Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cognitive deficits are common in Parkinson's disease (PD), but the pathophysiology and relationship to Alzheimer's disease (AD) are not understood. We used a case-control format to investigate putative risk factors for the development of dementia in patients with Parkinson's disease. We compared 52 cognitively intact patients with PD to 43 PD patients with dementia with regard to factors previously suggested as relevant to either AD or PD. Multiple logistic regression yielded the following significant predictors of dementia in PD: lack of education (less than a high school graduate) (OR 21); severity of motor deficit (UPDRS total motor score greater than 20; OR 6.34), and PD onset at greater than 60 years of age (OR 4.12). The predictive probability of dementia in our subjects when all three variables were positive was 97.9%. We conclude that education may modify the risk of cognitive decline in PD. Protective effects of educational attainment, independent of dementia etiology, may be due to greater functional brain reserve.
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PMID:Risk factors for dementia in Parkinson's disease: effect of education. 871 45

The paper reports the profile of impairment across a variety of cognitive functions with special emphasis on tests sensitive to frontal lobe dysfunction, in 24 elderly depressed patients during and on recovery from mood disorder, compared with 15 age- and sex-matched controls. Traditional neuropsychological tests and a recently developed battery of computerized tests (CANTAB) were used. Impairments were found in the depressed group compared to controls and to themselves on recovery across all domains examined. The depressed group showed deficits on visuospatial recognition memory, attentional shifting at the extra-dimensional shift stage and in measures of both processing and motor speed without impaired accuracy in a visual search task. Impairments were also found on a planning task with disproportionately increased numbers of moves needed for more difficult problems and evidence of both slowed motor response and increased processing time once the task was commenced. Performance on recovery improved across all tasks. Comparisons were made with the performance of patients suffering from dementia of the Alzheimer type (DAT) and Parkinson's disease on similar tests. Response latencies in test performance were found to correlate with the number of episodes of depression suffered and with ventricular size on CT scan, as measured by computerized planimetry. On recovery, residual depression scores correlated with latency of test performance and with ventricular brain ratio. The results, thus, show that depression in the elderly is associated with a significant degree of deficit on tests sensitive to frontostriatal dysfunction. Some of the deficits appear specific to depression and some do not remit following clinical recovery. However, these impairments have to be interpreted in the context of a broad profile of cognitive deficit.
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PMID:Cognitive performance in tests sensitive to frontal lobe dysfunction in the elderly depressed. 873 17

We studied 45 non-demented patients with Parkinson's disease (PD), 12 with progressive supranuclear palsy (PSP), 10 with multiple system atrophy (MSA) and 12 with neuroleptic-induced parkinsonism (NIP) for the presence of apraxia. Our aim was to determine whether a standard comprehensive assessment of different praxic functions would demonstrate specific types of errors not attributable to bradykinesia, rigidity, tremor or any other abnormal elementary motor deficit. PD patients on chronic levodopa treatment were examined in the 'on' and 'off' (treatment) states. Based on apraxia assessment scores, bilateral ideomotor apraxia for transitive movements was found in eight (75%) and 12 (27%) of PSP and PD patients, respectively. Ideomotor apraxia was mainly characterized by spatial errors (i.e., external and internal configuration, body-part-as-object and trajectory). Four PSP but no PD patients exhibited ideomotor apraxia for intransitive movements. PSP as well as PD patients with ideomotor apraxia also had difficulties in imitating hand and finger postures, but none of them failed on pantomime comprehension and pantomime recognition/discrimination. Some PSP patients exhibited, in addition, a limbkinetic type of apraxia and a minority of them displayed deficits on tasks involving multiple steps. Neither MSA nor NIP patients showed any disturbance of praxic functions. There were no differences in age, disease duration, Mini Mental State Examination (MMSE), Unified Parkinson's disease Rating Scale and Hoehn-Yahr scores between apraxic and non-apraxic PD patients, and ideomotor apraxia scores were similar in the 'on' and 'off' states. A correlation was found between ideomotor apraxia scores in PD patients and deficits in frontal lobe-related neuropsychological tasks such as the Tower of Hanoi, verbal fluency and the Trail Making Test. Furthermore, PD patients with apraxia showed higher Hamilton depression scores than non-apraxic PD patients. In PSP patients, ideomotor apraxia scores correlated significantly with cognitive deficit as measured with MMSE. The presence or absence of cortical involvement, and its severity and distribution might determine the presence and type of apraxia in PD and PSP. Apraxia in these conditions would therefore reflect combined cortico-striatal dysfunction.
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PMID:Apraxia in Parkinson's disease, progressive supranuclear palsy, multiple system atrophy and neuroleptic-induced parkinsonism. 905 99

