Publications by authors named "Andreas Johnen"

34 Publications

Oral and Periodontal Health in Patients with Alzheimer's Disease and Other Forms of Dementia - A Cross-sectional Pilot Study.

Oral Health Prev Dent 2021 Jan;19(1):255-261

Purpose: Systemic inflammation is characteristic for the pathogenesis of Alzheimer's disease (AD) and is responsible for the accumulation of its disease-specific Tau-protein and β-amyloid plaques. Studies focusing on an association with periodontitis showed worse periodontal conditions in patients with dementia, but until now, no study has investigated the differences between AD and other forms of dementia (noAD/DEM). Expecting severe periodontal disease in AD, the aim of this pilot-study was to compare the periodontal and dental status in patients with either AD or noAD/DEM.

Materials And Methods: Twenty patients recently diagnosed with AD and 20 with noAD/DEM between the ages of 50 and 70 years were recruited at the Department of Neurology, University Hospital, Münster, Germany and clinically examined at the Department of Periodontology, School of Dental Medicine, Münster, Germany. Neuropsychological testing, levels of Tau-protein and β-amyloid in serum and liquor were used to distinguish between both groups. Dental and periodontal parameters such as clinical attachment loss (CAL), probing pocket depth (PPD), bleeding-on-probing (BOP), radiographic bone loss, full-mouth plaque score (FMPS), and missing and restored teeth were recorded.

Results: Periodontitis was diagnosed in all patients. Patients with AD presented mean BOP of 54.7 ± 31.1% and radiographic bone loss of 42.5 ± 25.3%; the mean BOP of those with noAD/DEM was 52.0 ± 23.7% and radiographic bone loss was 40.9 ± 32.3%. There was also no statistically significant difference regarding other periodontal and dental parameters.

Conclusions: Both patients with AD and noAD/DEM had periodontal disease. Consequently, patients with all forms of dementia (AD/other) need special dental care to improve periodontal and oral health.
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http://dx.doi.org/10.3290/j.ohpd.b1248937DOI Listing
January 2021

Apolipoprotein E homozygous ε4 allele status: Effects on cortical structure and white matter integrity in a young to mid-age sample.

Eur Neuropsychopharmacol 2021 May 27;46:93-104. Epub 2021 Feb 27.

Department of Psychiatry, University of Münster, Münster, Germany. Electronic address:

Apolipoprotein E (APOE) genotype is the strongest single gene predictor of Alzheimer's disease (AD) and has been frequently associated with AD-related brain structural alterations before the onset of dementia. While previous research has primarily focused on hippocampal morphometry in relation to APOE, sporadic recent findings have questioned the specificity of the hippocampus and instead suggested more global effects on the brain. With the present study we aimed to investigate associations between homozygous APOE ε4 status and cortical gray matter structure as well as white matter microstructure. In our study, we contrasted n = 31 homozygous APOE ε4 carriers (age=34.47 years, including a subsample of n = 12 subjects with depression) with a demographically matched sample without an ε4 allele (resulting total sample: N = 62). Morphometry analyses included a) Freesurfer based cortical segmentations of thickness and surface area measures and b) tract based spatial statistics of DTI measures. We found pronounced and widespread reductions in cortical surface area of ε4 homozygotes in 57 out of 68 cortical brain regions. In contrast, no differences in cortical thickness were observed. Furthermore, APOE ε4 homozygous carriers showed significantly lower fractional anisotropy in the corpus callosum, the right internal and external capsule, the left corona radiata and the right fornix. The present findings support a global rather than regionally specific effect of homozygous APOE ε4 allele status on cortical surface area and white matter microstructure. Future studies should aim to delineate the clinical implications of these findings.
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http://dx.doi.org/10.1016/j.euroneuro.2021.02.006DOI Listing
May 2021

Intravenous methadone causes acute toxic and delayed inflammatory encephalopathy with persistent neurocognitive impairments.

BMC Neurol 2021 Feb 22;21(1):85. Epub 2021 Feb 22.

Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, A1, 48149, Münster, Germany.

