umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Cognitive function in the early phase of Parkinson's disease, a longitudinal follow-up
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
(English)Manuscript (preprint) (Other academic)
Keyword [en]
Parkinson's Disease, prospective, Mild Cognitive Impairment, Dementia
National Category
Neurology
Research subject
Neurology
Identifiers
URN: urn:nbn:se:umu:diva-83079OAI: oai:DiVA.org:umu-83079DiVA: diva2:664844
Projects
NYPUM
Available from: 2013-11-18 Created: 2013-11-18 Last updated: 2014-11-19Bibliographically approved
In thesis
1. Cognitive and motor dysfunction in the early phase of Parkinson's disease
Open this publication in new window or tab >>Cognitive and motor dysfunction in the early phase of Parkinson's disease
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Kognitiv och motorisk funktion i tidig fas av Parkinsons sjukdom.
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
Parkinson's disease, Mild Cognitive Impairment, Dementia, population based, prospective, newly diagnosed
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:umu:diva-82897 (URN)978-91-7459-767-7 (ISBN)
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
2. Functional brain imaging of cognitive status in Parkinson's disease
Open this publication in new window or tab >>Functional brain imaging of cognitive status in Parkinson's disease
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Parkinson’s disease (PD) is next to Alzheimer’s disease (AD) the second most common neurodegenerative disease. PD has traditionally been characterised as a motor disorder, but more recent research has revealed that cognitive impairments are frequent. Cognitive impairments in executive functions, attention, and working memory with reliance on dopaminergic transmission, are often described as dominating the cognitive profile in early-phase PD. However, although knowledge about the neuropathology that underlies the cognitive impairments in PD has increased, its features are complex and knowledge remains insufficient. Therefore, the aim of the current thesis was to improve the understanding of how task-evoked brain responses relate to cognitive status in patients with PD, with and without mild cognitive impairment (MCI), and to evaluate the predictive value of PD-MCI in respect of prodromal Parkinson’s disease dementia (PDD). This was conducted within the “new Parkinsonism in Umeå” (NYPUM) project, which is a prospective cohort study. Patients with idiopathic PD were included in this thesis, and the patients were examined with a comprehensive neuropsychological battery and with a functional MRI (fMRI) working memory protocol. During scanning, patients conducted a verbal two-back task in which they needed to maintain and actively update relevant information, and the primary outcome measure was blood-oxygen-level-dependent (BOLD) signal. This thesis shows that patients with PD-MCI had significantly lower BOLD signal responses than patients without MCI in frontal (anterior cingulate cortex) and striatal (right caudate) regions (Study I). The altered BOLD response in the right caudate was associated with altered presynaptic dopamine binding. The fronto-striatal alterations persisted across time but without any additional change. However, decreased posterior cortical (right fusiform gyrus) BOLD signal responses were observed in patients with PD-MCI relative to patients without MCI across time (Study II). Finally, PD-MCI at baseline examination is highly predictive for prodromal PDD with a six-fold increased risk. Cognitive tests with a posterior cortical basis, to a greater extent, are predictive for prodromal PDD than tests with a fronto-striatal basis. The observed working memory related alterations in patients with PD-MCI suggest that early cognitive impairments in PD are linked to fronto-striatal dopaminergic dysfunction. The longitudinal development of cognitive impairment in PD reflects additional posterior cortical dysfunction. This might reflect a dual syndrome, with dopamine-depleted fronto-striatal alterations that characterise PD-MCI in general, whereas additional posterior cortical cognitive alterations with a non-dopaminergic basis to a greater extent characterise prodromal PDD. If, and how, the two potential syndromes interact, is still unclear. Thus, this thesis provides information on cognitive neuropathological changes in PD that might contribute to more relevant choices of pharmacotherapy and diagnostic accuracy in respect of PDD. However, additional large-scale longitudinal imaging studies are needed to further clarify the neuropatholgogical features of PD-MCI in respect of prodromal PDD.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2014. 67 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1671
Keyword
Parkinson’s disease, functional MRI, Mild cognitive impairment, Working memory, Parkinson’s disease dementia, BOLD
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-96368 (URN)978-91-7601-156-0 (ISBN)
Public defence
2014-12-10, Sal BIA 201, Biologihuset, Umeå Universitet, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2014-11-19 Created: 2014-11-18 Last updated: 2014-11-19Bibliographically approved

Open Access in DiVA

No full text

Authority records BETA

Domellöf, MagdalenaForsgren, LarsEkman, UrbanElgh, Eva

Search in DiVA

By author/editor
Domellöf, MagdalenaForsgren, LarsEkman, UrbanElgh, Eva
By organisation
Department of Pharmacology and Clinical NeuroscienceClinical NeurosciencePhysiologyGeriatric Medicine
Neurology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 158 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf