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Linder, Jan
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Bäckström, D. C., Linder, J., Jakobson Mo, S., Riklund, K., Zetterberg, H., Blennow, K., . . . Lenfeldt, N. (2020). NfL as a biomarker for neurodegeneration and survival in Parkinson disease. Neurology, 95(7), e827-e838
Öppna denna publikation i ny flik eller fönster >>NfL as a biomarker for neurodegeneration and survival in Parkinson disease
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2020 (Engelska)Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 95, nr 7, s. e827-e838Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

OBJECTIVE: To determine whether neurofilament light chain protein in CSF (cNfL), a sensitive biomarker of neuroaxonal damage, reflects disease severity or can predict survival in Parkinson disease (PD).

METHODS: We investigated whether disease severity, phenotype, or survival in patients with new-onset PD correlates with cNfL concentrations around the time of diagnosis in the population-based New Parkinsonism in Umeå (NYPUM) study cohort (n = 99). A second, larger new-onset PD cohort (n = 194) was used for independent validation. Association of brain pathology with the cNfL concentration was examined with striatal dopamine transporter imaging and repeated diffusion tensor imaging at baseline and 1 and 3 years.

RESULTS: Higher cNfL in the early phase of PD was associated with greater severity of all cardinal motor symptoms except tremor in both cohorts and with shorter survival and impaired olfaction. cNfL concentrations above the median of 903 ng/L conferred an overall 5.8 times increased hazard of death during follow-up. After adjustment for age and sex, higher cNfL correlated with striatal dopamine transporter uptake deficits and lower fractional anisotropy in diffusion tensor imaging of several axonal tracts.

CONCLUSIONS: cNfL shows usefulness as a biomarker of disease severity and to predict survival in PD. The present results indicate that the cNfL concentration reflects the intensity of the neurodegenerative process, which could be important in future clinical trials.

CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with PD, cNfL concentrations are associated with more severe disease and shorter survival.

Ort, förlag, år, upplaga, sidor
Wolters Kluwer, 2020
Nationell ämneskategori
Neurologi
Forskningsämne
neurologi
Identifikatorer
urn:nbn:se:umu:diva-178856 (URN)10.1212/WNL.0000000000010084 (DOI)000619277100005 ()32680941 (PubMedID)2-s2.0-85089787234 (Scopus ID)
Tillgänglig från: 2021-02-09 Skapad: 2021-02-09 Senast uppdaterad: 2023-09-05Bibliografiskt granskad
Puschmann, A., Jimenez-Ferrer, I., Lundblad-Andersson, E., Martensson, E., Hansson, O., Odin, P., . . . Swanberg, M. (2019). Low prevalence of known pathogenic mutations in dominant PD genes: A Swedish multicenter study. Parkinsonism & Related Disorders, 66, 158-165
Öppna denna publikation i ny flik eller fönster >>Low prevalence of known pathogenic mutations in dominant PD genes: A Swedish multicenter study
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2019 (Engelska)Ingår i: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 66, s. 158-165Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective: To determine the frequency of mutations known to cause autosomal dominant Parkinson disease (PD) in a series with more than 10% of Sweden's estimated number of PD patients.

Methods: The Swedish Parkinson Disease Genetics Network was formed as a national multicenter consortium of clinical researchers who together have access to DNA from a total of 2,206 PD patients; 85.4% were from population-based studies. Samples were analyzed centrally for known pathogenic mutations in SNCA (duplications/triplications, p.Ala30Pro, p.Ala53Thr) and LRRK2 (p.Asn1437His, p.Arg1441His, p.Tyr1699Cys, p.Gly2019Ser, p.Ile2020Thr). We compared the frequency of these mutations in Swedish patients with published PD series and the gnomAD database.

Results: A family history of PD in first- and/or second-degree relatives was reported by 21.6% of participants. Twelve patients (0.54%) carried LRRK2 p.(Gly2019Ser) mutations, one patient (0.045%) an SNCA duplication. The frequency of LRRK2 p.(Gly2019Ser) carriers was 0.11% in a matched Swedish control cohort and a similar 0.098% in total gnomAD, but there was a marked difference between ethnicities in gnomAD, with 42-fold higher frequency among Ashkenazi Jews than all others combined.

