Neuropsychological impairment in Parkinson's disease with and without depression.

OBJECTIVES: To compare quantitative and qualitative aspects of neuropsychological test performance in patients with Parkinson's disease who currently had depression (PDD) and those without depression (PDN) so as to evaluate the influence of depression on cognition in Parkinson's disease. DESIGN: Cross-sectional comparisons among PDN, PDD, and normal control (NC) groups. The setting was a neurodegenerative disease research center in a teaching hospital. Groups consisted of 44 patients with PDN and 44 patients with PDD matched for age, education, gender, age at onset of disease, disease duration, and disease severity; a group of 44 NC subjects matched for age, education, and gender; and a second set of comparisons between 15 patients with PDN and 15 patients with PDD also matched for overall severity of cognitive impairment. MEASURES: The neuropsychological measures used were the Mattis Dementia Rating Scale, Beck Depression Inventory, Wisconsin Card Sorting Test, Controlled Oral Word Association Test, Logical Memory subtest of the Wechsler Memory Scale-Revised, Digit Span subtest of the Wechsler Adult Intelligence Scale-Revised, and the Boston Diagnostic Aphasia Examination's Animal Naming test and Boston Naming Test. RESULTS: Relative to the NC group, both PDN and PDD groups demonstrated impairments in immediate and delayed verbal recall, semantic fluency, and problem solving. When PDN and PDD groups were matched for demographic and disease variables, only the PDD group evidenced impairment relative to NC in visual confrontation naming, and in lexical and semantic fluency. In addition, impairments on immediate recall and semantic fluency in the PDD group were more pronounced than those in the PDN group. However, when PDN and PDD groups were also matched for overall severity of cognitive impairment, no significant differences emerged among the two groups' neuropsychological test performances. CONCLUSIONS: Depression exacerbates some memory and language impairments associated with PD, even when the PDN and PDD groups are matched for demographic and disease variables. However, the extent and pattern of cognitive impairment is similar in PDN and PDD when the groups are also matched also for overall severity of cognitive impairment. Depression influences the quantity rather than the quality of cognitive impairment associated with Parkinson's disease.

Unilateral pallidal stimulation for Parkinson's disease: neurobehavioral functioning before and 3 months after electrode implantation.

Unilateral pallidotomy is thought to have a low risk for cognitive morbidity. Nonetheless, recent research suggests that some patients experience declines in memory and language and that pallidal stimulation might be a safer treatment for Parkinson's disease (PD). We investigated the neurobehavioral effects of unilateral pallidal stimulation. Nine consecutive PD patients undergoing unilateral deep brain-stimulating electrode implantation in the globus pallidus interna were evaluated with a neuropsychological test battery approximately 1 month before and 3 months after surgery. Patients reported significantly fewer symptoms of anxiety and greater vigor after surgery. There was a trend toward fewer depressive symptoms. Semantic verbal fluency and visuoconstructional test scores declined significantly after surgery. However, among five patients showing declines in semantic verbal fluency, only one patient's score declined by more than 2 SD. No patient showed significant decline or improvement in the overall level of cognitive functioning. This study supports the relative safety, in terms of cognitive function, of unilateral pallidal stimulation in PD.

The influence of depression on cognition in Parkinson's disease: a pattern of impairment distinguishable from Alzheimer's disease.

Conflicting reports about the effects of depression on cognition in Parkinson's disease (PD) are difficult to interpret because they are based on small sample sizes and confound depression with other variables. We found that a sample of 45 PD patients with current depression was cognitively more impaired than a sample of 45 PD patients without current depression matched for age, education, gender, age at disease onset, disease duration, and disease severity. The domains of cognition impaired in the two PD groups (compared with 45 age-, education-, and gender-matched controls) overlapped considerably, but only the depressed PD group had impaired memory relative to the control group. Our comparison of 22 depressed PD patients and 22 Alzheimer's disease (AD) patients matched for over-all severity of cognitive impairment, age, education, and gender indicated that the depressed PD group performed significantly worse on visuoconstructive tasks and marginally worse on conceptualization tasks. In contrast, the AD group performed significantly worse than the depressed PD group on memory tasks. Together, our results suggest that depression has a negative impact on cognition (and, in particular, memory) in PD, and that the pattern of this cognitive impairment is distinguishable from that associated with AD.

Bilateral thalamic stimulation for the treatment of essential tremor.

