Brain Advance Access originally published online on January 31, 2007
Brain 2007 130(3):731-739; doi:10.1093/brain/awl385
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Profiles of neuropsychological impairment in autopsy-defined Alzheimer's disease and cerebrovascular disease
1University of California, Davis, 2VA Northern California Health Care System, 3University of California, San Francisco, 4University of California, Los Angeles, 5University of Southern California and 6University of California, Berkeley, CA, USA
Corresponding author: Dr R. Reed, UCD-Alzheimer's Disease Center, 150 Muir Rd (127A), Martinez, CA 94553, USA E-mail: brreed{at}ucdavis.edu
Differentiating the cognitive effects of cerebrovascular disease, particularly small vessel disease, from those of Alzheimer's disease is a difficult clinical challenge. An influential model of how subcortical cerebrovascular disease causes cognitive dysfunction posits that damage to frontostriatal loops impairs frontal lobe function, leading to predominant impairment of executive function and secondary impairments of associated cognitive functions such as memory. Consistent with this, neuropsychological studies of clinically diagnosed patients have reported that individuals with vascular dementia do better on memory tests and worse on executive function tests compared with patients with Alzheimer's disease. This observation has led to the suggestion that predominant cognitive executive dysfunction might serve as a useful diagnostic marker for vascular dementia. We sought to test this idea in a series of cases with autopsy-defined pathologies. Subjects were 62 autopsied cases from a prospective study of vascular contributions to dementia. Using neuropathological features alone, 23 were diagnosed with Alzheimer's disease (AD), 11 with cerebrovascular disease (CVD), 9 with both (mixed pathology) and 19 with normal elderly brain (NEB). Three psychometrically matched composite scales of different cognitive abilities were used: Verbal Memory, Nonverbal Memory and Executive Function. Analysis of group data showed that for Alzheimer's disease memory scores were lower than Executive Function by nearly a standard deviation on average. In contrast, and contrary to the model, CVD was rather equally impaired on Executive Function, Verbal Memory and Nonverbal Memory. Individual patterns of cognitive impairment were examined by defining three profiles based on reliable differences between neuropsychological scores to characterize cases with predominant memory impairment, predominant executive dysfunction, and ‘other’ patterns. Analysis of individual impairment profiles showed that predominant memory impairment was present in 71% of Alzheimer's disease while predominant executive dysfunction described only 45% of CVD. A stronger pattern emerged when cognitively normal cases were excluded; among the six cognitively impaired CVD patients four had predominant executive dysfunction and none had predominant memory impairment. This report, comprised of a substantial sample of autopsy confirmed cases, delineates the patterns of neuropsychological impairment associated with small vessel cerebrovascular disease and Alzheimer's disease While the findings show that memory loss usually exceeds executive dysfunction in patients with Alzheimer's disease, the reverse is not the case in CVD. Taken as a whole, the results indicate that the cognitive effects of the small vessel cerebrovascular disease are variable and not especially distinct, thus raising question about the utility of executive impairment as a diagnostic marker for vascular dementia.
Key Words: Alzheimer's disease; vascular dementia; memory performance; executive control; neuropathology
Abbreviations: DRS, Dementia Rating Scale; CERAD, Consortium to Establish a Registry for Alzheimer's Disease; CVDPS, cerebrovascular disease parenchymal pathology score; HS, hippocampal sclerosis; AD, Alzheimer's disease, defined by pathology; CVD, cerebrovascular disease, defined by pathology; NEB, normal elderly brain, defined by pathology
Received September 1, 2006. Revised December 5, 2006. Accepted December 18, 2006.
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