Faculty Bibliography

Although improved cognition has been reported in patients with mild Parkinson's disease (PD) following the administration of levodopa, mixed results have been found in moderately-to-severely affected PD patients (MSPD), particularly in studies conducted since 1980. In the present study, 16 MSPD patients were tested on separate days, once following overnight levodopa withdrawal and once while optimally treated. A battery of neuropsychological tests that assess a range of cognitive functions (i.e., attention, language, visuospatial, memory, and executive), as well as a measure of depression, were used. Although patients performed better on a measure of confrontation naming in the untreated than in the treated condition, there were no significant differences for any of the other cognitive variables or for the depression scale variable. Thus, these data suggest that there are generally no adverse or beneficial effects of levodopa therapy on cognition in MSPD patients

OBJECTIVE: To characterize cognitive status in a sample of individuals with late-onset GM2 gangliosidosis (commonly referred to as late-onset Tay-Sachs disease). METHODS: Seventeen subjects (13 men, 4 women) diagnosed with GM2 gangliosidosis were evaluated. Subjects ranged in age from 18 to 56 years and were in various stages of disease progression. Subjects underwent comprehensive neuropsychological assessment. Impairment was defined as performance more than 1.6 SD below the normative mean. RESULTS: Group mean performance was within the denoted normal range on all measures except on a task assessing visual sequencing and set shifting. Approximately one-half of the sample scored in the impaired range on measures of processing speed, visual sequencing, and set shifting. One-third of the sample also scored in the impaired range on measures of delayed verbal recall. Impairment tended to be restricted to a subset of the sample, as 5 of the 14 subjects able to undergo formal testing accounted for 70% of the total number of impaired scores. If the three subjects unable to participate in formal testing are also considered impaired, 47% of the current sample exhibited significant cognitive impairment in at least one cognitive domain. CONCLUSION: In late-onset GM2 gangliosidosis, there is a risk of impairment in executive functioning and memory as well as cerebellar dysfunction. Dementia was not present in any subjects in the current sample

Many commonly used measures of figural reproduction have been found to be relatively insensitive to the effects of right temporal lobe dysfunction. More positive findings are present in studies using measures of figural learning over repeated trials. This study examined the use of a commercially available measure of figural learning in a sample of epilepsy patients undergoing presurgical neuropsychological testing. The Brief Visuospatial Memory Test-Revised (BVMT-R) was administered to 47 subjects undergoing comprehensive presurgical workups with video and EEG monitoring. Groups with left (N = 25) and right (N = 22) temporal lobe seizures did not differ on BVMT-R measures of learning, delayed recall, or yes/no recognition. Approximately 29% of the sample exhibited 'impaired' performance in comparison to published norms. The results of receiver operating curve analyses revealed little discrimination in performance between groups. The BVMT-R does not appear to have the sensitivity required for assessing nonverbal memory in this population

The cognitive effects of subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) have been examined. However, there are no reported studies that evaluate, by incorporating a disease control group, whether neuropsychological performance in surgical patients changes beyond the variability of the assessment measures. To examine this issue, 17 PD patients were tested before and after bilateral STN stimulator implantation, both on and off stimulation. Eleven matched PD controls were administered the same repeatable neuropsychological test battery twice. Relative to changes seen in the controls, the surgery for electrode placement mildly adversely affected attention and language functions. STN stimulation, per se, had little effect on cognition. The STN DBS procedure as a whole resulted in a mild decline in delayed verbal recall and language functions. There were no surgery, stimulation, or procedure effects on depression scale scores. In contrast to these group findings, one DBS patient demonstrated significant cognitive decline following surgery

BACKGROUND: Myoclonus-dystonia (M-D) is a movement disorder with involuntary jerks and dystonic contractions. Autosomal dominant alcohol-responsive M-D is associated with mutations in the epsilon-sarcoglycan gene (SGCE) (six families) and with a missense change in the D2 dopamine receptor (DRD2)gene (one family). OBJECTIVE: To investigate the clinical phenotype associated with M-D including motor symptoms, psychiatric disorders, and neuropsychological deficits. METHODS: Fifty individuals in three M-D families were evaluated and a standardized neurologic examination and DNA analysis were performed. Psychiatric profiles were established with the Diagnostic Interviews for Genetic Studies (DIGS) and the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Cognition was evaluated with standardized neuropsychological tests. RESULTS: Distinct truncating mutations in the SGCE gene were identified in each family. Additionally, a missense alteration in the DRD2 gene was previously found in one family. Motor expression was variable, with onset of myoclonus or dystonia or both affecting the upper body and progression to myoclonus and dystonia in most cases. Psychiatric profiles revealed depression, obsessive-compulsive disorder, substance abuse, anxiety/panic/phobic disorders, and psychosis in two families, and depression only in the third family. Averaged scores from cognitive testing showed impaired verbal learning and memory in one family, impaired memory in the second family, and no cognitive deficits in the third family. CONCLUSIONS: Cognitive deficits may be associated with M-D. Psychiatric abnormalities correlate with the motor symptoms in affected individuals. Assessment of additional M-D families with known mutations is needed to determine whether these are characteristic phenotypic manifestations of M-D.

