Cerebrovascular Reactivity Predicts Cognitive Impairment Independent of AD

MRI of the blood vessels in the brain and cerebrovascular disease. brain stroke x-ray image.
MRI-based cerebrovascular reactivity is associated with cognitive function independent of Alzheimer disease pathology.

Magnetic resonance imaging (MRI)-based cerebrovascular reactivity (CVR) may predict cognitive function independent of Alzheimer disease pathology, according to study results published in Neurology.

Previous studies have suggested that CVR can be used to measure vessel perfusion reserve as a potential marker for vascular cognitive impairment and dementia. The objective of the study was to assess whether MRI-based CVR in elderly patients with known mild cognitive impairment (MCI), mild dementia, and normal cognition can predict cognitive performance independent of Alzheimer pathology.

Researchers assessed CVR using a procedure based on the inhalation of a gas enriched in carbon dioxide, while continuously acquiring BOLD MR images. Cognitive status was assessed using the Montreal Cognitive Assessment (MoCA), cognitive domains scores, and a global composite cognitive score. Cerebrospinal fluid (CSF) was collected and samples were analyzed for CSF Aβ42 and tau. The T2 FLAIR images were reviewed to generate Fazekas scores, which quantified white matter hyperintensities. Researchers calculated Vascular Risk Score based on several vascular risk factors, including hypertension, hypercholesterolemia, diabetes, smoking, and obesity.

The study included 72 patients (mean age, 69 years; 40 women), including 28 with normal cognitive function and 44 with impaired cognitive function (mild cognitive impairment or dementia). In participants with normal cognitive function, whole-brain CVR was higher than those with impaired cognitive function (mean 0.151 vs 0.132 mmHg, respectively).

After adjustment for age, sex, and education, the data showed a positive association between whole-brain CVR and MoCA (P =.003), as well as composite cognitive score (P =.020). With regard to individual cognitive domains, higher whole-brain CVR was associated with better performance in language domain score (P =.016), but not executive function, episodic memory, or processing speed.

The association between whole-brain CVR and MoCA (β=29.69, 95% CI, 9.81-49.56; P =.004), as well as composite cognitive scores (β=4.39, 95% CI, 0.331-8.45; P =.035) remained significant after adjustment for Fazekas score, age, sex, education, and CSF Aβ42 and tau. There was no significant association between Vascular Risk Score or Fazekas score with CVR, MoCA, or composite cognitive score.

The study had several limitations, including the modest sample size, limited range of vascular pathology in study participants, exclusion of patients with prior cardiovascular or neurologic events, additional unmeasured vascular risk factors, and the possibility that CVR actually reflects other pathologic mechanisms of dementia.

“CVR was more sensitive in predicting cognition compared to white matter hyperintensities or vascular risk factors. CVR is a promising candidate biomarker for cognitive impairment due to vascular diseases,” the researchers concluded.


Sur S, Lin Z, Li Y, et al. Association of cerebrovascular reactivity and Alzheimer pathologic markers with cognitive performance. Neurology. Published online July 13, 2020. doi:10.1212/WNL.0000000000010133