Joel Eppig

Verbal Serial List Learning in Mild Cognitive Impairment: A Profile Analysis of Interference, Forgetting, and Errors

Using cluster analysis Libon et al. (2010) found three verbal serial list-learning profiles involving delay memory test performance in patients with mild cognitive impairment (MCI). Amnesic MCI (aMCI) patients presented with low scores on delay free recall and recognition tests; mixed MCI (mxMCI) patients scored higher on recognition compared to delay free recall tests; and dysexecutive MCI (dMCI) patients generated relatively intact scores on both delay test conditions. The aim of the current research was to further characterize memory impairment in MCI by examining forgetting/savings, interference from a competing word list, intrusion errors/perseverations, intrusion word frequency, and recognition foils in these three statistically determined MCI groups compared to normal control (NC) participants. The aMCI patients exhibited little savings, generated more highly prototypic intrusion errors, and displayed indiscriminate responding to delayed recognition foils. The mxMCI patients exhibited higher saving scores, fewer and less prototypic intrusion errors, and selectively endorsed recognition foils from the interference list. dMCI patients also selectively endorsed recognition foils from the interference list but performed similarly compared to NC participants. These data suggest the existence of distinct memory impairments in MCI and caution against the routine use of a single memory test score to operationally define MCI.

Neuropsychological deficits associated with Complex Regional Pain Syndrome.

We sought to elucidate the existence of neuropsychological subtypes in Complex Regional Pain Syndrome (CRPS). One hundred thirty seven patients with CRPS were administered tests that assess executive control, naming/lexical retrieval, and declarative memory. A 2-step cluster analysis that does not require any a priori specification regarding the number of clusters, classified patients into three groups. Group 1 obtained scores that were in the average range on all tests (n = 48; normal CRSP group). Group 2 (n = 58; dysexecutive CRSP group) presented with mild impairment or statistically low average test performance on working memory/verbal fluency tests. Group 3 (n = 31; global CRSP group) produced scores in the statistically low average/borderline range on all tests with particularly reduced scores on naming/declarative memory tests. Between-group analyses found that the CRPS group 1 obtained higher scores than CRPS groups 2 and 3 on all tests. However, groups 2 and 3 were equally impaired on executive tests. CRPS group 3 was impaired on tests of naming/memory tests compared to the other groups. Significant neuropsychological deficits are present in 65% of patients, with many patients presenting with elements of a dysexecutive syndrome and some patients presenting with global cognitive impairment.

Everyday Action Impairment in Parkinson's Disease Dementia

This study examined everyday action impairment in participants with Parkinsons disease dementia (PDD) by comparison with participants with Parkinsons disease-no dementia (PD) or Alzheimers disease (AD) and in reference to a neuropsychological model. Participants with PDD (n = 20), PD (n = 20), or AD (n = 20) were administered performance-based measures of everyday functioning that allowed for the quantification of overall performance and error types. Also, caregiver ratings of functional independence were obtained. On performance-based tests, the PDD group exhibited greater functional impairment than the PD group but comparable overall impairment relative to the AD group. Error patterns did not differ between PDD and PD participants but the PDD group demonstrated a higher proportion of commission errors and lower proportion of omission errors relative to the AD group. Hierarchical regression analyses showed omission errors were significantly predicted by neuropsychological measures of episodic memory, whereas commission errors were predicted by both measures of general dementia severity (MMSE) and executive control. Everyday action impairment in PDD differs quantitatively from PD but qualitatively from AD and may be characterized by a relatively high proportion of commission errors-an error type associated with executive control deficits. (JINS, 2012, 18, 1-12).

Dysexecutive Functioning in Mild Cognitive Impairment: Derailment in Temporal Gradients

Libon et al. (2010) provided evidence for three statistically determined clusters of patients with mild cognitive impairment (MCI): amnesic (aMCI), dysexecutive (dMCI), and mixed (mxMCI). The current study further examined dysexecutive impairment in MCI using the framework of Fusters (1997) derailed temporal gradients, that is, declining performance on executive tests over time or test epoch. Temporal gradients were operationally defined by calculating the slope of aggregate letter fluency output across 15-s epochs and accuracy indices for initial, middle, and latter triads from the Wechsler Memory Scale-Mental Control subtest (Boston Revision). For letter fluency, slope was steeper for dMCI compared to aMCI and NC groups. Between-group Mental Control analyses for triad 1 revealed worse dMCI performance than NC participants. On triad 2, dMCI scored lower than aMCI and NCs; on triad 3, mxMCI performed worse versus NCs. Within-group Mental Control analyses yielded equal performance across all triads for aMCI and NC participants. mxMCI scored lower on triad 1 compared to triads 2 and 3. dMCI participants also performed worse on triad 1 compared to triads 2 and 3, but scored higher on triad 3 versus triad 2. These data suggest impaired temporal gradients may provide a useful heuristic for understanding dysexecutive impairment in MCI.

