Association Between Gas-Free Cerebrovascular Reactivity (CVR) and Cognitive Function in Older Adults With a High Risk for Vascular Dementia

Abstract

Background: Vascular cognitive impairment and dementia (VCID) is the second leading cause of dementia. Cerebrovascular reactivity (CVR) is a promising biomarker for VCID. However, CVR is not commonly measured in clinical practice due to logistical difficulties in applying a hypercapnia challenge during MR imaging. Purpose: To investigate whether CVR measured by intermittent breath modulation (bm-CVR) without hypercapnia gas-inhalation can be a sensitive biomarker in VCID. Study Type: Prospective cohort study. Subjects: Eighty-two participants (aged 66.8 ± 6.8 years, 54 females, 28 males) with normal cognition (N = 36), mild cognitive impairment (MCI, N = 37), or mild dementia (N = 9). Field strength/Sequence: 3.0 T; Blood-oxygenation-level-dependence (BOLD) MRI. Assessment: CVR was measured with BOLD MRI using intermittent breath modulation. Cognitive function was measured with Montreal Cognitive Assessment (MoCA) score, cognitive domains scores, and a global composite cognitive score. Physical function was measured with gait-speed and chair-stand test scores. Statistical Tests: Multi-linear regression models were performed within the participants to test the associations between bm-CVR and measures of cognitive and physical functions. A p value < 0.05 was considered significant. Bonferroni multiple comparison correction was performed when multiple cognitive domains were tested. Results: Whole-brain bm-CVR values were significantly associated with the diagnosis group of normal, MCI, and early dementia (β = −3.00%/mm Hg, 95% confidence interval (CI) [−5.42, −0.58]), and were lower in the impaired participants relative to participants with normal cognition (β = −2.18, CI [−3.91, −0.45]). Bm-CVR was positively associated with global cognition measured by both MoCA (β = 14.73, CI [1.74, 27.73]) and composite cognitive score (β = 2.22, CI [0.77, 3.66]). For domain-specific cognitive scores, bm-CVR was significantly associated with processing speed (β = 3.19, CI [1.36, 5.02]) and language (β = 2.81, CI [0.70, 4.94]), but not with executive function (p = 0.43) or episodic memory (p = 0.79). Data Conclusion: Bm-CVR is a sensitive biomarker for VCID. This gas-free CVR method may be a more practical approach than hypercapnia gas-inhalation CVR for characterizing vascular pathology. Evidence Level: 2. Technical Efficacy: Stage 2.