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Psychosis in Alzheimer disease—mechanisms, genetics and therapeutic opportunities
Open accessAbstract
Psychosis is a common and distressing symptom in people with Alzheimer disease, and few safe and effective treatments are available. However, new approaches to symptom assessment and treatment are beginning to drive the field forward. New nosological perspectives have been provided by incorporating the emergence of psychotic symptoms in older adults - even in advance of dementia - into epidemiological and neurobiological frameworks as well as into diagnostic and research criteria such as the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders, the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) research criteria for psychosis in neurodegenerative disease, and the ISTAART criteria for mild behavioural impairment. Here, we highlight the latest findings in genomics, neuroimaging and neurobiology that are informing approaches to drug discovery and repurposing. Current pharmacological and non-pharmacological treatment options are discussed, with a focus on safety and precision medicine. We also explore trial data for pimavanserin, a novel agent that shows promise for the treatment of psychosis in people with dementia, and discuss existing agents that might be useful but need further exploration such as escitalopram, lithium, cholinesterase inhibitors and vitamin D. Although the assessment and management of psychosis in people with dementia remain challenging, new opportunities are providing direction and hope to the field.
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“Methylphenidate, a dopamine transporter blocker that increases dopamine levels, seems to show mild improvement in apathy, the most prevalent disorder among the neuropsychiatric symptoms of AD [73].”
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Lapid, M. I., & Ho, J. B. (2020) · International Psychogeriatrics · doi:10.1017/s1041610219001352 · Cited by 7
Sex differences in the association of mild behavioral impairment with cognitive agingPreprint
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Self-citationGill, S., Wang, M., Forkert, N. D., MacMaster, F. P., Smith, E. E., & Ismail, Z. (2019) · Neurology · doi:10.1212/wnl.92.15_supplement.p5.1-025 · Cited by 6
Self-citationHypertension and Neuropsychiatric Symptoms in Patients with Drug-Naïve Alzheimer's Disease
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Self-citation
Research works printed but not linked: 2
- Nathan, S., Gill, S. & Ismail, Z. in Alzheimer’s Association International Conference (ALZ, 2020).
- Lussier, F. et al. Mild behavioral impairment is associated with beta-amyloid and tau across the alzheimer’s disease spectrum. J. Cereb. Blood Flow. Metab. 39, 158–159 (2019).
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Self-citation
Metadata
- Authors
- Ismail, Z., Creese, B., Aarsland, D., Kales, H. C., Lyketsos, C. G., Sweet, R. A., & Ballard, C.
- Affiliations
- University of Calgary (CA)
- University of Exeter (GB)
- King's College London (GB)
- University of California Davis Medical Center (US)
- Johns Hopkins University (US)
- University of Pittsburgh (US)
- Corresponding author
- Ballard, Clive
- ORCID
- Venue
- Nature Reviews Neurology
- Published
- 2022-01-04
- Volume
- 18
- Issue
- 3
- Pages
- 131-144
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- PMC
- PMC9074132
- OpenAlex
- W4205106947
- Cited by
- 189
- References
- 179
- Citations by year
- 2026: 24 · 2025: 47 · 2024: 61 · 2023: 32 · 2022: 25
- FWCI
- 7.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Reviews Neurology (publishedVersion, other-oa)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Brunel University Research Archive (BURA) (Brunel University London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Biogen
- Fondation Brain Canada
- Sunovion
- National Football League Players Association
- Eisai
- Astellas Pharma
- Servier
- H. Lundbeck A/S
- Genentech
- National Institute on Aging (P30AG066468, P30AG066507)
- National Institute of Mental Health (R01MH116046)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- dementia, drug repurposing, pimavanserin, escitalopram, lithium, cholinesterase inhibitors, vitamin D, non-pharmacological treatment, precision medicine, neuroimaging, neurobiology of psychosis
- MeSH terms
- Aged, Alzheimer Disease, Humans, Psychotic Disorders, Neurodegenerative Diseases, Neurocognitive Disorders, Neuroimaging
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