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Advanced cerebral amyloid angiopathy and small vessel disease are associated with psychosis in Alzheimer’s disease
  1. Audun Osland Vik-Mo1,2,
  2. János Bencze3,
  3. Clive Ballard4,
  4. Tibor Hortobágyi5,6,
  5. Dag Aarsland2,7
  1. 1 Department of Clinical Science, University of Bergen, Bergen, Norway
  2. 2 Centre for Age-Related Diseases (SESAM), Stavanger University Hospital, Stavanger, Norway
  3. 3 Division of Neuropathology, Institute of Pathology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
  4. 4 University of Exeter Medical School, Exeter, UK
  5. 5 MTA-DE Cerebrovascular and Neurodegenerative Research Group, University of Debrecen, Debrecen, Hungary
  6. 6 Institute of Pathology, Faculty of Medicine, University of Szeged, Szeged, Hungary
  7. 7 Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK
  1. Correspondence to Dr Audun Osland Vik-Mo, Department of Clinical Science, University of Bergen, Bergen 5007, Norway; auvikmo{at}

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Psychotic symptoms may occur in any dementia, including Alzheimer’s disease (AD), but are particularly common in Lewy body dementia (LBD). The mechanisms of psychotic symptoms are largely unknown. Psychosis has been found to be associated with more severe AD and Lewy body pathology in patients with AD and cerebrovascular disease-related vasculopathy.1 One form of vascular pathology, cerebral amylod angiopathy (CAA), is defined as deposits of amyloid in the vessel walls that increase risk of haemorrhage and ischaemia. CAA contributes to neurodegeneration, but its relation to clinical symptoms and course in dementia is not fully understood.2

The aim of this study was to investigate the postmortem pathological correlates of severe psychotic symptoms in moderate AD and LBD, which were followed annually from the time of diagnosis until death.


This is a 12-year prospective follow-up study of dementia ending in neuropathological examination. The 223 patients of the dementia study in Western Norway (Demvest) were diagnosed as mild dementia and followed annually with standardised clinical assessments until death. Patient were diagnosed according to standardised clinical criteria for AD3 and DLB4 or Parkinson's disease dementia (PDD) (both combined as LBD) and mild dementia defined as Mini Mental Status Examination (MMSE) score of at least 20 or a Clinical Dementia Rating scale(CDR) global score=1. The procedures are described in detail elsewhere.5 All comparisons are between groups are based on pathological defined diagnosis.

The validated Norwegian 12-item Neuropsychiatric Inventory (NPI) was used to assess neuropsychiatric symptoms. Presence of severe psychosis was based on the first 5 years after diagnosis and MMSE value above 10. NPI score of >4 on either item 1 (delusions) or 2 (hallucinations) was used as clinical significant cut-off.

Brain dissection, …

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  • Contributors Study concept and design: all authors. Gathering of data: AOV-M, TH, JB and DA. Analysis and interpretation of data: AOV-M, TH, CB and DA. Drafting of the manuscript: AOV-M and DA. Critical revision of the manuscript: all authors.

  • Funding This study was funded by Norwegian Health Association. This paper represents independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

  • Competing interests AOV-M, JB and TH declare that they have no conflict of interest. CB has received grants and personal fees from Acadia and Lundbeck, personal fees Heptares, Roche, Lilly, Otsuka, Orion, GSK and Pfizer. DA has received research support and/or honoraria from Astra-Zeneca, H Lundbeck, Novartis Pharmaceuticals and GE Health and serves as paid consultant for H Lundbeck, Eisai and Axovant.

  • Patient consent Obtained.

  • Ethics approval The regional committee for medical and health research ethics in western Norway approved of the study (REK 2010/633). All patients signed informed consent to participate in the study. 

  • Provenance and peer review Not commissioned; externally peer reviewed.