Conclusions: In relative terms, the LRRK2 p.(Gly2019Ser) variant is the most frequent mutation among Swedish or international PD patients, and in gnomAD. SNCA duplications were the second.most common of the mutations examined. In absolute terms, however, these known pathogenic variants in dominant PD genes are generally very rare and can only explain a minute fraction of familial aggregation of PD. Additional genetic and environmental mechanisms may explain the frequent co-occurrence of PD in close relatives.

Ort, förlag, år, upplaga, sidor
Elsevier, 2019
Nationell ämneskategori
Medicinsk genetik
Identifikatorer
urn:nbn:se:umu:diva-165118 (URN)10.1016/j.parkreldis.2019.07.032 (DOI)000491684100026 ()31422003 (PubMedID)2-s2.0-85070555795 (Scopus ID)
Tillgänglig från: 2019-11-11 Skapad: 2019-11-11 Senast uppdaterad: 2023-03-24Bibliografiskt granskad
Karlsson, F., Malinova, E., Olofsson, K., Blomstedt, P., Linder, J. & Nordh, E. (2019). Voice Tremor Outcomes of Subthalamic Nucleus and Zona Incerta Deep Brain Stimulation in Patients With Parkinson Disease. Journal of Voice, 33(4), 545-549
Öppna denna publikation i ny flik eller fönster >>Voice Tremor Outcomes of Subthalamic Nucleus and Zona Incerta Deep Brain Stimulation in Patients With Parkinson Disease
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2019 (Engelska)Ingår i: Journal of Voice, ISSN 0892-1997, E-ISSN 1873-4588, Vol. 33, nr 4, s. 545-549Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objectives: We aimed to study the effect of deep brain stimulation (DBS) in the subthalamic nucleus (STN) and caudal zona incerta (cZi) on level of perceived voice tremor in patients with Parkinson disease (PD).

Study Design: This is a prospective nonrandomized design with consecutive patients.

Methods: Perceived voice tremor was assessed in patients with PD having received either STN-DBS (8 patients, 5 bilateral and 3 unilateral, aged 43.1-73.6 years; median = 61.2 years) or cZi-DBS (14 bilateral patients, aged 39.0-71.9 years; median = 56.6 years) 12 months before the assessment. Sustained vowels that were produced OFF and ON stimulation (with simultaneous L-DOPA medication) were assessed perceptually in terms of voice tremor by two raters on a four-point rating scale. The assessments were repeated five times per sample and rated in a blinded and randomized procedure.

Results: Three out of the 22 patients (13%) were concluded to have voice tremor OFF stimulation. Patients with PD with STN-DBS showed mild levels of perceived voice tremor OFF stimulation and a group level improvement. Patients with moderate/severe perceived voice tremor and cZi-DBS showed marked improvements, but there was no overall group effect. Six patients with cZi-DBS showed small increases in perceived voice tremor severity.

Conclusions: STN-DBS decreased perceived voice tremor on a group level. cZi-DBS decreased perceived voice tremor in patients with PD with moderate to severe preoperative levels of the symptom.

Ort, förlag, år, upplaga, sidor
Elsevier, 2019
Nyckelord
DBS; Parkinson disease; STN; Voice tremor; cZi
Nationell ämneskategori
Annan klinisk medicin
Forskningsämne
oto-rhino-laryngologi; neurokirurgi
Identifikatorer
urn:nbn:se:umu:diva-144189 (URN)10.1016/j.jvoice.2017.12.012 (DOI)000476489700020 ()29361338 (PubMedID)2-s2.0-85040578940 (Scopus ID)
Forskningsfinansiär
Vetenskapsrådet, 2009-946
Tillgänglig från: 2018-01-25 Skapad: 2018-01-25 Senast uppdaterad: 2023-03-23Bibliografiskt granskad
Lunde, K. A., Chung, J., Dalen, I., Pedersen, K. F., Linder, J., Domellöf, M. E., . . . Maple-Grødem, J. (2018). Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease. Alzheimer's & Dementia: Journal of the Alzheimer's Association, 14(10), 1293-1301
Öppna denna publikation i ny flik eller fönster >>Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease
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2018 (Engelska)Ingår i: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, ISSN 1552-5260, Vol. 14, nr 10, s. 1293-1301Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Introduction

