Alexandra Gaenslen

Hertie Institute for Clinical Brain Research

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Daniela Berg

University of Tübingen

Jana Godau

Klinikum Kassel

Walter Maetzler

German Center for Neurodegenerative Diseases

Thomas Gasser

Hertie Institute for Clinical Brain Research

Kathrin Brockmann

German Center for Neurodegenerative Diseases

Inga Liepelt

University of Luxembourg

Isabel Wurster

German Center for Neurodegenerative Diseases

Stefanie Lerche

German Center for Neurodegenerative Diseases

Stefanie Behnke

Knappschaftsklinikum Saar

Heiko Huber

University of Tübingen

Cooperative Institutions

Health and Education Research Management and Epidemiologic Services (United States)

University of Melbourne

Charité - Universitätsmedizin Berlin

Heidelberg University

Klinik und Poliklinik für Neurologie

Inserm

Universität Hamburg

German Center for Neurodegenerative Diseases

Hertie Institute for Clinical Brain Research

University of Tübingen

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Pre-motor signs of PD are related to SN hyperechogenicity assessed by TCS in an elderly population

Neurobiology of Aging (2009)

Inga Liepelt Stefanie Behnke K. Schweitzer Björn Wolf Jana Godau

Hyposmia

10.1016/j.neurobiolaging.2009.10.004

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Citations (45)

Higher frequency of regulatory T cells in the elderly and increased suppressive activity in neurodegeneration

Journal of Neuroimmunology (2007)

Daniela Rosenkranz Sascha W. Weyer Eva Tolosa Alexandra Gaenslen Daniela Berg

10.1016/j.jneuroim.2007.05.011

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Citations (235)

Enlarged hyperechogenic substantia nigra is related to motor performance and olfaction in the elderly

Movement Disorders (2010)

Daniela Berg Klaus Seppi Inga Liepelt Katherine J. Schweitzer Frank A. Wollenweber

Abstract Enlarged substantia nigra hyperechogenicity (SN+) assessed by transcranial sonography (TCS) may be associated with Parkinson's disease (PD) risk markers such as impaired motor performance and hyposmia. The aim of this multicenter cross‐sectional study was to define the association between SN+ and these risk markers in a large population older than 50 years without the diagnosis of PD. In three centers (Tuebingen, Homburg, and Innsbruck), 1,839 individuals were examined. The echostatus of the SN was assessed by TCS, motor performance by the Unified Parkinson's Disease Rating Scale (UPDRS) motor score, and olfactory function with Sniffin' Sticks. From the 1,603 subjects included in the analysis, 16.2% were SN+, 23.0% scored above zero in the UPDRS motor section, and 28.0% were hyposmic as defined by less than 75% correctly classified Sniffin' Sticks. SN+ was associated with a UPDRS motor score above zero (OR 1.45, 95% CI 1.08–1.96) and with a lower odor identification capability (OR 1.48, 95% CI 1.12–1.96). The combination of these two features (OR 1.98, 95% CI 1.25–3.15) and UPDRS motor scores ≥3 lead to higher OR. It is concluded that SN+, impaired motor performance, and hyposmia are frequently observed in the elderly and in isolation are unspecific and of limited use to predict a subject's risk for PD. Whether the association of SN+ with both impaired motor performance and hyposmia as seen in this study predicts an increased risk for the development of PD needs to be evaluated in the follow‐up investigations. © 2010 Movement Disorder Society

Hyposmia

10.1002/mds.23114

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Citations (52)

Poor Trail Making Test Performance Is Directly Associated with Altered Dual Task Prioritization in the Elderly – Baseline Results from the TREND Study

PLoS ONE (2011)

Markus A. Hobert Raphael Niebler Sinja I. Meyer Kathrin Brockmann Clemens Becker

Background Deterioration of executive functions in the elderly has been associated with impairments in walking performance. This may be caused by limited cognitive flexibility and working memory, but could also be caused by altered prioritization of simultaneously performed tasks. To disentangle these options we investigated the associations between Trail Making Test performance—which specifically measures cognitive flexibility and working memory—and dual task costs, a measure of prioritization. Methodology and Principal Findings Out of the TREND study (Tuebinger evaluation of Risk factors for Early detection of Neurodegenerative Disorders), 686 neurodegeneratively healthy, non-demented elderly aged 50 to 80 years were classified according to their Trail Making Test performance (delta TMT; TMT-B minus TMT-A). The subjects performed 20 m walks with habitual and maximum speed. Dual tasking performance was tested with walking at maximum speed, in combination with checking boxes on a clipboard, and subtracting serial 7 s at maximum speeds. As expected, the poor TMT group performed worse when subtracting serial 7 s under single and dual task conditions, and they walked more slowly when simultaneously subtracting serial 7 s, compared to the good TMT performers. In the walking when subtracting serial 7 s condition but not in the other 3 conditions, dual task costs were higher in the poor TMT performers (median 20%; range −6 to 58%) compared to the good performers (17%; −16 to 43%; p<0.001). To the contrary, the proportion of the poor TMT performance group that made calculation errors under the dual tasking situation was lower than under the single task situation, but higher in the good TMT performance group (poor performers, −1.6%; good performers, +3%; p = 0.035). Conclusion Under most challenging conditions, the elderly with poor TMT performance prioritize the cognitive task at the expense of walking velocity. This indicates that poor cognitive flexibility and working memory are directly associated with altered prioritization.