At present, there are three major surgical approaches to Parkinson's disease (PD): (1) Ablative surgery (i.e. pallidotomy, thalamotomy); (2) deep brain stimulation (DBS) of the thalamus, internal globus pallidus (GPi) and subthalamic nucleus (STN); and (3) grafting fetal mesencephalic cells into the striatum. As a result of increasing understanding of the pathophysiology of the basal ganglia and the demonstration of surgical alleviation of experimental parkinsonism, surgery has regained a paramount importance in the management of PD. The aim of pallidotomy and DBS is to reduce the excessive inhibitory output from the GPi and substantia nigra reticulata (SNr). Pallidotomy and DBS of the STN or GPi aim to reverse the pathophysiological consequences of dopamine deficiency in PD, and should be considered entirely symptomatic treatments. The ideal candidates for pallidotomy are young patients in good general health in whom dyskinesias are the main reasons for disability. Patients with severe bilateral problems uncontrollable with present pharmacological tools are candidates for DBS. As yet, there are no formal data to help decide how to choose between GPi and STN stimulation. In our practice, patients are allocated to GPi stimulation when 'on' dyskinesias are extremely severe. In most other instances, we prefer to perform STN stimulation. At present there is almost no reason to decide for the thalamic stimulation since tremor is equally arrested by STN stimulation, which in addition improves all other features of PD. Equally the only indication for thalamotomy would be a patient with long-standing tremor as the main clinical manifestation, which can not be controlled with drugs. The proportion of patients in whom the thalamus will be the preferable target for either DBS or thalamotomy is small (less than 5%). Grafting aims to repair the nigrostriatal pathway and restore dopaminergic function in the striatum. In the future implants containing not only dopaminergic cells but also growth factors and a variety of other substances could become a method to not only functionally compensate the biochemical abnormalities of PD but also to arrest its progression. This technique is limited to a few centres around the world owing to the technical, logistical and ethical problems of obtaining and handling embryonic cells. At present, grafting of dopaminergic cells is perhaps best suited for patients with young-onset PD (less than 45 years old) who are at high risk of developing complications within a short time of beginning pharmacological treatment and in whom the idea of making lesions or implanting electrodes into the brain for decades seems less appealing. Consideration of surgery in any given patient should be weighed against the risks (about 1% mortality and 2-6% of severe morbidity-hemiplegia, cognitive deficit, speech problems, etc.) associated with these techniques. The development of better imaging methods and the growing expertise of multidisciplinary teams will undoubtedly make surgery for PD safer and more effective in the future.
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PMID:Surgical treatment of Parkinson's disease. 942 72

Parkinson's Disease (PD) is often associated with a subcortico-frontal syndrome (SCFS) that is mainly characterized by executive dysfunctions. The complete biochemistry of these dysfunctions remain misunderstood. Most studies have focused on the well-known nigro-striatal dopaminergic degenerations of PD, but a more satisfying understanding of the SCFS has come from the study of the cholinergic systems. We present here two new experiments carried out with long-term and acute anticholinergic treatments in PD. In the first experiment, the effects of a 2-week treatment with trihexyphenidyl were compared to those observed under placebo on a neuropsychological battery. Results showed that anticholinergic-induced deficits in PD were exclusively concerned with executive functions. In the second experiment, the effects of an acute subclinical dose of scopolamine were compared between normal controls and PD patients who were devoid of cognitive deficit on a subset of executive tasks. Results indicates that PD patients but not normal controls developed a transient SCFS for the duration of the drug action. In contrast to other populations with cholinergic depletions-such as Alzheimer's disease-cholinergic blockade in PD exacerbates specifically the SCFS. Such a discrepancy between these two neuropsychological profiles are discussed in terms of the specificity of the underlying cholinergic lesions.
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PMID:Acute and long-term administration of anticholinergics in Parkinson's disease: specific effects on the subcortico-frontal syndrome. 1041 63

The beneficial effects of ventral intermediate nucleus (VIM) stimulation were evaluated in 20 patients with tremor refractory to medical therapy. Thalamic stimulation is a non-ablative procedure which has the advantage of a reversible, non-destructive lesion. Eleven patients [7 with Parkinson's disease (PD) and 4 with essential tremor (ET)] received unilateral VIM implantation, while 9 patients had staged bilateral VIM implantation (4 with PD, 5 with ET). PD patients showed a significant improvement in contralateral arm and leg rest tremor and ipsilateral leg rest tremor (p < 0.02) at a mean follow-up period of 16.2 +/- 7.0 months. Patients with PD did not demonstrate any significant decrease in medication use at follow-up. ET patients demonstrated significant improvement in postural and action tremor in the contralateral arm (p < 0.001), but no significant improvement in the contralateral leg tremor at follow-up. Significant improvements were also seen in ET patients in the Clinical Rating Scale for Tremor (p < 0.001) with respect to several activities of daily living at a mean follow-up of 14.9 +/- 8. 1 months. Deep brain stimulation is a safe and effective treatment for severe tremor refractory to medications. It is a highly effective, reversible, adaptable, and predictable procedure which avoids the complication of cognitive deficit seen in patients with bilateral thalamotomies.
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PMID:Deep brain stimulation of the ventral intermediate nucleus of the thalamus for control of tremors in Parkinson's disease and essential tremor. 1064 Sep 20