Both polymorphisms and mutations in glucocerebrosidase (GBA) may influence the development of dementia in patients with Parkinson's disease.

Methods

Four hundred forty-two patients and 419 controls were followed for 7 years. Dementia was diagnosed using established criteria. Participants were analyzed for GBA genetic variants, including E326K, T369M, and L444P. Associations between GBA carrier status and dementia were assessed with Cox survival analysis.

Results

A total of 12.0% of patients with Parkinson's disease carried a GBA variant, and nearly half (22/53) of them progressed to dementia during follow-up. Carriers of deleterious GBA mutations (adjusted hazard ratio 3.81, 95% confidence interval 1.35 to 10.72; P = .011) or polymorphisms (adjusted hazard ratio 1.79; 95% confidence interval 1.07 to 3.00; P = .028) progressed to dementia more rapidly than noncarriers.

Discussion

GBA variants are of great clinical relevance for the development of dementia in Parkinson's disease, especially due to the relatively higher frequency of these alleles compared with other risk alleles.

Ort, förlag, år, upplaga, sidor
Elsevier, 2018
Nyckelord
Parkinson's Disease
Nationell ämneskategori
Neurologi
Forskningsämne
genetik; neurologi
Identifikatorer
urn:nbn:se:umu:diva-148814 (URN)10.1016/j.jalz.2018.04.006 (DOI)000446086000006 ()2-s2.0-85049877845 (Scopus ID)
Projekt
NYPUM projectParkWest studyPINE study
Forskningsfinansiär
KempestiftelsernaVästerbottens läns landstingKempestiftelsernaVästerbottens läns landsting
Tillgänglig från: 2018-06-12 Skapad: 2018-06-12 Senast uppdaterad: 2023-03-28Bibliografiskt granskad
Blomstedt, P., Stenmark Persson, R., Hariz, G.-M., Linder, J., Fredricks, A., Häggström, B., . . . Hariz, M. (2018). Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease: a randomised blinded evaluation. Journal of Neurology, Neurosurgery and Psychiatry, 89(7), 710-716
Öppna denna publikation i ny flik eller fönster >>Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease: a randomised blinded evaluation
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2018 (Engelska)Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 89, nr 7, s. 710-716Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Several open-label studies have shown good effect of deep brain stimulation (DBS) in the caudal zona incerta (cZi) on tremor, including parkinsonian tremor, and in some cases also a benefit on akinesia and axial symptoms. The aim of this study was to evaluate objectively the effect of cZi DBS in patients with Parkinson's disease (PD).

Method: 25 patients with PD were randomised to either cZi DBS or best medical treatment. The primary outcomes were differences between the groups in the motor scores of the Unified Parkinson's Disease Rating Scale (UPDRS-III) rated single-blindly at 6 months and differences in the Parkinson's Disease Questionnaire 39 items (PDQ-39). 19 patients, 10 in the medical arm and 9 in the DBS arm, fulfilled the study.

Results: The DBS group had 41% better UPDRS-III scores off-medication on-stimulation compared with baseline, whereas the scores of the non-surgical patients off-medication were unchanged. In the on-medication condition, there were no differences between the groups, neither at baseline nor at 6 months. Subitems of the UPDRS-III showed a robust effect of cZi DBS on tremor. The PDQ-39 domains 'stigma' and 'ADL' improved only in the DBS group. The PDQ-39 summary index improved in both groups.

