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Forsgren, Lars
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Publications (10 of 140) Show all publications
Nilsson, J., Constantinescu, J., Nellgård, B., Jakobsson, P., Brum, W. S., Gobom, J., . . . Brinkmalm, A. (2023). Cerebrospinal fluid biomarkers of synaptic dysfunction are altered in Parkinson's disease and related disorders. Movement Disorders, 38(2), 267-277
Open this publication in new window or tab >>Cerebrospinal fluid biomarkers of synaptic dysfunction are altered in Parkinson's disease and related disorders
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2023 (English)In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 38, no 2, p. 267-277Article in journal (Refereed) Published
Abstract [en]

Background: Synaptic dysfunction and degeneration are central contributors to the pathogenesis and progression of parkinsonian disorders. Therefore, identification and validation of biomarkers reflecting pathological synaptic alterations are greatly needed and could be used in prognostic assessment and to monitor treatment effects.

Objective: To explore candidate biomarkers of synaptic dysfunction in Parkinson's disease (PD) and related disorders.

Methods: Mass spectrometry was used to quantify 15 synaptic proteins in two clinical cerebrospinal fluid (CSF) cohorts, including PD (n1 = 51, n2 = 101), corticobasal degeneration (CBD) (n1 = 11, n2 = 3), progressive supranuclear palsy (PSP) (n1 = 22, n2 = 21), multiple system atrophy (MSA) (n1 = 31, n2 = 26), and healthy control (HC) (n1 = 48, n2 = 30) participants, as well as Alzheimer's disease (AD) (n2 = 23) patients in the second cohort.

Results: Across both cohorts, lower levels of the neuronal pentraxins (NPTX; 1, 2, and receptor) were found in PD, MSA, and PSP, compared with HC. In MSA and PSP, lower neurogranin, AP2B1, and complexin-2 levels compared with HC were observed. In AD, levels of 14-3-3 zeta/delta, beta- and gamma-synuclein were higher compared with the parkinsonian disorders. Lower pentraxin levels in PD correlated with Mini-Mental State Exam scores and specific cognitive deficits (NPTX2; rho = 0.25–0.32, P < 0.05) and reduced dopaminergic pre-synaptic integrity as measured by DaTSCAN (NPTX2; rho = 0.29, P = 0.023). Additionally, lower levels were associated with the progression of postural imbalance and gait difficulty symptoms (All NPTX; β-estimate = −0.025 to −0.038, P < 0.05) and cognitive decline (NPTX2; β-estimate = 0.32, P = 0.021).

Conclusions: These novel findings show different alterations of synaptic proteins in parkinsonian disorders compared with AD and HC. The neuronal pentraxins may serve as prognostic CSF biomarkers for both cognitive and motor symptom progression in PD. 

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
biomarkers, multiple system atrophy, Parkinson's disease, progressive supranuclear palsy, synaptic dysfunction
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-202012 (URN)10.1002/mds.29287 (DOI)000897656300001 ()36504237 (PubMedID)2-s2.0-85144096881 (Scopus ID)
Funder
Stiftelsen Gamla Tjänarinnor, 2020-00959Stiftelsen Gamla Tjänarinnor, 2021-01153Familjen Erling-Perssons StiftelseThe Swedish Brain FoundationUmeå UniversityRegion VästerbottenParkinsonfondenThe Kempe Foundations
Available from: 2022-12-29 Created: 2022-12-29 Last updated: 2023-06-20Bibliographically approved
Gonzalez, M. C., Tovar-Rios, D. A., Alves, G., Dalen, I., Williams-Gray, C. H., Camacho, M., . . . Maple-Grødem, J. (2023). Cognitive and motor decline in dementia with lewy bodies and Parkinson's disease dementia. Movement Disorders Clinical Practice, 10(6), 980-986
Open this publication in new window or tab >>Cognitive and motor decline in dementia with lewy bodies and Parkinson's disease dementia
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2023 (English)In: Movement Disorders Clinical Practice, E-ISSN 2330-1619, Vol. 10, no 6, p. 980-986Article in journal (Refereed) Published
Abstract [en]

Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD).

Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohorts.

Methods: The annual change in MMSE and MDS-UPDRS part III was estimated using linear mixed regression models in patients with at least one follow-up (DLB n = 837 and PDD n = 157).

