Cerebral Vasoreactivity, Apolipoprotein E, and the Risk of Dementia

Objective Cerebral vasoreactivity (CVR) is a key factor in maintenance of continuous cerebral perfusion and a marker of (micro)vascular damage. We aimed to determine the longitudinal relation between CVR and the risk of dementia in the general population. Approach and Results We determined CVR in nondemented participants who underwent transcranial Doppler with induced hypercapnia from 1997 to 1999, as part of the ongoing population-based Rotterdam Study. We used a Cox model to determine the risk of dementia in relation to CVR, adjusted for age, sex, cardiovascular risk factors, and carotid intima-media thickness. We furthermore determined decline on a cognitive test battery in relation to CVR, using linear mixed models. Among 1629 participants (meanSD age 70.6 +/- 6.2 years, 46.2% female) with a mean follow-up of 11.5 years, 209 were diagnosed with dementia, of whom 171 had Alzheimer disease. Higher CVR at baseline was associated with lower risk of dementia (adjusted hazard ratio, 95% confidence interval, per SD increase: 0.87, 0.75-1.00) and Alzheimer disease (adjusted hazard ratio, 0.84; 0.71-0.99). This association was more profound in APOE epsilon 4 carriers than in noncarriers (adjusted hazard ratio for all dementia: 0.77, 0.60-0.98 versus 0.89, 0.73-1.07). Performance on cognitive tests at baseline was better with higher CVR (g-factor: P=0.02), but during 3 cognitive assessments over 11 years of follow-up, higher CVR at baseline was associated with less decline in test scores on the Stroop reading and interference tasks in APOE epsilon 4 carriers only (P=0.01 and 0.02, respectively). Conclusions Impaired CVR is associated with an increased risk of dementia in the general population.