Background: The mu-opioid agonist methadone is administered orally and used in opioid detoxification and in the treatment of moderate-to-severe pain. Acute oral methadone-use and -abuse have been associated with inflammatory and toxic central nervous system (CNS) damage in some cases and cognitive deficits can develop in long-term methadone users. In contrast, reports of intravenous methadone adverse effects are rare.

Case Presentation: Here, we report a patient who developed acute bilateral hearing loss, ataxia and paraparesis subsequently to intravenous methadone-abuse. While the patient gradually recovered from these deficits, widespread magnetic resonance imaging changes progressed and delayed-onset encephalopathy with signs of cortical dysfunction persisted. This was associated with changes in the composition of monocyte and natural killer cell subsets in the cerebrospinal fluid.

Conclusion: This case suggests a potential bi-phasic primary toxic and secondary inflammatory CNS damage induced by intravenous methadone.
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http://dx.doi.org/10.1186/s12883-021-02108-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898738PMC
February 2021

Advances in automatic identification of flying insects using optical sensors and machine learning.

Sci Rep 2021 Jan 15;11(1):1555. Epub 2021 Jan 15.

DTU Compute, Technical University of Denmark, 2800, Kongens Lyngby, Denmark.

Worldwide, farmers use insecticides to prevent crop damage caused by insect pests, while they also rely on insect pollinators to enhance crop yield and other insect as natural enemies of pests. In order to target pesticides to pests only, farmers must know exactly where and when pests and beneficial insects are present in the field. A promising solution to this problem could be optical sensors combined with machine learning. We obtained around 10,000 records of flying insects found in oilseed rape (Brassica napus) crops, using an optical remote sensor and evaluated three different classification methods for the obtained signals, reaching over 80% accuracy. We demonstrate that it is possible to classify insects in flight, making it possible to optimize the application of insecticides in space and time. This will enable a technological leap in precision agriculture, where focus on prudent and environmentally-sensitive use of pesticides is a top priority.
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http://dx.doi.org/10.1038/s41598-021-81005-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810676PMC
January 2021

The Agony of Choice? Preserved Affective Decision Making in Early Multiple Sclerosis.

Front Neurol 2020 2;11:914. Epub 2020 Sep 2.

Department of Neurology With Institute of Translational Neurology, University Hospital Münster, Westfälische-Wilhelms-University Münster, Münster, Germany.

Cognitive impairment (CI) is an early and frequent symptom of multiple sclerosis (MS). Likewise, affective symptoms (e.g., depression and anxiety) and alterations in the processing of emotional stimuli have been frequently reported. Thus, abilities that integrate affective and cognitive processes such as decision making (DM) based on affective feedback are potentially valuable early diagnostic markers for MS. The available research on this topic, however, is still inconclusive and suffers from methodological issues. We compared DM ability in a clinically homogeneous cohort of 24 patients with early relapsing-remitting MS (RRMS) and 59 age-matched healthy controls (HCs). A modified version of the Iowa gambling task (IGT) allowed us to control for individual differences in search strategies during the risk exploration phase. Besides standard IGT measures (netscore, obtained play money, and learning index), we also examined reaction times and post-error slowing (PES) patterns as a proxy for abnormalities in the processing of affective feedback. The performance of patients did not significantly deviate from HCs in any standard parameter of the modified IGT. Furthermore, although RRMS patients reacted significantly slower than HCs overall, we found similar patterns of PES in both groups, suggesting similarly efficient processing of affective feedback. We conclude that there is no specific deficit in affective feedback processing in early RRMS. Previous findings of IGT impairments in this patient group may thus not represent a genuine deficit in affective DM but rather be related to sample characteristics, general CI, and/or differences in individual search strategies. Future research should explore the potential influence of lesion volumes and locations on DM ability by employing brain imaging techniques.
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http://dx.doi.org/10.3389/fneur.2020.00914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492612PMC
September 2020

[Young onset dementia].

Nervenarzt 2020 Oct;91(10):936-945

Klinik für Neurologie mit Institut für Translationale Neurologie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude A1, 48149, Münster, Deutschland.

