Brain Advance Access originally published online on September 18, 2007
Brain 2007 130(11):2830-2836; doi:10.1093/brain/awm228
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Identification of Alzheimer and vascular lesion thresholds for mixed dementia
Departments of 1Geriatrics and 2Psychiatry, University of Geneva School of Medicine, Geneva and 3Division of Old Age Psychiatry, University of Lausanne School of Medicine, Lausanne, Switzerland
Correspondence to: Dr Gabriel Gold, Department of Rehabilitation and Geriatrics, University of Geneva Hospitals, 1226 Thônex, Switzerland or Dr Panteleimon Giannakopoulos, Department of Psychiatry, University of Geneva Hospitals, 1225 Chêne-Bourg, Switzerland E-mail: gabriel.gold{at}hcuge.ch or panteleimon.giannakopoulos{at}hcuge.ch
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.
Key Words: Alzheimer's disease; cognition; lacunar infarction; subcortical dementia; vascular dementia
Abbreviations: NFT, neurofibrillary tangles; CMI, cortical microinfarcts; CAA, cerebral amyloid angiopathy
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Received May 24, 2007. Revised August 10, 2007. Accepted August 23, 2007.
*These authors contributed equally to this work.
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