Cognitive–motor learning in Parkinson's disease.

Procedural learning deficits are common in Parkinson's disease (PD), but contradictory results have been reported in rotary pursuit learning. This article compared rotary pursuit learning in 2 nondemented PD groups and 2 normal control (NC) groups, using a between-subjects group design in which 3 rotation speeds were presented either randomly or in blocks. The pattern of learning differed between the randomized and the blocked conditions in the NC, but not in the PD groups. Learning was impaired in the PD group in the random condition only. Memory, visuospatial, or executive skills were not associated with the PD group's poorer learning in the randomized context. Results show that procedural learning deficits are not universal with basal ganglia abnormalities but rather depend on the specific cognitive requirements of the learning context. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Progression of motor and cognitive impairment in Parkinson's disease

We performed a longitudinal study (mean follow-up 86.7 months) to evaluate motor and mental deterioration in patients with Parkinson's disease. Of the original 91 patients, only 61 could be re-examined 7 years later and 11 of these had become demented (PD-Dems). PD-Dems were older with worse motor and, obviously, cognitive performance than non-demented parkinsonian patients (PDs). A global cognitive decay index (DI) was calculated for each patient. Based on this, non-demented PDs were further split into 38 stable parkinsonian patients (S-PDs) with DI-30% to +30%, and 10 deteriorated but non-demented parkinsonian patients (D-PDs) with a DI worse than -30% (as had PD-Dems). D-PDs were older and had greater motor impairment than S-PDs but did not differ from PD-Dems on these measures. D-PDs and PD-Dems deteriorated especially in attention, visuospatial and executive ability tests. Ageing seems to be the main predictive factor for mental deterioration.     

Association of a monoamine oxidase B allele with Parkinson's disease

Monoamine oxidase B (MAO-B) is implicated in the cause of Parkinson's disease (PD) because of its role in metabolizing the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and forming H2O2 during dopamine metabolism. Altered MAO-B activity has been observed in PD platelets. Polymerase chain reaction was used to amplify a portion of the MAO-B gene. Polymerase chain reaction products were screened with restriction enzymes to identify fragments useful for single-stranded conformational polymorphism analysis. A single-stranded conformational polymorphism was identified in an MAO-B polymerase chain reaction product after Hae III digestion. One hundred twenty-one control individuals were allelotyped with frequencies of 0.45 and 0.55 for alleles 1 and 2, respectively. Frequencies of 0.62 and 0.38 (1 and 2, respectively) were observed in a population of 46 patients with PD. The presence of MAO-B allele 1 is associated with a relative risk for PD of 2.03-fold (confidence interval, 1.44-2.61; p < 0.02). For comparison, a monoamine oxidase A polymorphism was used to determine allelic frequencies in these same populations and no statistically significant differences were found. These results suggest that an inherited variant of MAO-B may be involved in a genetic predisposition for PD.     

Opposite motor effects of pallidal stimulation in Parkinson's disease

We studied the effects--on parkinsonian signs, on levodopa-induced dyskinesias, and on levodopa response--of acute experimental high-frequency stimulation of the internal pallidum (GPi) during off-drug and on-drug phases. Thirteen quadripolar electrodes were evaluated in 8 patients with Parkinson's disease (PD). Stimulation of the most ventral contacts, lying at the ventral margin of or just below the GPi, led to pronounced improvement in rigidity and a complete arrest of levodopa-induced dyskinesias. The antiakinetic effect of levodopa was also blocked and the patients became severely akinetic. Stimulation of the most dorsal contacts, lying at the dorsal border of the GPi or inside the external pallidum, usually led to moderate improvement of off-drug akinesia and could also induce dyskinesias in some patients. When using an intermediate contact for chronic stimulation, a good compromise between these opposite effects was usually obtained, mimicking the effect of pallidotomy. We conclude that there are at least two different functional zones within the globus pallidus, at the basis of a different pathophysiology of the cardinal symptoms of PD. The opposite effects may explain the variable results of pallidal surgery reported in the literature and may also largely explain the paradox of PD surgery. A possible anatomical basis for these differential functional effects could be a functional somatotopy within the GPi, with the segregation of the pallidofugal fibers from the outer portion of the GPi, on one hand, forming the ventral ansa lenticularis and from the inner portion of the GPi, on the other hand, forming the dorsal lenticular fasciculus.     

Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease

OBJECTIVE: To determine the effects of the N-methyl-D-aspartate (NMDA) antagonist amantadine on levodopa-associated dyskinesias and motor fluctuations in Parkinson's disease (PD). BACKGROUND: NMDA receptor blockade can ameliorate levodopa-induced dyskinesias in primates and PD patients. Amantadine, a well-tolerated and modestly effective antiparkinsonian agent, was recently found to possess NMDA antagonistic properties. METHODS: Eighteen patients with advanced PD participated in a double-blind, placebo-controlled, cross-over study. At the end of each 3-week treatment arm, parkinsonian and dyskinesia scores were obtained during a steady-state intravenous levodopa infusion. Motor fluctuations and dyskinesias were also documented with patient-kept diaries and Unified Parkinson's Disease Rating Scale (UPDRS) interviews. RESULTS: In the 14 patients completing this trial, amantadine reduced dyskinesia severity by 60% (p = 0.001) compared to placebo, without altering the antiparkinsonian effect of levodopa. Motor fluctuations occurring with patients' regular oral levodopa regimen also improved according to UPDRS and patient-kept diaries. CONCLUSIONS: These findings suggest that amantadine given as adjuvant to levodopa can markedly improve motor response complications and support the view that hyperfunction of NMDA receptors contributes to the pathogenesis of levodopa-associated motor complications.     

PET studies on brain monoamine transporters with carbon-11-beta-CIT in Parkinson's disease

The cocaine analog 2 beta-carbomethoxy-3 beta-[4-iodophenyl]tropane (beta-CIT) labeled with 11C was used to study dopamine reuptake sites with PET. METHODS: Three normal subjects and nine patients with Parkinson's disease were investigated. Each of them underwent a dynamic PET scan (25 timeframes over 80 min) with [11C]-beta-CIT. A dose of 102.5-211.3 MBq (2.77-5.71 mCi) of this ligand was administered intravenously and a PET examination with an ECAT 931/08 PET camera was carried out. Ratios between the striatal/cortical/thalamic/midbrain and cerebellar uptake of this radioligand were calculated. RESULTS: The highest accumulation of [11C]beta-CIT was observed in the caudate and putamen, though there was some uptake in the thalamus and the midbrain. Cortical uptake was negligible. Carbon-11-beta-CIT accumulated significantly less in the putamen of the Parkinson's patients than in the normal subjects. The putamen-to-cerebellum ratio in the Parkinson's patients was 1.59 +/- 0.04 and 1.80 +/- 0.13s (p = 0.028) in the normal subjects. In the caudate, there was no significant difference between the Parkinson's patients and the normal subjects. CONCLUSION: These results imply that [11C]beta-CIT is a useful compound for carrying out a PET examination of the function of the presynaptic monoaminergic neurons both in normal and pathological brains.     

Neuropsychological impairment, depression, and Parkinson's disease.

Examined the nature of cognitive impairment in Parkinson's disease (PD) and its relation to depression in 89 nondemented (mean age 69.35 yrs) and 19 demented (mean age 79.94 yrs) PD patients and 64 control Ss (mean age 66.44 yrs). PD Ss were significantly more depressed than controls on the Beck Depression Inventory and the Geriatric Depression Scale (GDS). There were significant, negative associations between scores on the GDS and performance on 8 neuropsychological test variables. Both PD groups were significantly impaired on 7 neuropsychologial test variables, including measures of visuomotor, memory, and executive functions. The demented PD group was more impaired than the nondemented PD and control groups on 9 neuropsychological test variables. Cognitive impairments in the nondemented PD group were relatively subtle and not apparent on the Mini-Mental State Examination. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Understanding verbal fluency in healthy aging, Alzheimer's disease, and Parkinson's disease.

