Spontaneous Cerebrovascular Reactivity at Rest in Older Adults with and Without Mild Cognitive Impairment and Memory Deficits

Overview

Journal medRxiv

Date 2024 Jul 1

PMID 38946941

Authors

Allison C Engstrom

John Paul Alitin

Arunima Kapoor

Shubir Dutt

Trevor Lohman

Isabel J Sible

Anisa J Marshall

Fatemah Shenasa

Aimee Gaubert

Farrah Ferrer

Amy Nguyen

David Robert Bradford

Kathleen Rodgers

Lorena Sordo

Elizabeth Head

Xingfeng Shao

Danny Jj Wang

Daniel A Nation

Affiliations

Soon will be listed here.

Abstract

Background: Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment.

Methods: 161 older adults free of dementia or major neurological/psychiatric disorders were recruited. Participants underwent clinical interviews, cognitive testing, venipuncture for Alzheimer's biomarkers, and brain MRI. Spontaneous CVR was quantified during 5 minutes of rest.

Results: Whole brain CVR was negatively associated with age, but not MCI. Lower CVR in the parahippocampal gyrus (PHG) was found in participants with MCI and was linked to worse memory performance on memory tests. Results remained significant after adjusting for Alzheimer's biomarkers and vascular risk factors.

Conclusion: Spontaneous CVR deficits in the PHG are observed in older adults with MCI and memory impairment, indicating medial temporal microvascular dysfunction's role in cognitive decline.

References

Marshall O, Lu H, Brisset J, Xu F, Liu P, Herbert J . Impaired cerebrovascular reactivity in multiple sclerosis. JAMA Neurol. 2014; 71(10):1275-81. PMC: 4376108. DOI: 10.1001/jamaneurol.2014.1668. View

Kannurpatti S, Motes M, Biswal B, Rypma B . Assessment of unconstrained cerebrovascular reactivity marker for large age-range FMRI studies. PLoS One. 2014; 9(2):e88751. PMC: 3923811. DOI: 10.1371/journal.pone.0088751. View

Verheggen I, de Jong J, van Boxtel M, Gronenschild E, Palm W, Postma A . Increase in blood-brain barrier leakage in healthy, older adults. Geroscience. 2020; 42(4):1183-1193. PMC: 7394987. DOI: 10.1007/s11357-020-00211-2. View

Zlokovic B, Gottesman R, Bernstein K, Seshadri S, McKee A, Snyder H . Vascular contributions to cognitive impairment and dementia (VCID): A report from the 2018 National Heart, Lung, and Blood Institute and National Institute of Neurological Disorders and Stroke Workshop. Alzheimers Dement. 2020; 16(12):1714-1733. DOI: 10.1002/alz.12157. View

Lipp I, Murphy K, Caseras X, Wise R . Agreement and repeatability of vascular reactivity estimates based on a breath-hold task and a resting state scan. Neuroimage. 2015; 113:387-96. PMC: 4441043. DOI: 10.1016/j.neuroimage.2015.03.004. View

Sible I, Yew B, Dutt S, Li Y, Blanken A, Jang J . Selective vulnerability of medial temporal regions to short-term blood pressure variability and cerebral hypoperfusion in older adults. Neuroimage Rep. 2022; 2(1). PMC: 9249026. DOI: 10.1016/j.ynirp.2022.100080. View

Mokhber N, Shariatzadeh A, Avan A, Saber H, Babaei G, Chaimowitz G . Cerebral blood flow changes during aging process and in cognitive disorders: A review. Neuroradiol J. 2021; 34(4):300-307. PMC: 8447819. DOI: 10.1177/19714009211002778. View

Kapoor A, Yew B, Jang J, Dutt S, Li Y, Alitin J . Older adults with perivascular spaces exhibit cerebrovascular reactivity deficits. Neuroimage. 2022; 264:119746. PMC: 10033456. DOI: 10.1016/j.neuroimage.2022.119746. View

Tarawneh R, Kasper R, Sanford J, Phuah C, Hassenstab J, Cruchaga C . Vascular endothelial-cadherin as a marker of endothelial injury in preclinical Alzheimer disease. Ann Clin Transl Neurol. 2022; 9(12):1926-1940. PMC: 9735377. DOI: 10.1002/acn3.51685. View

10.

