Neurovascular Decoupling Is Associated With Lobar Intracerebral Hemorrhages and White Matter Hyperintensities

Abstract

Background: Neurovascular coupling is a fundamental aspect of brain function by regulating cerebral blood flow in response to regional neuronal activity. Increasing evidence suggest neurovascular decoupling occurs early in the progression of Alzheimer disease (AD), potentially reflecting early vascular damage. Therefore, understanding the relationship between neurovascular coupling and established vascular risk factors for AD is essential to gain deeper insights into the vascular mechanisms underlying AD.

Methods: This cross-sectional observational study investigated the association between neurovascular coupling and vascular risk factors for AD, specifically small vessel disease magnetic resonance imaging markers, cardiovascular risk factors, and the apolipoprotein E genotype. The cohort included 119 participants diagnosed with subjective cognitive impairment, mild cognitive impairment, and AD-related dementia, as well as individuals without cognitive complaints. Neurovascular coupling was measured by blood-oxygen-level-dependent functional magnetic resonance imaging amplitude in response to visual stimulation.

Results: Our findings revealed that decreased neurovascular coupling is linked to structural brain changes typically seen in small vessel disease; specifically we found an association between neurovascular coupling and white matter hyperintensities load (β=-0.199, P=0.030) and presence of lobar intracerebral hemorrhage (β=-0.228, P=0.011).

Conclusions: This raises the suggestion that a decreased neurovascular coupling in the disease process of AD is related to comorbid small vessel disease.

Keywords: Alzheimer disease; cerebral amyloid angiopathy; functional magnetic resonance imaging; neurovascular coupling; small vessel disease.

Figure 1. Scatterplot of the neurovascular coupling parameter BOLD amplitude plotted on the y‐axis against WMHs load plotted on the x‐axis.

Lower BOLD amplitude is associated with larger WMH volume (β=−0.199, P=0.030) in the whole study sample. BOLD indicates blood‐oxygen‐level‐dependent; and WMHs, white matter hyperintensities.

Figure 2. Boxplot of the neurovascular coupling parameter BOLD amplitude plotted on the y‐axis and presence of lobar ICH plotted as a dichotomous variable on the x‐axis.

Lower BOLD amplitude is associated with the presence of lobar ICH (β=−0.228, P=0.011) in the whole study sample. BOLD indicates blood‐oxygen‐level‐dependent; and ICH, intracerebral hemorrhage.

Figure 3. Scatterplots of the neurovascular coupling parameter BOLD amplitude plotted on the y‐axis against WMHs load plotted on the x‐axis for the (A) non‐CAA subgroup and (B) CAA subgroup.

In the non‐CAA subgroup (A), BOLD amplitude is not significantly associated with WMHs load (β=−0.116, P=0.274). In the CAA subgroup (B), lower BOLD amplitude is significantly associated with larger WMH volume (β=−0.370, P=0.046). BOLD indicates blood‐oxygen‐level‐dependent; CAA, cerebral amyloid angiopathy; and WMHs, white matter hyperintensities.