn, M., Duffin, J., Tartaglia, M. C., Black, S. E., Fisher, J. A., Wasserman, B., & Mikulis, D. J. (2020). Slowed Temporal and Parietal Cerebrovascular Response in Patients with Alzheimer's Disease. Canadian Journal of Neurological Sciences, 47(3), 366-373. https://doi.org/10.1017/cjn.2020.30

Holmes, KR, Tang-Wai, D, Sam, K, Mcketton, L, Poublanc, J, Crawley, AP, Sobczyk, O, Cohn, M, Duffin, J, Tartaglia, MC, Black, SE, Fisher, JA, Wasserman, B & Mikulis, DJ 2020, 'Slowed Temporal and Parietal Cerebrovascular Response in Patients with Alzheimer's Disease', Canadian Journal of Neurological Sciences, vol. 47, no. 3, pp. 366-373. https://doi.org/10.1017/cjn.2020.30

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title = "Slowed Temporal and Parietal Cerebrovascular Response in Patients with Alzheimer's Disease",

abstract = "Background: Recent investigations now suggest that cerebrovascular reactivity (CVR) is impaired in Alzheimer's disease (AD) and may underpin part of the disease's neurovascular component. However, our understanding of the relationship between the magnitude of CVR, the speed of cerebrovascular response, and the progression of AD is still limited. This is especially true in patients with mild cognitive impairment (MCI), which is recognized as an intermediate stage between normal aging and dementia. The purpose of this study was to investigate AD and MCI patients by mapping repeatable and accurate measures of cerebrovascular function, namely the magnitude and speed of cerebrovascular response (τ) to a vasoactive stimulus in key predilection sites for vascular dysfunction in AD.Methods: Thirty-three subjects (age range: 52-83 years, 20 males) were prospectively recruited. CVR and τ were assessed using blood oxygen level-dependent MRI during a standardized carbon dioxide stimulus. Temporal and parietal cortical regions of interest (ROIs) were generated from anatomical images using the FreeSurfer image analysis suite.Results: Of 33 subjects recruited, 3 individuals were excluded, leaving 30 subjects for analysis, consisting of 6 individuals with early AD, 11 individuals with MCI, and 13 older healthy controls (HCs). τ was found to be significantly higher in the AD group compared to the HC group in both the temporal (p = 0.03) and parietal cortex (p = 0.01) following a one-way ANCOVA correcting for age and microangiopathy scoring and a Bonferroni post-hoc correction.Conclusion: The study findings suggest that AD is associated with a slowing of the cerebrovascular response in the temporal and parietal cortices.",

keywords = "Alzheimer's disease, Cerebral blood flow regulation, Cerebrovascular reactivity, Magnetic resonance imaging",

author = "Holmes, {Kenneth R.} and David Tang-Wai and Kevin Sam and Larissa Mcketton and Julien Poublanc and Crawley, {Adrian P.} and Olivia Sobczyk and Melanie Cohn and James Duffin and Tartaglia, {Maria Carmela} and Black, {Sandra E.} and Fisher, {Joseph A.} and Bruce Wasserman and Mikulis, {David J.}",

note = "Funding Information: KRH and DM received financial support for this work from the Canadian Institutes of Health Research. DM received a grant from the American Society of Neuroradiology during the conduct of this study. JF and JD are senior scientists at Thornhill Research Inc. (TRI), a spin-off company affiliated with the University Health Network that developed the RespirActTM, a non-commercial research tool assembled by TRI to enable cerebrovascular reactivity studies. JF and DM hold a patent related to the RespirActTM. Also, DM is a shareholder in TRI and reports non-financial support from TRI. OS is a part time employee of TRI. Outside of the submitted work, SEB reports institutional grants from GE Healthcare, Eli Lilly, Biogen, Novartis, Genentech, Optina, Roche, and personal fees from Novartis, Roche, and Eli Lilly. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher Copyright: {\textcopyright} 2020 The Canadian Journal of Neurological Sciences Inc.",

year = "2020",

month = may,

day = "1",

doi = "10.1017/cjn.2020.30",

language = "English (US)",

volume = "47",

pages = "366--373",

journal = "Canadian Journal of Neurological Sciences",

issn = "0317-1671",

publisher = "Canadian Journal of Neurological Sciences",

number = "3",

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TY - JOUR

T1 - Slowed Temporal and Parietal Cerebrovascular Response in Patients with Alzheimer's Disease

AU - Holmes, Kenneth R.

AU - Tang-Wai, David

AU - Sam, Kevin

AU - Mcketton, Larissa

AU - Poublanc, Julien

AU - Crawley, Adrian P.

AU - Sobczyk, Olivia

AU - Cohn, Melanie

AU - Duffin, James

AU - Tartaglia, Maria Carmela

AU - Black, Sandra E.

