title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Litwin Zucker Alzheimer's Research Center, Manhasset, NY. Electronic address: jkoppel@nshs.edu.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Koppel
authors.affiliation: Litwin Zucker Alzheimer's Research Center, Manhasset, NY.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Sunday
authors.affiliation: Litwin Zucker Alzheimer's Research Center, Manhasset, NY.
authors.forename: Terry E
authors.initials: TE
authors.lastname: Goldberg
authors.affiliation: Litwin Zucker Alzheimer's Research Center, Manhasset, NY.
authors.forename: Peter
authors.initials: P
authors.lastname: Davies
authors.affiliation: Litwin Zucker Alzheimer's Research Center, Manhasset, NY.
authors.forename: Erica
authors.initials: E
authors.lastname: Christen
authors.affiliation: Litwin Zucker Alzheimer's Research Center, Manhasset, NY.
authors.forename: Blaine S
authors.initials: BS
authors.lastname: Greenwald
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology* / Q000523:psychology; D016022:Case-Control Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D005625:Frontal Lobe / Q000378:metabolism* / Q000503:physiopathology; D059907:Functional Neuroimaging; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D008570:Memory, Short-Term; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011618:Psychotic Disorders / Q000150:complications / Q000378:metabolism* / Q000523:psychology
chemical_list: D019788:Fluorodeoxyglucose F18; D005947:Glucose
keywords: Alzheimer disease; frontal; hypofrontality; psychosis; working memory