Determinants, MRI Correlates, and Prognosis of Mild Cognitive Impairment: The Rotterdam Study

Mild cognitive impairment (MCI) marks a transitional stage between healthy aging and dementia, but the understanding of MCI in the general population remains limited. We investigated determinants, MRI-correlates, and prognosis of MCI within the population-based Rotterdam Study. Firstly, we studied age, APOE-epsilon 4 carriership, waist circumference, hypertension, diabetes mellitus, total and HDL-cholesterol levels, smoking, and stroke as potential determinants of MCI. Determinants were assessed cross-sectionally at baseline (2002-2005) and up to 7 years prior to baseline (1997-2001). Secondly, we compared volumetric, microstructural, and focal MRI-correlates in persons with and without MCI. Thirdly, we followed participants for incident dementia and mortality until 2012. Out of 4,198 participants, 417 had MCI, of whom 163 amnestic and 254 non-amnestic MCI. At baseline, older age, APOE-epsilon 4 carriership, lower total cholesterol levels, and stroke were associated with MCI. Additionally, lower HDL-cholesterol levels and smoking were related to MCI when assessed 7 years prior to baseline. Persons with MCI, particularly those with non-amnestic MCI, had larger white matter lesion volumes, worse microstructural integrity of normal-appearing white matter, and a higher prevalence of lacunes, compared to cognitively healthy participants. MCI was associated with an increased risk of dementia (hazard ratio (HR) 3.98, 95% confidence interval (CI) 2.97;5.33), Alzheimer's disease (HR 4.03, 95% CI 2.92;5.56), and mortality (HR 1.54, 95% CI 1.28;1.85). In conclusion, we found that several vascular risk factors and MRI-correlates of cerebrovascular disease were related to MCI in the general population. Participants with MCI had an increased risk of dementia, including Alzheimer's disease, and mortality.