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To determine whether the DCTclock can detect differences across groups of patients seen in the memory clinic for suspected dementia.
Patients (n = 123) were classified into the following groups: cognitively normal (CN), subtle cognitive impairment (SbCI), amnestic cognitive impairment (aMCI), and mixed/dysexecutive cognitive impairment (mx/dysMCI). Nine outcome variables included a combined command/copy total score and four command and four copy indices measuring drawing efficiency, simple/complex motor operations, information processing speed, and spatial reasoning.
Total combined command/copy score distinguished between groups in all comparisons with medium to large effects. The mx/dysMCI group had the lowest total combined command/copy scores out of all groups. The mx/dysMCI group scored lower than the CN group on all command indices (p < .050, all analyses); and lower than the SbCI group on drawing efficiency (p = .011). The aMCI group scored lower than the CN group on spatial reasoning (p = .019). Smaller effect sizes were obtained for the four copy indices.
These results suggest that DCTclock command/copy parameters can dissociate CN, SbCI, and MCI subtypes. The larger effect sizes for command clock indices suggest these metrics are sensitive in detecting early cognitive decline. Additional research with a larger sample is warranted.
To determine how well machine learning algorithms can classify mild cognitive impairment (MCI) subtypes and Alzheimer’s disease (AD) using features obtained from the digital Clock Drawing Test (dCDT).
dCDT protocols were administered to 163 patients diagnosed with AD(n = 59), amnestic MCI (aMCI; n = 26), combined mixed/dysexecutive MCI (mixed/dys MCI; n = 43), and patients without MCI (non-MCI; n = 35) using standard clock drawing command and copy procedures, that is, draw the face of the clock, put in all of the numbers, and set the hands for “10 after 11.” A digital pen and custom software recorded patient’s drawings. Three hundred and fifty features were evaluated for maximum information/minimum redundancy. The best subset of features was used to train classification models to determine diagnostic accuracy.
Neural network employing information theoretic feature selection approaches achieved the best 2-group classification results with 10-fold cross validation accuracies at or above 83%, that is, AD versus non-MCI = 91.42%; AD versus aMCI = 91.49%; AD versus mixed/dys MCI = 84.05%; aMCI versus mixed/dys MCI = 84.11%; aMCI versus non-MCI = 83.44%; and mixed/dys MCI versus non-MCI = 85.42%. A follow-up two-group non-MCI versus all MCI patients analysis yielded comparable results (83.69%). Two-group classification analyses were achieved with 25–125 dCDT features depending on group classification. Three- and four-group analyses yielded lower but still promising levels of classification accuracy.
Early identification of emergent neurodegenerative illness is criterial for better disease management. Applying machine learning to standard neuropsychological tests promises to be an effective first line screening method for classification of non-MCI and MCI subtypes.
Previous research in mild cognitive impairment (MCI) suggests that visual episodic memory impairment may emerge before analogous verbal episodic memory impairment. The current study examined working memory (WM) test performance in MCI to assess whether patients present with greater visual versus verbal WM impairment. WM performance was also assessed in relation to hippocampal occupancy (HO), a ratio of hippocampal volume to ventricular dilation adjusted for demographic variables and intracranial volume.
Jak et al. (2009) (The American Journal of Geriatric Psychiatry, 17, 368–375) and Edmonds, Delano-Wood, Galasko, Salmon, & Bondi (2015) (Journal of Alzheimer’s Disease, 47(1), 231–242) criteria classify patients into four groups: little to no cognitive impairment (non-MCI); subtle cognitive impairment (SCI); amnestic MCI (aMCI); and a combined mixed/dysexecutive MCI (mixed/dys MCI). WM was assessed using co-normed Wechsler Adult Intelligence Scale-IV (WAIS-IV) Digit Span Backwards and Wechsler Memory Scale-IV (WMS-IV) Symbol Span Z-scores.
Between-group analyses found worse WMS-IV Symbol Span and WAIS-IV Digit Span Backwards performance for mixed/dys MCI compared to non-MCI patients. Within-group analyses found no differences for non-MCI patients; however, all other groups scored lower on WMS-IV Symbol Span than WAIS-IV Digit Span Backwards. Regression analysis with HO as the dependent variable was statistically significant for WMS-IV Symbol Span performance. WAIS-IV Digit Span Backwards performance failed to reach statistical significance.
Worse WMS-IV Symbol Span performance was observed in patient groups with measurable neuropsychological impairment and better WMS-IV Symbol Span performance was associated with higher HO ratios. These results suggest that visual WM may be particularly sensitive to emergent illness compared to analogous verbal WM tests.