Conclusion: This is the first randomised blinded evaluation of cZi DBS showing its efficacy on PD symptoms. The most striking effect was on tremor; however, the doses of dopaminergic medications could not be decreased. cZi DBS in PD may be an addition to existing established targets, enabling tailoring the surgery to the needs of the individual patient.

Ort, förlag, år, upplaga, sidor
BMJ Publishing Group Ltd, 2018
Nationell ämneskategori
Neurologi
Identifikatorer
urn:nbn:se:umu:diva-150375 (URN)10.1136/jnnp-2017-317219 (DOI)000438044100010 ()29386253 (PubMedID)2-s2.0-85050267457 (Scopus ID)
Tillgänglig från: 2018-08-08 Skapad: 2018-08-08 Senast uppdaterad: 2023-11-13Bibliografiskt granskad
Jakobson Mo, S., Axelsson, J., Jonasson, L., Larsson, A., Ögren, M. J., Ögren, M., . . . Riklund, K. (2018). Dopamine transporter imaging with [18F]FE-PE2I PET and [123I]FP-CIT SPECT – a clinical comparison. EJNMMI Research, 8, Article ID 100.
Öppna denna publikation i ny flik eller fönster >>Dopamine transporter imaging with [18F]FE-PE2I PET and [123I]FP-CIT SPECT – a clinical comparison
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2018 (Engelska)Ingår i: EJNMMI Research, E-ISSN 2191-219X, Vol. 8, artikel-id 100Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Dopamine transporter (DAT) imaging may be of diagnostic value in patients with clinically suspected parkinsonian disease. The purpose of this study was to compare the diagnostic performance of DAT imaging with positron emission computed tomography (PET), using the recently developed, highly DAT-selective radiopharmaceutical [18F]FE-PE2I (FE-PE2I), to the commercially available and frequently used method with [123I]FP-CIT (FP-CIT) single-photon emission computed tomography (SPECT) in early-stage idiopathic parkinsonian syndrome (PS).

Methods: Twenty-two patients with a clinical de novo diagnosis of PS and 28 healthy controls (HC) participating in an on-going clinical trial of FE-PE2I were analyzed in this study. Within the trial protocol, participants are clinically reassessed 2 years after inclusion. A commercially available software was used for automatic calculation of FP-CIT-specific uptake ratio (SUR). MRI-based volumes of interest combined with threshold PET segmentation were used for FE-PE2I binding potential relative to non-displaceable binding (BPND) quantification and specific uptake value ratios (SUVR).

Results: PET with FE-PE2I revealed significant differences between patients with a clinical de novo diagnosis of PS and healthy controls in striatal DAT availability (p < 0.001), with excellent accuracy of predicting dopaminergic deficit in early-stage PS. The effect sizes were calculated for FE-PE2I BPND (Glass’s Δ = 2.95), FE-PE2I SUVR (Glass’s Δ = 2.57), and FP-CIT SUR (Glass’s Δ = 2.29). The intraclass correlation (ICC) between FE-PE2I BPND FP-CIT SUR was high in the caudate (ICC = 0.923), putamen (ICC = 0.922), and striatum (ICC = 0.946), p < 0.001. Five of the 22 patients displayed preserved striatal DAT availability in the striatum with both methods. At follow-up, a non-PS clinical diagnosis was confirmed in three of these, while one was clinically diagnosed with corticobasal syndrome. In these patients, FE-PE2I binding was also normal in the substantia nigra (SN), while significantly reduced in the remaining patients. FE-PE2I measurement of the mean DAT availability in the putamen was strongly correlated with BPND in the SN (R = 0.816, p < 0.001). Olfaction and mean putamen DAT availability was correlated using both FE-PE2I BPND and FP-CIT SUR (R ≥ 0.616, p < 0.001).

Conclusion: DAT imaging with FE-PE2I PET yields excellent basic diagnostic differentiation in early-stage PS, at least as good as FP-CIT SPECT.