Results: When adjusting for confounders, we found no difference in the annual change in MMSE between DLB and PDD (−1.8 [95% CI −2.3, −1.3] vs. −1.9 [95% CI −2.6, −1.2] [P = 0.74]). MDS-UPDRS part III showed nearly identical annual changes (DLB 4.8 [95% CI 2.1, 7.5]) (PDD 4.8 [95% CI 2.7, 6.9], [P = 0.98]).

Conclusions: DLB and PDD showed similar rates of cognitive and motor decline. This is relevant for future clinical trial designs.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
dementia with Lewy bodies, international cohort, Parkinson's disease dementia, parkinsonism, rate of cognitive decline
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-208964 (URN)10.1002/mdc3.13752 (DOI)000991805100001 ()2-s2.0-85158093631 (Scopus ID)
Funder
Familjen Erling-Perssons StiftelseParkinsonfondenNIH (National Institutes of Health)Wellcome trustRegion VästerbottenThe Swedish Brain FoundationKnut and Alice Wallenberg Foundation, G0502Knut and Alice Wallenberg Foundation, G0914Knut and Alice Wallenberg Foundation, G1302Umeå UniversityThe Research Council of Norway, 177966Konung Gustaf V:s och Drottning Victorias FrimurarestiftelseThe Kempe Foundations
Available from: 2023-06-02 Created: 2023-06-02 Last updated: 2023-09-29Bibliographically approved
Christensen, J., Dreier, J. W., Sun, Y., Linehan, C., Tomson, T., Marson, A., . . . Jennum, P. J. (2023). Estimates of epilepsy prevalence, psychiatric co-morbidity and cost. Seizure, 107, 162-171
Open this publication in new window or tab >>Estimates of epilepsy prevalence, psychiatric co-morbidity and cost
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2023 (English)In: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 107, p. 162-171Article in journal (Refereed) Published
Abstract [en]

Purpose: This study estimated epilepsy prevalence, psychiatric co-morbidity and annual costs associated with epilepsy.

Methods: We used Danish national health registers to identify persons diagnosed with epilepsy and psychiatric disorders, and persons using antiseizure medication and persons using drugs for psychiatric disorders. We calculated the prevalence of epilepsy and co-morbid psychiatric disorders in Denmark on December 31, 2016, using information on epilepsy and psychiatric disorders based on combinations of hospital contacts and use of antiseizure and psychoactive medication. Further, direct and indirect annual costs associated with epilepsy were calculated using individual-level data from a range of socioeconomic registers.

Results: There were 5,044,367 persons alive and living in Denmark on December 31, 2016, including 33,628 persons with at least one hospital contact with epilepsy in the previous five years (epilepsy prevalence 0.67% (0.69% males; 0.65% females)). Among these persons with epilepsy, we identified 12,562 (37.4%) persons with a psychiatric disorder or use of drugs used for psychiatric disorders as compared with 801,052 (15.9%) persons in the general population. The estimated total annual individual net costs associated with epilepsy was €30,683. Compared with prevalence estimates on December 31, 2006, the prevalence of epilepsy on December 31, 2016, was slightly higher in the older population and slightly lower in children

Conclusions: Population estimates from national registers provide epilepsy prevalence estimates of approximately 0.6–0.7% - similar to previous reviews of epilepsy prevalence. In addition, the national sample allowed idenitfication of high prevalence of psychiatric disorders and high societal costs associated with epielspy.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Cost, Epidemiology, Prevalence, Psychiatric co-morbidity
National Category
Psychiatry Neurology
Identifiers
urn:nbn:se:umu:diva-198231 (URN)10.1016/j.seizure.2022.06.010 (DOI)000996363100001 ()35811222 (PubMedID)2-s2.0-85133777678 (Scopus ID)
Funder
European Commission, 2014//199564
Available from: 2022-07-21 Created: 2022-07-21 Last updated: 2023-07-12Bibliographically approved
Zhu, S., Bäckström, D. C., Forsgren, L. & Trupp, M. (2022). Alterations in Self-Aggregating Neuropeptides in Cerebrospinal Fluid of Patients with Parkinsonian Disorders. Journal of Parkinson's Disease, 12(4), 1169-1189
Open this publication in new window or tab >>Alterations in Self-Aggregating Neuropeptides in Cerebrospinal Fluid of Patients with Parkinsonian Disorders
2022 (English)In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 12, no 4, p. 1169-1189Article in journal (Refereed) Published
Abstract [en]

Background: Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA) present with similar movement disorder symptoms but distinct protein aggregates upon pathological examination.