OBJECTIVE: To determine the safety and efficacy of bilateral thalamic stimulation in the treatment of essential tremor (ET). METHODS: Nine ET patients with disabling tremor refractory to pharmacotherapy underwent bilateral staged implants. Tremor was assessed by the Fahn-Tolosa-Marin Tremor Rating Scale at baseline 1 (before first implant), baseline 2 (before second implant), and at 6-month and 1-year follow-up. Blinded evaluations were performed at 3 months. Associated changes in speech were evaluated in six patients. There were seven men and two women with a mean age of 73.8 years. RESULTS: There was a significant improvement in the mean total tremor score from a baseline of 66.1+/-11.6 to 28.4+/-12.8 12 months after the second surgery. Similarly, the mean motor tremor subscore was 20.1+/-5.0 before the first surgery and improved significantly to 14.1+/-3.6 before the second surgery. Motor tremor scores 6 months after the second surgery (6.0+/-3.7) and 12 months after the second surgery (7.5+/-3.9) also improved significantly relative to the preoperative scores. The mean activities of daily living (ADL) subscore at baseline was 18.2+/-2.9 and improved significantly before the second surgery to 9.0+/-3.2. These ADL scores further improved 6 months (6.2+/-5.2) and 12 months (7.9+/-5.7) following the second surgery, but these gains were not significant. Blinded evaluations also revealed a similar degree of improvement. Complications were noted in five patients: asymptomatic intracranial hematoma (1), postoperative seizures (1), a hematoma over the implanted pulse generator (IPG) (1), lead repositioning (1), and IPG malfunction (1). Adverse effects related to stimulation were mild and resolved with adjustment of the stimulation parameters. Three of the six patients demonstrated worsening of dysarthria with both stimulators on. CONCLUSIONS: Bilateral thalamic stimulation is effective in reducing tremor and functional disability in ET; however, dysarthria is a possible complication.

Neuropsychological and quality of life outcome after thalamic stimulation for essential tremor.

OBJECTIVE: To evaluate short-term effects of unilateral thalamic deep brain stimulation (DBS) on cognition, mood state, and quality of life in patients with essential tremor (ET). BACKGROUND: Unilateral thalamotomy and thalamic DBS are effective in alleviating refractory tremor contralateral to the side of surgery. Thalamotomy can lead to cognitive morbidity, and DBS might be a preferable surgical intervention given potential avoidance or reversibility of such morbidity. Although unilateral thalamic DBS is cognitively safe and leads to quality of life improvement in PD, its neurobehavioral effects in ET are unknown. METHODS: Forty patients with ET were administered a broad neuropsychological test battery, measures of mood state, and generic and disease-specific quality of life measures approximately 1 month before and 3 months after surgery (left hemisphere, 38 patients). RESULTS: Unilateral thalamic DBS was associated with significant improvements in tremor and dominant-hand fine visuomotor coordination. Statistically significant but clinically modest gains were observed on tasks of visuoperceptual and constructional ability, visual attention, delayed word list recognition, and prose recall. Only lexical verbal fluency declined significantly after surgery. Patients rated themselves as less anxious after surgery, and they perceived their quality of life as improved significantly. In particular, patients reported improved quality of life with respect to activities of daily living, stigma, emotional well-being, and communication. CONCLUSIONS: Unilateral thalamic DBS for ET is cognitively safe and associated with improvements in anxiety and quality of life in the near term and in the absence of operative complications. Patients were better able to carry out activities of daily living after surgery, and they reported improvement in several psychosocial domains of quality of life.

Action (verb naming) fluency as an executive function measure: convergent and divergent evidence of validity.

Numerous studies have demonstrated dissociable neuroanatomic underpinnings for the retrieval of grammatical classes of words such as nouns and verbs. Whereas retrieval of common and proper nouns is primarily mediated by posterior and anterior temporal regions, respectively, verb retrieval is primarily mediated by frontal regions. The majority of studies evaluating verb production have utilized tasks requiring subjects to name a graphically depicted action (i.e. action naming), leaving tests of verb generation in the absence of prompting stimuli (i.e. action fluency) largely unexamined. In a recent study, Piatt, Fields, Paolo, Koller and Tröster (in press) found that an action fluency task discriminated demented Parkinson's disease (PD) patients from non-demented PD patients and healthy control subjects, whereas lexical and categorical fluency tasks did not. These authors suggested that action fluency was sensitive to the fronto-striatal pathophysiology associated with PD dementia, and thus, that action fluency might serve as an indicator of executive functioning. This study was undertaken to evaluate the construct validity of action fluency as an executive function measure in a group of healthy elderly control subjects. Findings revealed modest to moderate relationships between action fluency and several putative executive measures. Action fluency was unrelated to indices of semantic and episodic memory. Results support the construct validity of action fluency as an executive function measure and suggest that this task may provide some unique information not tapped by traditional executive function tasks.