Background: Due to the demographic change dementia is a common and dramatically increasing reason for medical presentations. In approximately 8% of cases dementia occurs before the age of 65 years. The psychosocial and economic consequences are often severe, particularly in younger patients. Clinicians face major diagnostic challenges. A rapid diagnosis is crucial for patient counselling and management.

Objective: This review article presents the special features of dementia in younger people, the most important underlying diseases and a rational clinical diagnostic approach.

Methods: Narrative review. The literature search was carried out in PubMed.

Results: The differential diagnostic spectrum of dementia in younger people under the age of 65 years is very broad. The most common causes are Alzheimer's disease with typical or atypical clinical presentations and frontotemporal lobar degeneration. The younger the age of onset, the higher the proportion of treatable and potentially reversible causes of dementia.

Conclusion: The diagnostics of primary neurodegenerative diseases have continuously improved, especially due to the availability of an increasing number of clinical, molecular and imaging biomarkers. Nevertheless, in order to avoid unnecessary and burdensome examinations, the diagnostic work-up of young onset dementia must be hypothesis-driven, i.e. following a precise clinical syndromic classification of the symptoms.
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http://dx.doi.org/10.1007/s00115-020-00967-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532136PMC
October 2020

Disease-modifying treatments and cognition in relapsing-remitting multiple sclerosis: A meta-analysis.

Neurology 2020 06 19;94(22):e2373-e2383. Epub 2020 May 19.

From the Clinic of Neurology with Institute of Translational Neurology (N.C.L., H.W., T.R., S.G.M., A.J.), University Hospital Münster, Westphalian-Wilhelms-University Münster, Germany; Department of Statistics (P.-C.B., H.H.), Faculty of Psychology, Westphalian-Wilhelms-University Münster, Germany; and Department of Neurology (H.-P.H.), UKD and Center for Neurology and Neuropsychiatry, LVR Klinikum, Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany.

Objective: Disease-modifying treatments (DMTs) are the gold standard for slowing disability progression in multiple sclerosis (MS), but their effects on cognitive impairment, a key symptom of the disease, are mostly unknown. We conducted a systematic review and meta-analysis to evaluate the differential effects of DMTs on cognitive test performance in relapsing-remitting MS (RRMS).

Methods: PubMed, Scopus, and Cochrane Library were searched for studies reporting longitudinal cognitive performance data related to all major DMTs. The standardized mean difference (Hedges ) between baseline and follow-up cognitive assessment was used as the main effect size measure.

Results: Forty-four studies, including 55 distinct MS patient samples, were found eligible for the systematic review. Twenty-five studies were related to platform therapies (mainly β-interferon [n = 17] and glatiramer acetate [n = 4]), whereas 22 studies were related to escalation therapies (mainly natalizumab [n = 14] and fingolimod [n = 6]). Reported data were mostly confined to the cognitive domain processing speed. A meta-analysis including 41 studies and 7,131 patients revealed a small to moderate positive effect on cognitive test performance of DMTs in general (g = 0.27, 95% confidence interval [CI] = [0.21-0.33]), but no statistically significant differences between platform (g = 0.27, 95% CI = [0.18-0.35]) and escalation therapies (g = 0.28, 95% CI = [0.19-0.37]) or between any single DMT and β-interferon.

Conclusions: DMTs are effective in improving cognitive test performance in RRMS, but a treatment escalation mainly to amend cognition is not supported by the current evidence. Given the multitude of DMTs and their widespread use, the available data regarding differential treatment effects on cognitive impairment are remarkably scant. Clinical drug trials that use more extensive cognitive outcome measures are urgently needed.
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http://dx.doi.org/10.1212/WNL.0000000000009522DOI Listing
June 2020

Gray matter integrity predicts white matter network reorganization in multiple sclerosis.

Hum Brain Mapp 2020 03 5;41(4):917-927. Epub 2019 Nov 5.

