Publications by authors named "Hubertus Lohmann"

33 Publications

Accelerated long-term forgetting in focal epilepsies with special consideration given to patients with diagnosed and suspected limbic encephalitis.

Cortex 2019 01 31;110:58-68. Epub 2018 Jan 31.

Department of Epileptology, University of Bonn Medical Center, Bonn, Germany.

Rationale: Accelerated long-term forgetting (ALF) is a phenomenon found in late onset epilepsy and in transient epileptic amnesia (TEA). Here we evaluated ALF in patients with focal epilepsies and limbic encephalitis (LE) in particular.

Methods: ALF was assessed in 36 patients with focal epilepsy and 154 healthy subjects using an extended version of the Verbal Learning and Memory Test (VLMT), with free recall after 30 min and again after one week. From these patients, 89% had temporal lobe epilepsy; 42% left-lateralized; 39% right; 19% bilateral; 17% were diagnosed with hippocampal sclerosis; 64% displayed features indicating LE; 52% with amygdala pathology, and 61% were antibody positive. ALF was defined as either having unimpaired free recall after 30 min and impaired recall after a week (A) or as a loss in recall exceeding the absolute (B) and percentage loss (C) in the interval of the 30 min and one week recall seen in controls by more than one standard deviation.

Results: Repeated measures analysis revealed an association between LE and ALF. Depending on its definition (A, B, or C), ALF was evident in 31%, 42%, or 67% of the patients. Poor verbal memory and ALF (C) were prominent in left-lateralized epilepsies. ALF (A) appeared more frequently in auto-antibody negative patients with LE, ALF (B) less frequently with hippocampal sclerosis. Seizures during the interval did not explain ALF.

Conclusion: Depending on its definition, ALF is seen in patients with normal or impaired memory at ½ h. ALF seems related to LE but might as well be the first sign of memory impairment in patients with milder epilepsies and not yet definite structural temporal lobe pathology. Longitudinal assessment would be essential for discerning when ALF becomes evident, whether conditions exist in which ALF precedes short-term forgetting, and whether ALF responds to treatment.
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http://dx.doi.org/10.1016/j.cortex.2018.01.003DOI Listing
January 2019

Alemtuzumab Improves Cognitive Processing Speed in Active Multiple Sclerosis-A Longitudinal Observational Study.

Front Neurol 2017 16;8:730. Epub 2018 Jan 16.

Department of Neurology, University Hospital Muenster, Muenster, Germany.

Background: Several disease-modifying drugs have shown promising effects on cognitive impairment in multiple sclerosis (MS). Alemtuzumab, a humanized monoclonal antibody, is effective in controlling disease activity, however, has not been evaluated for its effects on cognition in detail so far.

Objective: To explore the influence of alemtuzumab on cognitive impairment in active relapsing-remitting MS (RRMS) as well as possible clinical and neuroimaging predictors of cognitive changes during the first year of therapy.

Methods: Extensive neuropsychological assessment was administered to 21 patients with active RRMS at baseline and again after the second treatment with alemtuzumab (mean time span: 15.05 months). Clinical and routine structural neuroimaging markers were explored for their capacity to predict individual courses of cognitive change.

Results: Overall cognitive functioning remained stable or improved during the observational period of alemtuzumab treatment on average. Scores on two neuropsychological tests of processing speed significantly improved and clinically relevant individual gains of processing speed were seen in the majority of patients. Linear regression models showed that clinical and routine neuroimaging measures of disease activity could not fully account for these cognitive changes.

Conclusion: Results suggest that alemtuzumab treatment in active RRMS stabilizes overall cognitive functioning and furthermore positively affects cognitive processing speed. Changes in processing speed were independent from clinical and structural neuroimaging parameters of disease activity and may thus represent an underrated and independent outcome measure to evaluate treatment effects.
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http://dx.doi.org/10.3389/fneur.2017.00730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775967PMC
January 2018

Can cognitive assessment really discriminate early stages of Alzheimer's and behavioural variant frontotemporal dementia at initial clinical presentation?

Alzheimers Res Ther 2017 Aug 9;9(1):61. Epub 2017 Aug 9.

Department of Neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.

Background: Neuropsychological testing is considered crucial for differential diagnosis of Alzheimer's disease (AD) and behavioural variant frontotemporal dementia (bvFTD). In-depth neuropsychological assessment revealed specific dysfunctions in the two dementia syndromes. However, a significant overlap of cognitive impairments exists in early disease stages. We questioned whether a standard neuropsychological assessment at initial clinical presentation can delineate patients with AD versus bvFTD.

Methods: In a retrospective approach, we evaluated and compared how cognitive profiles assessed at initial clinical presentation predicted the diagnosis of later verified AD (n = 43) and bvFTD (n = 26). Additionally, the neuropsychological standard domains memory, language, visuospatial skills, executive functions, praxis and social cognition were subjected to stepwise discriminant analysis to compare their differential contribution to diagnosis.

Results: Regardless of diagnosis, a percentage of patients presented with major deterioration in a wide range of cognitive domains when compared with age-matched normative data. Only few significant differences were detected on the group level: Patients with AD were relatively more impaired in the verbal recall, verbal recognition, figure copy, and surprisingly in the executive subdomains, set shifting and processing speed whereas bvFTD was characterised by more deficits in imitation of face postures. A combination of tests for verbal recall, imitation of limb and face postures, and figure copy showed the greatest discriminatory power.

Conclusions: Our results imply that the contribution of a standard neuropsychological assessment is limited for differential diagnosis of AD and bvFTD at initial presentation. In contrast to current clinical guidelines, executive functions are neither particularly nor exclusively impaired in patients with bvFTD when assessed within a standard clinical neuropsychological test battery. The significant overlap of bvFTD and AD concerning the profile of cognitive impairments questions current neuropsychological diagnostic criteria and calls for revision, regarding both the degree and the profile of cognitive deficits.
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http://dx.doi.org/10.1186/s13195-017-0287-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5550986PMC
August 2017

Diagnostic criteria for Susac syndrome.

J Neurol Neurosurg Psychiatry 2016 Dec 25;87(12):1287-1295. Epub 2016 Oct 25.

Department of Neurology, University Hospital of Münster, Münster, Germany.

Background: Susac syndrome is characterised by the triad of encephalopathy with or without focal neurological signs, branch retinal artery occlusions and hearing loss. Establishment of the diagnosis is often delayed because the triad is complete only in a minority of patients at disease onset. This leads to a critical delay in the initiation of appropriate treatment. Our objective was to establish criteria for diagnosis of either definite or probable Susac syndrome.