Twenty non-demented patients with idiopathic Parkinson's disease (PD) underwent single photon emission computed tomography (SPECT) with [123I]beta-CIT to further investigate the contribution of nigrostriatal dysfunction to cognitive and motor deficits. Compared to matched controls PD patients showed normal verbal intelligence, short-term memory and phasic alertness. There were significant (p < 0.05) deficits in tests of verbal working memory (digit ordering, reading span), strategic memory (story recall) and executive functions (card sorting), indicating a "prefrontal" cognitive deficit. Significant (p < 0.05) correlations were observed between dopamine transporter (DAT) density in the putamen and motor deficits as well as between DAT density in both striatal compartments (head of the caudate nucleus and putamen) and prefrontal functioning. Age was a major contributing factor to both cognitive status and nigrostriatal integrity as measured by [123I]beta-CIT SPECT. These results support the view that the striatum is part of a neuronal network that is mediating prefrontal cognitive functions.
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PMID:Striatal [123I]beta-CIT SPECT and prefrontal cognitive functions in Parkinson's disease. 1082 39

Rating scales in Parkinson's disease (PD) are generally reliable but are not widely used in practice. UPDRS is the core assessment of PD, its metrologic properties are well known, and it is simple to use after training. However, cognitive and psychic disorders need complementary approaches. For example, MATTIS seems to be more appropriate in assessing the cognitive deficit and MADRS the depressive symptoms. A patient diary best appreciates motor fluctuations. Activities of daily living rated by the UPDRS allow a global assessment of the patient handicap that may be completed by "the patient's own point of view" through quality of life scales (SF36, PDQ39). For clinical research purposes, time tests and dyskinesia scales following the CAPIT or CAPSIT procedure are required.
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PMID:[Contribution and limitations of evaluation scales in Parkinson's disease]. 1091 40

Along with dementia, Parkinson's disease (PD) is associated with subtle but widespread cognitive impairment even in the absence of clinically apparent cognitive decline. Many of the deficits are reminiscent of those observed in patients with lesions of the prefrontal cortex, that is, failure in executive function that involves skills required for anticipation, planning, initiation and monitoring of goal-directed behaviours. This paper reviews the dopaminergic brain circuitry, and preclinical and clinical evidence supporting the regulation of prefrontal cortex activity by dopamine, and the role of dopamine in cognitive impairment in patients with PD. It addresses the need to integrate these facts and the findings of positive, neutral or detrimental frontal cognitive response to dopaminergic drugs in PD which should be viewed mainly in the context of methodological differences for subject selection. The cognitive effect of levodopa does not much depend on a neuropsychological specificity of the drug, the years of evolution of the disease or the severity of the motor signs. Instead, it may be a function of the level of dopamine depletion in different parts of the basal ganglia and prefrontal cortex. Consequently, dopaminergic agents may enhance cognitive functions in some patients and impair them in others. De novo patients tend to improve during the first year of treatment; stable responders to oral levodopa tend to show no changes; and wearing-off responders tend to deteriorate with acute levodopa challenge. Enhancement and impairment of cognitive function with dopaminergic treatment is incomplete and task-specific, suggesting the need to integrate the above dopamine facts with other neurotransmitter systems findings in PD. Meanwhile, such cognitive dissociation can be useful in refining the definition of the cognitive deficit in PD patients without dementia and emphasising the need to develop new and specific strategies for treatment.
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PMID:Role of dopamine in learning and memory: implications for the treatment of cognitive dysfunction in patients with Parkinson's disease. 1091 74

Cognitive deficits in Alzheimer's and Parkinson's disease are closely related to disturbed cholinergic transmission. The decrease of nicotinic acetylcholine receptor protein has been assessed by Western blotting and immunohistochemistry. Stereology, however, has not been used to assess numbers of receptor-expressing human cerebrocortical neurons. Our approach applies a combination of alpha7 subunit-immunohistochemistry with a stereological technique using defined stretches of pial surface as reference standard. The number of alpha7 subunit protein-expressing neurons in the Alzheimer temporal cortices amounted to approximately half of that of controls while numbers in Parkinson patients lay in between. No differences in the total number of neurons were seen. These results corroborate nonstereological studies on Alzheimer cortices and for the first time show a similar decrease in receptor expression in Parkinson's disease. They provide evidence that not only Alzheimer dementia but also cognitive deficits in Parkinson's disease may be related to decreased nicotinic receptor expression.
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PMID:Cellular expression of alpha7 nicotinic acetylcholine receptor protein in the temporal cortex in Alzheimer's and Parkinson's disease--a stereological approach. 1111 64


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