Ort, förlag, år, upplaga, sidor
Springer, 2018
Nyckelord
Parkinson's disease, PET, SPECT, Dopamine transporter (DAT), [F-18]FE-PE2I
Nationell ämneskategori
Radiologi och bildbehandling
Identifikatorer
urn:nbn:se:umu:diva-154944 (URN)10.1186/s13550-018-0450-0 (DOI)000450488800002 ()30443684 (PubMedID)2-s2.0-85056664892 (Scopus ID)
Tillgänglig från: 2019-01-07 Skapad: 2019-01-07 Senast uppdaterad: 2023-03-24Bibliografiskt granskad
Bäckström, D., Granåsen, G., Eriksson Domellöf, M., Linder, J., Jakobson Mo, S., Riklund, K., . . . Forsgren, L. (2018). Early predictors of mortality in parkinsonism and Parkinson disease: A population-based study. Neurology, 91(22), E2045-E2056
Öppna denna publikation i ny flik eller fönster >>Early predictors of mortality in parkinsonism and Parkinson disease: A population-based study
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2018 (Engelska)Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 91, nr 22, s. E2045-E2056Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective To examine mortality and associated risk factors, including possible effects of mild cognitive impairment, imaging, and CSF abnormalities, in a community-based population with incident parkinsonism and Parkinson disease. Methods One hundred eighty-two patients with new-onset, idiopathic parkinsonism were diagnosed from January 2004 through April 2009, in a catchment area of 142,000 inhabitants in Sweden. Patients were comprehensively investigated according to a multimodal research protocol and followed prospectively for up to 13.5 years. A total of 109 patients died. Mortality rates in the general Swedish population were used to calculate standardized mortality ratio and expected survival, and Cox proportional hazard models were used to investigate independent predictors of mortality. Results The standardized mortality ratio for all patients was 1.84 (95% confidence interval 1.50-2.22, p < 0.001). Patients with atypical parkinsonism (multiple system atrophy or progressive supranuclear palsy) had the highest mortality. In early Parkinson disease, a mild cognitive impairment diagnosis, freezing of gait, hyposmia, reduced dopamine transporter activity in the caudate, and elevated leukocytes in the CSF were significantly associated with shorter survival. Conclusion Although patients presenting with idiopathic parkinsonism have reduced survival, the survival is highly dependent on the type and characteristics of the parkinsonian disorder. Patients with Parkinson disease presenting with normal cognitive function seem to have a largely normal life expectancy. The finding of a subtle CSF leukocytosis in patients with Parkinson disease with short survival may have clinical implications.

