Cardiovascular risk factors, brain structure, and cognitive decline in old age : a population-based study

Sammanfattning: This doctoral thesis investigated the burden of cardiovascular risk factors among older adults (age ≥60 years) living in central Stockholm (Study I) and the associations of these risk factors with structural brain characteristics and cognitive decline in aging, taking genetic background (APOE gene) into account (Studies II, III, and IV). All studies in this thesis use data from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) and the embedded SNAC-K Magnetic Resonance Imaging (MRI) study. Study I investigated the distribution and control of major cardiometabolic risk factors in the SNAC-K population. Among older adults living in central Stockholm, the age- and sex-standardized prevalence of diabetes was 9.6%; obesity, 11.7%; high cholesterol, 48.6%; and hypertension, 76.4%. The prevalence of hypertension and diabetes increased with age, whereas the prevalence of obesity and high cholesterol decreased with age. Forty-nine percent of older adults had two or more of these factors. Overall, 55.5% of people with hypertension, 50.3% with diabetes, and 25.0% with high cholesterol received pharmacological treatment. Of those treated pharmacologically, 49.4% reached the therapeutic goals for hypertension; 38.1% for diabetes; and 85.5% for high cholesterol. Study II explored the cross-sectional associations between global white-matter hyperintensities (WMH) and brain volumes among SNAC-K MRI participants. Results suggest that the marker of cerebral small vessel diseases—a higher load of global WMH—was significantly associated with global cerebral atrophic markers (smaller gray-matter volume and larger ventricular volume) independent of age, major cardiovascular risk factors, and APOE gene. In contrast, the association between global WMH and hippocampal volume was no longer significant after adjusting for age. Study III examined the role of brain structure in the association between cardiovascular risk burden and cognitive decline in the SNAC-K and SNAC-K MRI cohorts. We found that higher cardiovascular risk burden, assessed by the Framingham General Cardiovascular Risk Score (FGCRS), was associated with faster annual decline rate in Mini-Mental State Examination (MMSE) score. Larger WMH and ventricular volume and smaller total gray-matter and hippocampal volume were all associated with accelerated MMSE decline; these links were stronger among APOE ε4 carriers than non-carriers. The association between FGCRS and MMSE decline largely disappeared when WMH volume was entered into the model together with gray-matter or ventricular volume. The association between FGCRS and global atrophic marker (gray-matter or ventricular volume) remained after WMH volume was entered into the model as a mediator. Study IV investigated the associations among cardiovascular risk factors, microstructural white-matter integrity, and cognitive decline in the SNAC-K MRI cohort. The results showed that heavy alcohol consumption, hypertension, and diabetes were significantly associated with reduced microstructural white-matter integrity (P <0.05), measured as lower fractional anisotropy (FA) or higher mean diffusivity (MD). After aggregating these three factors with current smoking (P <0.10), an increasing number of these factors was associated with decreasing FA and increasing MD, independent of WMH. Cardiovascular risk factors and the APOE ε4 allele interacted to negatively affect white-matter microstructure. Furthermore, reduced microstructural white-matter integrity was significantly associated with faster MMSE decline. Conclusion. Cardiovascular risk factors and clusters of such factors are common in older adults, and higher cardiovascular risk burden accelerates the rate of global cognitive decline. The association between cardiovascular burden and cognitive decline may reflect the harmful effects of cardiovascular risk burden on pathological brain aging, including microvascular lesions, atrophy, and reduced microstructural white-matter integrity. Carrying the APOE ɛ4 allele reinforces the adverse effect of cardiovascular risk burden on structural brain alterations and cognitive decline in aging.