OBJECTIVE: This technical report and feasibility study propose a standardized method for collecting neuropsychological data in patients undergoing the deep brain stimulation (DBS) procedure. BACKGROUND: Programs for standardizing motor data collected in studies investigating surgical therapies for Parkinson disease are already widely used (e.g., Core Assessment Program for Intracerebral Transplantations). The development and rationale for the proposed Program for Neuropsychological Investigation of Deep Brain Stimulation (PNIDBS) are outlined, and support for the feasibility of these methodologies is provided via preliminary data. METHOD: The PNIDBS includes a core battery of neuropsychological tests that assesses a wide range of cognitive functions (attention, language, visuospatial, memory, and executive) as well as depression. Using the PNIDBS, three Parkinson disease and two dystonia patients were evaluated at baseline and after surgery, once with stimulation off and once with stimulation on. RESULTS: Patients with severe motor disabilities were able to complete the PNIDBS. These preliminary data suggest that the DBS procedure as a whole had a minimal impact on cognitive functioning in most patients studied. There was also some evidence that the one patient who showed cognitive decline after the DBS procedure had demographic and clinical characteristics that may have put him at risk for this decline. CONCLUSIONS: The procedures in the PNIDBS were systematically developed and are feasible to execute. The relatively brief core battery has multiple versions and can be supplemented to meet individual investigator needs. By evaluating the components of the DBS procedure (electrode placement and stimulation), the PNIDBS can address clinical questions regarding the cognitive effects of the DBS procedure as well as investigate basic scientific issues regarding how different cognitive functions are affected when subcortical-prefrontal circuits are manipulated by the DBS procedure.

To determine whether dopamine metabolism is abnormal in HIV infected patients and whether dopamine metabolism abnormalities are related to specific neuropsychologic characteristics in HIV-infected patients, we measured cerebrospinal fluid (CSF) levels of homovanilic acid (HVA), the primary dopamine metabolite, in 10 HIV-infected patients and compared it to HVA levels in CSF in a group of 13 healthy control subjects. HIV-infected patients were also assessed with a battery of neuropsychologic tests and HVA levels were then correlated with performance on specific neuropsychologic tests. The mean (+/-SD) HVA level in CSF was 100.9 +/- 29.3 nmol/L in the HIV-infected study group and 230.5 +/- 50.0 nmol/L in the non-HIV-infected control group (p < 0.0001). The decrease in concentrations of HVA in CSF correlated with impairment on performance on neuropsychologic testing (Spearman r = 0.67; p = 0.03). When the relationship between HVA levels and specific cognitive domains was evaluated, we observed trends for positive correlation between HVA levels and tests that measure motor speed (r = 0.59; p = 0.074) and those testing attention, concentration, and executive control (r = 0.54; p = 0.108). There was no relationship between performance on memory tests and CSF HVA levels (r = -0.0061; p = 0.987). These results further support the hypothesis that dopaminergic dysfunction plays an important role in the pathogenesis of AIDS dementia complex (ADC) and suggest that specific motor and cognitive abnormalities may be related to depressed dopaminergic activity. This may have important implications for the development of treatments or preventive strategies for ADC

This study was designed to address the issue of whether there is a general processor for the perception of emotion or whether there are separate processors. We examined the relationships among three channels of emotional communication in 100 healthy right-handed adult males and females. The channels were facial, prosodic/intonational, and lexical/verbal; both identification and discrimination tasks of emotional perception were utilised. Statistical analyses controlled for nonemotional perceptual factors and subject characteristics (i.e. demographic and general cognitive). For identification, multiple significant correlations were found among the channels. For discrimination, fewer correlations were significant. Overall, these results provide support for the notion of a general processor for emotional perceptual identification in normal adult subjects