Association of cerebrovascular reactivity and Alzheimer pathologic markers with cognitive performance

Objective To determine whether MRI-based cerebrovascular reactivity (CVR) can predict cognitive performance independent of Alzheimer’s pathological markers, we studied the relationship between cognition, CVR, and CSF-derived Aâ42 and Tau in a group of elderly individuals with mixed Alzheimer’s and vascular cognitive impairment and dementia. Methods A cross-sectional study of 72 participants, aged 69±8 years, consisting of individuals with normal cognition (n=28) and cognitive impairment (n=44) (including 36 mild cognitive impairment, MCI, and 8 mild dementia). CVR was measured with hypercapnia-MRI. Whole-brain CVR (% BOLD per mmHg of EtCO2) was used to estimate vasodilatory capacity. Montreal Cognitive Assessment (MoCA), cognitive domains scores, and a global composite cognitive score were obtained. AD biomarkers included CSF assays of Aâ42 and Tau. Results Whole-brain CVR was lower in the impaired (mean±SE, 0.132±0.006%/mmHg) compared to the normal (0.151±0.007%/mmHg) group (β= -0.02 %/mmHg; 95% CI, -0.038 to -0.001). After adjusting for CSF Aβ42 and tau, higher whole-brain CVR was associated with better performance on the MoCA (β=29.64, 95% CI, 9.94 to 49.34) and with a global composite cognitive score (β=4.32, 95% CI, 0.05 to 8.58). When comparing the CVR marker with Fazekas score based on white-matter-hyperintensities and Vascular-Risk-Score in a single regression model predicting the MoCA, only CVR revealed a significant effect (β=28.09, 95% CI, 6.14 to 50.04), while the other two measures were not significant. Conclusions CVR was significantly associated with cognitive performance independent of AD pathology. Whole-brain CVR may be a useful biomarker for evaluating cognitive impairment related to vascular disease in older individuals. Classification of Evidence: This study provides Class II evidence that CVR was significantly associated with cognitive performance independent of AD pathology.