Clark L, Delano-Wood L, Libon D, McDonald C, Nation D, Bangen K . Are empirically-derived subtypes of mild cognitive impairment consistent with conventional subtypes?. J Int Neuropsychol Soc. 2013; 19(6):635-45. PMC: 3742806. DOI: 10.1017/S1355617713000313. View

11.

Duering M, Biessels G, Brodtmann A, Chen C, Cordonnier C, de Leeuw F . Neuroimaging standards for research into small vessel disease-advances since 2013. Lancet Neurol. 2023; 22(7):602-618. DOI: 10.1016/S1474-4422(23)00131-X. View

12.

Nation D, Delano-Wood L, Bangen K, Wierenga C, Jak A, Hansen L . Antemortem pulse pressure elevation predicts cerebrovascular disease in autopsy-confirmed Alzheimer's disease. J Alzheimers Dis. 2012; 30(3):595-603. PMC: 3370943. DOI: 10.3233/JAD-2012-111697. View

13.

Bondi M, Edmonds E, Jak A, Clark L, Delano-Wood L, McDonald C . Neuropsychological criteria for mild cognitive impairment improves diagnostic precision, biomarker associations, and progression rates. J Alzheimers Dis. 2014; 42(1):275-89. PMC: 4133291. DOI: 10.3233/JAD-140276. View

14.

Tarumi T, Zhang R . Cerebral blood flow in normal aging adults: cardiovascular determinants, clinical implications, and aerobic fitness. J Neurochem. 2017; 144(5):595-608. PMC: 5874160. DOI: 10.1111/jnc.14234. View

15.

Liu P, De Vis J, Lu H . Cerebrovascular reactivity (CVR) MRI with CO2 challenge: A technical review. Neuroimage. 2018; 187:104-115. PMC: 6150860. DOI: 10.1016/j.neuroimage.2018.03.047. View

16.

Cantin S, Villien M, Moreaud O, Tropres I, Keignart S, Chipon E . Impaired cerebral vasoreactivity to CO2 in Alzheimer's disease using BOLD fMRI. Neuroimage. 2011; 58(2):579-87. DOI: 10.1016/j.neuroimage.2011.06.070. View

17.

Wardlaw J, Smith E, Biessels G, Cordonnier C, Fazekas F, Frayne R . Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013; 12(8):822-38. PMC: 3714437. DOI: 10.1016/S1474-4422(13)70124-8. View

18.

Clark A, Weigand A, Bangen K, Merritt V, Bondi M, Delano-Wood L . Repetitive mTBI is associated with age-related reductions in cerebral blood flow but not cortical thickness. J Cereb Blood Flow Metab. 2020; 41(2):431-444. PMC: 8369996. DOI: 10.1177/0271678X19897443. View

19.

Sepehrband F, Barisano G, Sheikh-Bahaei N, Choupan J, Cabeen R, Lynch K . Volumetric distribution of perivascular space in relation to mild cognitive impairment. Neurobiol Aging. 2021; 99:28-43. PMC: 7902350. DOI: 10.1016/j.neurobiolaging.2020.12.010. View

20.

Jahanian H, Christen T, Moseley M, Pajewski N, Wright C, Kurella Tamura M . Measuring vascular reactivity with resting-state blood oxygenation level-dependent (BOLD) signal fluctuations: A potential alternative to the breath-holding challenge?. J Cereb Blood Flow Metab. 2016; 37(7):2526-2538. PMC: 5531349. DOI: 10.1177/0271678X16670921. View