Cerebral Vasoreactivity, Apolipoprotein E, and the Risk of Dementia: A Population-Based Study

Arterioscler Thromb Vasc Biol. 2016 Jan;36(1):204-10. doi: 10.1161/ATVBAHA.115.306768. Epub 2015 Nov 19.

Abstract

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 (mean ± SD 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 APOEε4 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 APOEε4 carriers only (P=0.01 and 0.02, respectively).

Conclusions: Impaired CVR is associated with an increased risk of dementia in the general population.

Keywords: Alzheimer disease; apolipoprotein E; dementia; epidemiology; hypercapnia; vasoreactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apolipoprotein E4 / genetics*
  • Cerebrovascular Circulation*
  • Cognition
  • Dementia / epidemiology*
  • Dementia / genetics
  • Dementia / physiopathology
  • Disease-Free Survival
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Humans
  • Kaplan-Meier Estimate
  • Linear Models
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Odds Ratio
  • Phenotype
  • Proportional Hazards Models
  • Risk Factors
  • Stroop Test
  • Time Factors
  • Ultrasonography, Doppler, Transcranial

Substances

  • Apolipoprotein E4
  • Genetic Markers