Method: The establishment of diagnostic criteria was based on the following three steps: (1) Definition of a reference group of 32 patients with an unambiguous diagnosis of Susac syndrome as assessed by all interdisciplinary experts of the European Susac Consortium (EuSaC) team (EuSaC cohort); (2) selection of diagnostic criteria, based on common clinical and paraclinical findings in the EuSaC cohort and on a review of the literature; and (3) validation of the proposed criteria in the previously published cohort of all Susac cases reported until 2012.

Results: Integrating the clinical presentation and paraclinical findings, we propose formal criteria and recommend a diagnostic workup to facilitate the diagnosis of Susac syndrome. More than 90% of the cases in the literature fulfilled the proposed criteria for probable or definite Susac syndrome. We surmise that more patients could have been diagnosed with the recommended diagnostic workup.

Conclusions: We propose diagnostic criteria for Susac syndrome that may help both experts and physicians not familiar with Susac syndrome to make a correct diagnosis and to prevent delayed treatment initiation.
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http://dx.doi.org/10.1136/jnnp-2016-314295DOI Listing
December 2016

Neurochondrin is a neuronal target antigen in autoimmune cerebellar degeneration.

Neurol Neuroimmunol Neuroinflamm 2017 Jan 5;4(1):e307. Epub 2016 Dec 5.

Institute of Experimental Immunology (R.M., M. Scharf, I.M.D., S.M., Y.D., B.T., C.P., S.B., W.S., L.K.), Euroimmun AG, Lübeck; Department of Neurology (C.C.G., K.S.G., M.H., U.B., A.S.-M., K.B., C.S., H.L., M.D., T.W., H.W., S.G.M., N.M.), University of Münster; Centre for Neurology and Hertie-Institute for Clinical Brain Research (L.S., M. Synofzik), Tübingen; German Center for Neurodegenerative Diseases (DZNE) (L.S., M. Synofzik), Tübingen; and Institute of Clinical Chemistry and Department of Neurology (K.-P.W.), University Hospital of Schleswig-Holstein, Lübeck, Germany.

Objective: To report on a novel neuronal target antigen in 3 patients with autoimmune cerebellar degeneration.

Methods: Three patients with subacute to chronic cerebellar ataxia and controls underwent detailed clinical and neuropsychological assessment together with quantitative high-resolution structural MRI. Sera and CSF were subjected to comprehensive autoantibody screening by indirect immunofluorescence assay (IFA) and immunoblot. Immunoprecipitation with lysates of hippocampus and cerebellum combined with mass spectrometric analysis was used to identify the autoantigen, which was verified by recombinant expression in HEK293 cells and use in several immunoassays. Multiparameter flow cytometry was performed on peripheral blood and CSF, and peripheral blood was subjected to T-cell receptor spectratyping.

Results: Patients presented with a subacute to chronic cerebellar and brainstem syndrome. MRI was consistent with cortical and cerebellar gray matter atrophy associated with subsequent neuroaxonal degeneration. IFA screening revealed strong immunoglobulin G1 reactivity in sera and CSF with hippocampal and cerebellar molecular and granular layers, but not with a panel of 30 recombinantly expressed established neural autoantigens. Neurochondrin was subsequently identified as the target antigen, verified by IFA and immunoblot with HEK293 cells expressing human neurochondrin as well as the ability of recombinant neurochondrin to neutralize the autoantibodies' tissue reaction. Immune phenotyping revealed intrathecal accumulation and activation of B and T cells during the acute but not chronic phase of the disease. T-cell receptor spectratyping suggested an antigen-specific T-cell response accompanying the formation of antineurochondrin autoantibodies. No such neurochondrin reactivity was found in control cohorts of various neural autoantibody-associated neurologic syndromes, relapsing-remitting multiple sclerosis, cerebellar type of multiple system atrophy, hereditary cerebellar ataxias, other neurologic disorders, or healthy donors.

Conclusion: Neurochondrin is a neuronal target antigen in autoimmune cerebellar degeneration.
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http://dx.doi.org/10.1212/NXI.0000000000000307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5141526PMC
January 2017

Shared neural correlates of limb apraxia in early stages of Alzheimer's dementia and behavioural variant frontotemporal dementia.

Cortex 2016 11 26;84:1-14. Epub 2016 Aug 26.

Department of Neurology, University Hospital Münster, Germany.

Limb apraxia denotes a cognitive impairment of gesture production. Lesion studies in patients with stroke point towards distinct neural processing streams for limb imitation and object-pantomime within left parietal and temporal cortex, respectively. Despite its frequent occurrence as an early symptom in both, Alzheimer's dementia (AD) and behavioural variant frontotemporal dementia (bvFTD), neural correlates of limb apraxia within these patient groups remain unexplored. Using voxel-based morphometry and multiple regression models, associations between limb apraxia and gray matter (GM) volume were investigated in 36 dementia patients (18 AD, 18 bvFTD) in early disease stages. Both dementia subtypes showed a comparable degree of limb apraxia. Although the patient groups showed distinct atrophy patterns with significantly more severe frontal GM loss in bvFTD, we found similar neural correlates of limb apraxia within posterior brain regions for both dementia subtypes: limb-imitation was associated with bilateral atrophy of superior, inferior and medial parietal cortex. Object-pantomime showed associations with GM volume in right middle temporal and angular gyrus. Our results argue for shared neural correlates of limb apraxia in AD and bvFTD and validate the syndrome as an important neuropsychological feature across different etiologies. Moreover, our results are compatible with neural models derived from patients with stroke, suggesting partly distinct neural representations of imitation and pantomime. Compared to patients with stroke however, AD and bvFTD showed more bilateral or even right lateralized neural representations of limb apraxia, proposing a greater influence of visuospatial impairments and spatial body representation deficits on praxis performance.
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http://dx.doi.org/10.1016/j.cortex.2016.08.009DOI Listing
November 2016

Evidence of a pathogenic role for CD8(+) T cells in anti-GABAB receptor limbic encephalitis.

Neurol Neuroimmunol Neuroinflamm 2016 Jun 29;3(3):e232. Epub 2016 Apr 29.

Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.

Objectives: To characterize the cellular autoimmune response in patients with γ-aminobutyric acid (GABA)B receptor antibody-associated limbic encephalitis (GABAB-R LE).

Methods: Patients underwent MRI, extensive neuropsychological assessment, and multiparameter flow cytometry of peripheral blood and CSF.

