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The enigma of vascular cognitive disorder and vascular dementia

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Abstract

The prevalence, morphology and pathogenesis of vascular dementia (VaD), recently termed vascular cognitive impairment, are a matter of discussion, and currently used clinical diagnostic criteria show moderate sensitivity (average 50%) and variable specificity (range 64–98%). In Western clinic-based series, VaD is suggested in 8–10% of cognitively impaired aged subjects. Its prevalence in autopsy series varies from 0.03 to 58%, with reasonable values of 8–15%, while in Japan it is seen in 22–35%. Neuropathologic changes associated with cognitive impairment include multifocal and/or diffuse disease and focal lesions: multi-infarct encephalopathy, white matter lesions or arteriosclerotic subcortical (leuko)encephalopathy, multilacunar state, mixed cortico-subcortical type, borderline/watershed lesions, rare granular cortical atrophy, post-ischemic encephalopathy and hippocampal sclerosis. They result from systemic, cardiac and local large or small vessel disease. Recent data indicate that cognitive decline is commonly associated with widespread small ischemic/vascular lesions (microinfarcts, lacunes) throughout the brain with predominant involvement of subcortical and functionally important brain areas. Their pathogenesis is multifactorial, and their pathophysiology affects neuronal networks involved in cognition, memory, behavior and executive functioning. Vascular lesions often coexist with Alzheimer disease (AD) and other pathologies. Minor cerebrovascular lesions, except for severe amyloid angiopathy, appear not essential for cognitive decline in full-blown AD, while both mild Alzheimer pathology and small vessel disease may interact synergistically. The lesion pattern of “pure” VaD, related to arteriosclerosis and microangiopathies, differs from that in mixed-type dementia (AD with vascular encephalopathy), more often showing large infarcts, which suggests different pathogenesis of both types of lesions. Due to the high variability of cerebrovascular pathology and its causative factors, no validated neuropathologic criteria for VaD are available, and a large variability across laboratories still exists in the procedures for morphologic examination and histology techniques.

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Acknowledgments

The study was supported by the Society for the Support of Research in Experimental Neurology, Vienna, Austria. The author thanks the medical staff of many Vienna hospitals for the clinical and autopsy reports and brain material. Special thanks are due to Mrs. V. Rappelsberger for excellent laboratory work and Mr. E. Mitter-Ferstl, PhD, for secretarial and computer work.

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  1. Institute of Clinical Neurobiology, Kenyongasse 18, 1070, Vienna, Austria

    Kurt A. Jellinger

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After a lecture at the XI International Congress of Neuropathology, San Francisco, CA, on 11 September 2006.

Addendum

In a recent clinicopathological evaluation of 79 autopsy cases derived from a prospective longitudinal study of subcortical ischemic vascular disease (SIVD) and Alzheimer disease (AD), Chui et al. [555] found significant cerebrovascular lesions (CVL) in 30%, AD pathology in 54%, and hippocampal sclerosis (HS) in 18%. Statistical assessment showed that all three pathology variables contributed independently to cognitive status, but only the neuritic Braak scores contributed significantly to cognitive impairment, indicating that advancing AD pathology overwhelms the effects of the two other factors that, in the absence of considerable AD, contribute to mild cognitive impairment. A recent histologic-neuroimaging study in two patients with SIVD showed correspondence between subinsular T2 hyperintensive lesions and demyelination, gliosis, and dilated perivascular spaces [556].

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Jellinger, K.A. The enigma of vascular cognitive disorder and vascular dementia. Acta Neuropathol 113, 349–388 (2007). https://doi.org/10.1007/s00401-006-0185-2

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