Psychomotor slowing has been documented in depression. The digital Clock Drawing Test (dCDT) provides: (i) a novel technique to assess both cognitive and motor aspects of psychomotor speed within the same task and (ii) the potential to uncover subtleties of behavior not previously detected with non-digitized modes of data collection. Using digitized pen technology in 106 participants grouped by Age (younger/older) and Affect (euthymic/unmedicated depressed), we recorded cognitive and motor output by capturing how the clock is drawn rather than focusing on the final product. We divided time to completion (TTC) for Command and Copy conditions of the dCDT into metrics of percent of drawing (%Ink) versus non-drawing (%Think) time. We also obtained composite Z-scores of cognition, including attention/information processing (AIP), to explore associations of %Ink and %Think times to cognitive and motor performance. Despite equivalent TTC, %Ink and %Think Command times (Copy n.s.) were significant (AgeXAffect interaction: p=.03)—younger depressed spent a smaller proportion of time drawing relative to thinking compared to the older depressed group. Command %Think time negatively correlated with AIP in the older depressed group (r=−.46; p=.02). Copy %Think time negatively correlated with AIP in the younger depressed (r=−.47; p=.03) and older euthymic groups (r=−.51; p=.01). The dCDT differentiated aspects of psychomotor slowing in depression regardless of age, while dCDT/cognitive associates for younger adults with depression mimicked patterns of older euthymics. (JINS, 2014, 20, 1–9)
Given the importance of identifying dementia prodromes for future treatment efforts, we examined two methods of diagnosing mild cognitive impairment (MCI) and determined whether empirically-derived MCI subtypes of these diagnostic methods were consistent with one another as well as with conventional MCI subtypes (i.e., amnestic, non-amnestic, single-domain, multi-domain). Participants were diagnosed with MCI using either conventional Petersen/Winblad criteria (n = 134; >1.5 SDs below normal on one test within a cognitive domain) or comprehensive neuropsychological criteria developed by Jak et al. (2009) (n = 80; >1 SD below normal on two tests within a domain), and the resulting samples were examined via hierarchical cluster and discriminant function analyses. Results showed that neuropsychological profiles varied depending on the criteria used to define MCI. Both criteria revealed an Amnestic subtype, consistent with prodromal Alzheimer's disease (AD), and a Mixed subtype that may capture individuals in advanced stages of MCI. The comprehensive criteria uniquely yielded Dysexecutive and Visuospatial subtypes, whereas the conventional criteria produced a subtype that performed within normal limits, suggesting its susceptibility to false positive diagnostic errors. Whether these empirically-derived MCI subtypes correspond to dissociable neuropathologic substrates and represent reliable prodromes of dementia will require additional follow-up. (JINS, 2013, 19, 1–11)
This study examined everyday action impairment in participants with Parkinson's disease dementia (PDD) by comparison with participants with Parkinson's disease-no dementia (PD) or Alzheimer's 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)
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 Fuster's (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. (JINS, 2012, 18, 20–28)
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. (JINS, 2011, 17, 905–914)
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. (JINS, 2010, 16, 566–573.)
This study evaluated the impact of distractor objects and their similarity to target objects on everyday task performance in dementia. Twenty participants with dementia due to Alzheimer’s disease (n = 12) or subcortical vascular disease (n = 8) were videotaped while they performed 3 discrete tasks: (1) make a cup of coffee, (2) wrap a gift, and (3) pack a lunch under two conditions that were counterbalanced across participants. The conditions differed in terms of the type of distractor objects included in the workspace: (1) Target-Related Distractor Condition - distractor objects were functionally and visually similar to target objects (e.g., salt for sugar) (2) Unrelated Distractor Condition - distractors were neither visually nor functionally similar to targets (e.g., glue for sugar). Participants touched (t = 4.19; p < .01) and used (z = 3.00; p < .01) significantly more distractors, made more distractor errors (i.e., substitutions; t = 2.93; p < .01), and took longer to complete tasks (t = 2.27; p < .05) in the Target-Related Distractor condition. The percent of steps accomplished and non-distractor errors did not differ across conditions (t < 1.26; p > .05 for both). In summary, distractors that were similar to targets elicited significant interference effects circumscribed to object selection. (JINS, 2010, 16, 484–494.)
