Impact of Vascular Risk Factors, Axial Medial Temporal Atrophy, White Matter Hyperintensity on Cognitive Outcome in Alzheimer's Diseases

ABSTRACT

BACKGROUND: There is epidemiologic evidence to support vascular disease as a possible cause of Alzheimer's dementia (AD). The primary aim of this study was to determine the prevalence of vascular risk factors (vRFs) with respect to various clinical measures, such as axial-rated medial temporal lobe atrophy (MTA), ischemic white-matter changes, and cognition. The secondary aim was to determine the most significant clinical measure associated with cognitive outcome. METHODS: The study subjects comprised 198 probable AD and 38 subjective memory impairment-no cognitive impairment controls (SMI-NCI), for whom medical data including history vRF-related blood tests, clinical dementia evaluation, cognitive assessment, and brain MRI, were available. The grading of white-matter hyperintensities (WMHs) was achieved using Fazekas' method. MTA was graded by two neurologists independently based on axial T1-weighted MRI images. The prevalence of risk factors for Koreans aged > or =65 years was reviewed for comparison. RESULTS: All vRFs except smoking were more severe in the AD group than in both the SMI-NCI group and Koreans aged > or =65 years, but the high prevalence of vRFs had no impact on WMH lesions, axial MTA, or cognitive outcome. Both white-matter changes and MTA were significantly worse in AD than in SMI-NCI (p<0.001). The degree of MTA was negatively correlated with WMH grade (p<0.001), but the severity of clinical dementia was correlated only with increased axial MTA in AD (Instrumental Activities of Daily Living and Clinical Dementia Rating scores, p<0.001; Clinical Dementia Rating-Sum of Boxes score, p<0.005). CONCLUSIONS: WMHs and axial MTA were significantly more severe in the AD group than in the SMI-NCI subjects. The findings of this study indicate that worsening of cognitive dysfunction in AD appears to be driven by MTA, which is evident even in axial MTA visual grading, irrespective of WMH severity and the presence of vRFs.