Department of Neurology and Neuroimaging Center (NIC) of the Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease leading to gray matter atrophy and brain network reconfiguration as a response to increasing tissue damage. We evaluated whether white matter network reconfiguration appears subsequently to gray matter damage, or whether the gray matter degenerates following alterations in white matter networks. MRI data from 83 patients with clinically isolated syndrome and early relapsing-remitting MS were acquired at two time points with a follow-up after 1 year. White matter network integrity was assessed based on probabilistic tractography performed on diffusion-weighted data using graph theoretical analyses. We evaluated gray matter integrity by computing cortical thickness and deep gray matter volume in 94 regions at both time points. The thickness of middle temporal cortex and the volume of deep gray matter regions including thalamus, caudate, putamen, and brain stem showed significant atrophy between baseline and follow-up. White matter network dynamics, as defined by modularity and distance measure changes over time, were predicted by deep gray matter volume of the atrophying anatomical structures. Initial white matter network properties, on the other hand, did not predict atrophy. Furthermore, gray matter integrity at baseline significantly predicted physical disability at 1-year follow-up. In a sub-analysis, deep gray matter volume was significantly related to cognitive performance at baseline. Hence, we postulate that atrophy of deep gray matter structures drives the adaptation of white matter networks. Moreover, deep gray matter volumes are highly predictive for disability progression and cognitive performance.
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http://dx.doi.org/10.1002/hbm.24849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268008PMC
March 2020

Serial position effects rapidly distinguish Alzheimer's from frontotemporal dementia.

J Neurol 2020 Apr 5;267(4):975-983. Epub 2019 Dec 5.

Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus, Building A1, 48149, Münster, Germany.

Objective: A significant proportion of patients with behavioural variant frontotemporal dementia (bvFTD) show memory impairments similar to patients with Alzheimer's disease (AD), making them prone to misdiagnosis in early disease stages. Our objective was to establish a rapid and efficient memory measure that enhances discrimination between patients with dementia due to Alzheimer's disease and amnestic presentations of behavioural variant frontotemporal dementia.

Method: Word list learning data of patients with diagnoses of AD and both amnestic and non-amnestic presentations of bvFTD were analysed. The overall recall rate and the relative contributions of the first two (primacy items) and last two words (recency items) to recall performance were compared between groups.

Results: Overall recall rate was indistinguishable between patients with AD and amnestic bvFTD. However, AD patients' recall was mostly driven by recency items, whereas amnestic bvFTD patients' performance was mostly driven by primacy items.

Conclusion: We conclude that obtaining a simple recency dominance index from a single, 15-item word list memory trial can help discriminate patients with AD from patients with bvFTD, even if they present with similarly severe memory impairment.
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http://dx.doi.org/10.1007/s00415-019-09662-wDOI Listing
April 2020

Resolving the cognitive clinico-radiological paradox - Microstructural degeneration of fronto-striatal-thalamic loops in early active multiple sclerosis.

Cortex 2019 12 26;121:239-252. Epub 2019 Sep 26.

Department of Neurology with Institute for Translational Neurology, University Hospital Münster, Münster, Germany.

Background: Associations between cognitive impairment (CI) and both global and regional brain volumes can be weak in early multiple sclerosis (MS), a dilemma known as cognitive clinico-radiological paradox. We hypothesized that white-matter (WM) integrity within fronto-striatal-thalamic networks may be a sensitive marker for impaired performance in speed-dependent tasks, typical for early MS.

Methods: Twenty-seven patients with early active relapsing-remitting MS (RRMS) received comprehensive neuropsychological assessment and underwent structural and diffusion-weighted brain magnetic resonance imaging (MRI). Global and regional brain volumes were obtained using FreeSurfer software. Fractional anisotropy (FA) was computed from diffusion tensor images to assess microstructural alterations within three anatomically predefined fronto-striatal-thalamic loops known to be relevant for speed-dependent attention and executive functions.

Results: Overall cognitive performance (Spearman's ρ = .51) and performance in the domains processing speed (ρ = .44) and executive functions (ρ = .41) were correlated with patients' mean FA within the right dorsolateral-prefrontal loop. In addition, overall cognitive performance correlated with mean FA within the right lateral orbitofrontal loop (ρ = .39) - but only before controlling for WM lesion count. In contrast, regional volumes of grey-matter structures within these fronto-striatal-thalamic loops (including the thalamus) were not significantly related to CI. The total brain volume was associated with performance in the domain verbal memory (ρ = .43) only.

