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Cognitive and motor dysfunction in the early phase of Parkinson's disease
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.ORCID iD: 0000-0002-2348-1164
2013 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Kognitiv och motorisk funktion i tidig fas av Parkinsons sjukdom. (Swedish)
Abstract [en]

Background: Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease. The diagnosis is based on a combination of the motor signs: tremor, bradykinesia, rigidity and postural abnormalities. Mild Cognitive Impairment (MCI) is common early in the disease and a large proportion of patients with PD develop dementia (PDD). Associations between motor symptoms and cognitive decline have been suggested but the results are inconclusive due to differences in the selection of participants and variables tested. Large population based studies with comprehensive neuropsychological investigation in newly diagnosed cases with PD followed prospectively are rare. The aim of this thesis was to improve characterization and understanding of cognition in PD, and to explore the relationship to motor impairment in the early phase of PD.

Methods: All new patients with suspected idiopathic parkinsonism in the catchment area (142 ooo inhabitants) were examined during a period of five years and four months. Among other investigations, a comprehensive neuropsychological evaluation was carried out in 119 of 148 patients with PD together with 30 age matched healthy controls. Assessments were repeated after one three and five years.

Results: Patients performed worse than healthy controls in a majority of neuropsychological tests. MCI at the time of diagnosis were found in 36% according to recently published MCI criteria. Thirty % were cognitively impaired using another definition. One fourth of the patients developed PDD within five years after diagnosis and 25 % of those with MCI at baseline reversed back to normal cognition. Age and MCI were significant predictors of dementia. Education was an independent predictor for severe cognitive dysfunction at diagnosis but did not predict PDD. Patients with MCI converting to PDD had worse performance on visuospatial function, semantic fluency, episodic memory, mental flexibility and conceptual thinking. There were no differences in cognitive performance between patients with predominant Postural and Gait Disturbances (PIGD) and the tremor dominant subtype at the baseline investigation and belonging to the PIGD subgroup at baseline did not predict PDD. Dementia converters declined more rapidly than non-converters in posture/gait function. Associations between bradykinesia and measures of executive functions and working memory were found, and between posture and gait disturbances and visuospatial function. Some of these associations were persistent after one year. Patients receiving the dopamine agonist pramipexole performed significantly worse on a measure of verbal fluency at the one year follow up.

Conclusions: The differences in proportions of cognitively impaired in the different studies emphasize the value of joint criteria for PD-MCI. Even when using such criteria, a substantial proportion of patients revert back to normal function. The increase in motor disability in patients with PDD could have several different causes that need to be further investigated. Associated motor and cognitive dysfunctions could reflect common pathophysiological processes in partly shared networks. Both dopaminergic and non-dopaminergic motor and cognitive functions seems to be involved in PDD which suggests that pharmacological treatment in PD needs to go beyond the scope of dopaminergic deficiency in search for new therapies that would also be effective for non-motor symptoms.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet , 2013. , 70 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1615
Keyword [en]
Parkinson's disease, Mild Cognitive Impairment, Dementia, population based, prospective, newly diagnosed
National Category
Neurology
Research subject
Neurology
Identifiers
URN: urn:nbn:se:umu:diva-82897ISBN: 978-91-7459-767-7 (print)OAI: oai:DiVA.org:umu-82897DiVA: diva2:664855
Public defence
2013-12-13, Hörsal E04, byggnad 6E, Norrlands universitetssjukhus, Umeå, 13:00 (Swedish)
Opponent
Supervisors
Projects
NYPUM
Available from: 2013-11-22 Created: 2013-11-13 Last updated: 2013-11-22Bibliographically approved
List of papers
1. Cognitive function in early Parkinson's disease: a population-based study
Open this publication in new window or tab >>Cognitive function in early Parkinson's disease: a population-based study
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2009 (English)In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 16, no 12, 1278-1284 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE: The study aims to describe the frequency, pattern and determinants of cognitive function in patients with newly diagnosed Parkinson's disease (PD); to compare patients with impaired cognition to patients with intact cognition; and to compare to matched healthy controls.

METHODS: Patients were identified in a longitudinal population based study of idiopathic non-drug induced parkinsonism. Eighty-eight newly diagnosed patients with PD and no dementia were included during a four year period. The patients and 30 age- and sex-matched healthy control subjects underwent a comprehensive neuropsychological assessment.

RESULTS: Patients performed significantly worse than healthy controls in a majority of neuropsychological tests. Test results in attention, psychomotor function, episodic memory (free recall), executive function and category fluency were significantly lower in the patient group. Comparison with normative data revealed that 30% of the patients had deficits in > or =1 cognitive domain (episodic memory, executive function and verbal function). Seventy per cent of the patients had normal performance. Unified Parkinson's Disease Rating Scale (UPDRS) III sub scores; speech, facial expression, rigidity and bradykinesia were significantly higher, and disease duration shorter amongst the cognitively impaired than amongst the cognitively intact patients. Tremor showed no difference. Education level was an independent predictor of dysfunction in patients with > or =2 cognitive domains affected.

