Predicting conversion from mild cognitive impairment to Alzheimer's disease using neuropsychological tests and multivariate methods

Abstract

Behavioral markers measured through neuropsychological testing in Mild Cognitive Impairment (MCI) were analyzed and combined in multivariate ways to predict conversion to Alzheimer’s disease (AD) in a longitudinal study of 43 MCI patients. The test measures taken at a baseline evaluation were first reduced to underlying components (Principal Components Analysis, PCA) and then the component scores were used in discriminant analysis to classify MCI individuals as likely to convert or not. When empirically weighted and combined, episodic memory, speeded executive functioning, recognition memory (false and true positives), visuospatial memory processing speed, and visuospatial episodic memory were together strong predictors of conversion to AD. These multivariate combinations of the test measures achieved through the PCA were good, statistically significant predictors of MCI conversion to AD (84% accuracy, 86% sensitivity, and 83% specificity). Importantly, the posterior probabilities of group membership that accompanied the binary prediction for each participant indicated the confidence of the prediction. Most of the subjects (81%) were in the highly confident probability bins (0.70 – 1.00), where the obtained prediction accuracy was more than 90%. The strength and reliability of this multivariate prediction method were tested by cross-validation and randomized resampling.

Alpha-Band Hypersynchronization in Progressive Mild Cognitive Impairment: A Magnetoencephalography Study

“…It is considered that, in this brain structure, the AD pathology begins (Khan et al, 2014) and that it is the interface between the hippocampus and the neocortex that has a critical role in memory (Takehara-Nishiuchi, 2014). Therefore, the differences obtained in verbal memory between both groups may be explained by the higher atrophy observed in the pMCI group, although it is important to note that the deficits in executive functioning exhibited by this group may influence verbal memory performance Chang et al, 2010). Notwithstanding that hippocampal atrophy is one of the anatomical changes that better predicts the subsequent conversion to AD (Jack et al, 1999), our anatomical results seem to be consistent with the role of the entorhinal cortex at the onset of AD, because our pMCI patients were faster converters and there was greater involvement of the entorhinal than the parahippocampal cortex in predicting the conversion to AD (Devanand et al, 2007).…”

“…One of the main finding in AD studies is the decrease in synchronization in high-frequency bands, especially in alpha (Locatelli et al, 1998;Berendse et al, 2000), so the hypersynchronization usually observed in pMCI patients seems to be paradoxical. However, the synaptic disruption produced in the cholinergic system (Requena et al, 2006;Schliebs and Arendt, 2006) and the loss of inhibitory neurons caused by the accumulation of neuritic plaques (Garcia-Marin et al, 2009) may produce the increase in synchronization in high oscillations in these patients.…”

Latent information in fluency lists predicts functional decline in persons at risk for Alzheimer disease

“…It is therefore important to know the limits of cognitive testing for diagnosing AD or making predictions of functional decline. Several studies evaluate cognitive predictors in the absence of biological markers for predicting conversion (Powell, et al, 2006; Tabert, et al, 2006; Chapman, et al, 2011; Pozueta, et al, 2011). These studies report good results using cognitive tests alone, but none of them report results from any form of cross-validation or on a held-out sample of subjects.…”

Neuropsychological Tests for Predicting Cognitive Decline in Older Adults

“…Additionally, the RCFT [38] measuring visuospatial and visuoconstructional abilities, perceptual organization and planning (executive functioning) and visual memory has been shown to be sensitive in discerning early stage AD [39] as well as predicting conversion [24,40–41]. The TMT B, a test of cognitive flexibility, is a popular measure of executive functioning and has been found to be a powerful predictor of conversion to AD [42,43]. In terms of language functioning, verbal semantic fluency is impaired in presymptomatic AD patients [44].…”