The Role of Cerebrovascular Disease on Cognitive and Functional Status and Psychosis in Severe Alzheimer's Disease.
The pathophysiology behind psychosis in patients with Alzheimer's disease (AD) remains unknown. Recently, vascular risk factors have been recognized as important modifiers of the clinical presentation of AD.



The purpose of our study is to investigate the mechanism through which vascular risk factors mediate psychosis and whether or not it involves cerebrovascular lesions.



Data was provided by the National Alzheimer's Coordinating Centre. The Uniform Data Set was used to collect information on subject-reported history of vascular risk factors, clinician-reported state of cognitive performance, and presence of psychosis based on the Neuropsychiatric Inventory Questionnaire (NPI-Q). The Neuropathology Data Set was used to evaluate the presence of vascular lesions and the severity of AD pathology. Subjects with high probability of AD based on the NIA/AA Reagan criteria were included in the analysis.



We identified 1,459 patients with high probability of AD and corresponding NPI-Q scores. We confirmed the association between hypertension and diabetes on psychosis, specifically in delusions and the co-occurrence of delusions and hallucinations. Furthermore, the presence of white matter rarefaction based on pathological evaluation was associated with hallucinations. A history of vascular risk factors was positively associated with vascular lesions. However, vascular lesions in the presence of vascular risk factors did not increase the likelihood of psychosis. Furthermore, vascular lesions were not associated with greater cognitive or functional impairments in this group with severe AD pathology.



Vascular risk factors and vascular lesions are independently associated with psychosis in patients with severe AD. However, vascular lesions are not the mechanism through which vascular risk factors mediate psychosis.
Keenan Research Centre for Biomedical Research, the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.|Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
Julia
J
Kim
Keenan Research Centre for Biomedical Research, the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.|Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.|Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.|Department of Surgery, Division of Neurosurgery, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.|Division of Neurosurgery, St. Michael's Hospital, Toronto, ON, Canada.
Tom A
TA
Schweizer
Keenan Research Centre for Biomedical Research, the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.|Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Corinne E
CE
Fischer
Keenan Research Centre for Biomedical Research, the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.|Division of Pathology, St. Michael's Hospital, Toronto, ON, Canada.
David G
DG
Munoz
D000368:Aged; D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D001921:Brain / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D048909:Diabetes Complications / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D016631:Lewy Bodies / Q000473:pathology; D008297:Male; D011618:Psychotic Disorders / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D012307:Risk Factors; D011795:Surveys and Questionnaires
Cerebrovascular diseases; delusions; dementia; hallucinations; infarction; neuropathology; pathology; risk factors; vascular
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