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  • 1
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    Effects of working memory training in patients with Parkinson's disease without cognitive impairment: A randomized controlled trial
    Elsevier BV ; 2020
    In:  Parkinsonism & Related Disorders Vol. 72 ( 2020-03), p. 13-22
    Details
    In: Parkinsonism & Related Disorders, Elsevier BV, Vol. 72 ( 2020-03), p. 13-22
    Type of Medium: Online Resource
    ISSN: 1353-8020
    URL: Article
    DOI: 10.1016/j.parkreldis.2020.02.002
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2027635-7
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  • 2
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    Serum Biomarkers of a Pro-Neuroinflammatory State May Define the Pre-Operative Risk for Postoperative Delirium in Spine Surgery
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 12 ( 2023-06-19), p. 10335-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 12 ( 2023-06-19), p. 10335-
    Abstract: Advances in spine surgery enable technically safe interventions in older patients with disabling spine disease, yet postoperative delirium (POD) poses a serious risk for postoperative recovery. This study investigates biomarkers of pro-neuroinflammatory states that may help objectively define the pre-operative risk for POD. This study enrolled patients aged ≥60 scheduled for elective spine surgery under general anesthesia. Biomarkers for a pro-neuroinflammatory state included S100 calcium-binding protein β (S100β), brain-derived neurotrophic factor (BDNF), Gasdermin D, and the soluble ectodomain of the triggering receptor expressed on myeloid cells 2 (sTREM2). Postoperative changes of Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and C-reactive protein (CRP) were assessed as markers of systemic inflammation preoperatively, intraoperatively, and early postoperatively (up to 48 h). Patients with POD (n = 19, 75.7 ± 5.8 years) had higher pre-operative levels of sTREM2 (128.2 ± 69.4 pg/mL vs. 97.2 ± 52.0 pg/mL, p = 0.049) and Gasdermin D (2.9 ± 1.6 pg/mL vs. 2.1 ± 1.4 pg/mL, p = 0.29) than those without POD (n = 25, 75.6 ± 5.1 years). STREM2 was additionally a predictor for POD (OR = 1.01/(pg/mL) [1.00–1.03], p = 0.05), moderated by IL-6 (Wald-χ2 = 4.06, p = 0.04). Patients with POD additionally showed a significant increase in IL-6, IL-1β, and S100β levels on the first postoperative day. This study identified higher levels of sTREM2 and Gasdermin D as potential markers of a pro-neuroinflammatory state that predisposes to the development of POD. Future studies should confirm these results in a larger cohort and determine their potential as an objective biomarker to inform delirium prevention strategies.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241210335
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
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    Subtypes of mild cognitive impairment in patients with Parkinson's disease: evidence from the LANDSCAPE study
    BMJ ; 2016
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 87, No. 10 ( 2016-10), p. 1099-1105
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 87, No. 10 ( 2016-10), p. 1099-1105
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    DOI: 10.1136/jnnp-2016-313838
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2016
    detail.hit.zdb_id: 1480429-3
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  • 4
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    Cognitive decline in Parkinson’s disease: the impact of the motor phenotype on cognition
    BMJ ; 2019
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 90, No. 2 ( 2019-02), p. 171-179
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 90, No. 2 ( 2019-02), p. 171-179
    Abstract: Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is further associated with progressive cognitive decline. In respect to motor phenotype, there is some evidence that akinetic-rigid PD is associated with a faster rate of cognitive decline in general and a greater risk of developing dementia. The objective of this study was to examine cognitive profiles among patients with PD by motor phenotypes and its relation to cognitive function. Methods Demographic, clinical and neuropsychological cross-sectional baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort study of 538 patients with PD were analysed, stratified by motor phenotype and cognitive syndrome. Analyses were performed for all patients and for each diagnostic group separately, controlling for age, gender, education and disease duration. Results Compared with the tremor-dominant phenotype, akinetic-rigid patients performed worse in executive functions such as working memory (Wechsler Memory Scale-Revised backward; p=0.012), formal-lexical word fluency (p=0.043), card sorting (p=0.006), attention (Trail Making Test version A; p=0.024) and visuospatial abilities (Leistungsprüfungssystem test 9; p=0.006). Akinetic-rigid neuropsychological test scores for the executive and attentive domain correlated negatively with non-tremor motor scores. Covariate-adjusted binary logistic regression analyses showed significant odds for PD-mild cognitive impairment for not-determined as compared with tremor-dominant (OR=3.198) and akinetic-rigid PD (OR=2.059). The odds for PD-dementia were significant for akinetic-rigid as compared with tremor-dominant phenotype (OR=8.314). Conclusion The three motor phenotypes of PD differ in cognitive performance, showing that cognitive deficits seem to be less severe in tremor-dominant PD. While these data are cross-sectional, longitudinal data are needed to shed more light on these differential findings.