Improving everyday error detection, one picture at a time: a performance-based study of everyday task training.

OBJECTIVE Research suggests that dementia patients detect fewer action errors than age-matched controls; however, little is known about the derivation of their error-monitoring difficulties. The aims of the study are to evaluate a novel, task-training action intervention (TT-NAT) designed to increase error monitoring in dementia patients and to pinpoint the relation between error monitoring and neuropsychological processes. METHOD Participants (n = 45) with dementia were administered the Standard NAT, a performance-based test requiring completion of three everyday tasks. A second group (n = 42) was administered the TT-NAT, which includes a brief training session prior to the commencement of each task. All participants were compared on the following variables: total errors, proportion of errors detected, and proportion of errors corrected. Correlations between error-monitoring variables and neuropsychological tests of executive functioning and language were performed. RESULTS TT-NAT participants produced fewer total errors and detected significantly more errors than Standard NAT participants (z = 3.0; t = 3.36; p < .05). Error detection was strongly related to only the language composite index (r = .57, p = .00) in the TT-NAT, whereas it was moderately related to both the language (r = .31, p = .04) and executive composite (r = .36, p = .02) indices in the Standard NAT condition. CONCLUSION Review of task steps and objects before task performance may be a promising intervention for error-monitoring deficits in dementia patients; this finding has implications for neuropsychological rehabilitation of functional deficits in this population.

Neuropsychological Syndromes Associated with Alzheimer's/Vascular Dementia: A Latent Class Analysis

BACKGROUND Epidemiologic autopsy studies show mixed Alzheimers disease (AD)/vascular pathology in many patients. Moreover, clinical research shows that it is not uncommon for AD and vascular dementia (VaD) patients to be equally impaired on memory, executive, or other neurocognitive tests. However, this clinical heterogeneity has not been incorporated into the new diagnostic criteria for AD (Dubois et al., 2010; McKhann et al., 2011). OBJECTIVE The current research applied Latent Class Analysis (LCA) to a protocol of six neuropsychological parameters to identify phenotypic subtypes from a large group of AD/VaD participants. Follow-up analyses examined difference between groups on neuroradiological parameters and neuropsychological measures of process and errors. METHODS 223 AD/VaD patients were administered a comprehensive neuropsychological protocol. Measures of whole brain and hippocampal volume were available for a portion of the sample (n = 76). RESULTS LCA identified four distinct groups: moderate/mixed dementia (n = 54; 24.21%), mild/mixed dementia (n = 91; 40.80%); dysexecutive (n = 49, 21.97%), and amnestic (n = 29, 13.00%). Follow-up analyses comparing the groups on neuropsychological process and error scores showed that the dysexecutive group exhibited difficulty sustaining mental set. The moderate/mixed group evidenced pronounced impairment on tests of lexical retrieval/naming along with significant amnesia. Amnestic patients also presented with gross amnesia, but showed relative sparing on other neuropsychological measures. Mild/mixed patients exhibited milder memory deficits that were intermediary between the amnestic and moderate/mixed groups. CONCLUSIONS There are distinct neuropsychological profiles in patients independent of clinical diagnosis, suggesting that the two are not wholly separate and that this information should be integrated into new AD diagnostic paradigms.

Heterogeneous cortical atrophy patterns in MCI not captured by conventional diagnostic criteria