Objective: Verbal fluency measures are frequently part of batteries designed to assess executive function (EF), but are also used to assess semantic processing ability or word knowledge. The goal of the present study was to identify the cognitive components underlying fluency performance. Method: Healthy young and older adults, adults with Parkinson's disease, and adults with Alzheimer's disease performed letter, category, and action fluency tests. Performance was assessed in terms of number of items generated, clustering, and the time course of output. A series of neuropsychological assessments were also administered to index verbal ability, working memory, EF, and processing speed as correlates of fluency performance. Results: Findings indicated that regardless of the particular performance measure, young adults performed the best and adults with Alzheimer's disease performed most poorly, with healthy older adults and adults with Parkinson's disease performing at intermediate levels. The exception was the action fluency task, where adults with Parkinson's disease performed most poorly. The time course of fluency performance was characterized in terms of slope and intercept parameters and related to neuropsychological constructs. Speed of processing was found to be the best predictor of performance, rather than the efficiency of EF or semantic knowledge. Conclusions: Together, these findings demonstrate that the pattern of fluency performance looks generally the same regardless of how performance is measured. In addition, the primary role of processing speed in performance suggests that the use of fluency tasks as measures of EF or verbal ability warrants reexamination. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Determination of conjugated monoamine metabolites in brain tissue

Levels of free and conjugated monoamine metabolites were analysed in brain tissue of rat and man. In the rat the conjugates were mainly of the sulfate ester type. The levels of conjugated dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) constituted 40--50% of the total amount of the metabolites. 4-Hydroxy-3-methoxy-phenylglycol (HMPG) and 5-hydroxy-3-indoleacetic acid (5-HIAA) were present as conjugates in 90 and 10% of the total levels. Chlorpromazine treatment resulted in an elevation of both the free and the conjugated forms of the dopamine metabolites and HMPG. In a human caudate nucleus obtained at autopsy both DOPAC and HMPG were present in the free form and as sulfate and glucuronide conjugates. The major dopamine metabolite found in this human brain was HVA. This metabolite and 5-HIAA occurred predominantly as free metabolites.     

Verb learning in Parkinson's disease.

The relative roles of grammatical processing and memory in the language comprehension difficulties of patients with Parkinson's disease (PD) were evaluated. 20 PD patients who did not have dementia were exposed to a new verb in a naturalistic setting. After 10 min, the semantic and grammatical information that they learned about the new verb was probed. Significant impairments in recalling some aspect of the new verb were seen in 55% of PD patients. Most of these patients demonstrated a language-sensitive deficit in appreciating grammatical information represented in the new verb. A small number of PD patients responded randomly to probes of all information about the new word, which suggests a memory impairment. It is concluded that difficulty in appreciating grammatical information contributes to the language impairments of PD patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Extent, pattern, and correlates of remote memory impairment in Alzheimer's disease and Parkinson's disease.

Content and contextual memory for remote public figures and events was assessed with a modified version of the Presidents Test in patients with Alzheimer's disease (AD) or Parkinson's disease (PD). Contributions of executive functioning, semantic memory, and explicit anterograde memory to remote memory abilities were also examined. The AD group had temporally extensive deficits in content and contextual remote memory not accountable for by dementia severity. The PD group did not differ from the control group in remote memory, despite anterograde memory impairment. These results support the position that different component processes characterize remote memory, various mnemonic and nonmnemonic cognitive processes contribute to remote memory performance, and anterograde and remote memory processes are dissociable and differentially disrupted by neurodegenerative disease. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Blockade of glutamatergic transmission as treatment for dyskinesias and motor fluctuations in Parkinson's disease

In animal models of Parkinson's disease (PD), glutamate antagonists diminish levodopa (LD)-associated motor fluctuations and dyskinesias. We sought to investigate if these preclinical observations can be extended to the human disease, by evaluating the effects of three non-competitive NMDA antagonists (dextrorphan, dextromethorphan and amantadine) on the motor response to LD in patients with advanced PD. In four separate trials, adjuvant therapy with these drugs reduced LD-induced dyskinesias and motor fluctuations. These findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate LD associated motor response complications.     

