Cerebral small vessel disease and cognitive impairment

Abstract

Cerebral small vessel disease (SVD) is manifested as lacunar infarcts (LI) and white matter changes (WMC). Compared to Caucasians, studies have consistently shown a larger burden of SVD among Asians. Today, SVD is considered to be the major cause of vascular cognitive impairment (VCI) and vascular dementia (VaD). There are four studies in this thesis, each addressing an important aspect of this disease. The first study investigated the relationship between hyperhomocysteinemia and volumetric WMC in lacunar stroke patients. We found that hyperhomocysteinemia accounted for a small but significant amount of WMC volume variance (adjusted R2 = 0,058, p In the second study we compared two brief bedside screening tests, the Frontal Assessment Battery and Mattis Dementia Rating Scale Initiation/Perseveration subset, in their ability to discriminate lacunar stroke patients from healthy controls. Both tests were found to be equally excellent in this regard. We also identified the tests items that can be incorporated in the future development of better screening tests for VCI. In the third project we investigated the rate and determinants for cognitive decline up to 3 years after lacunar stroke. We found that a quarter of these patients experienced decline. Interestingly, we showed that markers of AD pathology such as medial temporal lobe atrophy and APOE &egr; 4 allele, but not baseline SVD markers, predicted this longitudinal decline. Our fourth study was the first double-blind, randomized placebo-controlled trial to investigate the efficacy and safety of rivastigimine in Chinese subcortical VaD patients. Although we did not find any cognitive benefits with this drug, we showed trends in behavioral symptoms improvement in the treated group. This pilot study has provided the basis for future larger investigation to evaluate its effects upon behavioral symptoms in subcortical VaD patients. In conclusion, VCI associated with SVD is a prevalent health problem in Chinese. It is my hope that results of these studies will not only contribute to the diagnosis and management for these patients in our country, but also add useful information to generate future research in order to fulfill an ultimate goal of ameliorating the burden of this disease worldwide.