Results: We identified a series of 3 cases of nonparaneoplastic GABAB-R LE and one case of paraneoplastic GABAB-R LE associated with small cell lung cancer. All patients exhibited temporal lobe epilepsy, neuropsychological deficits, and MRI findings typical of LE. Absolute numbers of CD19(+) B cells, CD138(+) CD19(+) plasma cells, CD4(+) T cells, activated HLADR(+) CD4(+) T cells, as well as CD8(+) T cells and HLADR(+) CD8(+) T cells did not differ in peripheral blood but were elevated in CSF of patients with GABAB-R LE compared to controls. Augmented absolute numbers of CD138(+) CD19(+) plasma cells and activated HLADR(+) CD8(+) T cells in CSF corresponded to higher overall neuropsychological and memory deficits in patients with GABAB-R LE. A histologic specimen of one patient following selective amygdalohippocampectomy revealed perivascular infiltrates of CD138(+) plasma cells and CD4(+) T cells, whereas cytotoxic CD8(+) T cells were detected within the brain parenchyma in close contact to neurons.

Conclusion: Our data suggest a pathogenic role for CD8(+) T cells in addition to the established role of plasma cell-derived autoantibodies in GABAB-R LE.
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http://dx.doi.org/10.1212/NXI.0000000000000232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4853055PMC
June 2016

Immunoadsorption therapy in autoimmune encephalitides.

Neurol Neuroimmunol Neuroinflamm 2016 Apr 26;3(2):e207. Epub 2016 Feb 26.

Epilepsy Center Bethel (M.D.O., C.B., M.B.-H., C.G.B.), Krankenhaus Mara, Bielefeld; Department of Neurology (M.D.O.), University Hospital Erlangen; Department of Neurology (K.S.G., H.L., H.W., N.M.), University of Münster; Department of Nephrology (M.A.-T., R.V.), Bethel-EvKB, Bielefeld; Department of Medicine D (M.B., H.P., G.T.), Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster; and Laboratory Krone (D.M.), Bad Salzuflen, Germany.

Objective: It was hypothesized that in encephalitides with autoantibodies directed to CNS surface antigens an antibody-removing intervention might speed up recovery.

Methods: The outcome of autoimmune encephalitis in 19 patients with antibodies against surface antigens (leucine-rich, glioma inactivated 1 [LGI1], n = 3; contactin-associated protein-2 [CASPR2], n = 4; NMDA receptor [NMDAR], n = 7) and intracellular antigens (glutamic acid decarboxylase [GAD], n = 5) after immunoadsorption in addition to corticosteroid therapy was evaluated retrospectively. Modified Rankin scale (mRS) scores and data on seizures, memory, and antibody titers directly after immunoadsorption (early follow-up) and after a median of 4 months (late follow-up) were compiled.

Results: Immediately after immunoadsorption, 9 of 14 patients with antibodies against LGI1, CASPR2, or NMDAR (64%), but none with GAD antibodies, had improved by at least one mRS point. Five of the 7 patients with LGI1 or CASRP2 antibodies had become seizure-free, and 2 patients with NMDAR antibodies had a memory improvement of more than 1 SD of a normal control population. At late follow-up, 12 of 14 patients with surface antibodies had improved (86%), and none of the patients with GAD antibodies.

Conclusions: It is suggested that addition of immunoadsorption to immunosuppression therapy in patients with surface antibodies may accelerate recovery. This supports the pathogenic role of surface antibodies.

Classification Of Evidence: This study provides Class IV evidence that immunoadsorption combined with immunosuppression therapy is effective in patients with autoimmune encephalitis with surface antibodies.
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http://dx.doi.org/10.1212/NXI.0000000000000207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772911PMC
April 2016

Impaired Autonomic Responses to Emotional Stimuli in Autoimmune Limbic Encephalitis.

Front Neurol 2015 30;6:250. Epub 2015 Nov 30.

Institute of Medical Psychology and Systems Neuroscience, University of Muenster , Muenster , Germany.

Limbic encephalitis (LE) is an autoimmune-mediated disorder that affects structures of the limbic system, in particular, the amygdala. The amygdala constitutes a brain area substantial for processing of emotional, especially fear-related signals. The amygdala is also involved in neuroendocrine and autonomic functions, including skin conductance responses (SCRs) to emotionally arousing stimuli. This study investigates behavioral and autonomic responses to discrete emotion evoking and neutral film clips in a patient suffering from LE associated with contactin-associated protein-2 (CASPR2) antibodies as compared to a healthy control group. Results show a lack of SCRs in the patient while watching the film clips, with significant differences compared to healthy controls in the case of fear-inducing videos. There was no comparable impairment in behavioral data (emotion report, valence, and arousal ratings). The results point to a defective modulation of sympathetic responses during emotional stimulation in patients with LE, probably due to impaired functioning of the amygdala.
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http://dx.doi.org/10.3389/fneur.2015.00250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4663278PMC
December 2015

Dementia Apraxia Test (DATE): A Brief Tool to Differentiate Behavioral Variant Frontotemporal Dementia from Alzheimer's Dementia Based on Apraxia Profiles.

J Alzheimers Dis 2016 ;49(3):593-605

Background: Standardized praxis assessments with modern, empirically validated screening tests have substantially improved clinical evaluation of apraxia in patients with stroke. Although apraxia may contribute to early differential diagnosis of Alzheimer's dementia (AD) and behavioral variant frontotemporal dementia (bvFTD), no comparable test is readily available to clinicians for this purpose to date.

Objective: To design a clinically useful apraxia test for the differentiation of AD and bvFTD.

Methods: 84 test items pertaining to twelve praxis subdomains were evaluated for their efficacy to discriminate between patients with bvFTD (n = 24), AD (n = 28), and elderly healthy controls (HC; n = 35). Items were then selected based on discriminative value and psychometric properties.

Results: Items indicative of mild AD comprised spatially complex imitation of hand and finger postures and to a lesser degree, pantomime of common object-use. Buccofacial apraxia including imitation of face postures, emblematic face postures, and repetition of multisyllabic pseudowords differentiated bvFTD from HC and AD. The final test version consisting of 20 items proved highly efficient for the discrimination of biologically confirmed dementia patients from HC (sensitivity 91% , specificity 71%) but also for differential diagnosis of bvFTD and AD (sensitivity 74% , specificity 93%).

