Gordon J. Chelune

Minimal Neuropsychological Assessment of MS Patients: A Consensus Approach

Cognitive impairment is common in multiple sclerosis (MS), yet patients seen in MS clinics and neurologic practices are not routinely assessed neuropsychologically. In part, poor utilization of NP services may be attributed to a lack of consensus among neuropsychologists regarding the optimal approach for evaluating MS patients. An expert panel composed of neuropsychologists and psychologists from the United States, Canada, United Kingdom, and Australia was convened by the Consortium of MS Centers (CMSC) in April, 2001. Our objectives were to: (a) propose a minimal neuropsychological (NP) examination for clinical monitoring of MS patients and research, and (b) identify strategies for improving NP assessment of MS patients in the future. The panel reviewed pertinent literature on MS-related cognitive dysfunction, considered psychometric factors relevant to NP assessment, defined the purpose and optimal characteristics of a minimal NP examination in MS, and rated the psychometric and practical properties of 36 candidate NP measures based on available literature. A 90-minute NP battery, the Minimal Assessment of Cognitive Function in MS (MACFIMS), emerged from this discussion. The MACFIMS is composed of seven neuropsychological tests, covering five cognitive domains commonly impaired in MS (processing speed/working memory, learning and memory, executive function, visual-spatial processing, and word retrieval). It is supplemented by a measure of estimated premorbid cognitive ability. Recommendations for assessing other factors that may potentially confound interpretation of NP data (e.g., visual/sensory/motor impairment, fatigue, and depression) are offered, as well as strategies for improving NP assessment of MS patients in the future.

Putamen coactivation during motor task execution

Models of corticostriatal motor circuitry have focused on the role of the circuit in the hemisphere of the motor cortex providing primary control (contralateral to the movement). We used functional magnetic resonance imaging and functional connectivity analyses to study circuit function in both the controlling and noncontrolling hemispheres. During the completion of a unilateral motor task with either hand, each putamen nucleus demonstrated strong coactivation with structures in both hemispheres. The putamen in the noncontrolling hemisphere (ipsilateral to the movement) coactivated more strongly with the controlling motor cortex than with the noncontrolling cortex. These findings suggest that the two corticostriatal circuits are functionally integrated. New circuit models based on functional connectivity may need to be developed.

Evidence-Based Research and Practice in Clinical Neuropsychology

While a definition for evidence-based clinical neuropsychological practice (EBCNP) has yet to emerge, it is likely to integrate the same core features as evidence-based medicine; namely, best research evidence, clinical expertise, and individual patient needs. Given the nascent stage of EBCNP, suggestions are made to advance evidence-based approaches in both research and practice. The common elements are: recognition that clinical outcomes are recorded at the level of the individual; and to be useful, outcomes research must be presented in a way that can be directly applied on a case-by-case basis. Tracking the outcomes of our clinical services in an evidence-based manner that is publicly verifiable will demonstrate the value of neuropsychological services to our patients, our referral sources, and ultimately to payers.

Differential neuropsychological test sensitivity to left temporal lobe epilepsy

We examined the sensitivity of the Rey Auditory Verbal Learning Test (AVLT), California Verbal Learning Test (CVLT), Boston Naming Test (BNT), and Multilingual Aphasia Examination Visual Naming subtest (MAE VN) to lateralized temporal lobe epilepsy (TLE) in patients who subsequently underwent anterior temporal lobectomy. For the AVLT (n = 189), left TLE patients performed more poorly than their right TLE counterparts [left TLE = 42.9 (10.6), right TLE = 47.7 (9.9); p < .002 (Cohens d = .47)]. Although statistically significant, the CVLT group difference (n = 212) was of a smaller magnitude [left LTE = 40.7 (11.1), right TLE = 43.8 (9.9); (p < .03, Cohens d = .29)] than the AVLT. Group differences were also present for both measures of confrontation naming ability [BNT: left LTE = 43.1 (8.9), right TLE = 48.1 (8.9); p < .001 (Cohens d = .56); MAE VN: left TLE = 42.2, right TLE = 45.6, p = .02 (Cohens d = .36)]. When these data were modeled in independent logistic regression analyses, the AVLT and BNT both significantly predicted side of seizure focus, although the positive likelihood ratios were modest. In the subset of 108 patients receiving both BNT and AVLT, the AVLT was the only significant predictor of seizure laterality, suggesting individual patient variability regarding whether naming or memory testing may be more sensitive to lateralized TLE.

Cognitive-behavioral profiles of neurodegenerative dementias: beyond Alzheimer's disease.

The neurocognitive and behavioral profiles of vascular dementia and vascular cognitive impairment, dementia with Lewy bodies and Parkinsons disease with dementia, and dementia syndromes associated with frontotemporal lobar degenerations are compared and contrasted with Alzheimers dementia (AD). Vascular dementia/vascular cognitive impairment is characterized by better verbal memory performance, worse quantitative executive functioning, and prominent depressed mood. Dementia with Lewy bodies and Parkinsons disease with dementia are equally contrasted with AD by defective processing of visual information, better performance on executively supported verbal learning tasks, greater attentional variability, poorer qualitative executive functioning, and the presence of mood-congruent visual hallucinations. The frontal variant of frontotemporal lobar degeneration (frontotemporal dementia) differs from AD by better multimodal retention on learning tasks, different patterns of generative word fluency, defective qualitative executive functioning, and by markedly impairment of comportment. For temporal variants of frontotemporal lobar degenerations, progressive aphasia and semantic dementia, worse language performance relative to AD is typically characteristic. (J Geriatr Psychiatry Neurol 2007;20:227-238)