Objective: Discovery and validation of candidate biomarkers in parkinsonian disorders for differential diagnosis of subgroup molecular etiologies.

Methods: Untargeted liquid chromatography (LC)-mass spectrometry (MS) proteomics was used for discovery profiling in cerebral spinal fluid (CSF) followed by LC-MS/MS based multiple reaction monitoring for validation of candidates. We compared clinical variation within the parkinsonian cohort including PD subgroups exhibiting tremor dominance (TD) or postural instability gait disturbance and those with detectable leukocytes in CSF.

Results: We have identified candidate peptide biomarkers and validated related proteins with targeted quantitative multiplexed assays. Dopamine-drug naïve patients at first diagnosis exhibit reduced levels of signaling neuropeptides, chaperones, and processing proteases for packaging of self-aggregating peptides into dense core vesicles. Distinct patterns of biomarkers were detected in the parkinsonian disorders but were not robust enough to offer a differential diagnosis. Different biomarker changes were detected in male and female patients with PD. Subgroup specific candidate biomarkers were identified for TD PD and PD patients with leukocytes detected in CSF.

Conclusion: PD, MSA, and PSP exhibit overlapping as well as distinct protein biomarkers that suggest specific molecular etiologies. This indicates common sensitivity of certain populations of selectively vulnerable neurons in the brain, and distinct therapeutic targets for PD subgroups. Our report validates a decrease in CSF levels of self-aggregating neuropeptides in parkinsonian disorders and supports the role of native amyloidogenic proteins in etiologies of neurodegenerative diseases.

Place, publisher, year, edition, pages
IOS Press, 2022
Keywords
biomarkers, cerebrospinal fluid, mass-spectrometry, Neurodegeneration, parkinsonism, proteomics
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-196523 (URN)10.3233/JPD-213031 (DOI)000802224800008 ()35253777 (PubMedID)2-s2.0-85131211833 (Scopus ID)
Funder
Familjen Erling-Perssons StiftelseThe Kempe FoundationsParkinsonfondenThe Swedish Brain FoundationSwedish Research Council
Available from: 2022-06-15 Created: 2022-06-15 Last updated: 2023-03-23Bibliographically approved
Stenmark Persson, R., Nordin, T., Hariz, G.-M., Wårdell, K., Forsgren, L., Hariz, M. & Blomstedt, P. (2022). Deep Brain Stimulation of Caudal Zona Incerta for Parkinson's Disease: One-Year Follow-Up and Electric Field Simulations. Neuromodulation, 25(6), 935-944
Open this publication in new window or tab >>Deep Brain Stimulation of Caudal Zona Incerta for Parkinson's Disease: One-Year Follow-Up and Electric Field Simulations
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2022 (English)In: Neuromodulation, ISSN 1094-7159, E-ISSN 1525-1403, Vol. 25, no 6, p. 935-944Article in journal (Refereed) Published
Abstract [en]

Objective: To evaluate the effects of bilateral caudal zona incerta (cZi) deep brain stimulation (DBS) for Parkinson's disease (PD) one year after surgery and to create anatomical improvement maps based on patient-specific simulation of the electric field.

Materials and Methods: We report the one-year results of bilateral cZi-DBS in 15 patients with PD. Patients were evaluated on/off medication and stimulation using the Unified Parkinson's Disease Rating Scale (UPDRS). Main outcomes were changes in motor symptoms (UPDRS-III) and quality of life according to Parkinson's Disease Questionnaire-39 (PDQ-39). Secondary outcomes included efficacy profile according to sub-items of UPDRS-III, and simulation of the electric field distribution around the DBS lead using the finite element method. Simulations from all patients were transformed to one common magnetic resonance imaging template space for creation of improvement maps and anatomical evaluation.

Results: Median UPDRS-III score off medication improved from 40 at baseline to 21 on stimulation at one-year follow-up (48%, p < 0.0005). PDQ-39 summary index did not change but the subdomains activities of daily living (ADL) and stigma improved (25%, p < 0.03 and 75%, p < 0.01), whereas communication worsened (p < 0.03). For UPDRS-III sub-items, stimulation alone reduced median tremor score by 9 points, akinesia by 3, and rigidity by 2 points at one-year follow-up in comparison to baseline (90%, 25%, and 29% respectively, p < 0.01). Visual analysis of the anatomical improvement maps based on simulated electrical fields showed no evident relation with the degree of symptom improvement and neither did statistical analysis show any significant correlation.