The longitudinal assessment of episodic and semantic memory was obtained from 236 patients diagnosed with Alzheimer’s disease (AD, n = 128) and with frontotemporal lobar degeneration (FTLD, n = 108), including patients with a social comportment/dysexecutive (SOC/EXEC) disorder, progressive nonfluent aphasia (PNFA), semantic dementia (SemD), and corticobasal syndrome (CBS). At the initial assessment, AD patients obtained a lower score on the delayed free recall test than other patients. Longitudinal analyses for delayed free recall found converging performance, with all patients reaching the same level of impairment as AD patients. On the initial evaluation for delayed recognition, AD patients also obtained lower scores than other groups. Longitudinal analyses for delayed recognition test performance found that AD patients consistently produced lower scores than other groups and no convergence between AD and other dementia groups was seen. For semantic memory, there were no initial between-group differences. However, longitudinal analyses for semantic memory revealed group differences over illness duration, with worse performance for SemD versus AD, PNFA, SOC/EXEC, and CBS patients. These data suggest the presence of specific longitudinal patterns of impairment for episodic and semantic memory in AD and FTLD patients suggesting that all forms of dementia do not necessarily converge into a single phenotype. (JINS, 2010, 16, 278–286.)
A group of 94 nondemented patients self-referred to an outpatient memory clinic for memory difficulties were studied to determine the incidence of single versus multi-domain mild cognitive impairment (MCI) using Petersen criteria. Fifty-five community dwelling normal controls (NC) participants without memory complaints also were recruited. Tests assessing executive control, naming/lexical retrieval, and declarative memory were administered. Thirty-four patients exhibited single-domain MCI, 43 patients presented with multi-domain MCI. When the entire MCI sample (n = 77) was subjected to a cluster analysis, 14 patients were classified with amnesic MCI, 21 patients with dysexecutive MCI, and 42 patients were classified into a mixed/multi-domain MCI group involving low scores on tests of letter fluency, “animal” fluency, and delayed recognition discriminability. Analyses comparing the three cluster-derived MCI groups versus a NC group confirmed the presence of memory and dysexecutive impairment for the amnesic and dysexecutive MCI groups. The mixed MCI group produced lower scores on tests of letter fluency compared with the amnesic MCI and NC groups and lower scores on tests of naming and memory compared with the NC group. In summary, multi-domain MCI is quite common. These data suggest that MCI is a highly nuanced and complex clinical entity. (JINS, 2010, 16, 84–93.)
This study examined whether distinct neuropsychological profiles could be delineated in a sample with Mild Cognitive Impairment (MCI) and whether white matter lesion (WML) burden contributed to MCI group differences. A heterogeneous, clinical sample of 70 older adults diagnosed with MCI was assessed using cognitive scores, and WML was quantified using a semi-automated, volumetric approach on T2-weighted fluid-attenuated inversion recovery (FLAIR) images. Using cluster and discriminant analyses, three distinct groups (Memory/Language, Executive/Processing Speed, and Pure Memory) were empirically derived based on cognitive scores. Results also showed a dose dependent relationship of WML burden to MCI subgroup, with the Executive/Processing Speed subgroup demonstrating significantly higher levels of WML pathology when compared to the other subgroups. In addition, there was a dissociation of lesion type by the two most impaired subgroups (Memory/Language and Executive/Processing Speed) such that the Memory/Language subgroup showed higher periventricular lesion (PVL) and lower deep white matter lesion (DWML) volumes, whereas the Executive/Processing Speed demonstrated higher DWML and lower PVL volumes. Results demonstrate that distinct MCI subgroups can be empirically derived and reliably differentiated from a heterogeneous MCI sample, and that these profiles differ according to WML burden. Overall, findings suggest different underlying pathologies within MCI and contribute to our understanding of MCI subtypes. (JINS, 2009, 15, 906–914.)
Recent evidence suggests that patients with Alzheimer’s disease (AD) and vascular comorbidities (VC) perform worse across measures of verbal reasoning and abstraction when compared to patients with AD alone. We performed a qualitative error analysis of Wechsler Adult Intelligence Scale-III Similarities zero-point responses in 45 AD patients with varying numbers of VC, including diabetes, hypertension, and hypercholesterolemia. Errors were scored in set if the answer was vaguely related to how the word pair was alike (e.g., dog-lion: “they can be trained”) and out of set if the response was unrelated (“a lion can eat a dog”). AD patients with 2–3 VC did not differ on Similarities total score or qualitative errors from AD patients with 0–1 VC. When analyzing the group as a whole, we found that increasing numbers of VC were significantly associated with increasing out of set errors and decreasing in set errors in AD. Of the vascular diseases investigated, it was only the severity of diastolic blood pressure that significantly correlated with out of set responses. Understanding the contribution of VC to patterns of impairment in AD may provide support for directed patient and caregiver education concerning the presentation of a more severe pattern of cognitive impairment in affected individuals. (JINS, 2010, 16, 77–83.)
