Instrumental activities of daily living and mild cognitive impairment.

BACKGROUND: Functional impairments are a necessary requirement for the diagnosis of a dementia along with observed cognitive impairment. Comparatively, functional abilities are often relatively intact in those with mild cognitive impairment (MCI). OBJECTIVE: The current research examined the associations between memory clinic participants classified as cognitively intact, amnestic MCI, and mixed/dysexecutive MCI, using Jak-Bondi criteria, and Instrumental Activities of Daily Living - Compensation Scale (IADL-C) abilities, an informant-based questionnaire that quantifies functional abilities. The associations between functional abilities as assessed with the IADL-C and performance on neuropsychological tests were also investigated. METHODS: IADLC scores were obtained along with a comprehensive neuropsychological protocol on memory clinic participants (n = 100) classified as cognitively normal (CN), amnestic MCI (aMCI), or a combined mixed/dysexecutive (mixed/dys) MCI. Regression analyses were employed to determine how the IADLC related to neuropsychological test performance. RESULTS: On the IADLC, greater functional impairment was commonly observed in the mixed/dys MCI group compared to CN participants. Furthermore, the mixed/dys MCI group had lower scores on activities such as Money and Self-Management, Travel and Event Memory subscales compared to the CN group. Linear regression analyses found greater functional impairment in relation to lower scores on executive and episodic memory tests. CONCLUSIONS: Greater functional impairment as assessed with the IADL-C appears to be disproportionately associated with dysexecutive difficulty, and to a lesser degree, episodic memory.

Estimating dementia risk in an African American population using the DCTclock.

The prevalence of Alzheimer's disease (AD) and related dementias (ADRD) is increasing. African Americans are twice as likely to develop dementia than other ethnic populations. Traditional cognitive screening solutions lack the sensitivity to independently identify individuals at risk for cognitive decline. The DCTclock is a 3-min AI-enabled adaptation of the well-established clock drawing test. The DCTclock can estimate dementia risk for both general cognitive impairment and the presence of AD pathology. Here we performed a retrospective analysis to assess the performance of the DCTclock to estimate future conversion to ADRD in African American participants from the Rush Alzheimer's Disease Research Center Minority Aging Research Study (MARS) and African American Clinical Core (AACORE). We assessed baseline DCTclock scores in 646 participants (baseline median age = 78.0 ± 6.4, median years of education = 14.0 ± 3.2, 78% female) and found significantly lower baseline DCTclock scores in those who received a dementia diagnosis within 3 years. We also found that 16.4% of participants with a baseline DCTclock score less than 60 were significantly more likely to develop dementia in 5 years vs. those with the highest DCTclock scores (75-100). This research demonstrates the DCTclock's ability to estimate the 5-year risk of developing dementia in an African American population. Early detection of elevated dementia risk using the DCTclock could provide patients, caregivers, and clinicians opportunities to plan and intervene early to improve cognitive health trajectories. Early detection of dementia risk can also enhance participant selection in clinical trials while reducing screening costs.

Visuospatial performance in patients with statistically-defined mild cognitive impairment.

Introduction: The Oblique Effect denotes superior performance for perceiving horizontal or vertical rather than diagonal or oblique stimuli. The current research investigated responding to oblique test stimuli in patients with mild cognitive impairment (MCI).Method: Four statistically-determined groups (n = 112) were studied; patients with little to no cognitive impairment (non-MCI, n = 39); subtle cognitive impairment (SCI, n = 15); amnestic MCI (aMCI, n = 28); and a combined mixed/dysexecutive MCI (mixed/dys MCI, n = 30). The ability to respond to oblique versus non-oblique test stimuli was assessed using the Judgment of Line Orientation Test (JOLO). Comprehensive neuropsychological assessment was also obtained. Between-group differences for JOLO oblique and non-oblique test stimuli were analyzed. Hierarchical linear regression models were constructed to identify relations between accuracy for oblique and non-oblique test items and neurocognitive domains.Results: The mixed/dys MCI group demonstrated lower accuracy for oblique test items compared to non-MCI patients. Accurate responding to oblique test items was associated with better performance on tests measuring executive control, processing speed, naming/lexical retrieval, and verbal concept formation. No between-group differences were seen for non-oblique items and these items were not associated with cognition.Conclusions:Significant impairment on oblique test items distinguished patients with multi-domain/dysexecutive MCI from non-MCI patients. Accurate responding to oblique test items was associated with a complex array of neuropsychological tests suggesting that multidimensional neuropsychological skills underlie the visuospatial reasoning abilities necessary for successful oblique line identification. Research associating responding to oblique versus non-oblique test stimuli using additional neuropsychological test paradigms, and MRI-defined neuroanatomical regions of interest may provide additional information about the brain-behavior relations that underlie MCI subtypes.

Alzheimer's/Vascular Spectrum Dementia: Classification in Addition to Diagnosis.

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common types of dementia. Although the combination of these disorders, called 'mixed' dementia, is recognized, the prevailing clinical and research perspective continues to consider AD and VaD as independent disorders. A review of recent neuropathological and neuropsychological literature reveals that these two disorders frequently co-occur and so-called 'pure' AD or VaD is comparatively rare. In addition, recent research shows that vascular dysfunction not only potentiates AD pathology, but that pathological changes in AD may subsequently induce vascular disorders. On the basis of these data, we propose that the neurobiological underpinnings underlying AD/VaD dementia and their neuropsychological phenotypes are best understood as existing along a clinical/pathological continuum or spectrum. We further propose that in conjunction with current diagnostic criteria, statistical modeling techniques using neuropsychological test performance should be leveraged to construct a system to classify AD/VaD spectrum dementia in order to test hypotheses regarding how mechanisms related to AD and VaD pathology interact and influence each other.