Conclusions: Assessment of praxis profiles effectively contributes to diagnosis and differential diagnosis of AD and bvFTD. The Dementia Apraxia Test (DATE) is a brief and easy to administer cognitive tool for dementia assessment, has a high inter-rater reliability (Cohen's κ= 0.885) and demonstrates content validity.
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http://dx.doi.org/10.3233/JAD-150447DOI Listing
November 2016

Neurocognitive decline in HIV patients is associated with ongoing T-cell activation in the cerebrospinal fluid.

Ann Clin Transl Neurol 2015 Sep 18;2(9):906-19. Epub 2015 Aug 18.

Department of Neurology, University Hospital of Muenster Albert-Schweitzer-Campus 1, D-48149, Muenster, Germany.

Objective: HIV-associated neurocognitive disorders (HAND) remain a challenge despite combination antiretroviral therapy (cART). Immune cell activation has been implicated to play a major role in the development of HAND.

Methods: In this study, we used multicolor flow cytometry on peripheral blood (PB) and cerebrospinal fluid (CSF) samples to determine the expression of HLA-DR and programmed death-1 (PD-1) on CD4+ and CD8+ T cells in patients with chronic HIV infection. Expression levels were correlated with HI virus load in PB and CSF, classification of HAND and severity of magnetic resonance imaging (MRI) signal abnormalities.

Results: In a cohort of 86 HIV patients we found that the grade of neurocognitive impairment and the severity of MRI signal abnormalities correlated with decreasing CD4/CD8-ratios and increased frequencies of HLA-DR expressing CD4+ and CD8+ T cells reaching the highest values in the CSF samples. Importantly, HLA-DR upregulation was still detectable in virologically suppressed HIV patients. Further, T-cell subpopulation analysis of 40 HIV patients showed a significant shift from naïve to effector memory (EM) T cells that was negatively correlated with the grade of neurocognitive impairment in the PB samples. Moreover, PD-1 was significantly increased on CD4+ memory T cells with highest levels on EM T cells in HIV patients with mild or severe neurocognitive alterations.

Interpretation: The CD4/CD8 ratio, the proportion of EM to naïve T cells and the immune activation profile of CD4+ and CD8+ T cells in PB and CSF might be useful parameters to monitor the efficacy of cART and to identify HIV patients at risk of further neurocognitive deterioration.
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http://dx.doi.org/10.1002/acn3.227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574808PMC
September 2015

Clinical relevance of specific T-cell activation in the blood and cerebrospinal fluid of patients with mild Alzheimer's disease.

Neurobiol Aging 2015 Jan 23;36(1):81-9. Epub 2014 Aug 23.

Department of Neurology, University Hospital Münster, Münster, Germany. Electronic address:

In Alzheimer's disease, the contribution of inflammation is still controversially discussed. The aim of this study was to identify a particular immune profile in the peripheral blood (PB) and cerebrospinal fluid (CSF) in patients with mild Alzheimer's disease (mAD) and mild cognitive impairment (MCI) and its potential functional relevance and association with neurodegeneration. A total of 88 patients with cognitive decline (54 mAD, 19 MCI, and 15 other dementias) were included in this study and compared with a group of younger (mean age, 31.3 years) and older (mean age, 68.9 years) healthy volunteers. Patients underwent detailed neurologic and neuropsychological examination, magnetic resonance imaging including voxel-based morphometry of gray matter, voxel-based diffusion tensor imaging, and white matter lesion volumetry, and PB and CSF analysis including multiparameter flow cytometry. Multiparameter flow cytometry revealed that proportions of activated HLA-DR positive CD4(+) and CD8(+) T-cells were slightly and significantly increased in the PB of MCI and mAD patients, respectively, when compared with healthy elderly controls but not in patients with other dementias. Although only a slight enhancement of the proportion of activated CD4(+) T-cells was observed in the CSF of both MCI and mAD patients, the proportion of activated CD8(+) T-cells was significantly increased in the CSF of mAD patients when compared with healthy elderly individuals. A slight increase in the proportion of activated CD8(+) T-cells was also observed in the intrathecal compartment of MCI patients. Activation of cytotoxic CD8(+) T-cells was considerably related to AD-typical neuropsychological deficits. Voxel-based regression analysis revealed a significant correlation between CD8(+) T-cell activation and microstructural tissue damage within parahippocampal areas as assessed by diffusion tensor imaging. Taken together, peripheral and intrathecal CD8(+) T-cell activation in mAD was significantly different from other dementias, suggesting a specific adaptive immune response. Lymphocyte activation seems to have a clinical impact because levels of activated CD8(+) T-cells were correlated with clinical and structural markers of AD pathology.
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http://dx.doi.org/10.1016/j.neurobiolaging.2014.08.008DOI Listing
January 2015

Apraxia profile differentiates behavioural variant frontotemporal from Alzheimer's dementia in mild disease stages.

J Neurol Neurosurg Psychiatry 2015 Jul 23;86(7):809-15. Epub 2014 Sep 23.

Department of Neurology, University Hospital Münster, Münster, Germany.

Objective: Despite refined criteria for behavioural variant frontotemporal dementia (bvFTD), its differentiation from Alzheimer's dementia (AD) remains difficult at early clinical presentation. Apraxia is not considered as a supportive feature for the diagnosis of bvFTD, but for AD. However, only few studies have quantified praxis disturbances in mild disease stages and their specificity for AD compared with bvFTD remains indistinct. We explore apraxia in bvFTD and investigate the differential validity of apraxia screening tests to distinguish between AD, bvFTD and healthy controls (HC).

Methods: We compared composite apraxia scores assessed with standardised neuropsychological screening tests as well as performance in praxis subdomains in patients who fulfil current clinical criteria for AD (N=20), bvFTD (N=20), and in HC (N=20).

Results: Composite scores of apraxia screening tests provided high diagnostic accuracy for detecting mild stages of both neurodegenerative disorders compared with HC (sensitivity: 75-95%; specificity: 70-90%). Both patient groups showed pronounced impairments in limb praxis, especially in imitation of hand and finger postures (bvFTD: 71.7%; AD: 55.5%; HC: 86.7%) and pantomime of object use (bvFTD: 88.6%; AD: 81.4%; HC: 97.5%). Beyond that, patients with bvFTD displayed a unique profile of deficits for imitating face postures (bvFTD: 69%; AD: 88%; HC: 95.5%).

Conclusions: Praxis disturbances are important but under-represented diagnostic features in mild stages of AD and bvFTD. Apraxia screening tests are easily applicable diagnostic tools, which may support clinical diagnoses of both neurodegenerative diseases. The analysis of individual apraxia profiles can effectively facilitate differential diagnosis of AD and bvFTD.
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http://dx.doi.org/10.1136/jnnp-2014-308773DOI Listing
July 2015

Age- and gender-adjusted normative data for the German version of Rey's Auditory Verbal Learning Test from healthy subjects aged between 50 and 70 years.