Ort, förlag, år, upplaga, sidor
Wolters Kluwer, 2018
Nationell ämneskategori
Neurologi
Identifikatorer
urn:nbn:se:umu:diva-154849 (URN)10.1212/WNL.0000000000006576 (DOI)000452519500002 ()30381367 (PubMedID)2-s2.0-85057199126 (Scopus ID)
Tillgänglig från: 2019-01-04 Skapad: 2019-01-04 Senast uppdaterad: 2023-03-24Bibliografiskt granskad
Håglin, L., Bäckman, L., Linder, J., Forsgren, L. & Domellöf, M. (2018). Early Recognition of Cognitive Ability and Nutritional Markers for Dementia in Parkinson’s Disease. Journal of Aging Research & Clinical Practice, 7, 156-162
Öppna denna publikation i ny flik eller fönster >>Early Recognition of Cognitive Ability and Nutritional Markers for Dementia in Parkinson’s Disease
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2018 (Engelska)Ingår i: Journal of Aging Research & Clinical Practice, ISSN 2258-8094, Vol. 7, s. 156-162Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Cognitive decline and dementia are common non-motor problems in Parkinson’s disease (PD). The underlying aetiology is multifaceted and both chronic and reversible causes for cognitive decline are likely to be present. Malnutrition is frequent in the Parkinson population, both early and late in the disease, and nutritional deficiencies could play a role in some cognitive deficits. Objectives: The objective is to study the association between nutritional status with focus on iron intake and homeostasis, mild cognitive impairment (MCI), and PD dementia (PDD). Setting and Participants: This study included 73 out of 145 patients with PD participating in a population-based study in northern Sweden. Measurements: Registration of nutritional status by laboratory analyses of blood plasma and neuropsychological assessments at time of diagnosis were performed. MCI and PDD were assessed yearly up to ten years after diagnosis. Mini Nutritional Assessments (Full-MNA score) and plasma variables detecting iron homeostasis were compared between patients with MCI and patients with normal cognition (NC). Motor severity was measured using the Unified Parkinson´s disease rating scale III, (UPDRS III) and Hoehn and Yahr (H&Y) staging scale. Cox proportional Hazard model were performed to see if any variables that differed between MCI and NC could predict PDD at follow-up. Results: Patients with MCI at time of diagnosis had lower levels of plasma iron (P-Fe) and albumin (P-Albumin) as well as a lower score on Full-MNA score. Dietary intake of iron was higher in patients with MCI than in patients with NC (p = 0.012). In logistic regression models adjusted for age, sex, and UPDRS III, lower levels of P-Fe (p = 0.025) and P-Albumin (p = 0.011) and higher dietary iron intake (p = 0.019) were associated with MCI at baseline. A Cox regression model with dementia as endpoint revealed that lower levels of P-Fe increase the risk of dementia at follow-up with adjustments for age, sex, UPDRS III, and MCI at baseline (HR 95% CI = 0.87 (0.78-0.98), p = 0.021). Conclusions: Low P-Fe was associated with cognitive disturbance at baseline and predicted dementia up to ten years after diagnosis in patients with PD. Low P-Albumin and malnutrition assessed with Full-MNA score were associated with MCI at baseline but did not predict dementia at follow-up.

Ort, förlag, år, upplaga, sidor
Auzeville-Tolosane: SERDI, 2018
Nyckelord
Cognition, dementia, iron deficiency, Parkinson’s disease
Nationell ämneskategori
Neurologi
Identifikatorer
urn:nbn:se:umu:diva-159274 (URN)10.14283/jarcp.2018.26 (DOI)
Tillgänglig från: 2019-05-23 Skapad: 2019-05-23 Senast uppdaterad: 2019-05-24Bibliografiskt granskad
Bäckström, D., Eriksson Domellöf, M., Granåsen, G., Linder, J., Mayans, S., Elgh, E., . . . Forsgren, L. (2018). Polymorphisms in dopamine-associated genes and cognitive decline in Parkinson's disease. Acta Neurologica Scandinavica, 137(1), 91-98
Öppna denna publikation i ny flik eller fönster >>Polymorphisms in dopamine-associated genes and cognitive decline in Parkinson's disease
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2018 (Engelska)Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 137, nr 1, s. 91-98Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objectives: Cognitive decline is common in Parkinson's disease (PD), but the underlying mechanisms for this complication are incompletely understood. Genotypes affecting dopamine transmission may be of importance. This study investigates whether genotypes associated with reduced prefrontal dopaminergic tone and/or reduced dopamine D2-receptor availability (Catechol-O-methyltransferase [COMT] Val(158)Met genotype and DRD2 (CT)-T-957 genotype) affect the development of cognitive deficits in PD.

Materials and methods: One hundred and 34 patients with idiopathic PD, participating in a regional, population-based study of incident parkinsonism, underwent genotyping. After extensive baseline investigations (including imaging and biomarker analyses), the patients were followed prospectively during 6-10 years with neuropsychological evaluations, covering six cognitive domains. Cognitive decline (defined as the incidence of either Parkinson's disease mild cognitive impairment [PD-MCI] or dementia [PDD], diagnosed according to published criteria and blinded to genotype) was studied as the primary outcome.

Results: Both genotypes affected cognition, as shown by Cox proportional hazards models. While the COMT(158)Val/Val genotype conferred an increased risk of mild cognitive impairment in patients with normal cognition at baseline (hazard ratio: 2.13, P=.023), the DRD2(957)T/T genotype conferred an overall increased risk of PD dementia (hazard ratio: 3.22, P<.001). The poorer cognitive performance in DRD2(957)T/T carriers with PD occurred mainly in episodic memory and attention.

