Association of cerebrovascular reactivity and Alzheimer pathologic markers with cognitive performance
Sandeepa Sur, Zixuan Lin, Yang Li, Sevil Yaşar, Paul B. Rosenberg, Abhay Moghekar, Xirui Hou, Rita R. Kalyani, Kaisha Hazel, George Pottanat, Cuimei Xu, Peter C.M. van Zijl, Jay J. Pillai, Peiying Liu, Marilyn Albert, Hanzhang Lu
Abstract
<h3>Objective</h3> To determine whether MRI-based cerebrovascular reactivity (CVR) can predict cognitive performance independently of Alzheimer pathologic markers, we studied the relationship between cognition, CVR, and CSF-derived β-amyloid<sub>42</sub> (Aβ<sub>42</sub>) and tau in a group of elderly individuals with mixed Alzheimer and vascular cognitive impairment and dementia. <h3>Methods</h3> This was a cross-sectional study of 72 participants 69 ± 8 years of age consisting of individuals with normal cognition (n = 28) and cognitive impairment (n = 44) (including 36 with mild cognitive impairment [MCI] and 8 with mild dementia). CVR was measured with hypercapnia-MRI. Whole-brain CVR (percent blood oxygen level–dependent per 1 mm Hg Etco<sub>2</sub>) was used to estimate vasodilatory capacity. Montreal Cognitive Assessment (MoCA) scores, cognitive domains scores, and a global composite cognitive score were obtained. AD biomarkers included CSF assays of Aβ<sub>42</sub> and tau. <h3>Results</h3> Whole-brain CVR was lower in the impaired (mean ± SE, 0.132 ± 0.006%/mm Hg) compared to the normal (0.151 ± 0.007%/mm Hg) group (β = −0.02%/mm Hg; 95% confidence interval [CI] −0.038 to −0.001). After adjustment for CSF Aβ<sub>42</sub> and tau, higher whole-brain CVR was associated with better performance on the MoCA (β = 29.64, 95% CI 9.94–49.34) and with a global composite cognitive score (β = 4.32, 95% CI 0.05–8.58). When the CVR marker was compared with the Fazekas score based on white matter hyperintensities and vascular risk-score in a single regression model predicting the MoCA score, only CVR revealed a significant effect (β = 28.09, 95% CI 6.14–50.04), while the other 2 measures were not significant. <h3>Conclusions</h3> CVR was significantly associated with cognitive performance independently of AD pathology. Whole-brain CVR may be a useful biomarker for evaluating cognitive impairment related to vascular disease in older individuals. <h3>Classification of evidence</h3> This study provides Class II evidence that CVR was significantly associated with cognitive performance independent of AD pathology.