CONCLUSION: Cognitive dysfunction is common in untreated patients in early PD, affecting attention, psychomotor function, episodic memory, executive function and category fluency. Education level was an independent predictor of severe cognitive dysfunction.

Place, publisher, year, edition, pages
John Wiley & Sons, 2009
National Category
Geriatrics Neurology
Identifiers
urn:nbn:se:umu:diva-30600 (URN)10.1111/j.1468-1331.2009.02707.x (DOI)19538208 (PubMedID)
Available from: 2010-01-08 Created: 2010-01-08 Last updated: 2017-12-12Bibliographically approved
2. The relation between cognition and motor dysfunction in drug-naive newly diagnosed patients with parkinson's disease
Open this publication in new window or tab >>The relation between cognition and motor dysfunction in drug-naive newly diagnosed patients with parkinson's disease
2011 (English)In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 26, no 12, 2183-2189 p.Article in journal (Refereed) Published
Abstract [en]

Recent studies have reported cognitive decline to be common in the early phase of Parkinson's disease. Imaging data connect working memory and executive functioning to the dopamine system. It has also been suggested that bradykinesia is the clinical manifestation most closely related to the nigrostriatal lesion. Exploring the relationship between motor dysfunction and cognition can help us find shared or overlapping systems serving different functions. This relationship has been sparsely investigated in population-based studies of untreated Parkinson's disease. The aim of the present study was to investigate the association between motor signs and cognitive performance in the early stages of Parkinson's disease before the intake of dopaminergic medication. Patients were identified in a population-based study of incident cases with idiopathic parkinsonism. Patients with the postural instability and gait disturbances phenotype were compared with patients with the tremor-dominant phenotype on demographics and cognitive measures. Associations between cognitive and motor scores were investigated, with age, education, and sex controlled for. Bradykinesia was associated with working memory and mental flexibility, whereas axial signs were associated with episodic memory and visuospatial functioning. No significant differences in the neuropsychological variables were found between the postural instability and gait disturbances phenotype and the tremor phenotype. Our results indicate a shared system for slow movement and inflexible thinking that may be controlled by a dopaminergic network different from dopaminergic networks involved in tremor and/or rigidity. The association between axial signs and memory and visuospatial function may point to overlapping systems or pathologies related to these abilities.

(C) 2011 Movement Disorder Society

Place, publisher, year, edition, pages
New York, N.Y.: Raven Press, 2011
Keyword
Parkinson's disease, cognition, population based, newly diagnosed
National Category
Neurosciences Neurology
Identifiers
urn:nbn:se:umu:diva-50164 (URN)10.1002/mds.23814 (DOI)000296610900011 ()
Available from: 2011-11-29 Created: 2011-11-28 Last updated: 2017-12-08Bibliographically approved
3. Persistence of associations between cognitive impairment and motor dysfunction in the early phase of Parkinson's disease
Open this publication in new window or tab >>Persistence of associations between cognitive impairment and motor dysfunction in the early phase of Parkinson's disease
2013 (English)In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 260, no 9, 2228-2236 p.Article in journal (Refereed) Published
Abstract [en]

The relation between cognitive and motor functions in Parkinson's disease is not fully understood. In an incidence population of newly diagnosed drug na < ve patients with Parkinson's disease, associations were found between the degree of bradykinesia and postural instability and gait disturbances, measured by the Unified Disease Rating Scale, and different types of cognitive functions. To investigate the stability of these associations over time, we explored the association of differences between baseline and 1-year follow-up in 91 incident cases with Parkinson's disease. The magnitude of change between the two assessments was assessed together with analysis of differences based on which dopaminergic medication was used. Change in bradykinesia was associated with change in working memory and mental flexibility. Changes in postural instability and gait disturbances were associated with change in visuospatial memory. A negative effect of the dopamine agonist pramipexole on phonemic fluency performance was found compared to treatment with other dopaminergic drugs. Change in cognitive and motor functions were associated from time of diagnosis until 1 year after diagnosis. These persisting findings strengthen results from a previous cross-sectional study suggesting similar associations. The effects of dopamine agonists on phonemic fluency should be investigated further.

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2013
Keyword
Parkinson's disease, Cognition, Population-based, Prospective, Dopamine agonist
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-81313 (URN)10.1007/s00415-013-6971-6 (DOI)000324099200004 ()
Available from: 2013-10-14 Created: 2013-10-07 Last updated: 2017-12-06Bibliographically approved
4. Cognitive function in the early phase of Parkinson's disease, a longitudinal follow-up
Open this publication in new window or tab >>Cognitive function in the early phase of Parkinson's disease, a longitudinal follow-up
(English)Manuscript (preprint) (Other academic)
Keyword
Parkinson's Disease, prospective, Mild Cognitive Impairment, Dementia
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:umu:diva-83079 (URN)
Projects
NYPUM
Available from: 2013-11-18 Created: 2013-11-18 Last updated: 2014-11-19Bibliographically approved

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