Cortical and Subcortical Cerebrovascular Resistance Index in Mild Cognitive Impairment and Alzheimer's Disease

Article type: Research Article

Authors: Nation, Daniel A.^a | Wierenga, Christina E.^{a; b} | Clark, Lindsay R.^c | Dev, Sheena I.^c | Stricker, Nikki H.^{d; e} | Jak, Amy J.^{a; b} | Salmon, David P.^f | Delano-Wood, Lisa^{a; b} | Bangen, Katherine J.^b | Rissman, Robert A.^f | Liu, Thomas T.^g | Bondi, Mark W.^{a; b; *}

Affiliations: [a] Veterans Affairs San Diego Healthcare System, San Diego, CA, USA | [b] Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA | [c] San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA | [d] Veterans Affairs Boston Healthcare System, Boston, MA, USA | [e] Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA | [f] Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA | [g] Department of Radiology, University of California, San Diego, La Jolla, CA, USA

Correspondence: [*] Correspondence to: Mark W. Bondi, Ph.D., VA San Diego Healthcare System (116B), 3350 La Jolla Village Drive, San Diego, CA 92161, USA. E-mail: [email protected].

Abstract: Background:Reduced regional cerebral blood flow (rCBF) is a well-established finding in Alzheimer’s disease (AD), although fewer studies have examined the role of increased regional cerebrovascular resistance. By calculating the ratio of mean arterial pressure to rCBF, it is possible to estimate an index of regional cerebrovascular resistance (CVRi) that may be a sensitive measure of occult cerebrovascular disease. Objective:To compare probable AD patients to mild cognitive impairment (MCI) and normal control (NC) participants on CVRi, the ratio of mean arterial pressure to rCBF. Methods:Eighty-one participants (12 AD, 23 MCI, 46 NC) were compared on CVRi using voxel-wise analyses. Region-of-interest analyses examined correlations between subcortical CVRi and both cognition and white matter lesion (WML) volume. Results:Voxel-wise analyses revealed CVRi elevation in AD relative to NCs (subcortical, medial temporal, posterior cingulate, precuneus, inferior parietal, superior temporal) and MCI (subcortical, posterior cingulate). MCI participants exhibited intermediate CVRi values within cortical and medial temporal areas. Significant CVRi clusters were larger and more widespread than those of parallel CBF analyses. Among MCI and AD participants, subcortical CVRi elevation was associated with lower Dementia Rating Scale score (r = −0.52, p = 0.001, for both thalamus and caudate), and caudate CVRi correlated with WML volume (r = 0.45, p = 0.001). Conclusions:Cortical and subcortical CVRi is elevated in AD, particularly within the caudate and thalamus, where it is associated with decreased cognitive performance and increased WMLs. Findings suggest CVRi may play a role in cognitive decline and cerebrovascular disease in MCI and AD.

Keywords: Alzheimer's disease, cerebral blood flow, cerebrovascular resistance, mild cognitive impairment

DOI: 10.3233/JAD-130086

Journal: Journal of Alzheimer's Disease, vol. 36, no. 4, pp. 689-698, 2013