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Neurobiology of Delusions in Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is associated with cognitive and functional impairment as well as neuropsychiatric sequelae, including psychotic symptoms such as delusions and hallucinations. Strong evidence supports the need to study delusions separate from hallucinations. Integrating the epidemiology, clinical correlates, and neuropathological and genetic literature for delusions in AD allows us to speculate on etiology and mechanisms. Plaque and tangle deposition in individuals with susceptible alleles of serotonergic, muscarinic, nicotinic, or Apoε4 genes appears to result in disruption of cortical circuitry, culminating in delusions. While delusions in AD correspond to a phenotype distinct from AD without delusions, subtypes of delusions may also define further distinct clinical entities. Persecutory delusions may occur earlier in the illness and have a more significant genetic component than misidentification delusions, which are associated with increased cognitive impairment and advanced dementia. Clearly distinguishing between these two syndromes is essential to making progress in the area of delusions in AD.

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Acknowledgments

Dr. Mulsant has served on boards for the Center for Addiction and Mental Health (CAMH) and the CAMH Foundation and has received grant support from the National Institutes of Health and the Canadian Institutes of Health Research.

Dr. Mamo has received grant support from the National Institute of Mental Health and the Canadian Institute of Health Research.

Disclosure

Dr. Mulsant has received donations of medication for use in National Institutes of Health–funded clinical trials from Bristol-Myers Squibb, Pfizer, and Wyeth and previously held stock in AkzoNobel, Alkermes, AstraZeneca, Biogen Idec, Celsion Corp., Elan Corp., Eli Lilly and Company, Forest Laboratories, Orchestra Therapeutics, and Pfizer.

Dr. Mamo has received grant support from Pfizer.

Drs. Ismail, Fischer, and Schweizer, and Minh-Quan Nguyen reported no potential conflicts of interest relevant to this article.

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Authors and Affiliations

  1. Centre for Addiction and Mental Health, Geriatric Mental Health Program, University of Toronto, 1001 Queen St W, Toronto, Ontario, M6J 1H4, Canada

    Zahinoor Ismail, Minh-Quan Nguyen, Benoit H. Mulsant & David Mamo

  2. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

    Corinne E. Fischer, Benoit H. Mulsant & David Mamo

  3. Mental Health Service/Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada

    Corinne E. Fischer

  4. Keenan Research Centre of the Li Ka Shing Knowledge Institute and the Division of Neurosurgery, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada

    Tom A. Schweizer

  5. Department of Psychiatry, University of Calgary, 1403 29 St NW, Calgary, Alberta, T2N 2T9, Canada

    Zahinoor Ismail

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  1. Zahinoor Ismail
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  2. Minh-Quan Nguyen
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  5. Benoit H. Mulsant
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Correspondence to Zahinoor Ismail.

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Ismail, Z., Nguyen, MQ., Fischer, C.E. et al. Neurobiology of Delusions in Alzheimer’s Disease. Curr Psychiatry Rep 13, 211–218 (2011). https://doi.org/10.1007/s11920-011-0195-1

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