Table 2.

Summary of most cited articles of predictors of conversion from mild cognitive impairment to Alzheimer’s disease. These studies were based in a clinic based cohort of persons with mild cognitive impairment (PI: D. Devanand)

Study [Ref]	Participants/design	Exposures/outcomes	Findings
MH Tabert, JJ Manly, X Liu, GH Pelton, S Rosenblum, M Jacobs, D Zamora, M Goodkind, K Bell, Y Stern, DP Devanand (2006) Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment. [7]	148 patients reporting memory problems and 63 group-matched controls. Patients were followed up semiannually and controls annually	Subtypes of MCI were determined by using demographically adjusted regression norms on neuropsychological tests. Survival analysis was used to identify the most predictive neuropsychological measures. The outcome was a consensus diagnosis of probable AD	At baseline, 108 patients met criteria for amnestic MCI: 87 had memory plus other cognitive domain deficits and 21 had pure memory deficits. The mean duration of follow-up for the 148 patients was 46.6 ± 24.6 months. In 3 years, 32 (50.0%) of 64 amnestic-“plus” and 2 (10.0%) of 20 “pure” amnestic patients converted to AD (p = 0.001). In 148 patients, of 5 a priori predictors, the percent savings from immediate to delayed recall on the SRT and the WAIS-R Digit Symbol were the strongest predictors of time to conversion. From the entire neuropsychological test battery, a stepwise selection procedure retained 2 measures in the final model: total immediate recall on the SRT (OR per 1-point decrease, 1.10; 95% CI, 1.05–1.14; p = 0.0001) and WAIS-R Digit Symbol coding (OR, 1.06; 95% CI, 1.01–1.11; p = 0.01). The combined predictive accuracy of these 2 measures for conversion by 3 years was 86%
DP Devanand, G Pradhaban, X Liu, A Khandji, S DeSanti, Segal, H Rusinek, GH Pelton, LS Honig, R Mayeux, Y Stern, MH Tabert, MJ de Leon (2007) Hippocampal and entorhinal atrophy in mild cognitive impairment: prediction of Alzheimer disease. [9]	Baseline brain MRI was done in 139 patients with MCI, broadly defined, and 63 healthy controls followed for an average of 5 years (range 1 to 9 years)	Exposures: Hippocampal and entorhinal cortex volumes from brain MRI. Outcomes: Conversion to AD	Hippocampal and entorhinal cortex volumes were each largest in controls, intermediate in MCI non-converters, and smallest in MCI converters to AD (37 of 139 patients converted to AD). In separate Cox proportional hazards models, covarying for intracranial volume, smaller hippocampal volume (RR 3.62, 95% CI 1.93, 6.80, p < 0.0001) and entorhinal cortex volume (RR 2.43, 95% CI 1.56, 3.79, p < 0.0001) each predicted time to conversion to AD. Similar results were obtained for hippocampal and entorhinal cortex volume in patients with MCI with MMSE ≥27/30 (21% converted to AD), and in the subset of patients with amnestic MCI (35% converted to AD). In the total patient sample, when both hippocampal and entorhinal volume were entered into an age-stratified Cox model with gender, MMSE, education, and intracranial volume, smaller hippocampal volume (RR 2.21, 95% CI 1.14, 4.29, p < 0.02) and entorhinal cortex volume (RR 2.48, 95% CI 1.54, 3.97, p < 0.0002) predicted time to conversion to AD. Similar results were obtained in a Cox model that also included SRT delayed recall and WAIS-R Digit Symbol as predictors. Based on logistic regression models in the 3-year follow-up sample, for a fixed specificity of 80%, the sensitivities for MCI conversion to AD were as follows: age 43.3%, MMSE 43.3%, age + MMSE 63.7%, age + MMSE + SRT delayed recall + WAIS-R Digit Symbol 80.6% (79.6% correctly classified), hippocampus + entorhinal cortex 66.7%, age + MMSE + hippocampus + entorhinal cortex 76.7% (85% correctly classified), age + MMSE + SRT delayed recall + WAIS-R Digit Symbol + hippocampus + entorhinal cortex 83.3% (86.8% correctly classified)

AD, Alzheimer’s disease; MCI, mild cognitive impairment; MMSE, Mini-Mental Status Exam; MRI, magnetic resonance imaging; OR, odds ratio; RR, risk ratio; SRT, Selective Reminding Test; WAIS-R Digit Symbol, Wechsler Adult Intelligence Scale–Revised Digit Symbol Test.