Assessing Working Memory in Mild Cognitive Impairment with Serial Order Recall.

BACKGROUND: Working memory (WM) is often assessed with serial order tests such as repeating digits backward. In prior dementia research using the Backward Digit Span Test (BDT), only aggregate test performance was examined. OBJECTIVE: The current research tallied primacy/recency effects, out-of-sequence transposition errors, perseverations, and omissions to assess WM deficits in patients with mild cognitive impairment (MCI). METHODS: Memory clinic patients (n = 66) were classified into three groups: single domain amnestic MCI (aMCI), combined mixed domain/dysexecutive MCI (mixed/dys MCI), and non-MCI where patients did not meet criteria for MCI. Serial order/WM ability was assessed by asking participants to repeat 7 trials of five digits backwards. Serial order position accuracy, transposition errors, perseverations, and omission errors were tallied. RESULTS: A 3 (group)×5 (serial position) repeated measures ANOVA yielded a significant group×trial interaction. Follow-up analyses found attenuation of the recency effect for mixed/dys MCI patients. Mixed/dys MCI patients scored lower than non-MCI patients for serial position 3 (p < 0.003) serial position 4 (p < 0.002); and lower than both group for serial position 5 (recency; p < 0.002). Mixed/dys MCI patients also produced more transposition errors than both groups (p < 0.010); and more omissions (p < 0.020), and perseverations errors (p < 0.018) than non-MCI patients. CONCLUSIONS: The attenuation of a recency effect using serial order parameters obtained from the BDT may provide a useful operational definition as well as additional diagnostic information regarding working memory deficits in MCI.

Learning Classification Models of Cognitive Conditions from Subtle Behaviors in the Digital Clock Drawing Test.

The Clock Drawing Test - a simple pencil and paper test - has been used for more than 50 years as a screening tool to differentiate normal individuals from those with cognitive impairment, and has proven useful in helping to diagnose cognitive dysfunction associated with neurological disorders such as Alzheimer's disease, Parkinson's disease, and other dementias and conditions. We have been administering the test using a digitizing ballpoint pen that reports its position with considerable spatial and temporal precision, making available far more detailed data about the subject's performance. Using pen stroke data from these drawings categorized by our software, we designed and computed a large collection of features, then explored the tradeoffs in performance and interpretability in classifiers built using a number of different subsets of these features and a variety of different machine learning techniques. We used traditional machine learning methods to build prediction models that achieve high accuracy. We operationalized widely used manual scoring systems so that we could use them as benchmarks for our models. We worked with clinicians to define guidelines for model interpretability, and constructed sparse linear models and rule lists designed to be as easy to use as scoring systems currently used by clinicians, but more accurate. While our models will require additional testing for validation, they offer the possibility of substantial improvement in detecting cognitive impairment earlier than currently possible, a development with considerable potential impact in practice.

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.

Digital Clock Drawing: differentiating "thinking" versus "doing" in younger and older adults with depression.

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.

Edith Kaplan and the Boston Process Approach.

The history including some of the intellectual origins of the Boston Process Approach and some misconceptions about the Boston Process Approach are reviewed. The influence of Gestalt psychology and Edith Kaplan's principal collaborators regarding the development of the Boston Process Approach is discussed.

Leukoaraiosis severity and list-learning in dementia.

In patients with dementia, leukoaraiosis (LA) was hypothesized to result in differential patterns of impairment on a verbal serial list-learning test. Using a visual rating scale, 144 dementia patients with ischemic scores <4 were re-categorized as having mild (n = 73), moderate (n = 44), or severe LA (n = 27). Mild LA was predicted to be associated with an amnestic list-learning profile, while severe LA was predicted to be associated with a dysexecutive profile. List-learning performances were standardized to a group of healthy older adults (n = 24). Analyses were conducted on a set of four factors derived from the list-learning paradigm, as well as error scores. Data indicate that LA severity is an important marker for understanding list learning in dementia.

Linking MRI hyperintensities with patterns of neuropsychological impairment: evidence for a threshold effect.

BACKGROUND AND PURPOSE: Leukoaraiosis (LA) might interrupt intra- and interhemispheric communication and thus induce cognitive impairments and dementia. It remains unclear, however, if there is a volume threshold of LA that is needed before either the signs of dementia and/or a specific pattern of neuropsychological impairment become manifest. Roman et al has suggested that 25% of white matter may need to be involved before white matter alterations influence the clinical signs associated with dementia. The purpose of this study is to ascertain the threshold of MRI-LA as measured with a visual rating scale needed to induce specific patterns of neuropsychological impairment associated with dementia. METHODS: One hundred fifteen patients with dementia received a comprehensive neuropsychological examination and the severity of MRI-LA was measured using a 40-point LA scale. RESULTS: Patients were categorized into low (mean LA=4.21+/-2.92; 3.22%-17.82%), moderate (mean LA=12.58+/-2.54; 25.01%-37.80%), and severe (mean LA=22.36+/-4.04; 45.80%-66.00%) LA groups. Patients in the mild LA group obtained markedly lower scores on tests of episodic memory compared with working memory, a neuropsychological profile often associated with Alzheimer disease. Patients with moderate LA displayed equal impairment on neuropsychological tests. Patients in the severe LA group obtained significantly lower scores on tests of working memory as compared with episodic memory. CONCLUSIONS: These data provide evidence that a threshold of moderate MRI-LA as measured with a visual rating scale is associated with greater and/or equal impairment on tests of working memory versus episodic memory and provides a benchmark to assess the effect of MRI-LA on the clinical presentation of dementia.