AU - Fisher, Joseph A.

AU - Wasserman, Bruce

AU - Mikulis, David J.

N1 - Funding Information: KRH and DM received financial support for this work from the Canadian Institutes of Health Research. DM received a grant from the American Society of Neuroradiology during the conduct of this study. JF and JD are senior scientists at Thornhill Research Inc. (TRI), a spin-off company affiliated with the University Health Network that developed the RespirActTM, a non-commercial research tool assembled by TRI to enable cerebrovascular reactivity studies. JF and DM hold a patent related to the RespirActTM. Also, DM is a shareholder in TRI and reports non-financial support from TRI. OS is a part time employee of TRI. Outside of the submitted work, SEB reports institutional grants from GE Healthcare, Eli Lilly, Biogen, Novartis, Genentech, Optina, Roche, and personal fees from Novartis, Roche, and Eli Lilly. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher Copyright: © 2020 The Canadian Journal of Neurological Sciences Inc.

PY - 2020/5/1

Y1 - 2020/5/1

N2 - Background: Recent investigations now suggest that cerebrovascular reactivity (CVR) is impaired in Alzheimer's disease (AD) and may underpin part of the disease's neurovascular component. However, our understanding of the relationship between the magnitude of CVR, the speed of cerebrovascular response, and the progression of AD is still limited. This is especially true in patients with mild cognitive impairment (MCI), which is recognized as an intermediate stage between normal aging and dementia. The purpose of this study was to investigate AD and MCI patients by mapping repeatable and accurate measures of cerebrovascular function, namely the magnitude and speed of cerebrovascular response (τ) to a vasoactive stimulus in key predilection sites for vascular dysfunction in AD.Methods: Thirty-three subjects (age range: 52-83 years, 20 males) were prospectively recruited. CVR and τ were assessed using blood oxygen level-dependent MRI during a standardized carbon dioxide stimulus. Temporal and parietal cortical regions of interest (ROIs) were generated from anatomical images using the FreeSurfer image analysis suite.Results: Of 33 subjects recruited, 3 individuals were excluded, leaving 30 subjects for analysis, consisting of 6 individuals with early AD, 11 individuals with MCI, and 13 older healthy controls (HCs). τ was found to be significantly higher in the AD group compared to the HC group in both the temporal (p = 0.03) and parietal cortex (p = 0.01) following a one-way ANCOVA correcting for age and microangiopathy scoring and a Bonferroni post-hoc correction.Conclusion: The study findings suggest that AD is associated with a slowing of the cerebrovascular response in the temporal and parietal cortices.

AB - Background: Recent investigations now suggest that cerebrovascular reactivity (CVR) is impaired in Alzheimer's disease (AD) and may underpin part of the disease's neurovascular component. However, our understanding of the relationship between the magnitude of CVR, the speed of cerebrovascular response, and the progression of AD is still limited. This is especially true in patients with mild cognitive impairment (MCI), which is recognized as an intermediate stage between normal aging and dementia. The purpose of this study was to investigate AD and MCI patients by mapping repeatable and accurate measures of cerebrovascular function, namely the magnitude and speed of cerebrovascular response (τ) to a vasoactive stimulus in key predilection sites for vascular dysfunction in AD.Methods: Thirty-three subjects (age range: 52-83 years, 20 males) were prospectively recruited. CVR and τ were assessed using blood oxygen level-dependent MRI during a standardized carbon dioxide stimulus. Temporal and parietal cortical regions of interest (ROIs) were generated from anatomical images using the FreeSurfer image analysis suite.Results: Of 33 subjects recruited, 3 individuals were excluded, leaving 30 subjects for analysis, consisting of 6 individuals with early AD, 11 individuals with MCI, and 13 older healthy controls (HCs). τ was found to be significantly higher in the AD group compared to the HC group in both the temporal (p = 0.03) and parietal cortex (p = 0.01) following a one-way ANCOVA correcting for age and microangiopathy scoring and a Bonferroni post-hoc correction.Conclusion: The study findings suggest that AD is associated with a slowing of the cerebrovascular response in the temporal and parietal cortices.

KW - Alzheimer's disease

KW - Cerebral blood flow regulation

KW - Cerebrovascular reactivity

KW - Magnetic resonance imaging

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U2 - 10.1017/cjn.2020.30

DO - 10.1017/cjn.2020.30

M3 - Article

C2 - 32051047

AN - SCOPUS:85084180702

SN - 0317-1671

VL - 47

SP - 366

EP - 373

JO - Canadian Journal of Neurological Sciences

JF - Canadian Journal of Neurological Sciences

IS - 3

ER -

Slowed Temporal and Parietal Cerebrovascular Response in Patients with Alzheimer's Disease

Abstract

Keywords

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