Cortical and subcortical influences on clustering and switching in the performance of verbal fluency tasks.

Impairments on lexical and semantic fluency tasks occur in both cortical and subcortical dementia. Recent reports that the average size of phonemic and semantic clusters is reduced in Alzheimer's disease (AD), but not in Parkinson's disease (PD) could support the hypothesis that in AD verbal fluency deficits arise from degraded memory storage while in PD the same impairments result from defective retrieval. In the present study, patients with AD, PD with dementia, or Huntington's disease produced fewer words, fewer switching responses and smaller semantic cluster sizes. Patients with multiple sclerosis, regardless of whether or not they were demented, produced fewer words and switching responses, but normal size clusters, and patients with PD without dementia performed normally on all fluency measures. These results indicate that reductions in cluster size on verbal fluency tests are best interpreted as changes in the efficiency of access to lexical and semantic memory stores. The findings are also consistent with the idea that patterns of cognitive impairment may differ among diseases that result in subcortical dementia.

Test-retest stability of the California verbal learning test in older persons.

One hundred fifty-one healthy older persons were administered the California Verbal Learning Test (CVLT) on 2 occasions, an average of 1.30 years apart. Means for age and education were 69.63 years (SD = 6.46) and 14.91 years (SD = 2.54), respectively. Stability coefficients ranged from .24 on number of perseverations to .76 for both List A total recall and long-delay free recall. Only 5 CVLT scores demonstrated a significant change on retest, and the overall magnitude of improvement was small. To assist clinicians in the process of detecting significant change on retest, the authors provide standard error of difference values and 90% confidence intervals for 22 CVLT scores.

Analysis of pallidotomy lesion positions using three-dimensional reconstruction of pallidal lesions, the basal ganglia, and the optic tract.

OBJECTIVE: To assess the position of radiofrequency pallidotomy lesions placed using microelectrode stimulation and cellular recordings in relation to a stereotactically defined starting point. Radiofrequency lesion locations were also evaluated in relation to the putamen, posterior limb of the internal capsule, and optic tract. METHODS: Magnetic resonance images obtained from 23 patients with Parkinson's disease who underwent pallidotomy at the University of Kansas Medical Center were analyzed. Using computerized techniques, lesion positions in relation to the midcommissural point and a hypothetical starting point were determined. Data segmentation and three-dimensional reconstruction of pallidal lesions, the internal capsule, and the optic tract allowed assessment of lesion position in relation to internal anatomy. Clinical outcome of pallidotomy was assessed using both the Unified Parkinson's Disease Rating Scale and the Dementia Rating Scale. RESULTS: Pallidal lesions were usually placed anterior and dorsal to the stereotactically defined starting point. The position of pallidal lesions in the men were observed, in four trials, to be significantly more dorsal than the lesions in the women. The outer zone of the lesion was usually adjacent to the internal capsule and the putamen and relatively close to the optic tract. The inner zone of the lesion was usually several millimeters removed from anatomic boundaries of the putamen, internal capsule, and optic tract. Patients achieved favorable outcomes, with reduced dyskinesias and "off" time and improvement of their Parkinsonian symptoms, as evidenced by clinical assessment, the Unified Parkinson's Disease Rating Scale, and the Dementia Rating Scale. CONCLUSION: Microelectrode stimulation and cellular recordings usually led to a final pallidotomy lesion position that deviated from the stereotactically defined starting point. The pallidotomy lesions in the men were observed to be more dorsal than the lesions in the women. Clinical outcomes were not correlated with either lesion location relative to the starting point or distances between the pallidal lesion and the putamen, internal capsule, or optic tract. Kinesthetically responsive cells may be localized generally more anterior and dorsal to the starting point (within the globus pallidus) and may be grouped variably from patient to patient in relation to other basal ganglia structures. Although the primary lesion site is most likely within the sensorimotor region of the globus pallidus internus, the more dorsal locations of responsive cell groups may indicate that some lesion sites may be localized within the globus pallidus externus.