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    DOI: 10.1136/jnnp-2018-319008
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 1480429-3
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  • 5
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    Novel genetically encoded fluorescent probes enable real-time detection of potassium in vitro and in vivo
    Springer Science and Business Media LLC ; 2017
    In:  Nature Communications Vol. 8, No. 1 ( 2017-11-10)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2017-11-10)
    Abstract: Changes in intra- and extracellular potassium ion (K + ) concentrations control many important cellular processes and related biological functions. However, our current understanding of the spatiotemporal patterns of physiological and pathological K + changes is severely limited by the lack of practicable detection methods. We developed K + -sensitive genetically encoded, Förster resonance energy transfer-(FRET) based probes, called GEPIIs, which enable quantitative real-time imaging of K + dynamics. GEPIIs as purified biosensors are suitable to directly and precisely quantify K + levels in different body fluids and cell growth media. GEPIIs expressed in cells enable time-lapse and real-time recordings of global and local intracellular K + signals. Hitherto unknown Ca 2+ -triggered, organelle-specific K + changes were detected in pancreatic beta cells. Recombinant GEPIIs also enabled visualization of extracellular K + fluctuations in vivo with 2-photon microscopy. Therefore, GEPIIs are relevant for diverse K + assays and open new avenues for live-cell K + imaging.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-017-01615-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2553671-0
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  • 6
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    Working memory training increases neural efficiency in Parkinson’s disease: a randomized controlled trial
    Oxford University Press (OUP) ; 2020
    In:  Brain Communications Vol. 2, No. 2 ( 2020-07-01)
    Details
    In: Brain Communications, Oxford University Press (OUP), Vol. 2, No. 2 ( 2020-07-01)
    Abstract: Impairment of working memory and executive functions is already frequently observed in early stages of Parkinson’s disease. Improvements in working memory performance in this cohort could potentially be achieved via working memory training. However, the specific neural mechanisms underlying different working memory processes such as maintenance as opposed to manipulation are largely under-investigated in Parkinson’s disease. Moreover, the plasticity of these correlates as a function of working memory training is currently unknown in this population. Thus, the working memory subprocesses of maintenance and manipulation were assessed in 41 cognitively healthy patients with Parkinson’s disease using a newly developed working memory paradigm and functional MRI. Nineteen patients were randomized to a 5-week home-based digital working memory training intervention while the remaining patients entered a control, wait list condition. Working memory task-related activation patterns and context-dependent functional connectivity, as well as the change of these neural correlates as a function of training, were assessed. While both working memory processes activated an extended frontoparietal–cerebellar network, only the manipulation of items within working memory also recruited the anterior striatum. The intervention effect on the neural correlates was small, but decreased activation in areas relevant for working memory could be observed, with activation changes correlating with behavioural change. Moreover, training seemed to result in decreased functional connectivity when pure maintenance was required, and in a reorganization of functional connectivity when items had to be manipulated. In accordance with the neural efficacy hypothesis, training resulted in overall reduced activation and reorganized functional connectivity, with a differential effect on the different working memory processes under investigation. Now, larger trials including follow-up examinations are needed to further explore the long-term effects of such interventions on a neural level and to estimate the clinical relevance to potentially delay cognitive decline in cognitively healthy patients with Parkinson’s disease.