ECT in genetically confirmed Huntington's disease

The authors report successful ECT treatment of a severely depressed man with genetically confirmed Huntington's disease. He responded well to treatment and showed no abnormal movements or worsening in his cognitive status.     

Metamemory and prospective memory in Parkinson's disease.

Objective: Metamemory is integral for strategizing about memory intentions. This study investigated the prospective memory (PM) deficit in Parkinson's disease (PD) from a metamemory viewpoint, with the aim of examining whether metamemory deficits might contribute to PM deficits in PD. Method: Sixteen patients with PD and 16 healthy older adult controls completed a time-based PM task (initiating a key press at two specified times during an ongoing task), and an event-based PM task (initiating a key press in response to animal words during an ongoing task). To measure metamemory participants were asked to predict and postdict their memory performance before and after completing the tasks, as well as complete a self-report questionnaire regarding their everyday memory function. Results: The PD group had no impairment, relative to controls, on the event-based task, but had prospective (initiating the key press) and retrospective (recalling the instructions) impairments on the time-based task. The PD group also had metamemory impairments on the time-based task; they were inaccurate at predicting their performance before doing the task but, became accurate when making postdictions. This suggests impaired metamemory knowledge but preserved metamemory monitoring. There were no group differences regarding PD patients' self-reported PM performance on the questionnaire. Conclusions: These results reinforce previous findings that PM impairments in PD are dependent on task type. Several accounts of PM failures in time-based tasks are presented, in particular, ways in which mnemonic and metacognitive deficits may contribute to the difficulties observed on the time-based task. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Intellectual and cognitive functions in Parkinson's disease.

Compared the performance of 25 parkinson's disease patients and 25 normals matched for age, race, sex, and education on 32 behavioral variables including the wechsler-bellevue intelligence scale (form i), halstead neuropsychological battery, and R. Reitan's trail making test. Ss with parkinson's disease had lower mean scores than controls on all 32 measures. Statistical comparisons indicated these differences were significant beyond the .001 level for 25 tests, and on only 1 measure was the probability level greater than .05. Results indicate that parkinson's disease patients have suffered marked deterioration not only in motor abilities but also in problem-solving, sensory, memory, general cognitive, and abstracting and organizing abilities. (23 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Levodopa improves motor function without impairing cognition in mild non-demented Parkinson's disease patients. Parkinson Study Group

OBJECTIVE: The objective of the study was to determine the effects of short-term levodopa administration on motor, cognitive, and psychiatric aspects of Parkinson's disease (PD). BACKGROUND: The effects of levodopa on mental processes in PD are controversial. Opinions range from the claim that levodopa improves cognition to the opposite view that levodopa causes or exacerbates dementia, delusions, and hallucinations. Of the 800 idiopathic PD patients enrolled in the original DATATOP study, 387 reached the end point of functional disabilities sufficiently severe to require levodopa treatment. There were 263 men and 124 women who were comparable with regard to age, symptom duration of PD, and measures of PD severity. We compared test scores on motor performance, cognitive function, and psychiatric status before levodopa and again within 6 months after initiation of levodopa therapy. RESULTS: Levodopa administration improved all motor functions significantly. The improvement was significantly greater in women than in men. Levodopa administration did not worsen scores on any cognitive tests, and there were quantitatively small but significant improvements in tests of frontal lobe function. Levodopa exerted only minor effects on psychiatric measures. There were small but significant decreases in scores for depression, and increases in vivid dreams and hallucinations. CONCLUSIONS: Levodopa administration for up to 6 months in dosages sufficient to improve motor function has only small effects on cognitive function and psychiatric status in mild to moderate PD patients. We conclude that motor symptoms in early PD, which result from dopamine depletion, are dissociable from cognitive functions and psychiatric status, which may be more dependent on nondopaminergic mechanisms.