The roles of semantic networks and search efficiency in verbal fluency performance in intractable temporal lobe epilepsy.

Two competing hypotheses (i.e., disruption of semantic networks vs. search inefficiency) concerning the mechanisms underlying impaired semantic verbal fluency in temporal lobe epilepsy (TLE) were tested within a single paradigm. Reports that semantic verbal fluency is more impaired in left than right TLE groups were confirmed by the findings that the left TLE group produced fewer words on a supermarket fluency task than did the normal control (NC) group, and that the performance of the right TLE group was intermediate to that of the left TLE and NC groups. Because both TLE groups generated fewer words per category of supermarket items sampled, and produced a higher ratio of category labels relative to category exemplars than did the NC group, it can be surmised that TLE disrupts semantic memory networks. The findings did not support the competing hypothesis that reduced semantic verbal fluency in TLE is a manifestation of inefficient search/retrieval strategies, possibly associated with distal frontal lobe pathophysiology. Specifically, the TLE and NC groups did not differ significantly in their mean number of perseverations, intrusions, or search efficiency (operationalized as the ratio of the number of shifts between categories to the number of categories sampled).

Differentiation of the dementias of Alzheimer's and Parkinson's disease with the dementia rating scale.

The Mattis Dementia Rating Scale (DRS) was used to distinguish between 50 dementia of the Alzheimer's type (DAT) and 50 Parkinson's disease (PD) subjects matched for age, education, and DRS total score. Despite a similar level of overall cognitive impairment, the DAT group earned significantly lower scores than did the PD group on the Memory subscale, while the PD group displayed lower scores than did the DAT subjects on the Construction subscale. Ajackknifed, stepwise, linear discriminant function using the five DRS subscales revealed that the Memory, Construction, and Initiation subtests significantly distinguished the groups. These results suggest qualitative differences in the dementias of DAT and PD patients and reveal that such differences can emerge on brief mental status examinations.

Influence of demographic variables on the Dementia Rating Scale.

Demographic characteristics influence many cognitive assessment tools. We evaluated the impact of age, education, and gender on the Dementia Rating Scale (DRS) in a sample of 212 normal people. Separate regression analyses revealed that age was the most potent demographic factor, whereas education and gender had little impact. However, the amount of variance accounted for by age was small (less than 20%). Clinical utility of age-adjusted DRS total score cut-offs was investigated in samples of Alzheimer's and Parkinson's disease patients. Hit rate analysis revealed greater sensitivity for a single cut-off value than age-corrected cut-off scores. Overall, these findings revealed the lack of a clinically meaningful relationship between demographic characteristics and DRS scores, suggesting that age, education, and gender can be ignored for interpretative purposes based on cut-off scores.

Gender differences in Parkinson's disease.

We examined data from 630 patients entered into the University of Kansas Medical Center's Parkinson's Disease (PD) Registry to determine if gender differences exist in terms of both cognitive and motor symptoms of PD. An analysis of the Mini-Mental State Examination scores indicated slightly higher scores for women relative to men. Although women had significantly better scores than did men on the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS), they had a significantly greater prevalence of dyskinesias compared with men. These motor differences were significant only in patients with PD of greater than 5 years duration. There were no gender differences for age of diagnosis, Hoehn and Yahr Staging, Schwab and England Scale, or the mentation and activities of daily living sections of the UPDRS. We conclude that as PD progresses, gender differences emerge, with men exhibiting more severe parkinsonian motor features and women experiencing more levodopa-induced dyskinesia.

Effect and time course of deep brain stimulation of the globus pallidus and subthalamus on motor features of Parkinson's disease.

We studied the effect and temporal profile of deep brain stimulation (DBS) of the globus pallidus and subthalamic nucleus on the motor signs of Parkinson's disease (PD). Four patients with bilateral deep brain stimulators of the globus pallidus and four patients with bilateral deep brain stimulators of the subthalamus were studied while taking no medication and at 15 and 30 minutes and 1, 2, 4, and 6 hours after turning stimulation on. An immediate (15 minutes) and sustained (6 hours) benefit was observed for all the motor manifestations of PD for both stimulation sites. Deep brain stimulation of the globus pallidus and subthalamus is highly effective in reducing all the cardinal motor features of PD.

Motor complications of chronic levodopa therapy in Parkinson's disease.