J Clin Exp Neuropsychol 2014 16;36(1):32-42. Epub 2013 Dec 16.

a Department of Neurology , University Hospital Münster , Münster , Germany.

Rey's Auditory Verbal Learning Test (AVLT) is widely used to evaluate dysfunctional episodic memory. The current study aimed to provide extended age- and gender-specific norms for the German AVLT for individuals older than 50 years. In 690 subjects, a comprehensive medical examination including a structural 3.0-tesla magnetic resonance imaging scan was administered, as well as extensive neuropsychological tests. After controlling for exclusion criteria, 407 subjects were included in the analysis. AVLT performance decreased with age, and women outperformed men. We present age- and gender-specific normative data for the German AVLT from subjects aged between 50 and 70 years.
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http://dx.doi.org/10.1080/13803395.2013.863834DOI Listing
October 2014

Executive performance is related to regional gray matter volume in healthy older individuals.

Hum Brain Mapp 2013 Dec 19;34(12):3333-46. Epub 2012 Jul 19.

Department of Neurology, University Hospital of Münster, Münster, Germany; Department of Neurology, University of München, München, Germany.

Individual differences in executive functioning and brain morphology are considerable. In this study, we investigated their interrelation in a large sample of healthy older individuals. Digit span, trail-making, and Stroop tasks were used to assess different executive subfunctions in 367 nondemented community-dwelling individuals (50-81 years). Task performance was analyzed relative to brain structure using voxel-based morphometry, corrected for age and sex. Improved task performance was associated with increased local gray matter volume in task-specific patterns that showed partial, but not complete overlap with known task-specific functional imaging patterns. While all three tasks showed associations with prefrontal gray matter volume as expected for executive functioning, the strongest overlap between the three tasks was found in insular cortex, suggesting that it has a previously underestimated role for executive functions. The association between the insular cortex and executive functioning was corroborated using stereological region-of-interest measurement of insular volume in a subgroup of 93 subjects. Quantitatively, the volume of the single most strongly related region explained 2.4 ± 1.1% of the variance in executive performance over and above the variance explained by age, which amounted to 7.4 ± 4.1%. The age-independent peak associations between executive performance and gray matter described here occurred in regions that were also strongly affected by age-related gray matter atrophy, consistent with the hypothesis that age-related regional brain volume loss and age-related cognitive changes are linked.
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http://dx.doi.org/10.1002/hbm.22146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6869861PMC
December 2013

Non-invasive brain stimulation improves object-location learning in the elderly.

Neurobiol Aging 2012 Aug 17;33(8):1682-9. Epub 2011 Jun 17.

Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Remembering the location of objects, an integral part of everyday life, is known to decline with advancing age and early in the course of neurodegenerative dementia. Here, we aimed to test if object-location learning and its retention could be modified by noninvasive brain stimulation. In a group of 20 elderly (mean age 62.1 years) right-handed individuals, we applied transcranial direct current stimulation (tDCS; 20 minutes, 1 mA) over the right temporoparietal cortex, while subjects acquired the correct position of buildings on a street map using an associative learning paradigm. Each subject participated in a randomized and balanced order in 1 session of anodal tDCS and 1 session of sham stimulation, in a double-blind design with 2 parallel versions of the task. Outcome measures were learning success at the end of each session, and immediate as well as delayed (1 week) free recall. We found that subjects performed comparably in the learning task in the 2 conditions, but showed improved recall 1 week after learning with anodal tDCS compared with learning with sham stimulation. In conclusion, retention of object-location learning in the elderly may be modulated by noninvasive brain stimulation, a finding of potential relevance not only for normal aging but also for memory deficits in pathological aging.
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http://dx.doi.org/10.1016/j.neurobiolaging.2011.05.007DOI Listing
August 2012

Pain is associated with regional grey matter reduction in the general population.

Pain 2011 Apr 5;152(4):904-911. Epub 2011 Feb 5.

Department of Neurology, University of Münster, Münster, Germany Institute of Clinical Radiology, University of Münster, Münster, Germany Department of Neurology, Charité Universitätsmedizin, Berlin, Germany.

Regional decreases in grey matter volume as detected by magnetic resonance imaging-based volumetry have been reported in several clinical chronic pain cohorts. Here, we used voxel-based morphometry in a nonclinical cohort to investigate whether grey matter alterations also occur in older individuals (aged 40-85 years) from the general population. Based on self-report of pain, we identified 31 pain-free controls, 45 subjects with ongoing pain (low back pain, headache, or lower extremity joint pain) who had at least moderate pain on more than 3 days/month, and 29 individuals with past pain (stopped for >12 months). Relative to controls, the ongoing pain group showed regional grey matter volume decreases, predominantly in cingulate, prefrontal, and motor/premotor regions. No grey matter volume decreases were found in the group with pain that had stopped for >12 months. These results show that pain-related grey matter volume decreases are present in individuals from the general population. The lack of morphometric anomalies in subjects with past pain supports recent evidence suggesting that pain-related grey matter changes are reversible after cessation of pain.
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http://dx.doi.org/10.1016/j.pain.2011.01.013DOI Listing
April 2011

Presurgical functional transcranial Doppler sonography (fTCD) with intravenous echo enhancing agent SonoVue enables determination of language lateralization in epilepsy patients with poor temporal bone windows.

Epilepsia 2011 Mar 28;52(3):636-9. Epub 2011 Jan 28.

Hamburg Epilepsy Center, Protestant Hospital Alsterdorf, Hamburg, Germany.

Presurgical determination of language lateralization is important for planning and outcome estimation of neurosurgical interventions in patients with drug-refractory epilepsy. Functional transcranial Doppler sonography (fTCD) provides an established measure for language lateralization using the temporal bone windows for continuous recording of the cerebral blood flow velocity (CBFV) in both middle cerebral arteries (MCAs). However, because of insufficient temporal bone windows, fTCD cannot be applied properly in every patient. Here, we established stable and sufficient CBFV signals in both MCAs using continuous intravenous application of echo-enhancing agent SonoVue in 7 of 10 patients with poor temporal bone windows and were thus able to determine language lateralization. We conclude that the application of SonoVue can solve one principal disadvantage of fTCD and improves the applicability of the technique as a presurgical functional language lateralization procedure.
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http://dx.doi.org/10.1111/j.1528-1167.2010.02951.xDOI Listing
March 2011

Specific pattern of early white-matter changes in pure hereditary spastic paraplegia.

