Journal
AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
Volume 22, Issue 7, Pages 698-707Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jagp.2012.10.028
Keywords
Alzheimer disease; psychosis; working memory; frontal; hypofrontality
Categories
Funding
- ADNI (National Institutes of Health) [U01 AG024904]
- National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering
- Abbott
- AstraZeneca AB
- Bayer Schering Pharma AG
- Bristol-Myers Squibb
- Eisai Global Clinical Development
- Elan Corporation
- Genentech
- GE Healthcare
- GlaxoSmithKline
- Innogenetics
- Johnson and Johnson
- Eli Lilly and Co.
- Medpace, Inc.
- Merck and Co., Inc.
- Novartis AG
- Pfizer Inc.
- F. Hoffman-La Roche
- Schering-Plough
- Synarc, Inc.
- National Institutes of Health [P30 AG010129, K01 AG030514]
- Dana Foundation
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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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