Conclusions: The results favor the hypothesis that dopamine deficiency in PD not only relate to mild cognitive deficits in frontostriatal functions, but also to a decline in memory and attention. This could indicate that dopamine deficiency impairs a wide network of brain areas.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2018
Nyckelord
COMT, dementia, DRD2, mild cognitive impairment, neurodegeneration, Parkinson's disease, Parkinson's disease genetics, population-based
Nationell ämneskategori
Neurologi
Identifikatorer
urn:nbn:se:umu:diva-143002 (URN)10.1111/ane.12812 (DOI)000417029600014 ()2-s2.0-85028704401 (Scopus ID)
Tillgänglig från: 2017-12-14 Skapad: 2017-12-14 Senast uppdaterad: 2023-03-23Bibliografiskt granskad
Lizana, H., Johansson, L., Axelsson, J., Larsson, A., Ögren, M., Linder, J., . . . Jakobson Mo, S. (2018). Whole-Body Biodistribution and Dosimetry of the Dopamine Transporter Radioligand 18F-FE-PE2I in Human Subjects. Journal of Nuclear Medicine, 59(8), 1275-1280
Öppna denna publikation i ny flik eller fönster >>Whole-Body Biodistribution and Dosimetry of the Dopamine Transporter Radioligand 18F-FE-PE2I in Human Subjects
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2018 (Engelska)Ingår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 59, nr 8, s. 1275-1280Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

F-18-(E)-N-(3-iodoprop-2-enyl)-2 beta-carbofluoroethoxy-3 beta-(4'-methylphenyl) nortropane (F-18-FE-PE2I) was recently developed and has shown adequate affinity and high selectivity for the dopamine transporter (DAT). Previous studies have shown promising results for F-18-FE-PE2I as a suitable radioligand for DAT imaging. In this study, we investigated the whole-body biodistribution and dosimetry of F-18-FE-PE2I in healthy volunteers to support its utility as a suitable PET imaging agent for the DAT. Methods: Five healthy volunteers were given a mean activity of 2.5 MBq/kg, and 3 PET scans, head to thigh, were performed immediately after injection followed by 4 whole-body PET/CT scans between 0.5 and 6 h after injection. Blood samples were drawn in connection with the whole-body scans, and all urine was collected until 6 h after injection. Volumes of interest were delineated around 17 organs on all images, and the areas under the time-activity curves were calculated to obtain the total number of decays in the organs. The absorbed doses to organs and the effective dose were calculated using the software IDAC. Results: The highest activity concentration was observed in the liver (0.9%-1.2% injected activity/100 g) up to 30 min after injection. At later time points, the highest concentration was seen in the gallbladder (1.1%-0.1% injected activity/100 g). The activity excreted with urine ranged between 23% and 34%, with a mean of 28%. The urinary bladder received the highest absorbed dose (119 mu Gy/MBq), followed by the liver (46 mu Gy/MBq). The effective dose was 23 mu Sv/MBq (range, 19-28 mu Sv/MBq), resulting in an effective dose of 4.6 mSv for an administered activity of 200 MBq. Conclusion: The effective dose is within the same order of magnitude as other commonly used PET imaging agents as well as DAT agents. The reasonable effective dose, together with the previously reported favorable characteristics for DAT imaging and quantification, indicates that F-18-FE-PE2I is a suitable radioligand for DAT imaging.

Nyckelord
F-18-FE-PE2I, dosimetry, biodistribution, DAT, effective dose
Nationell ämneskategori
Radiologi och bildbehandling
Identifikatorer
urn:nbn:se:umu:diva-150823 (URN)10.2967/jnumed.117.197186 (DOI)000440582000020 ()29348315 (PubMedID)2-s2.0-85051260875 (Scopus ID)
Tillgänglig från: 2018-08-21 Skapad: 2018-08-21 Senast uppdaterad: 2023-03-23Bibliografiskt granskad
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