    Type of Medium: Online Resource
    ISSN: 2632-1297
    URL: Article
    DOI: 10.1093/braincomms/fcaa115
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 3020013-1
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  • 7
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    High CD206 levels in Hodgkin lymphoma‐educated macrophages are linked to matrix‐remodeling and lymphoma dissemination
    Wiley ; 2020
    In:  Molecular Oncology Vol. 14, No. 3 ( 2020-03), p. 571-589
    Details
    In: Molecular Oncology, Wiley, Vol. 14, No. 3 ( 2020-03), p. 571-589
    Abstract: Macrophages (Mφ) are abundantly present in the tumor microenvironment and may predict outcome in solid tumors and defined lymphoma subtypes. Mφ heterogeneity, the mechanisms of their recruitment, and their differentiation into lymphoma‐promoting, alternatively activated M2‐like phenotypes are still not fully understood. Therefore, further functional studies are required to understand biological mechanisms associated with human tumor‐associated Mφ (TAM). Here, we show that the global mRNA expression and protein abundance of human Mφ differentiated in Hodgkin lymphoma (HL)‐conditioned medium (CM) differ from those of Mφ educated by conditioned media from diffuse large B‐cell lymphoma (DLBCL) cells or, classically, by macrophage colony‐stimulating factor (M‐CSF). Conditioned media from HL cells support TAM differentiation through upregulation of surface antigens such as CD40, CD163, CD206, and PD‐L1. In particular, RNA and cell surface protein expression of mannose receptor 1 ( MRC1 )/CD206 significantly exceed the levels induced by classical M‐CSF stimulation in M2‐like Mφ; this is regulated by interleukin 13 to a large extent. Functionally, high CD206 enhances mannose‐dependent endocytosis and uptake of type I collagen. Together with high matrix metalloprotease9 secretion, HL‐TAMs appear to be active modulators of the tumor matrix. Preclinical in ovo models show that co‐cultures of HL cells with monocytes or Mφ support dissemination of lymphoma cells via lymphatic vessels, while tumor size and vessel destruction are decreased in comparison with lymphoma‐only tumors. Immunohistology of human HL tissues reveals a fraction of cases feature large numbers of CD206‐positive cells, with high MRC1 expression being characteristic of HL‐stage IV. In summary, the lymphoma‐TAM interaction contributes to matrix‐remodeling and lymphoma cell dissemination.
    Type of Medium: Online Resource
    ISSN: 1574-7891 , 1878-0261
    URL: Issue
    URL: Article
    DOI: 10.1002/mol2.v14.3
    DOI: 10.1002/1878-0261.12616
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2322586-5
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  • 8
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    Long-Term Cognitive Decline Related to the Motor Phenotype in Parkinson’s Disease
    IOS Press ; 2022
    In:  Journal of Parkinson's Disease Vol. 12, No. 3 ( 2022-04-05), p. 905-916
    Details
    In: Journal of Parkinson's Disease, IOS Press, Vol. 12, No. 3 ( 2022-04-05), p. 905-916
    Abstract: Background: Parkinson’s disease (PD) is associated with various non-motor symptoms, including cognitive deterioration. Objective: Here, we used data from the DEMPARK/LANDSCAPE cohort to describe the association between progression of cognitive profiles and the PD motor phenotypes: postural instability and gait disorder (PIGD), tremor-dominant (TR-D), and not-determined (ND). Methods: Demographic, clinical, and neuropsychological six-year longitudinal data of 711 PD-patients were included (age: M = 67.57; 67.4% males). We computed z-transformed composite scores for a priori defined cognitive domains. Analyses were controlled for age, gender, education, and disease duration. To minimize missing data and drop-outs, three-year follow-up data of 442 PD-patients was assessed with regard to the specific role of motor phenotype on cognitive decline using linear mixed modelling (age: M = 66.10; 68.6% males). Results: Our study showed that in the course of the disease motor symptoms increased while MMSE and PANDA remained stable in all subgroups. After three-year follow-up, significant decline of overall cognitive performance for PIGD-patients were present and we found differences for motor phenotypes in attention (β= –0.08, SE = 0.003, p  〈  0.006) and memory functions showing that PIGD-patients deteriorate per months by –0.006 compared to the ND-group (SE = 0.003, p = 0.046). Furthermore, PIGD-patients experienced more often difficulties in daily living. Conclusion: Over a period of three years, we identified distinct neuropsychological progression patterns with respect to different PD motor phenotypes, with early executive deficits yielding to a more amnestic profile in the later course. Here, in particular PIGD-patients worsened over time compared to TR-D and ND-patients, highlighting the greater risk of dementia for this motor phenotype.
