Decreased Self-Appraisal Accuracy on Cognitive Tests of Executive Functioning Is a Predictor of Decline in Mild Cognitive Impairment

The likelihood of conversion to Alzheimer disease (AD) in mild cognitive impairment (MCI) and the "optimal" early markers of conversion need to be established. To evaluate conversion rates to AD in subtypes of MCI and to identify neuropsychological measures most predictive of the time to conversion. 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. Memory disorders clinic. One hundred forty-eight patients reporting memory problems and 63 group-matched controls. 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 = .001). In 148 patients, of 5 a priori predictors, the percent savings from immediate to delayed recall on the Selective Reminding Test and the Wechsler Adult Intelligence Scale-Revised Digit Symbol Test 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 Selective Reminding Test (odds ratio per 1-point decrease, 1.10; 95% confidence interval, 1.05-1.14; P < .0001) and Digit Symbol Test coding (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .01). The combined predictive accuracy of these 2 measures for conversion by 3 years was 86%. Mild cognitively impaired patients with memory plus other cognitive domain deficits, rather than those with pure amnestic MCI, constituted the high-risk group. Deficits in verbal memory and psychomotor speed/executive function abilities strongly predicted conversion to AD.

Macro- and micro-adjustment of task set was studied using distributional analyses of performance data (reaction time and accuracy) obtained in a new experiment using the Simon task. Macro-adjustments involved the long-term strategic modifications in response to the relative probability of conflict trials, while micro-adjustment involved trial-by-trial modifications invoked by the commission of incidental errors. These adjustments were examined in detail in distributional analyses of RT and accuracy, which have been shown to be particularly useful in studying the role of activation and suppression in conflict tasks. The modification of behavioral strategies incurred by the commission of errors and by the relative probability that the irrelevant location corresponded to the incorrect response was found to involve a reduced location-driven direct response activation (as reflected in the early portions of the delta plots for accuracy) and a stronger selective suppression of that direct activation (as reflected in the delta plot slopes for RT). When the probability of conflict trials was high, the effects of irrelevant location were already precluded by macro-adjustment, so that error commission had no further micro-adjustment effect on subsequent behavior. These patterns were not disclosed by analysis of overall performance.

Biomarkers have become increasingly important in understanding neurodegenerative processes associated with Alzheimer disease. Markers include regional brain volumes, cerebrospinal fluid measures of pathological Aβ1-42 and total tau, cognitive measures, and individual risk factors. To determine the discriminative utility of different classes of biomarkers and cognitive markers by examining their ability to predict a change in diagnostic status from mild cognitive impairment to Alzheimer disease. Longitudinal study. We analyzed the Alzheimer's Disease Neuroimaging Initiative database to study patients with mild cognitive impairment who converted to Alzheimer disease (n = 116) and those who did not convert (n = 204) within a 2-year period. We determined the predictive utility of 25 variables from all classes of markers, biomarkers, and risk factors in a series of logistic regression models and effect size analyses. The Alzheimer's Disease Neuroimaging Initiative public database. Primary outcome measures were odds ratios, pseudo- R(2)s, and effect sizes. In comprehensive stepwise logistic regression models that thus included variables from all classes of markers, the following baseline variables predicted conversion within a 2-year period: 2 measures of delayed verbal memory and middle temporal lobe cortical thickness. In an effect size analysis that examined rates of decline, change scores for biomarkers were modest for 2 years, but a change in an everyday functional activities measure (Functional Assessment Questionnaire) was considerably larger. Decline in scores on the Functional Assessment Questionnaire and Trail Making Test, part B, accounted for approximately 50% of the predictive variance in conversion from mild cognitive impairment to Alzheimer disease. Cognitive markers at baseline were more robust predictors of conversion than most biomarkers. Longitudinal analyses suggested that conversion appeared to be driven less by changes in the neurobiologic trajectory of the disease than by a sharp decline in functional ability and, to a lesser extent, by declines in executive function.