Effects of anomalous language representation on neuropsychological performance in temporal lobe epilepsy

Objective: To examine the effects of anomalous language representation (i.e., mixed- and right-cerebral dominant) on neuropsychological performance. Background: Right cerebral language dominance resulting from early cerebral injury is associated with relatively preserved language function with decreased visuospatial ability. However, previous reports of this phenomenon have examined patients with relatively large cerebral injuries (e.g., infantile hemiplegia) or limited sample sizes. Methods: A total of 561 patients with complex partial seizures of left temporal lobe origin were studied. Patients were classified into left (n = 455), bilateral (n = 58), and right (n = 48) language dominant groups based on Wada testing. Results: Right language dominant patients performed more poorly on multiple tests of visuospatial function, including Performance IQ (PIQ), than did left language patients. No significant group differences were detected for measures of language or general verbal function. The effects of bilateral language on PIQ differed according to handedness. Lowered PIQ was present in the bilateral nondextral group but not for bilateral dextral patients, and this pattern was observed with other visuospatial measures. Conclusions: In patients with relatively small lesions restricted to the left mesial temporal lobe, a shift in language dominance to the right hemisphere is associated with decreased visuospatial functions but preserved verbal abilities. Nondextral patients with bilateral language representation also displayed decreased visuospatial performance, although dextral patients with bilateral language did not.

Age-related changes of the functional architecture of the cortico-basal ganglia circuitry during motor task execution

Normal human aging is associated with declining motor control and function. It is thought that dysfunction of the cortico-basal ganglia circuitry may contribute to age-related sensorimotor impairment, however the underlying mechanisms are poorly characterized. The aim of this study was to enhance our understanding of age-related changes in the functional architecture of these circuits. Fifty-nine subjects, consisting of a young, middle and old group, were studied using functional MRI and a motor activation paradigm. Functional connectivity analyses and examination of correlations of connectivity strength with performance on the activation task as well as neurocognitive tasks completed outside of magnet were conducted. Results indicated that increasing age is associated with changes in the functional architecture of the cortico-basal ganglia circuitry. Connectivity strength increased between subcortical nuclei and cortical motor and sensory regions but no changes were found between subcortical components of the circuitry. Further, increased connectivity was correlated with poorer performance on a neurocognitive task independently of age. This result suggests that increased connectivity reflects a decline in brain function rather than a compensatory process. These findings advance our understanding of the normal aging process. Further, the methods employed will likely be useful for future studies aimed at disambiguating age-related versus illness progression changes associated with neuropsychiatric disorders that involve the cortico-basal ganglia circuitry.

THE PREDICTION OF CHANGE: NORMATIVE NEUROPSYCHOLOGICAL TRAJECTORIES

While the application of normative standards is vital to the practice of clinical neuropsychology, data regarding normative change remains scarce despite the frequency of serial assessments. Based on 285 normal individuals, we provide co-normed baseline data with demographic adjustments and test-retest standardized regression based (SRB) models for three time points for several measures. These models delineate normal, expected change across time, and yield standardized z-scores that are comparable across tests. Using a new approach, performance on any previous trial was accounted for in the subsequent models of change, yielding serial normative formulas that model change trajectories rather than simple change from point to point. These equations provide indices of deviation from expected baseline and change for use in clinical or research settings.

Differential Patterns of Cognitive Decline in Anterior and Posterior White Matter Hyperintensity Progression

Background and Purpose— White matter hyperintensities (WMHs) found on brain MRI in elderly individuals are largely thought to be due to microvascular disease, and its progression has been associated with cognitive decline. The present study sought to determine patterns of cognitive decline associated with anterior and posterior WMH progression. Methods— Subjects included 110 normal controls, aged ≥60 years, who were participants in the Duke Neurocognitive Outcomes of Depression in the Elderly study. All subjects had comprehensive cognitive evaluations and MRI scans at baseline and after 2 years. Cognitive composites were created in 5 domains: complex processing speed, working memory, general memory, visual-constructional skills, and language. Change in cognition was calculated using standard regression-based models accounting for variables known to impact serial testing. A semiautomated segmentation method was used to measure WMH extent in anterior and posterior brain regions. Hierarchical multiple linear regression models were used to evaluate which of the 5 measured cognitive domains was most strongly associated with regional (anterior and posterior) and total WMH progression after adjusting for demographics (age, sex, and education). Results— Decline in complex processing speed was independently associated with both anterior (r2=0.06, P=0.02) and total WMH progression (r2=0.05, P=0.04). In contrast, decline in visual-constructional skills was uniquely associated with posterior progression (r2=0.05, P<0.05). Conclusions— Distinct cognitive profiles are associated with anterior and posterior WMH progression among normal elders. These differing profiles need to be considered when evaluating the cognitive correlates of WMHs.

Verbal and Nonverbal Fluency Performance Before and After Seizure Surgery

The utility of verbal (FAS) and nonverbal (Ruff Figural Fluency Test: RFFT) fluency tests for detecting deficits associated with focal seizures and surgical interventions was examined. The patients were 174 adults with intractable epilepsy who underwent epilepsy surgery: 152 temporal lobectomies and 22 frontal lobectomies. The results of the study suggest that the RFFT is somewhat superior to FAS in its ability to discriminate between frontal and temporal seizure foci, and is a useful component of preoperative neuropsychological batteries. Conversely, FAS appears more useful in detecting changes in neurocognitive outcome related to side of surgery. Controlling for postsurgical seizure outcome did not change the results, although continued seizures did have a deleterious effect on both FAS and RFFT, regardless of site of surgery.