We report on motor complications of chronic levodopa therapy among 811 levodopa-responsive patients with idiopathic Parkinson's disease (PD), stratified by duration after diagnosis. Predictable "offs" were noted in 20.2% of patients in the first 5 years, in 58.3% after 15 years. Unpredictable or sudden offs and early morning dystonia were less common. Longer duration was associated with greater percentages of patients with off periods or dyskinesias (up to 70% after 15 years), although patients with 6-15 years' duration saw relatively little increase in frequency of those complications, and a minority of patients (approximately 30%) with duration into the second decade did not experience off periods or dyskinesia. Across groups, mean Hoehn and Yahr stage and daily levodopa dosage progressively increase (and mean Schwab and England disability ratings decrease), but more conservatively than in prior reports in the postlevodopa era. We note that with advancing PD duration, levodopa complications are more common, but in many cases there appear to be relatively stable periods in terms of levodopa dosage and disease severity, and a minority of patients will be relatively free of motor complications into the second decade of their disease.

A comparison of Parkinson's disease symptoms and self-reported functioning and well being.

This study was designed to determine if the presence of tremor, rigidity, bradykinesia and postural instability and gait abnormalities differentially influence Parkinson's disease patients' ratings of quality of life as measured by the Parkinson's Disease Questionnaire (PDQ-39). A regression analysis indicated that the presence of postural instability and gait abnormalities and bradykinesia were strongly predictive of PDQ-39 quality of life scores. The presence of tremor and rigidity had little effect on patients' ratings of quality of life.

Psychogenic movement disorders.

The diagnosis of PMDs is by no means a simple task. Organic movement disorders are more often misdiagnosed as psychogenic rather than the reverse. The degree to which psychological factors underlie movement disorders may range from being the exclusive cause to being a reaction to the movement disorder. The most common psychiatric illnesses associated with PMDs are depression, conversion reactions, and anxiety disorders. Although the diagnosis of psychogenicity may seem elusive, the definitions and diagnostic criteria of PMDs outlined in this article serve as useful guidelines for obtaining a more accurate diagnosis. The emphasis on a multidisciplinary approach with a strong alliance of neurologist and psychologist or psychiatrist is essential to assure proper diagnoses and treatment.

Cognitive outcome following staged bilateral pallidal stimulation for the treatment of Parkinson's disease.

As neurosurgical treatment of parkinsonian symptoms has become increasingly popular, concern about the cognitive morbidity which may result from such interventions has risen proportionately. Previous reports of cognitive difficulties associated with pallidotomy and thalamotomy, especially in bilateral cases, have provided the impetus for research into chronic electrical deep brain stimulation procedures which are believed to be safer than ablation. Given the lack of neurobehavioral research following bilateral deep brain stimulation procedures, this preliminary study of six Parkinson's disease patients undergoing staged bilateral pallidal stimulation was undertaken. A battery of tests assessing attention, executive function, visuomotor coordination, language, visuoperceptual function, learning memory and mood revealed no significant change in overall level of cognitive functioning after either unilateral or bilateral pallidal deep brain stimulation. No significant declines were observed about three months following bilateral stimulation, and in fact, significant gains in delayed recall and relief of anxiety symptoms were noted. It was concluded from this preliminary data that bilateral pallidal stimulation for the treatment of Parkinson's disease, at least in the absence of operative complications, offers a cognitively safe alternative to ablation.

Neuropsychological sequelae of exposure to the chlorinated hydrocarbon solvents trichloroethylene and trichloroethane.

Reports in the literature concerning the acute neurobehavioral effects of trichloroethylene (TCE) and trichloroethane (TCA) conflict as to whether or not cognitive deficits ensue. Our study of two patients acutely exposed to low concentrations of TCE suggests that (a) acute, low-dose exposures are sufficient to produce the mild to moderate impairments in psychomotor speed, attention and memory also reported after chronic exposures; (b) these memory impairments may be characterized by storage and/or retrieval difficulties; (c) the neural damage produced by TCE exposure is likely to be diffuse, but temporal lobe structures supporting memory may be more sensitive to TCE exposure than other brain structures; and (d) even brief exposures can lead to prolonged, but not necessarily chronic mild to moderate cognitive impairment. In a third case, exposed to trichloroethane (TCA), the neuropsychological profile suggests that this substance has few, if any, neurobehavioral effects at low concentrations.