Journal Article

Identification of Alzheimer and vascular lesion thresholds for mixed dementia

Gabriel Gold, Panteleimon Giannakopoulos, François R Herrmann, Constantin Bouras and Enikö Kövari

in Brain

Published on behalf of The Guarantors of Brain

Volume 130, issue 11, pages 2830-2836
Published in print November 2007 | ISSN: 0006-8950
Published online September 2007 | e-ISSN: 1460-2156 | DOI:
Identification of Alzheimer and vascular lesion thresholds for mixed dementia

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To explore the pathological substrates of mixed dementia, we performed a detailed analysis of lacunar and microvascular pathology in 156 autopsied, elderly individuals with various degrees of Alzheimer's disease (AD) pathology. Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale; neuropathological evaluation included Braak neurofibrillary tangle (NFT) and Aß-protein deposition staging and bilateral semi-quantitative assessment of microvascular ischaemic pathology and lacunes; statistics included univariate and multiple regression models controlling for age, and receiver-operating characteristic analysis. Sensitivity analysis was performed in a randomized derivation sub-sample and tested in a validation sub-sample. White matter lacunes, periventricular and diffuse white matter demyelination and focal and diffuse cortical gliosis were not associated with cognition. Braak NFT, Aß deposition, cortical microinfarcts (CMI) and thalamic and basal ganglia lacunes (TBGL) predicted 27% of CDR variability and 49% of the presence of dementia. Braak NFT, CMI and TBGL thresholds determined in a derivation sample yielded 0.88 sensitivity, 0.79 specificity and 0.85 correct classification rate for dementia in a validation sample. The same thresholds distinguished three groups of demented cases consistent with mixed dementia, pure vascular dementia and AD. These findings indicate that the clinical expression of the vascular component in mixed cases is highly dependent on lesion type and location as well as severity of concomitant AD-related pathology. Proposed thresholds for vascular and degenerative lesions predict the presence of dementia with great accuracy and provide a basis for distinguishing pure vascular dementia or AD from mixed cases.

Keywords: Alzheimer's disease; cognition; lacunar infarction; subcortical dementia; vascular dementia

Journal Article.  4438 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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