    Type of Medium: Online Resource
    ISSN: 1877-7171 , 1877-718X
    URL: Article
    DOI: 10.3233/JPD-212787
    Language: Unknown
    Publisher: IOS Press
    Publication Date: 2022
    detail.hit.zdb_id: 2599550-9
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  • 9
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    Cognitive Performance and Learning Parameters Predict Response to Working Memory Training in Parkinson’s Disease
    IOS Press ; 2022
    In:  Journal of Parkinson's Disease Vol. 12, No. 7 ( 2022-10-14), p. 2235-2247
    Details
    In: Journal of Parkinson's Disease, IOS Press, Vol. 12, No. 7 ( 2022-10-14), p. 2235-2247
    Abstract: Background: Working memory (WM) training (WMT) is a popular intervention approach against cognitive decline in patients with Parkinson’s disease (PD). However, heterogeneity in WM responsiveness suggests that WMT may not be equally efficient for all patients. Objective: The present study aims to evaluate a multivariate model to predict post-intervention verbal WM in patients with PD using a supervised machine learning approach. We test the predictive potential of novel learning parameters derived from the WMT and compare their predictiveness to other more commonly used domains including demographic, clinical, and cognitive data. Methods: 37 patients with PD (age: 64.09±8.56, 48.6% female, 94.7% Hoehn & Yahr stage 2) participated in a 5-week WMT. Four random forest regression models including 1) cognitive variables only, 2) learning parameters only, 3) both cognitive and learning variables, and 4) the entire set of variables (with additional demographic and clinical data, ‘all’ model), were built to predict immediate and 3-month-follow-up WM. Result: The ‘all’ model predicted verbal WM with the lowest root mean square error (RMSE) compared to the other models, at both immediate (RMSE = 0.184; 95% -CI=[0.184;0.185] ) and 3-month follow-up (RMSE = 0.216; 95% -CI=[0.215;0.217]). Cognitive baseline parameters were among the most important predictors in the ‘all’ model. The model combining cognitive and learning parameters significantly outperformed the model solely based on cognitive variables. Conclusion: Commonly assessed demographic, clinical, and cognitive variables provide robust prediction of response to WMT. Nonetheless, inclusion of training-inherent learning parameters further boosts precision of prediction models which in turn may augment training benefits following cognitive interventions in patients with PD.
    Type of Medium: Online Resource
    ISSN: 1877-7171 , 1877-718X
    URL: Article
    DOI: 10.3233/JPD-223448
    Language: Unknown
    Publisher: IOS Press
    Publication Date: 2022
    detail.hit.zdb_id: 2599550-9
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  • 10
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    Predicting Working Memory Training Responsiveness in Parkinson’s Disease: Both “System Hardware” and Room for Improvement Are Needed
    SAGE Publications ; 2021
    In:  Neurorehabilitation and Neural Repair Vol. 35, No. 2 ( 2021-02), p. 117-130
    Details
    In: Neurorehabilitation and Neural Repair, SAGE Publications, Vol. 35, No. 2 ( 2021-02), p. 117-130
    Abstract: Background. Patients with Parkinson’s disease (PD) are highly vulnerable to develop cognitive dysfunctions, and the mitigating potential of early cognitive training (CT) is increasingly recognized. Predictors of CT responsiveness, which could help to tailor interventions individually, have rarely been studied in PD. This study aimed to examine individual characteristics of patients with PD associated with responsiveness to targeted working memory training (WMT). Methods. Data of 75 patients with PD (age: 63.99 ± 9.74 years, 93% Hoehn & Yahr stage 2) without cognitive dysfunctions from a randomized controlled trial were analyzed using structural equation modeling. Latent change score models with and without covariates were estimated and compared between the WMT group ( n = 37), who participated in a 5-week adaptive WMT, and a waiting list control group ( n = 38). Results. Latent change score models yielded adequate model fit (χ 2 -test p 〉 .05, SRMR ≤ .08, CFI ≥ .95). For the near-transfer working memory composite, lower baseline performance, younger age, higher education, and higher fluid intelligence were found to significantly predict higher latent change scores in the WMT group, but not in the control group. For the far-transfer executive function composite, higher self-efficacy expectancy tended to significantly predict larger latent change scores. Conclusions. The identified associations between individual characteristics and WMT responsiveness indicate that there has to be room for improvement (e.g., lower baseline performance) and also sufficient “hardware” (e.g., younger age, higher intelligence) to benefit in training-related cognitive plasticity. Our findings are discussed within the compensation versus magnification account. They need to be replicated by methodological high-quality research applying advanced statistical methods with larger samples.
    Type of Medium: Online Resource
    ISSN: 1545-9683 , 1552-6844
    URL: Article
    DOI: 10.1177/1545968320981956
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2100545-X
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