Conclusions: Bilateral cZi-DBS alleviates motor symptoms, especially tremor, and improves ADL and stigma in PD patients one year after surgery. Improvement maps may be a useful tool for visualizing the spread of the electric field. However, there was no clear-cut relation between anatomical location of the electric field and the degree of symptom relief.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Deep brain stimulation, electric field simulation, improvement maps, Parkinson's disease, quality of life, zona incerta
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-187193 (URN)10.1111/ner.13500 (DOI)000679040500001 ()34313376 (PubMedID)2-s2.0-85111082159 (Scopus ID)
Available from: 2021-09-13 Created: 2021-09-13 Last updated: 2023-11-13Bibliographically approved
Szwedo, A. A., Dalen, I., Pedersen, K. F., Camacho, M., Bäckström, D. C., Forsgren, L., . . . Maple-Grødem, J. (2022). GBA and APOE impact cognitive decline in Parkinson's disease: A 10-year population-based study. Movement Disorders, 37(5), 1016-1027
Open this publication in new window or tab >>GBA and APOE impact cognitive decline in Parkinson's disease: A 10-year population-based study
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2022 (English)In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 37, no 5, p. 1016-1027Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Common genetic variance in apolipoprotein E (APOE), β-glucocerebrosidase (GBA), microtubule-associated protein tau (MAPT), and α-synuclein (SNCA) has been linked to cognitive decline in Parkinson's disease (PD), although studies have yielded mixed results.

OBJECTIVES: To evaluate the effect of genetic variants in APOE, GBA, MAPT, and SNCA on cognitive decline and risk of dementia in a pooled analysis of six longitudinal, non-selective, population-based cohorts of newly diagnosed PD patients.

METHODS: 1002 PD patients, followed for up to 10 years (median 7.2 years), were genotyped for at least one of APOE-ε4, GBA mutations, MAPT H1/H2, or SNCA rs356219. We evaluated the effect of genotype on the rate of cognitive decline (Mini-Mental State Examanation, MMSE) using linear mixed models and the development of dementia (diagnosed using standardized criteria) using Cox regression; multiple comparisons were accounted for using Benjamini-Hochberg corrections.

RESULTS: Carriers of APOE-ε4 (n = 281, 29.7%) and GBA mutations (n = 100, 10.3%) had faster cognitive decline and were at higher risk of progression to dementia (APOE-ε4, HR 3.57, P < 0.001; GBA mutations, HR 1.76, P = 0.001) than non-carriers. The risk of cognitive decline and dementia (HR 5.19, P < 0.001) was further increased in carriers of both risk genotypes (n = 23). No significant effects were observed for MAPT or SNCA rs356219.

CONCLUSIONS: GBA and APOE genotyping could improve the prediction of cognitive decline in PD, which is important to inform the clinical trial selection and potentially to enable personalized treatment © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
Keywords
APOE, GBA, Parkinson's disease, cognitive decline, dementia
National Category
Neurology
Research subject
Human Anatomy; nanomaterials
Identifiers
urn:nbn:se:umu:diva-202430 (URN)10.1002/mds.28932 (DOI)000749610800001 ()35106798 (PubMedID)2-s2.0-85128723530 (Scopus ID)
Funder
Wellcome trustFamiljen Erling-Perssons StiftelseThe Swedish Brain FoundationUmeå UniversityRegion VästerbottenKonung Gustaf V:s och Drottning Victorias FrimurarestiftelseParkinsonfondenThe Kempe FoundationsEU, European Research CouncilKnut and Alice Wallenberg Foundation
Available from: 2023-01-09 Created: 2023-01-09 Last updated: 2023-01-10Bibliographically approved
Bäckström, D. C., Granåsen, G., Jakobson Mo, S., Riklund, K., Trupp, M., Zetterberg, H., . . . Eriksson Domellöf, M. (2022). Prediction and early biomarkers of cognitive decline in Parkinson disease and atypical parkinsonism: a population-based study. Brain Communications, 4(2)
Open this publication in new window or tab >>Prediction and early biomarkers of cognitive decline in Parkinson disease and atypical parkinsonism: a population-based study
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2022 (English)In: Brain Communications, E-ISSN 2632-1297, Vol. 4, no 2Article in journal (Refereed) Published
Abstract [en]