We hypothesized that specific neuropsychological deficits were associated with specific patterns of atrophy. A magnetic resonance imaging volumetric study and a neuropsychological protocol were obtained for patients with several frontotemporal lobar dementia phenotypes including a social/dysexecutive (SOC/EXEC, n = 17), progressive nonfluent aphasia (n = 9), semantic dementia (n = 7), corticobasal syndrome (n = 9), and Alzheimer’s disease (n = 21). Blinded to testing results, patients were partitioned according to pattern of predominant cortical atrophy; our partitioning algorithm had been derived using seriation, a hierarchical classification technique. Neuropsychological test scores were regressed versus these atrophy patterns as fixed effects using the covariate total atrophy as marker for disease severity. The results showed the model accounted for substantial variance. Furthermore, the “large-scale networks” associated with each neuropsychological test conformed well to the known literature. For example, bilateral prefrontal cortical atrophy was exclusively associated with SOC/EXEC dysfunction. The neuropsychological principle of “double dissociation” was supported not just by such active associations but also by the “silence” of locations not previously implicated by the literature. We conclude that classifying patients with degenerative dementia by specific pattern of cortical atrophy has the potential to predict individual patterns of cognitive deficits. (JINS, 2009, 15, 459–470.)
Comprehension difficulties associated with periventricular and deep white matter alterations (WMA) in mild dementia were investigated using portions of the Boston Diagnostic Aphasia Examination (BDAE) Complex Ideation subtest and Syntax subtests. Mild dementia participants were grouped according to the extent of their WMA as observed on magnetic resonance imaging (mild WMA n = 45 vs. moderate to severe WMA n = 52). Correlation and regression analyses also were performed to examine the link between WMA and comprehension abilities, as well as the link between comprehension abilities and neuropsychological measures of executive functioning, language, episodic memory, and overall dementia severity. Results showed that the WMA groups differed on the BDAE-Syntax subtests, with the severe WMA group demonstrating more impairment. Correlation and regression analyses including the entire sample also demonstrated that the extent of WMA was significantly linked to Syntax test scores but not Complex Ideation scores. Regression analyses including neuropsychological measures showed that the BDAE-Complex Ideation score was marginally predicted by only overall dementia severity, whereas the BDAE-Syntax scores were significantly predicted by independent measures of working memory/executive functioning. In conclusion, greater subcortical WMA and executive deficits are associated with greater difficulties in syntactic comprehension in individuals with mild dementia. (JINS, 2008, 14, 542–551.)
Error monitoring is critical to an individual's ability to function autonomously. This study characterized error detection and correction behaviors within the service of everyday tasks in individuals with dementia. Also, the impact of neuropsychological functioning on error detection and correction was examined. Fifty-three participants diagnosed with Alzheimer's disease (AD) or vascular dementia (VaD) were administered a neuropsychological protocol and the Naturalistic Action Test, which requires performance of three everyday tasks. Error detection, correction, and the point at which correction occurred (i.e., microslip—before the error was completed, immediate—just after the error was made, delayed—after performing other task steps) was coded. Dementia participants detected 32.7% of their errors and corrected 75.8% of detected errors. Participants were more likely to engage in microslips than delayed corrections. Tests of executive control and language predicted detection and correction variables; moreover, detection and correction were each related to different aspects of executive functioning. Microslips were related to naming ability. AD and VaD patients did not differ on detection/correction variables, and regression analyses indicated that dementia severity and memory abilities were unrelated to detection/correction. The results specify the error monitoring deficits in AD and VaD and have implications for improving functional abilities in dementia. (JINS, 2008, 14, 199–208.)
The relationship between dementia diagnosis and everyday action (e.g.,
meal preparation, grooming) is not well understood. This study examines
differences between individuals diagnosed with vascular dementia (VaD;
n = 25) versus Alzheimer's disease (AD; n
= 23) on the Naturalistic Action Test (NAT; Schwartz et
al., 2003), a performance-based measure that includes three tasks
of increasing complexity. The percentage of task steps accomplished,
number of errors, and performance times were recorded for each task. While
the groups did not differ in dementia severity or overall impairment on
the NAT, the VaD group committed more errors (3.3 vs. 1.6,
p = 02). The VaD group also accomplished significantly fewer
steps when salient distractor objects were present (74.0% vs.
91.3%, p < .01). Correlations between NAT variables and
neuropsychological tests suggest the executive control deficits associated
with VaD may contribute to specific action difficulties, such as
distractor interference and inefficient, error-prone action on complex
tasks. In AD, everyday action may be negatively influenced by episodic
memory failures. Thus, dementia diagnosis has relevance to everyday
function. (JINS, 2006, 12, 45–53.)