Mov Disord 2010 Sep;25(12):1986-92

Department of Neurology, University Hospital of Münster, Münster, Germany.

Hereditary spastic paraplegias (HSP) are genetically and clinically heterogeneous neurodegenerative disorders. Most MR studies on HSP include very heterogeneous samples of patients, and findings were inconsistent. Here, we examined six patients with pure HSP and SPG4 mutations by clinical evaluation, detailed neuropsychological testing, and neuroimaging analyses, including conventional MRI, diffusion tensor imaging (DTI), and brain volumetry. Differences of voxel-wise statistics and ROI-based analysis of DTI data between patients and 32 healthy volunteers were evaluated. Although conventional MRI and brain volumetry were normal, DTI revealed widespread disturbance of white matter (WM) integrity (P < 0.001), mainly affecting the corticospinal tract. With longer disease duration, frontal regions were also involved. The WM changes were also present in subclinical subjects harbouring the pathogenic mutation. These subtle WM abnormalities have functional relevance because they correlated with clinical symptoms. Thus, early alterations of nerve fibres, which can be detected by DTI, might serve as a biological marker in HSP, in particular with respect to future longitudinal studies.
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http://dx.doi.org/10.1002/mds.23211DOI Listing
September 2010

Endoscopic characteristics and levodopa responsiveness of swallowing function in progressive supranuclear palsy.

Mov Disord 2010 Jul;25(9):1239-45

Department of Neurology, University Hospital of Münster, Münster, Germany.

Dysphagia is a frequent and early symptom in progressive supranuclear palsy (PSP) predisposing patients to aspiration pneumonia. Fiberoptic endoscopic evaluation of swallowing (FEES) has emerged as a valuable apparative tool for objective evaluation of neurogenic dysphagia. This is the first study using FEES to investigate the nature of swallowing impairment in PSP. Eighteen consecutive PSP patients (mean age 69.7 +/- 9.0 years) were included. The salient findings of FEES in PSP patients were compared with those of 15 patients with Parkinson's disease (PD). In 7 PSP patients, a standardized FEES protocol was performed to explore levodopa (L-dopa) responsiveness of dysphagia. Most frequent abnormalities detected by FEES were bolus leakage, delayed swallowing reflex, and residues in valleculae and piriformes. Aspiration events with at least one food consistency occurred in nearly 30% of PSP patients. Significant pharyngeal saliva pooling was observed in 4 PSP patients. We found no difference of salient endoscopic findings between PSP and PD patients. Endoscopic dysphagia severity in PSP correlated positively with disease duration, clinical disability, and cognitive impairment. No correlation was found with dysarthria severity. In early PSP patients, swallowing dysfunction was solely characterized by liquid leakage with the risk of predeglutitive aspiration during the oral phase of swallowing. Two PSP patients showed relevant improvement of swallowing function after L-dopa challenge. Chin tuck-maneuver, hard swallow, and modification of food consistency were identified as the most effective therapeutic interventions. In conclusion, FEES assessment can deliver important findings for the diagnosis and refined therapy of dysphagia in PSP patients.
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http://dx.doi.org/10.1002/mds.23060DOI Listing
July 2010

Comprehension of complex instructions deteriorates with age and vascular morbidity.

Age (Dordr) 2011 Mar 30;33(1):101-6. Epub 2010 Jun 30.

Department of Neurology, University of Münster, Münster, Germany.

Verbal comprehension is critical to the success of medical counseling. Here, we tested how age and vascular risk factors affect the ability to understand complex instructions. Verbal comprehension, cognitive functions, and vascular risk factors were assessed in 39 mid- and 38 late-life community-dwelling individuals (48 to 59 years and >59 years of age, respectively). To test for verbal comprehension, we used a modified version of the Token Test (TT). In midlife individuals, education (β = 0.572, p < 0.05) was the only predictor for extended-TT performance. In late-life individuals, age (β = -1.015, p < 0.001) and body mass index (β = -0.651, p = 0.003) were significantly correlated with extended-TT performance and explained 50% of the variance in extended-TT performance (adjusted R (2) = 0.503). This relation is only partly explained by conventional neuropsychological measures as the ones used in our test battery. These results indicate that aging and overweight impair comprehension of complex instructions. Therefore, medical counseling appropriate for midlife individuals may be less successful in elderly people and particularly in those with metabolic disturbances.
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http://dx.doi.org/10.1007/s11357-010-9161-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063638PMC
March 2011

A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects.

Mov Disord 2010 Mar;25(4):413-20

Department of Neurology, University Hospital of Münster, Münster, Germany.

Hereditary spastic paraplegias (HSP) are genetically and clinically heterogeneous neurodegenerative disorders. The purpose of this study was to assess the genotype and phenotype in a family with a complicated form of autosomal recessive hereditary spastic paraplegia (ARHSP). Neurological and neuropsychological evaluation, neurophysiologic studies, fiberoptic endoscopic evaluation of swallowing (FEES), neuroimaging analysis including diffusion tensor imaging (DTI), and mutation analysis of SPG4 and SPG7 gene were performed. The index case (mother) was affected by an adult-onset form of complicated ARHSP due to the homozygous splice site mutation c.1552+1 G>T in the SPG7 gene. This mutation leads to an abnormally spliced mRNA lacking exon 11. Additional clinical features were bilateral ptosis and subtle deficits in executive function. All three asymptomatic daughters carried the sequence variation c.1552+1 G>T in heterozygous state. DTI of the mother revealed disturbance of white matter (WM) integrity in the left frontal lobe, the left corticospinal tract and both sides of the brainstem. DTI of the daughters showed subtle WM alteration in the frontal corpus callosum. The novel mutation is the first splice site mutation found in the SPG7 gene. It removes part of the AAA domain of paraplegin protein, probably leading to a loss-of-function of the paraplegin-AFG3L2 complex in the mitochondrial inner membrane. The pattern of WM damage in the homozygote index case may be specific for SPG7-HSP. The detection of cerebral WM alterations in the corpus callosum of asymptomatic heterozygote carriers confirms this brain region as the most prominent and early location of fiber damage in ARHSP.
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http://dx.doi.org/10.1002/mds.22949DOI Listing
March 2010

Hypoglycemia aggravates critical illness-induced neurocognitive dysfunction.

