Morphologic diagnosis of vascular dementia - A critical update

Vascular dementia/vascular cognitive impairment (VaD/VCI) is not a single entity, but a large group of conditions characterized by various clinical and morphological findings and variable pathophysiology. Clinical diagnostic criteria show moderate sensitivity (50-70%) and variable specificity (64-98%). Epidemiological studies are hampered by the lack of clear and validated diagnostic criteria, the complexity of brain pathologies, ethnic and geographic variations. In Western clinic-based series VaD/VCI is suggested in 8-15% of cognitively impaired aged subjects, with age-standardized incidence ratios 0.42-2.6 and clinical prevalence at age 70+ of 6-15/1000 person/ year. Prevalence in,autopsy series ranges from 0.03 to 58% (real mean 8-15% in Western series, 22-35% in Japan). Both prevalence and incidence increase with age. Neuropathology shows multifocal and/or diffuse lesions, ranging from lacunes and microinfarcts, white matter lesions, hippocampal sclerosis to multi-infarct encephalopathy, mixed cortico-subcortical and diffuse post-ischemic lesions. They result from systemic, cardiac, local large and small vessel disease. Pathogenesis is multifactorial and cognitive decline is commonly associated with small ischemic/vascular lesions, often involving subcortical and strategically important brain areas (thalamus, frontobasal, limbic system). Pathophysiology affects neuronal networks involved in cognition, behavior, execution and memory. Vascular lesions often coexist with Alzheimer disease (AD) and other lesions, multiple pathologies greatly increasing the odds of dementia; 25-80% of demented subjects show both AD and cerebrovascular lesions. While both factors by synergistic interaction contribute significantly to the risk of dementia, AD pathology is often less severe in the presence of vascular lesions. Due to the heterogeneity of cerebrovascular pathology and its causative factors, no validated neuropathologic criteria for VaD are currently available, and a large variability across laboratories still exists in morphologic examination procedures and techniques. Harmonization of neuropathologic procedures and evaluation criteria in future prospective clinico-pathologic studies are needed to validate diagnostic criteria for VaD and to clarify the impact of vascular lesions on cognition. (c) 2008 Elsevier B.V. All rights reserved.