Cognitive flexibility

Trail Making Test

Prioritization

10.1371/journal.pone.0027831

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Citations (88)

Risk factors and prodromal markers and the development of Parkinson’s disease

Journal of Neurology (2013)

Stefanie Lerche Klaus Seppi Stefanie Behnke Inga Liepelt‐Scarfone Jana Godau

Hyposmia

Neuroradiology

Prodromal Stage

10.1007/s00415-013-7171-0

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Citations (42)

Early Diagnosis of Parkinson’s Disease

International review of neurobiology (2010)

Alexandra Gaenslen Daniela Berg

10.1016/s0074-7742(10)90006-8

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Citations (33)

Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial

Stroke (2019)

Bastian Cheng Florent Boutitie Alina Nickel Anke Wouters Tae‐Hee Cho

Background and Purpose- Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods- FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. Results- FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 (P=0.169) and shift analysis (P=0.086) but reached significance for mRS score of 0 to 2 (P=0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. Conclusions- In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.

Fluid-attenuated inversion recovery

Stroke

10.1161/strokeaha.119.027390

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Citations (19)

Enlarged Substantia Nigra Hyperechogenicity and Risk for Parkinson Disease

Archives of Neurology (2011)

Daniela Berg Klaus Seppi Stefanie Behnke Inga Liepelt Katherine J. Schweitzer

Objective

To evaluate whether enlarged substantia nigra hyperechogenicity (SN+) is associated with an increased risk for Parkinson disease (PD) in a healthy elderly population.

Design

Longitudinal 3-center observational study with 37 months of prospective follow-up.

Setting

Individuals 50 years or older without evidence of PD or any other neurodegenerative disease.

Participants

Of 1847 participants who underwent a full medical history, neurological assessment, and transcranial sonography at baseline, 1535 could undergo reassessment.

Main Outcome Measure

Incidence of new-onset PD in relation to baseline transcranial sonography status.

Results

There were 11 cases of incident PD during the follow-up period. In participants with SN+ at baseline, the relative risk for incident PD was 17.37 (95% confidence interval, 3.71-81.34) times higher compared with normoechogenic participants.

Conclusions

In this prospective study, we demonstrate for the first time a highly increased risk for PD in elderly individuals with SN+. Transcranial sonography of the midbrain may therefore be a promising primary screening procedure to define a risk population for imminent PD.

10.1001/archneurol.2011.141

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Citations (144)

Cortical hypometabolism assessed by a metabolic ratio in Parkinson's disease primarily reflects cognitive deterioration—[¹⁸F]FDG‐PET

Movement Disorders (2009)

Inga Liepelt Matthias Reimold Walter Maetzler Jana Godau Gerald Reischl

Abstract In Parkinson's disease patients with cognitive deterioration, regional cortical hypometabolism has been observed with [ 18 F]fluorodeoxyglucose‐positron emission tomography (FDG‐PET). Our aim was to develop a robust method to subsume the overall degree of metabolic deterioration in Parkinson's disease by means of a single index and to investigate which of the clinical features correlates best with hypometabolism. Twenty‐two Parkinson's patients (10 demented) and seven controls underwent FDG‐PET. A metabolic index (mean relative uptake in typically affected regions) was calculated for each patient and compared with scores for cognition [Minimental State Examination (MMSE)], motor performance [Unified Parkinson's Disease Rating Scale (UPDRS III)” and behavior (Neuropsychiatric Inventory). In stepwise linear regression analysis, MMSE ( P < 0.001) score showed the only significant effect. Estimated sensitivity and specificity for DSM‐IV diagnosis of dementia were high for the metabolic index (MI), with 91 and 100%. Taken together, the presented data indicate that cerebral hypometabolism in Parkinson's disease is primarily associated with cognitive impairment. © 2009 Movement Disorder Society

Cognitive Decline

10.1002/mds.22662

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Citations (48)

The PRIPS study: screening battery for subjects at risk for Parkinson's disease

European Journal of Neurology (2012)

Daniela Berg Jana Godau Klaus Seppi Stefanie Behnke Inga Liepelt‐Scarfone

Background and purpose Screening batteries to narrow down a target‐at‐risk population are essential for trials testing neuroprotective compounds aiming to delay or prevent onset of P arkinson's disease ( PD ). Methods The PRIPS study focuses on early detection of incident PD in 1847 at baseline PD ‐free subjects, and assessed age, male gender, positive family history, hyposmia, subtle motor impairment and enlarged substantia nigra hyperechogenicity ( SN +). Results After 3 years follow‐up 11 subjects had developed PD . In this analysis of the secondary outcome parameters, sensitivity and specificity of baseline markers for incident PD were calculated in 1352 subjects with complete datasets (10 PD patients). The best approach for prediction of incident PD comprised three steps: (i) prescreening for age, (ii) primary screening for positive family history and/or hyposmia, and (iii) secondary screening for SN +. Conclusion With this approach, one out of 16 positively screened participants developed PD compared to one out of 135 in the original cohort. This corresponds to a sensitivity of 80.0%, a specificity of 90.6% and a positive predictive value of 6.1%. These values are higher than for any single screening instrument but still too low for a feasible and cost‐effective screening strategy which might require longer follow‐up intervals and application of additional instruments.

Hyposmia

10.1111/j.1468-1331.2012.03798.x

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Citations (118)