Diabetes Care 2010 Mar 23;33(3):639-44. Epub 2009 Dec 23.

Department of Neurology, University Hospital of Muenster, Muenster, Germany.

OBJECTIVE Tight glycemic control (TGC) in critically ill patients is associated with an increased risk of hypoglycemia. Whether those short episodes of hypoglycemia are associated with adverse morbidity and mortality is a matter of discussion. Using a case-control study design, we investigated whether hypoglycemia under TGC causes permanent neurocognitive dysfunction in patients surviving critical illness. RESEARCH DESIGN AND METHODS From our patient data management system, we identified adult survivors treated for >72 h in our surgical intensive care unit (ICU) between 2004 and 2007 (n = 4,635) without a history of neurocognitive dysfunction or structural brain abnormalities who experienced at least one episode of hypoglycemia during treatment (hypo group) (n = 37). For each hypo group patient, one patient stringently matched for demographic- and disease-related data were identified as a control subject. We performed a battery of neuropsychological tests investigating five areas of cognitive functioning in both groups at least 1 year after ICU discharge. Test results were compared with data from healthy control subjects and between groups. RESULTS Critical illness caused neurocognitive dysfunction in all tested domains in both groups. The dysfunction was aggravated in hypo group patients in one domain, namely that of visuospatial skills (P < 0.01). Besides hypoglycemia, both hyperglycemia (r = -0.322; P = 0.005) and fluctuations of blood glucose (r = -0.309; P = 0.008) were associated with worse test results in this domain. CONCLUSIONS Hypoglycemia was found to aggravate critical illness-induced neurocognitive dysfunction to a limited, but significant, extent; however, an impact of hyperglycemia and fluctuations of blood glucose on neurocognitive function cannot be excluded.
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http://dx.doi.org/10.2337/dc09-1740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827523PMC
March 2010

Imaging short- and long-term training success in chronic aphasia.

BMC Neurosci 2009 Sep 22;10:118. Epub 2009 Sep 22.

Department of Neurology, University of Münster, Münster, Germany.

Background: To date, functional imaging studies of treatment-induced recovery from chronic aphasia only assessed short-term treatment effects after intensive language training. In the present study, we show with functional magnetic resonance imaging (fMRI), that different brain regions may be involved in immediate versus long-term success of intensive language training in chronic post-stroke aphasia patients.

Results: Eight patients were trained daily for three hours over a period of two weeks in naming of concrete objects. Prior to, immediately after, and eight months after training, patients overtly named trained and untrained objects during event-related fMRI. On average the patients improved from zero (at baseline) to 64.4% correct naming responses immediately after training, and treatment success remained highly stable at follow-up. Regression analyses showed that the degree of short-term treatment success was predicted by increased activity (compared to the pretraining scan) bilaterally in the hippocampal formation, the right precuneus and cingulate gyrus, and bilaterally in the fusiform gyri. A different picture emerged for long-term training success, which was best predicted by activity increases in the right-sided Wernicke's homologue and to a lesser degree in perilesional temporal areas.

Conclusion: The results show for the first time that treatment-induced language recovery in the chronic stage after stroke is a dynamic process. Initially, brain regions involved in memory encoding, attention, and multimodal integration mediated treatment success. In contrast, long-term treatment success was predicted mainly by activity increases in the so-called 'classical' language regions. The results suggest that besides perilesional and homologue language-associated regions, functional integrity of domain-unspecific memory structures may be a prerequisite for successful (intensive) language interventions.
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http://dx.doi.org/10.1186/1471-2202-10-118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754483PMC
September 2009

How much does hypertension affect cognition?: explained variance in cross-sectional analysis of non-demented community-dwelling individuals in the SEARCH study.

J Neurol Sci 2009 Aug 23;283(1-2):149-52. Epub 2009 Mar 23.

Department of Neurology, University of Muenster, Albert-Schweitzer-Strasse 33, 48149 Muenster, Germany.

Vascular pathology impairs cognition and impaired cognition increases the risk of dementia. Hypertension is arguably the vascular risk factor that can be reverted best. Here we estimated the effect magnitude of hypertension by determining the variance in cognition explained by systolic blood pressure (sBP) in non-demented community-dwelling individuals. We recruited 525 individuals (mean age 65, range 40-85) selected from the city registry of Muenster, Germany, measured cognitive performance with a comprehensive test battery and assessed vascular risk based on glycosylated hemoglobin, serum cholesterol, high sensitive C-reactive protein, body mass index, smoking pack years, and blood pressure. Including gender and education as well as the vascular risk factors, multiple linear regression analysis for different age groups showed that in midlife age groups systolic blood pressure explained up to 11% of the variance in cognitive performance. These findings suggest that in non-demented community-dwelling individuals hypertension may account for one tenth of cognitive impairment and thus for an increased risk for dementia.
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http://dx.doi.org/10.1016/j.jns.2009.02.362DOI Listing
August 2009

Atrial fibrillation in stroke-free patients is associated with memory impairment and hippocampal atrophy.

Eur Heart J 2008 Sep 29;29(17):2125-32. Epub 2008 Jul 29.

Department of Neurology, University of Münster, A. Schweitzer Street 33, 48129 Münster, Germany.

Aims: To determine whether atrial fibrillation (AF) in stroke-free patients is associated with impaired cognition and structural abnormalities of the brain. AF contributes to stroke and secondary cognitive decline. In the absence of manifest stroke, AF can activate coagulation and cause cerebral microembolism which could damage the brain.

Methods And Results: We cross-sectionally evaluated 122 stroke-free individuals with AF recruited locally within the German Competence Network on AF. As comparator, we recruited 563 individuals aged 37-84 years without AF from the same community. Subjects underwent 3 T magnetic resonance imaging to assess covert territorial brain infarction, white matter lesions, and brain volume measures. Subjects with evidence for stroke, dementia, or depression were excluded. Cognitive function was assessed by an extensive neuropsychological test battery covering the domains learning and memory, attention and executive functions, working memory, and visuospatial skills. Cognitive scores and radiographic measures were compared across individuals with and without AF by stepwise multiple regression models. Stroke-free individuals with AF performed significantly worse in tasks of learning and memory (ß = -0.115, P < 0.01) as well as attention and executive functions (ß = -0.105, P < 0.01) compared with subjects without AF. There was also a trend (P = 0.062) towards worse performance in learning and memory tasks in patients with chronic as compared with paroxysmal AF. Corresponding to the memory impairment, hippocampal volume was reduced in patients with AF. Other radiographic measures did not differ between groups.

