Extension and refinement of the predictive value of different classes of markers in ADNI: Four-year follow-up data

Background: This study examined the predictive value of different classes of markers in the progression from mild cognitive impairment (MCI) to Alzheimer\u27s disease (AD) over an extended 4-year follow-up in the Alzheimer\u27s Disease Neuroimaging Initiative (ADNI) database. Methods: MCI patients were assessed for clinical, cognitive, magnetic resonance imaging (MRI), positron emission tomography-fluorodeoxyglucose (PET-FDG), and cerebrospinal fluid (CSF). markers at baseline and were followed on a yearly basis for 4 years to ascertain progression to AD. Logistic regression models were fitted in clusters, including demographics, APOE genotype, cognitive markers, and biomarkers (morphometric, PET-FDG, CSF, amyloid-beta, and tau). Results: The predictive model at 4 years revealed that two cognitive measures, an episodic memory measure and a Clock Drawing screening test, were the best predictors of conversion (area under the curve = 0.78). Conclusions: This model of prediction is consistent with the previous model at 2 years, thus highlighting the importance of cognitive measures in progression from MCI to AD. Cognitive markers were more robust predictors than biomarkers. (C) 2014 The Alzheimer\u27s Association. All rights reserved

Psychosis in Alzheimer\u27s Disease is Associated with Frontal Metabolic Impairment and Accelerated Decline in Working Memory: Findings from the Alzheimer\u27s Disease Neuroimaging Initiative

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\u27s 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