Objective: We investigated differences in regional cortical thickness between previously identified empirically derived mild cognitive impairment (MCI) subtypes (amnestic MCI, dysnomic MCI, dysexecutive/mixed MCI, and cluster-derived normal) in order to determine whether these cognitive subtypes would show different patterns of cortical atrophy. Methods: Participants were 485 individuals diagnosed with MCI and 178 cognitively normal individuals from the Alzheimers Disease Neuroimaging Initiative. Cortical thickness estimates were computed for 32 regions of interest per hemisphere. Statistical group maps compared each MCI subtype to cognitively normal participants and to one another. Results: The pattern of cortical thinning observed in each MCI subtype corresponded to their cognitive profile. No differences in cortical thickness were found between the cluster-derived normal MCI subtype and the cognitively normal group. Direct comparison between MCI subtypes suggested that the cortical thickness patterns reflect increasing disease severity. Conclusions: There is an ordered pattern of cortical atrophy among patients with MCI that coincides with their profiles of increasing cognitive dysfunction. This heterogeneity is not captured when patients are grouped by conventional diagnostic criteria. Results in the cluster-derived normal group further support the premise that the conventional MCI diagnostic criteria are highly susceptible to false-positive diagnostic errors. Findings suggest a need to (1) improve the diagnostic criteria by reducing reliance on conventional screening measures, rating scales, and a single memory measure in order to avoid false-positive errors; and (2) divide MCI samples into meaningful subgroups based on cognitive and biomarkers profiles—a method that may provide better staging of MCI and inform prognosis.

Neuroimaging correlates of everyday action in dementia

The everyday, functional impairments associated with dementia remain poorly understood from a neuropsychological perspective. This study investigated relations between brain structure volumes and two measures of everyday action—caregiver questionnaire and direct assessment—in 57 participants with dementia. Results showed that caregiver ratings reflecting more functional impairment were strongly associated with smaller volumes of deep white matter. Direct assessment of everyday task performance in a subsample revealed relations between unique neurological substrates and discrete everyday action error types. Findings emphasize differences in functional assessment methods and highlight the role of white matter in functional deficits in dementia.

Visuoconstructional Impairment in Subtypes of Mild Cognitive Impairment

Clock Drawing Test performance was examined alongside other neuropsychological tests in mild cognitive impairment (MCI). We tested the hypothesis that clock-drawing errors are related to executive impairment. The current research examined 86 patients with MCI for whom, in prior research, cluster analysis was used to sort patients into dysexecutive (dMCI, n = 22), amnestic (aMCI, n = 13), and multidomain (mMCI, n = 51) subtypes. First, principal components analysis (PCA) and linear regression examined relations between clock-drawing errors and neuropsychological test performance independent of MCI subtype. Second, between-group differences were assessed with analysis of variance (ANOVA) where MCI subgroups were compared to normal controls (NC). PCA yielded a 3-group solution. Contrary to expectations, clock-drawing errors loaded with lower performance on naming/lexical retrieval, rather than with executive tests. Regression analyses found increasing clock-drawing errors to command were associated with worse performance only on naming/lexical retrieval tests. ANOVAs revealed no differences in clock-drawing errors between dMCI versus mMCI or aMCI versus NCs. Both the dMCI and mMCI groups generated more clock-drawing errors than the aMCI and NC groups in the command condition. In MCI, language-related skills contribute to clock-drawing impairment.

Word-list intrusion errors predict progression to mild cognitive impairment.

Objective: Preclinical Alzheimer’s disease (AD) defined by a positive AD biomarker in the presence of normal cognition is presumed to precede mild cognitive impairment (MCI). Subtle cognitive deficits and cognitive inefficiencies in preclinical AD may be detected through process and error scores on neuropsychological tests in those at risk for progression to MCI. Method: Cognitively normal participants (n = 525) from the Alzheimer’s Disease Neuroimaging Initiative were followed for up to 5 years and classified as either stable normal (n = 305) or progressed to MCI (n = 220). Cox regressions were used to determine whether baseline process scores on the Rey Auditory Verbal Learning Test (AVLT; intrusion errors, learning slope, proactive interference, retroactive interference) predicted progression to MCI and a Clinical Dementia Rating (CDR) score of 1 after considering demographic characteristics, apolipoprotein E &egr;4 status, cerebrospinal fluid AD biomarkers, ischemia risk, mood, functional difficulty, and standard neuropsychological total test scores for the model. Results: Baseline AVLT intrusion errors predicted progression to MCI (hazard ratio = 1.04, 95% confidence interval 1.01–1.07, p = .008) and improved model fit after the other valuable predictors were already in the model, &khgr;2(df = 1) = 6.330, p = .012. AVLT intrusion errors also predicted progression to CDR = 1 (hazard ratio = 1.10, 95% confidence interval 1.02–1.18, p = .016) and again improved model fit, &khgr;2(df = 1) = 4.682, p = .030. Conclusions: Intrusion errors on the AVLT contribute unique value for predicting progression from normal cognition to MCI and normal cognition to mild dementia (CDR = 1). Intrusion errors appear to reflect subtle change and inefficiencies in cognition that precede impairment detected by neuropsychological total scores.