2008 Articles

Combining Early Markers Strongly Predicts Conversion from Mild Cognitive Impairment to Alzheimer's Disease

Devanand, Davangere P.; Liu, Xinhua; Tabert, Matthias H.; Pradhaban, Gnanavalli; Cuasay, Katrina; Bell, Karen; de Leon, Mony J.; Doty, Richard L.; Stern, Yaakov; Pelton, Gregory H.

Background—The utility of combining early markers to predict conversion from mild cognitive impairment (MCI) to Alzheimer’s Disease (AD) remains uncertain. Methods—148 outpatients with MCI, broadly defined, were 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, 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: FAQ (informant report of functioning), UPSIT (olfactory identification), SRT immediate recall (verbal memory), MRI hippocampal volume, MRI entorhinal cortex volume. For 10% false positives (90% specificity), this five-predictor combination showed 85.2% sensitivity, combining age and MMSE showed 39.4% sensitivity, and 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 fivepredictor combination (0.948) than age plus MMSE (0.821; p =.0009), and remained high in subsamples with MMSE ≥ 27/30 and amnestic MCI. For the entire patient sample, based on dichotomizing estimated risk at 0.5, positive likelihood ratio was 16.8 (95% CI 6.4, 44.3) and negative likelihood ratio was 0.2 (95% CI 0.1, 0.4). Conclusions—The five-predictor combination strongly predicted conversion to AD and was markedly superior to combining age and MMSE. Combining only clinically administered measures also led to strong predictive accuracy. If independently replicated, the findings have potential utility for early detection of AD.