Baseline hippocampal vascular reactivity predicts conversion to mild cognitive impairment: an analysis of the SPRINT‐MIND study

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AbstractBackgroundAlzheimer’s disease (AD) is characterized by gradual decline to mild cognitive impairment (MCI) and dementia. Vascular risk factors contribute to cognitive decline suggesting that maintaining cerebrovascular health could slow disease progression. Vascular reactivity, a measure of blood vessel elasticity and arterial stiffness, provides a quantitative neurobiological measure of cerebrovascular health. In the present study, we hypothesized that higher hippocampal and whole‐brain gray matter vascular reactivity would be associated with lower rate of conversion to MCI.Method518 participants enrolled in Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension (SPRINT‐MIND) study were selected for the current analyses. Participant structural MRI and vascular reactivity measures were included in the current analyses. Vascular reactivity was derived from a 16‐second breath‐holding BOLD fMRI scan. MCI conversion was determined by an expert panel from cognitive assessments. Cox proportional hazards model was used to test if disease progression was associated with hippocampal or whole‐brain gray matter vascular reactivity adjusting for age, sex, education, and treatment assignment (intensive vs. mild BP control). Entorhinal cortex and parahippocampal gyrus control regions were also tested.ResultParticipant demographics are presented in Table 1. Median follow‐up was 5.36 years (IQR=2.11), median time‐to‐MCI was 2.04 years (IQR=0.46). Hippocampal vascular reactivity was significantly associated with conversion to MCI (hazard ratio (HR)=0.52 per 1% ΔCBF/1mm Hg CO2, 95% confidence interval (CI):(0.21,0.84)); this association did not differ by treatment group. Hippocampal volumes were also significantly associated with conversion to MCI (HR=0.58 per 1cm3, 95% CI:(0.36, 0.92)), but there was no correlation between vascular reactivity and volume, and hippocampal volumes did not confound the relationship between vascular reactivity and conversion. Whole‐brain gray matter vascular reactivity was associated with conversion to MCI (HR=0.60 per 1% ΔCBF/1mm Hg CO2, 95% CI:(0.42,0.86)). There were no associations between the control regions and conversion (HR(entorhinal cortex)=0.9 per 1% ΔCBF/1mm Hg CO2, 95% CI: (0.75,1.08); HR(parahippocampus)=0.96 per 1% ΔCBF/1mm Hg CO2, 95% CI: (0.90,1.01)).ConclusionBaseline hippocampal and whole‐brain gray matter vascular reactivity is associated with MCI progression, such that those with more vessel elasticity and less arterial stiffness converted to MCI at a significantly lower rate.