Conclusions: Microstructural degeneration within specific fronto-striatal-thalamic WM networks, previously characterized as crucial for task-monitoring, better accounts for speed-dependent CI in patients with early active RRMS than global or regional brain volumes. Our findings may advance our understanding of the neural substrates underlying CI characteristic for early RRMS.
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http://dx.doi.org/10.1016/j.cortex.2019.08.022DOI Listing
December 2019

White matter microstructure mediates the association between physical fitness and cognition in healthy, young adults.

Sci Rep 2019 09 9;9(1):12885. Epub 2019 Sep 9.

Department of Psychiatry, University of Münster, Münster, Germany.

We aimed to extend our knowledge on the relationship between physical fitness (PF) and both white matter microstructure and cognition through in-depth investigation of various cognitive domains while accounting for potentially relevant nuisance covariates in a well-powered sample. To this end, associations between walking endurance, diffusion-tensor-imaging (DTI) based measures of fractional anisotropy (FA) within brain white matter and cognitive measures included in the NIH Toolbox Cognition Battery were investigated in a sample of n = 1206 healthy, young adults (mean age = 28.8; 45.5% male) as part of the human connectome project. Higher levels of endurance were associated with widespread higher FA (p < 0.05) as well as with enhanced global cognitive function (p < 0.001). Significant positive relationships between endurance and cognitive performance were similarly found for almost all cognitive domains. Higher FA was significantly associated with enhanced global cognitive function (p < 0.001) and FA was shown to significantly mediate the association between walking endurance and cognitive performance. Inclusion of potentially relevant nuisance covariates including gender, age, education, BMI, HBA1c, and arterial blood pressure did not change the overall pattern of results. These findings support the notion of a beneficial and potentially protective effect of PF on brain structure and cognition.
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http://dx.doi.org/10.1038/s41598-019-49301-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733843PMC
September 2019

Psychological and Cognitive Markers of Behavioral Variant Frontotemporal Dementia-A Clinical Neuropsychologist's View on Diagnostic Criteria and Beyond.

Front Neurol 2019 7;10:594. Epub 2019 Jun 7.

Univ Lille, Inserm UMR 1171 Degenerative and Vascular Cognitive Disorders, CHU Lille, Lille, France.

Behavioral variant frontotemporal dementia (bvFTD) is the second leading cognitive disorder caused by neurodegeneration in patients under 65 years of age. Characterized by frontal, insular, and/or temporal brain atrophy, patients present with heterogeneous constellations of behavioral and psychological symptoms among which progressive changes in social conduct, lack of empathy, apathy, disinhibited behaviors, and cognitive impairments are frequently observed. Since the histopathology of the disease is heterogeneous and identified genetic mutations only account for ~30% of cases, there are no reliable biomarkers for the diagnosis of bvFTD available in clinical routine as yet. Early detection of bvFTD thus relies on correct application of clinical diagnostic criteria. Their evaluation however, requires expertise and in-depth assessments of cognitive functions, history taking, clinical observations as well as caregiver reports on behavioral and psychological symptoms and their respective changes. With this review, we aim for a critical appraisal of common methods to access the behavioral and psychological symptoms as well as the cognitive alterations presented in the diagnostic criteria for bvFTD. We highlight both, practical difficulties as well as current controversies regarding an overlap of symptoms and particularly cognitive impairments with other neurodegenerative and primary psychiatric diseases. We then review more recent developments and evidence on cognitive, behavioral and psychological symptoms of bvFTD beyond the diagnostic criteria which may prospectively enhance the early detection and differential diagnosis in clinical routine. In particular, evidence on specific impairments in social and emotional processing, praxis abilities as well as interoceptive processing in bvFTD is summarized and potential links with behavior and classic cognitive domains are discussed. We finally outline both, future opportunities and major challenges with regard to the role of clinical neuropsychology in detecting bvFTD and related neurocognitive disorders.
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http://dx.doi.org/10.3389/fneur.2019.00594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6568027PMC
June 2019

Evaluation of Ocular Perfusion in Alzheimer's Disease Using Optical Coherence Tomography Angiography.

J Alzheimers Dis 2018 ;66(4):1745-1752

Department of Ophthalmology, University of Muenster Medical Center, Muenster, Germany.

