Corinne E Fischer1,2, Winnie Qian1,3, Tom A Schweizer1,3,4,5,6, Colleen P Millikin7, Zahinoor Ismail8, Eric E Smith8, Lisa M Lix9, Paul Shelton10, David G Munoz1,11,12. 1. Keenan Research Centre for Biomedical Research, The Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada. 2. Faculty of Medicine, Department of Psychiatry, University of Toronto, Canada. 3. Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada. 4. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada. 5. Division of Neurosurgery, Department of Surgery, Faculty of Medicine, University of Toronto, ON, Canada. 6. Division of Neurosurgery, St. Michael's Hospital, Toronto, ON, Canada. 7. Department of Clinical Healthy Psychology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada. 8. Departments of Psychiatry and Neurology, Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. 9. Department of Community Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB, Canada. 10. Division of Neurology, Department of Medicine, University of Manitoba, Winnipeg, MB, Canada. 11. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. 12. Division of Pathology, St. Michael's Hospital, Toronto, ON, Canada.
Abstract
BACKGROUND: The neuropathological correlates of psychosis in Alzheimer's disease (AD) is unclear, with some studies reporting a correlation between psychosis and increased AD pathology while others have found no association. OBJECTIVE: To determine the demographic, clinical, and neuropathological features associated with psychotic symptoms in clinically attributed and neuropathologically proven AD. METHOD: We separately reviewed two overlapping groups of clinically diagnosed (cAD) AD patients with neuropathology data and neuropathologically definite (npAD) cases (regardless of clinical diagnosis) from the NACC database, and explored the relationships between psychosis and clinical variables, neuropathologic correlates, and vascular risk factors. Delusions and hallucinations, defined according to the NPI-Q, were analyzed separately. RESULTS: 1,073 subjects in the database fulfilled our criteria (890 cAD and 728 npAD patients). 34% of cAD and 37% of npAD had psychotic symptoms during their illness. Hallucinations were associated with greater cognitive and functional impairments on the MMSE and CDR, while delusional patients showed less impairment on CDR, consistent across cAD and npAD groups. Burden of AD pathology appears to relate to presence of psychotic symptoms in the clinical AD group, but this result is not confirmed in the neuropathologically confirmed group suggesting the findings in the clinical group were due to misdiagnosis of AD. Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors, including a history of hypertension and diabetes, were associated with the development of psychosis. METHOD: Vascular and Lewy body pathologies and vascular risk factors are important modifiers of the risk of psychosis in AD.
BACKGROUND: The neuropathological correlates of psychosis in Alzheimer's disease (AD) is unclear, with some studies reporting a correlation between psychosis and increased AD pathology while others have found no association. OBJECTIVE: To determine the demographic, clinical, and neuropathological features associated with psychotic symptoms in clinically attributed and neuropathologically proven AD. METHOD: We separately reviewed two overlapping groups of clinically diagnosed (cAD) ADpatients with neuropathology data and neuropathologically definite (npAD) cases (regardless of clinical diagnosis) from the NACC database, and explored the relationships between psychosis and clinical variables, neuropathologic correlates, and vascular risk factors. Delusions and hallucinations, defined according to the NPI-Q, were analyzed separately. RESULTS: 1,073 subjects in the database fulfilled our criteria (890 cAD and 728 npAD patients). 34% of cAD and 37% of npAD had psychotic symptoms during their illness. Hallucinations were associated with greater cognitive and functional impairments on the MMSE and CDR, while delusionalpatients showed less impairment on CDR, consistent across cAD and npAD groups. Burden of AD pathology appears to relate to presence of psychotic symptoms in the clinical AD group, but this result is not confirmed in the neuropathologically confirmed group suggesting the findings in the clinical group were due to misdiagnosis of AD. Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors, including a history of hypertension and diabetes, were associated with the development of psychosis. METHOD: Vascular and Lewy body pathologies and vascular risk factors are important modifiers of the risk of psychosis in AD.
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