Premorbid cognitive testing predicts the onset of dementia and Alzheimer's disease better than and independently of APOE genotype

Objective: To determine whether a cognitive test package can predict the onset of dementia up to 11 years later, and the extent to which this prediction is independent of that provided by APOE genotype. Methods: Prospective cohort study based on 54 general practices in the UK; 657 survivors of the 1088 participants in the MRC treatment trial of hypertension in older adults were followed for up to 11 years; 370 participants (57% of survivors) were traced, screened for dementia, and genotyped for APOE in 1994. Baseline assessments included trail making test A, paired associated learning test, Raven's progressive matrices, and national adult reading test. At follow up, both mini-mental state examination and CAMCOG were used. Outcome measures were DSM-IIIR dementia and NINCDS-ADRDA possible and probable Alzheimer's disease. Results: All the cognitive tests completed in 1983 predicted onset of dementia and Alzheimer's disease up to 11 years later, as did APOE genotype. Cognitive test performance was not associated with APOE genotype. Addition of cognitive tests increased the area under the ROC curve for the prediction of Alzheimer's disease provided by age, family history, and APOE genotype (0.81 v 0.69, p = 0.048); addition of APOE genotype did not increase the area under the ROC curve for the prediction provided by age, family history, and cognitive tests ( 0.81 v 0.77, p = 0.28). Conclusions: Simple tests of cognitive ability provide useful predictive information up to a decade before the onset of dementia. The predictive information provided is independent of, but not enhanced by, the addition of APOE genotype.