The progression of cognitive decline is heterogeneous in the three most common idiopathic parkinsonian diseases: Parkinson disease, multiple system atrophy and progressive supranuclear palsy. The causes for this heterogeneity are not fully understood, and there are no validated biomarkers that can accurately identify patients who will develop dementia and when. In this population-based, prospective study, comprehensive neuropsychological testing was performed repeatedly in new-onset, idiopathic parkinsonism. Dementia was diagnosed until 10 years and participants (N = 210) were deeply phenotyped by multimodal clinical, biochemical, genetic and brain imaging measures. At baseline, before the start of dopaminergic treatment, mild cognitive impairment was prevalent in 43.4% of the patients with Parkinson disease, 23.1% of the patients with multiple system atrophy and 77.8% of the patients with progressive supranuclear palsy. Longitudinally, all three diseases had a higher incidence of cognitive decline compared with healthy controls, but the types and severity of cognitive dysfunctions differed. In Parkinson disease, psychomotor speed and attention showed signs of improvement after dopaminergic treatment, while no such improvement was seen in other diseases. The 10-year cumulative probability of dementia was 54% in Parkinson disease and 71% in progressive supranuclear palsy, while there were no cases of dementia in multiple system atrophy. An easy-to-use, multivariable model that predicts the risk of dementia in Parkinson disease within 10 years with high accuracy (area under the curve: 0.86, P < 0.001) was developed. The optimized model adds CSF biomarkers to four easily measurable clinical features at baseline (mild cognitive impairment, olfactory function, motor disease severity and age). The model demonstrates a highly variable but predictable risk of dementia in Parkinson disease, e.g. a 9% risk within 10 years in a patient with normal cognition and CSF amyloid-β42 in the highest tertile, compared with an 85% risk in a patient with mild cognitive impairment and CSF amyloid-β42 in the lowest tertile. Only small or no associations with cognitive decline were found for factors that could be easily modifiable (such as thyroid dysfunction). Risk factors for cognitive decline in multiple system atrophy and progressive supranuclear palsy included signs of systemic inflammation and eye movement abnormalities. The predictive model has high accuracy in Parkinson disease and might be used for the selection of patients into clinical trials or as an aid to improve the prevention of dementia. 

Place, publisher, year, edition, pages
Oxford University Press, 2022
Keywords
cognitive decline, dementia, Parkinson disease, multiple system atrophy, progressive supranuclear palsy
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:umu:diva-196241 (URN)10.1093/braincomms/fcac040 (DOI)000773021800001 ()35350553 (PubMedID)2-s2.0-85137588604 (Scopus ID)
Funder
Umeå UniversityRegion VästerbottenKnut and Alice Wallenberg FoundationSwedish Research Council, 2018-02532Familjen Erling-Perssons Stiftelse, FO2019-0228Familjen Erling-Perssons Stiftelse, 860197
Available from: 2022-06-10 Created: 2022-06-10 Last updated: 2022-09-26Bibliographically approved
Maple-Grødem, J., Dalen, I., Tysnes, O.-B., Macleod, A. D., Forsgren, L., Counsell, C. E. & Alves, G. (2021). Association of GBA Genotype With Motor and Functional Decline in Patients With Newly Diagnosed Parkinson Disease. Neurology, 96(7), e1036-e1044
Open this publication in new window or tab >>Association of GBA Genotype With Motor and Functional Decline in Patients With Newly Diagnosed Parkinson Disease
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2021 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 96, no 7, p. e1036-e1044Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To establish the significance of glucocerebrosidase gene (GBA) carrier status on motor impairment in a large cohort of patients with incident Parkinson disease (PD). METHODS: Three European population-based studies followed 528 patients with PD from diagnosis. A total of 440 with genomic DNA from baseline were assessed for GBA variants. We evaluated motor and functional impairment annually using the Unified Parkinson's Disease Rating Scale (UPDRS) motor and activities of daily living (ADL) sections. Differential effects of classes of GBA variants on disease progression were evaluated using mixed random and fixed effects models. RESULTS: A total of 387 patients with idiopathic disease (age at baseline 70.3 ± 9.5 years; 60.2% male) and 53 GBA carriers (age at baseline 66.8 ± 10.1 years; 64.2% male) were included. The motor profile of the groups was clinically indistinguishable at diagnosis. GBA carriers showed faster annual increase in UPDRS scores measuring ADL (1.5 point per year, 95% confidence interval [CI] 1.1-2.0) and motor symptoms (2.2 points per year, 95% CI 1.3-3.1) compared to noncarriers (ADL, 1.0 point per year, 95% CI 0.9-1.1, p = 0.003; motor, 1.3 point per year, 95% CI 1.1-1.6, p = 0.007). Simulations of clinical trial designs showed that recruiting only GBA carriers can reduce trial size by up to 65% compared to a trial recruiting all patients with PD. CONCLUSION: GBA variants are linked to a more aggressive motor disease course over 7 years from diagnosis in patients with PD. A better understanding of PD progression in genetic subpopulations may improve disease management and has direct implications for improving the design of clinical trials.

