title: Lewy Bodies, Vascular Risk Factors, and Subcortical Arteriosclerotic Leukoencephalopathy, but not Alzheimer Pathology, are Associated with Development of Psychosis in Alzheimer's Disease.
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.
  
  
  METHODS
  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.
  
  
  METHODS
  Vascular and Lewy body pathologies and vascular risk factors are important modifiers of the risk of psychosis in AD.
authors.affiliation: Keenan Research Centre for Biomedical Research, The Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.|Faculty of Medicine, Department of Psychiatry, University of Toronto, Canada.
authors.forename: Corinne E
authors.initials: CE
authors.lastname: Fischer
authors.affiliation: 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.
authors.forename: Winnie
authors.initials: W
authors.lastname: Qian
authors.affiliation: 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.|Division of Neurosurgery, Department of Surgery, Faculty of Medicine, University of Toronto, ON, Canada.|Division of Neurosurgery, St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: Tom A
authors.initials: TA
authors.lastname: Schweizer
authors.affiliation: Department of Clinical Healthy Psychology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Colleen P
authors.initials: CP
authors.lastname: Millikin
authors.affiliation: Departments of Psychiatry and Neurology, Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Zahinoor
authors.initials: Z
authors.lastname: Ismail
authors.affiliation: Departments of Psychiatry and Neurology, Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Smith
authors.affiliation: Department of Community Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Lix
authors.affiliation: Division of Neurology, Department of Medicine, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Shelton
authors.affiliation: 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.
authors.forename: David G
authors.initials: DG
authors.lastname: Munoz
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000523:psychology*; D003072:Cognition Disorders / Q000209:etiology*; D016208:Databases, Factual / Q000706:statistics & numerical data; D015140:Dementia, Vascular / Q000209:etiology*; D005260:Female; D006470:Hemorrhage; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000209:etiology*; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires
keywords: Alzheimer’s disease; arteriosclerotic leukoencephalopathy; delusion; hallucination; neuropathology; psychosis; vascular pathology