Conclusion: Even in the absence of manifest stroke, AF is a risk factor for cognitive impairment and hippocampal atrophy. Therefore, cognition and measures of structural brain integrity should be considered in the evaluation of novel treatments for AF.
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http://dx.doi.org/10.1093/eurheartj/ehn341DOI Listing
September 2008

Lifestyle and memory in the elderly.

Neuroepidemiology 2008 6;31(1):39-47. Epub 2008 Jun 6.

Department of Neurology, University of Münster, Münster, Germany.

Background: Healthy lifestyle has been associated with a decreased risk of developing cardiovascular disease, but its relationship with memory functions is still inconclusive. This study aims to analyze the association between a composite lifestyle index and memory performance.

Methods: In this cross-sectional survey, 198 healthy individuals (aged 65-84 years) underwent tests of verbal episodic memory. A composite lifestyle index was calculated that included the following lifestyle dimensions: physical exercise, dietary habits, BMI, smoking and alcohol consumption. The healthiest behavior was defined as: a BMI <22; a diet high in fruits, vegetables, wholemeal/low-fat foods and unsaturated fatty acids; energy expenditure through physical activity >13,000 kcal/week; a history of never smoking; an alcohol consumption of 4-10 drinks per week.

Results: Linear regression analysis revealed that a high lifestyle index score was associated with a better memory score (after adjusting for age, sex, education and blood pressure). The composite index had a stronger relationship with memory scores than single factors.

Conclusions: This cross-sectional study revealed that a healthy lifestyle, assessed by a simple composite index, is related to better memory performance in healthy elderly individuals. Our findings point to the importance of a comprehensive modulation of lifestyle factors when finding ways to preserve memory functions in the elderly.
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http://dx.doi.org/10.1159/000137378DOI Listing
December 2008

High-normal blood pressure is associated with poor cognitive performance.

Hypertension 2008 Mar 4;51(3):663-8. Epub 2008 Feb 4.

Department of Neurology, University of Münster, A. Schweitzer Str. 33, 48129 Münster, Germany.

While the relation between systolic blood pressure (SBP) and vascular events is linear down to the high-normal range, the relation between SBP and cognition is less clear. We cross-sectionally assessed the relation between SBP and cognition in a cohort extending from mid- to late-life. From a total of 2200 community-dwelling individuals we recruited 377 aged 44 to 82 years (median: 64 years, 171 male) in the SEARCH-Health study (Systematic evaluation and alteration of risk factors for cognitive health). Participants were studied with a comprehensive neuropsychological test battery that provided, based on principal component analysis, 5 composite scores for cognition (learning and memory, attention and executive function, spatial skills, working memory, and verbal skills). Global cognition was calculated from the sum of the composite scores. SBP (corrected R(2)=0.007), education (corrected R(2)=0.203), age (corrected R(2)=0.102), and gender (corrected R(2)=0.011) explained one third of variance in global cognitive performance (P<0.001) on multivariate analyses. Moreover, the relation between SBP (based on 10 mm Hg-categories from <120 mm Hg to >170 mm Hg) and global cognitive performance was linear in this range of SBP-values, ie, even in the normotensive range (beta=-0.110, P<0.05). Subgroup analysis showed that the association of SBP and cognition was driven by results in midlife (<60 years) individuals (beta=-0.291, P<0.005). Thus, even in the normotensive range increasing systolic blood pressure is inversely related to cognition.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.105577DOI Listing
March 2008

Functional transcranial Doppler sonography.

Front Neurol Neurosci 2006 ;21:251-260

Department of Neurology, University of Münster, Münster, Germany.

Functional transcranial Doppler sonography (fTCD) constitutes a complementary neuroimaging tool measuring cerebral perfusion changes due to neural activation. Functional TCD utilizes pulse-wave Doppler technology to record blood flow velocities in the anterior, middle, and posterior cerebral arteries. Comparable to other perfusion-sensitive neuroimaging techniques like functional magnetic resonance imaging or positron emission tomography, fTCD is based on a close coupling between regional cerebral blood flow changes and neural activation. Due to a continuous registration of blood flow, TCD offers an excellent temporal resolution in comparison to other neuroimaging techniques. The technique is noninvasive and easy to apply. Blood flow measurements are robust against movement artifacts. Thus, fTCD is predestinated for follow-up investigations, especially in individuals with diminished ability to cooperate, like patients or children. Since its introduction the technique has contributed substantially to the elucidation of the hemispheric organization of cognitive, motor, and sensory functions in adults and children. This chapter delineates the physical and physiological principles of the technique. A prototypical experimental setup and analysis techniques are described. Scientific and clinical applications of fTCD are presented.
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http://dx.doi.org/10.1159/000092437DOI Listing
May 2007

The association between scalp hair-whorl direction, handedness and hemispheric language dominance: is there a common genetic basis of lateralization?

Neuroimage 2007 Apr 29;35(2):853-61. Epub 2006 Dec 29.

Department of Neurology, University of Münster, Germany.

The hemispheres of the human brain are functionally asymmetric. The left hemisphere tends to be dominant for language and superior in the control of manual dexterity. The mechanisms underlying these asymmetries are not known. Genetic as well as environmental factors are discussed. Recently, atypical anticlockwise hair-whorl direction has been related to an increased probability for non-right-handedness and atypical hemispheric language dominance. These findings are fascinating and important since hair-whorl direction is a structural marker of lateralization and could provide a readily observable anatomical clue to functional brain lateralization. Based on data on handedness and hair-whorl direction, Amar Klar proposed a genetic model ("random-recessive model") in that a single gene with two alleles controls both handedness and hair-whorl orientation (Klar, A.J.S., 2003. Human handedness and scalp hair-whorl direction develop from a common genetic mechanism. Genetics 165, 269-276). The present study was designed to further investigate the relationship between scalp hair-whorl direction with handedness and hemispheric language dominance. 1212 subjects were investigated for scalp hair-whorl direction and handedness. Additionally, we determined hemispheric language dominance (as assessed by a word generation task) in a subgroup of 212 subjects using functional transcranial Doppler sonography (fTCD). As for the single attributes - hair-whorl direction, handedness, and language dominance - we reproduced previously published results. However, we found no association between hair-whorl direction and either language dominance or handedness. These results strongly argue against a common genetic basis of handedness or language lateralization with scalp hair-whorl direction. Inspection of hair patterns will not help us to determine language dominance.
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http://dx.doi.org/10.1016/j.neuroimage.2006.12.025DOI Listing
April 2007
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