Place, publisher, year, edition, pages
aan, 2021
National Category
Neurology Hematology
Identifiers
urn:nbn:se:umu:diva-181733 (URN)10.1212/WNL.0000000000011411 (DOI)000656635000022 ()2-s2.0-85102153745 (Scopus ID)
Available from: 2021-03-23 Created: 2021-03-23 Last updated: 2023-09-05Bibliographically approved
Szwedo, A. A., Pedersen, C. C., Ushakova, A., Forsgren, L., Tysnes, O.-B., Counsell, C. E., . . . Maple-Grødem, J. (2021). Association of SNCA Parkinson's Disease Risk Polymorphisms With Disease Progression in Newly Diagnosed Patients. Frontiers in Neurology, 11, Article ID 620585.
Open this publication in new window or tab >>Association of SNCA Parkinson's Disease Risk Polymorphisms With Disease Progression in Newly Diagnosed Patients
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2021 (English)In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 11, article id 620585Article in journal (Refereed) Published
Abstract [en]

Objectives: To evaluate the impact of SNCA polymorphisms originally identified as risk factors for Parkinson's disease (PD) on the clinical presentation and progression of the disease in a large cohort of population-based patients with incident PD. Methods: Four hundred thirty-three patients and 417 controls from three longitudinal cohorts were included in the study. Disease progression was recorded annually for up to 9 years using the Unified Parkinson's Disease Rating Scale (UPDRS) or Mini-Mental State Examination. Genotypes for five variants within the SNCA locus (rs2870004, rs356182, rs5019538, rs356219, and rs763443) were determined. We studied the association between each variant and disease progression using linear mixed-effects regression models. Results: The clinical profile of the patients with PD at the point of diagnosis was highly uniform between genotype groups. The rs356219-GG genotype was associated with a higher UPDRS II score than A-allele carriers (β = 1.52; 95% confidence interval 0.10–2.95; p = 0.036), but no differences were observed in the rate of progression of the UPDRS II scores. rs356219-GG was also associated with a faster annual change in Mini-Mental State Examination score compared with A-carriers (β = 0.03; 95% confidence interval 0.00–0.06; p = 0.043). Conclusions: We show that the known PD-risk variant rs356219 has a minor effect on modifying disease progression, whereas no differences were associated with rs2870004, rs356182, rs5019538, and rs763443. These findings suggest that SNCA variants associated with PD risk may not be major driving factors to the clinical heterogeneity observed for PD.

Place, publisher, year, edition, pages
Frontiers, 2021
Keywords
cognitive impairment, disease progression, genetic association, Parkinson's disease, SNCA
National Category
Neurology Geriatrics
Identifiers
urn:nbn:se:umu:diva-181578 (URN)10.3389/fneur.2020.620585 (DOI)000620982000001 ()2-s2.0-85101618880 (Scopus ID)
Available from: 2021-03-19 Created: 2021-03-19 Last updated: 2023-09-05Bibliographically approved
Hariz, G.-M., Fredricks, A., Stenmark Persson, R., Hariz, M., Forsgren, L. & Blomstedt, P. (2021). Blinded Versus Unblinded Evaluations of Motor Scores in Patients with Parkinson's Disease Randomized to Deep Brain Stimulation or Best Medical Therapy [Letter to the editor]. Movement Disorders Clinical Practice, 8(2), 285-287
Open this publication in new window or tab >>Blinded Versus Unblinded Evaluations of Motor Scores in Patients with Parkinson's Disease Randomized to Deep Brain Stimulation or Best Medical Therapy
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2021 (English)In: Movement Disorders Clinical Practice, E-ISSN 2330-1619, Vol. 8, no 2, p. 285-287Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
John Wiley & Sons, 2021
Keywords
Parkinson's disease, blinded trial, randomization, deep brain stimulation, UPDRS
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-179502 (URN)10.1002/mdc3.13141 (DOI)000607212300001 ()2-s2.0-85099384415 (Scopus ID)
Available from: 2021-02-05 Created: 2021-02-05 Last updated: 2023-03-24Bibliographically approved
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