Background: There is increasing evidence for the involvement of cerebrovascular factors in Alzheimer's disease (AD).

Objective: To evaluate retinal and optic nerve head perfusion in patients with AD using optical coherence tomography angiography (OCTA), and to analyze the correlations of quantitative OCTA metrics with AD pathology and vascular cerebral lesions in AD patients.

Methods: 36 eyes of 36 patients with AD (study group) and 38 eyes of 38 healthy subjects (control group) were prospectively included in this study. OCTA was performed using RTVue XR Avanti with AngioVue. In addition, patients underwent a detailed ophthalmological and neurological examination including Mini-Mental State Examination, cerebral magnetic resonance imaging, and amyloid-β (Aβ) and tau levels in the cerebrospinal fluid (CSF).

Results: The flow density in the superficial retinal OCT angiogram of the macula in the study group was significantly lower compared to the control group (p = 0.001). There was a significant correlation between the flow density in the superficial retinal OCT angiogram of the macula, as measured using OCTA, and the Fazekas scale (Spearman's correlation coefficient = -0.520; p = 0.003). There was no significant correlation between the Aβ or tau levels in the CSF and the flow density data.

Conclusion: Patients with AD showed a reduced flow density in the radial peripapillary capillaries layer and in the superficial retinal OCT angiogram when compared with healthy controls. The reduced retinal flow density measured using OCTA is not specifically associated with AD pathology but is associated with the vascular cerebral lesions in AD.
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http://dx.doi.org/10.3233/JAD-180738DOI Listing
November 2019

Can we predict cognitive decline after initial diagnosis of multiple sclerosis? Results from the German National early MS cohort (KKNMS).

J Neurol 2019 Feb 4;266(2):386-397. Epub 2018 Dec 4.

Department of Neurology, University Hospital Münster, Westfälische-Wilhelms-University Münster, Münster, Germany.

Background: Cognitive impairment (CI) affects approximately one-third of the patients with early multiple sclerosis (MS) and clinically isolated syndrome (CIS). Little is known about factors predicting CI and progression after initial diagnosis.

Methods: Neuropsychological screening data from baseline and 1-year follow-up of a prospective multicenter cohort study (NationMS) involving 1123 patients with newly diagnosed MS or CIS were analyzed. Employing linear multilevel models, we investigated whether demographic, clinical and conventional MRI markers at baseline were predictive for CI and longitudinal cognitive changes.

Results: At baseline, 22% of patients had CI (impairment in ≥2 cognitive domains) with highest frequencies and severity in processing speed and executive functions. Demographics (fewer years of academic education, higher age, male sex), clinical (EDSS, depressive symptoms) but no conventional MRI characteristics were linked to baseline CI. At follow-up, only 14% of patients showed CI suggesting effects of retesting. Neither baseline characteristics nor initiation of treatment between baseline and follow-up was able to predict cognitive changes within the follow-up period of 1 year.

Conclusions: Identification of risk factors for short-term cognitive change in newly diagnosed MS or CIS is insufficient using only demographic, clinical and conventional MRI data. Change-sensitive, re-test reliable cognitive tests and more sophisticated predictors need to be employed in future clinical trials and cohort studies of early-stage MS to improve prediction.
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http://dx.doi.org/10.1007/s00415-018-9142-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373354PMC
February 2019

Apraxia screening predicts Alzheimer pathology in frontotemporal dementia.

J Neurol Neurosurg Psychiatry 2019 05 10;90(5):562-569. Epub 2018 Oct 10.

Department of Neurology, University Hospital Münster, Münster, Germany

Objectives: Frontotemporal dementia (FTD) is a heterogeneous clinical syndrome linked to diverse types of underlying neuropathology. Diagnosis is mainly based on clinical presentation and accurate prediction of underlying neuropathology remains difficult.

Methods: We present a large cohort of patients with FTD spectrum diseases (n=84). All patients were thoroughly characterised by cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers, neuroimaging, neuropsychological testing and standardised apraxia screening.

