Different Effects of Dopaminergic and Anticholinergic Therapies on Cognitive and Motor Function in Parkinson's Disease

Cooper, James A.; Sagar, H. J.; Doherty, S. M.; Jordan, Nigel; Tidswell, P; Sullivan, Edith V.

doi:10.1093/brain/115.6.1701

Cited by 269 publications

(193 citation statements)

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“…87 Generally, many aspects of the dysexecutive syndrome improve with dopaminergic treatment. 88,89 However, dopaminergic medication has a detrimental eff ect on other aspects of cognition, such as reversal or conditional associative learning. These defi cits have been attributed to a dopamine overdose eff ect in the frontostriatal circuits through the ventral striatum (orbitofrontal, anterior cingulate, and inferotemporal circuits).…”

Section: Executive Dysfunctionmentioning

confidence: 99%

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Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms

Rodriguez-Oroz

Jahanshahi

Krack

et al. 2009

The Lancet Neurology

744

500

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A dopaminergic defi ciency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and akinesia) are associated with a defi ciency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. The classic pathophysiological model for PD (ie, hyperactivity in the globus pallidus pars interna and substantia nigra pars reticulata) does not explain rigidity and tremor, which might be caused by changes in primary motor cortex activity. Executive functions (ie, planning and problem solving) are also impaired in early PD, but are usually not clinically noticed. These impairments are associated with dopamine defi ciency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic defi cit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic defi ciency in the early phase of the parkinsonian state and the diff erent circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.

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Section: Executive Dysfunctionmentioning

confidence: 99%

“…Evidence also implicates other neurotransmitters such as acetylcholine in the cognitive manifestations of PD. 88,[103][104][105] …”

Section: Pathophysiology Of Executive Dysfunctionmentioning

confidence: 99%

Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms

Rodriguez-Oroz

Jahanshahi

Krack

et al. 2009

The Lancet Neurology

744

500

View full text Add to dashboard Cite

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“…Dopamine (DA) agonists have shown beneficial therapeutic effects on motor symptoms in PD, but their influence on cognitive functions is still controversial. Some studies suggest that DA ameliorates a certain frontal lobe function, such as focused attention (5), but other failed to demonstrate cognitive improving in patients treated with a DA agonist (6). In fact, the effects of levodopa and DA on cognitive functions have been reported as beneficial as well as deleterious (7).…”

Section: Introductionmentioning

confidence: 99%

A dopamine agonist, pramipexole, and cognitive functions in Parkinson's disease

Relja

Klepac

2006

Journal of the Neurological Sciences

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“…While most of the motor symptoms of PD can be related to a nigrostriatal dopaminergic defect, the relationship between the dopaminergic defect and cognitive deficits in PD is less clear. Some cognitive deficits in PD may be dopa-responsive but others are not (Cooper et al 1992;Lange et al 1992). Some cognitive problems in PD patients are even exacerbated by dopaminergic therapy (Gotham et al 1988).…”

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confidence: 99%

Effects of the Prolyl Endopeptidase Inhibitor S 17092 on Cognitive Deficits in Chronic Low Dose MPTP-Treated Monkeys

Schneider

2002

Neuropsychopharmacology

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A number of neuropeptides are affected in Parkinson's disease and the enzyme proline endopeptidase contributes to the degradation of many of these neuropeptides, some of which are linked to a variety of cognitive functions. In the present study, the effects of the highly potent proline endopeptidase inhibitor S 17092 on cognitive deficits in monkeys induced by chronic low dose 2,3, It is generally recognized that non-demented Parkinson's disease (PD) patients exhibit a number of neuropsychological deficits, some of which are present even at the earliest stages of the disease (Lees and Smith 1983;Levin et al. 1989;Owen et al. 1993). Many of these deficits are 'frontal-like' in nature and consist of problems in attentional set shifting (Owen et al. 1993), distractibility (Sharpe 1990) planning and 'executive functions ' (Morris et al. 1988) and spatial working memory ). Parkinson's disease patients also may have difficulty performing a delayed matching-to-sample shortterm visual recognition memory task, but their problems appear more related to attentional difficulties rather than to visual recognition memory problems . The neurochemical deficits underlying the cognitive disturbances in PD patients are not completely known. While most of the motor symptoms of PD can be related to a nigrostriatal dopaminergic defect, the relationship between the dopaminergic defect and cognitive deficits in PD is less clear. Some cognitive deficits in PD may be dopa-responsive but others are not (Cooper et al. 1992;Lange et al. 1992). Some cognitive problems in PD patients are even exacerbated by dopaminergic therapy (Gotham et al. 1988). These findings suggest that the cognitive deficits in PD patients most likely arise from dysfunction of several cortical and subcortical neurotransmitter systems and functional circuits that cannot be normalized by dopamine replacement therapy alone. This is supported by the recent finding that a sub-type specific neuronal nicotinic acetylcholine receptor agonist, but not levodopa, was able to improve cognitive functioning in dopamine lesioned monkeys (Schneider et al. 1999). The nicotinic receptor agonist effects on cognition were most likely related to the ability of this compound to release dopamine from striatal, limbic and frontal cortical sites, norepinephrine from hippocampal, thalamic and frontal cortical sites and acetylcholine from various cortical and subcortical sites (Menzaghi et al. 1996;Sacaan et al. 1997).In addition to deficits in levels of various neurotransmitters in PD and in animal models of PD, decreased levels of various neuropeptides may also contribute to parkinsonian symptomatology (Mauborgne et al. 1983). Several neuropeptides, particularly substance P, have been implicated in learning and memory (Huston and Hasenohrl 1995) and are present endogenously in cortex and striatum. Substance P levels are also depleted in the striatum of monkeys made parkinsonian by exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Since proline-containing neuropep...

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Different Effects of Dopaminergic and Anticholinergic Therapies on Cognitive and Motor Function in Parkinson's Disease

Cited by 269 publications

References 0 publications

Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms

Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms

A dopamine agonist, pramipexole, and cognitive functions in Parkinson's disease

Effects of the Prolyl Endopeptidase Inhibitor S 17092 on Cognitive Deficits in Chronic Low Dose MPTP-Treated Monkeys

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