Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer's disease.

TitleCombining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2008
AuthorsDevanand DP, Liu X, Tabert MH, Pradhaban G, Cuasay K, Bell K, de Leon MJ, Doty RL, Stern Y, Pelton GH
JournalBiol Psychiatry
Volume64
Issue10
Pagination871-9
Date Published2008 Nov 15
ISSN1873-2402
KeywordsAdult, Aged, Aged, 80 and over, Algorithms, Alzheimer Disease, Cognition Disorders, Disease Progression, Female, Hippocampus, Humans, Longitudinal Studies, Male, Middle Aged, Neuropsychological Tests, Predictive Value of Tests, ROC Curve, Sensitivity and Specificity, Statistics as Topic, Statistics, Nonparametric
Abstract

BACKGROUND: The utility of combining early markers to predict conversion from mild cognitive impairment (MCI) to Alzheimer's Disease (AD) remains uncertain.

METHODS: Included in the study were 148 outpatients with MCI, broadly defined, followed at 6-month intervals. Hypothesized baseline predictors for follow-up conversion to AD (entire sample: 39/148 converters) were cognitive test performance, informant report of functional impairment, apolipoprotein E genotype, olfactory identification deficit, and magnetic resonance imaging (MRI) hippocampal and entorhinal cortex volumes.

RESULTS: In the 3-year follow-up patient sample (33/126 converters), five of eight hypothesized predictors were selected by backward and stepwise logistic regression: Pfeffer Functional Activities Questionnaire (FAQ; informant report of functioning), University of Pennsylvania Smell Identification Test (UPSIT; olfactory identification), Selective Reminding Test (SRT) immediate recall (verbal memory), MRI hippocampal volume, and MRI entorhinal cortex volume. For 10% false positives (90% specificity), this five-predictor combination showed 85.2% sensitivity, combining age and Mini-Mental State Examination (MMSE) showed 39.4% sensitivity; combining age, MMSE, and the three clinical predictors (SRT immediate recall, FAQ, and UPSIT) showed 81.3% sensitivity. Area under ROC curve was greater for the five-predictor combination (.948) than age plus MMSE (.821; p = .0009) and remained high in subsamples with MMSE > or = 27/30 and amnestic MCI.

CONCLUSIONS: The five-predictor combination strongly predicted conversion to AD and was markedly superior to combining age and MMSE. Combining the clinically administered measures also led to strong predictive accuracy. If independently replicated, the findings have potential utility for early detection of AD.

DOI10.1016/j.biopsych.2008.06.020
Alternate JournalBiol Psychiatry
PubMed ID18723162
PubMed Central IDPMC2613777
Grant ListR01AG177601 / AG / NIA NIH HHS / United States
P50 AG008702 / AG / NIA NIH HHS / United States
R37 MH035636 / MH / NIMH NIH HHS / United States
P01 AG007232 / AG / NIA NIH HHS / United States
P30 AG08051 / AG / NIA NIH HHS / United States
R01 MH035636 / MH / NIMH NIH HHS / United States
P50 AG08702 / AG / NIA NIH HHS / United States
P01 AG007232-200011 / AG / NIA NIH HHS / United States
MH35636 / MH / NIMH NIH HHS / United States
R01AG12101 / AG / NIA NIH HHS / United States
P30 AG008051 / AG / NIA NIH HHS / United States
R01 AG017761 / AG / NIA NIH HHS / United States
R01 AG012101 / AG / NIA NIH HHS / United States
MH55735 / MH / NIMH NIH HHS / United States
MH55646 / MH / NIMH NIH HHS / United States
R01 AG017761-12 / AG / NIA NIH HHS / United States
R01 MH055735 / MH / NIMH NIH HHS / United States
Related Institute: 
Brain Health Imaging Institute (BHII)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065