Psychosis in Alzheimer's disease is associated with frontal metabolic impairment and accelerated decline in working memory: findings from the Alzheimer's Disease Neuroimaging Initiative
Abstract
Objective An ascendant body of evidence suggests that Alzheimer disease with psychosis (AD+P) is a distinct variant of illness with its own genetic diathesis and a unique clinical course. Impaired frontal lobe function has been previously implicated in AD+P. The current exploratory study, presented in two parts, evaluates both the regional brain metabolic and psychometric correlates of psychosis in a longitudinal sample of subjects with AD, made available by the Alzheimer's Disease Neuroimaging Initiative (ADNI).Methods In Part 1 of the study, 21 ADNI participants with AD who developed psychotic symptoms during the study but were not psychotic at baseline were matched with 21 participants with AD who never became psychotic during the study period, and mean brain [F(18)]fluorodeoxyglucose positron emission tomography (FDG-PET) Cerebral metabolic rate for glucose (CMRgl) by regions of interest (ROIs) were compared Additionally, 39 participants with active psychosis at the time of image acquisition were matched with 39 participants who were never psychotic during the study period, and mean brain FDG-PET CMRgl by sROI were compared. In Part 2 of the study, 354 ADNI participants with AD who were followed for 24 months with serial psychometric testing were identified, and cognitive performance and decline were evaluated for correlation with psychotic symptoms.Results Part 1: There were no regional brain metabolic differences between those with AD destined to become psychotic and those who did not become psychotic. There was a significant reduction in mean orbitofrontal brain metabolism in those with active psychosis. Part 2: Over the course of study follow-up, psychosis was associated with accelerated decline in functional performance as measured by the Functional Assessment Questionnaire, the Mini-Mental State Examination, and Forward Digit Span.Conclusion In a sample drawn from the ADNI dataset, our exploratory FDG-PET findings and longitudinal cognitive outcomes support the hypofrontality model of AD+P. Focal frontal vulnerability may mediate the accelerated decline seen in AD+P.
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Delusions in Alzheimer's disease are associated with decreased gray matter volume, perfusion or metabolism in frontal cortex and anterior cingulate cortex.
“Delusions were associated with decreased gray matter (GM) volume, perfusion or metabolism in frontal cortex and ACC (Bruen et al., 2008; Koppel et al., 2014; Mega et al., 2000; Nakaaki et al., 2013; Rafii et al., 2011; Sultzer et al., 2003; Whitehead et al., 2012).”
From Neuropsychiatric symptoms in Alzheimer's disease: what might be associated brain circuits? (2015) · cites this paper as Koppel et al., 2014
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- Authors
- Koppel, J., Sunday, S., Goldberg, T. E., Davies, P., Christen, E., & Greenwald, B. S.
- Corresponding author
- Koppel, Jeremy
- Venue
- The American Journal of Geriatric Psychiatry
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 22
- Issue
- 7
- Pages
- 698-707
- ISSN
- 1064-7481 (ISSN-L)
- OpenAlex
- W2046090892
- Cited by
- 65
- References
- 41
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 1 · 2022: 6 · 2021: 4 · 2020: 6 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 5 · 2015: 6 · 2014: 7 · 2013: 2
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Geriatric Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5u01ag024904-10)
- National Institute on Aging (U01-AG-024904, P30AG010129, K01AG030514)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- frontal lobe hypometabolism, orbitofrontal cortex, brain glucose metabolism, FDG-PET, cognitive decline, functional performance
- MeSH terms
- Aged, Alzheimer Disease, Female, Frontal Lobe, Glucose, Humans, Longitudinal Studies, Male, Memory Disorders, Memory, Short-Term, Neuropsychological Tests, Psychotic Disorders, Case-Control Studies, Fluorodeoxyglucose F18, Positron-Emission Tomography, Functional Neuroimaging
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