Results: A potential AD pathology was found in 43% of patients with FTD. CSF AD biomarker levels positively correlated with AD-typical apraxia scores in patients with FTD. The discriminative power of apraxia test results indicative of AD pathology was high (sensitivity: 90%, specificity: 66%).

Conclusions: Apraxia is common in neurodegenerative dementias but under-represented in clinical workup and diagnostic criteria. Standardised apraxia screening may serve as bedside test to objectify an AD-typical apraxia profile as an early and robust sign of AD pathology in patients with FTD.
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http://dx.doi.org/10.1136/jnnp-2018-318470DOI Listing
May 2019

Periodontal Pathogens and Associated Intrathecal Antibodies in Early Stages of Alzheimer's Disease.

J Alzheimers Dis 2018 ;66(1):105-114

Department of Periodontology, School of Dental Medicine, University of Bern, Switzerland.

Background: Recent studies suggest a link between periodontitis and Alzheimer's disease (AD).

Objective: Verification of the presence of periodontal pathogens and the intrathecal generation of pathogen-specific antibodies in 20 patients with AD and 20 with other forms of dementia (DEM-noAD).

Methods: Clinical periodontal indices were recorded. Cerebrospinal fluid (CSF) was analyzed for total tau protein (T-tau) and amyloid-β (Aβ1-42). In serum and CSF, antibody levels against Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema species were quantified. The presence of selected bacteria and inflammatory biomarkers were determined in periodontium, serum, and CSF.

Results: In line with diagnoses, CSF-levels of Aβ1-42 were significantly lower in AD than DEM-noAD patients. Periodontal destruction and inflammation were omnipresent with no difference between groups. P. gingivalis, T. forsythia, and Treponema species were detected in more than 50% of subgingival biofilm samples, but neither in serum nor in the CSF. Elevated levels of anti-pathogen antibodies in CSF of 16 patients (7 AD; 9 DEM-noAD) compared to serum highlight a possibility of the intrathecal immune response to pathogens. There was no significant difference in antibodies levels against selected bacteria in CSF and serum between groups. Multivariate regression analysis and general linear models revealed an association of the T-tau level in AD group with both serum levels of anti-P. gingivalis antibodies and MCP-1/CCL-2.

Conclusion: Periodontal pathogens may enter the brain and stimulate a local immune response. However, in patients with dementia at the age up to 70 years, periodontal pathogens do not act as a trigger for developing AD.
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http://dx.doi.org/10.3233/JAD-180620DOI Listing
September 2019

Apraxia profiles-A single cognitive marker to discriminate all variants of frontotemporal lobar degeneration and Alzheimer's disease.

Alzheimers Dement (Amst) 2018 16;10:363-371. Epub 2018 May 16.

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

Introduction: Apraxia is common in neurodegenerative dementias but underrepresented in clinical workup for differential diagnoses.

Methods: Praxis-profiles were assessed with the Dementia Apraxia Test in 93 patients with early stages of biologically supported Alzheimer's disease or frontotemporal lobar degeneration: semantic primary-progressive aphasia, nonfluent primary-progressive aphasia, and behavioral variant frontotemporal dementia. Associations with core cognitive deficits of the dementia subtypes (i.e., visuospatial, sociocognitive, and semantic-linguistic) were explored.

Results: Patients showed significant apraxia compared with healthy controls but also disease-specific praxis-profiles. Using only the Dementia Apraxia Test, all four dementia subtypes could be correctly discriminated in 64.4% of cases, and in 78.2% when only distinguishing Alzheimer's disease versus frontotemporal lobar degeneration. Praxis-profiles showed consistent associations with core cognitive impairments of the different dementia subtypes.

Discussion: The Dementia Apraxia Test is a valid, time-efficient and versatile cognitive marker to delineate variants of frontotemporal lobar degeneration and Alzheimer's disease in clinical routine, facilitating differential diagnoses of dementia subtypes in early disease stages.
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http://dx.doi.org/10.1016/j.dadm.2018.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039699PMC
May 2018

Onconeural antigen spreading in paraneoplastic neurological disease due to small cell lung cancer.

Oxf Med Case Reports 2018 Jul 9;2018(7):omy034. Epub 2018 Jul 9.

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

Cellular and humoral immunity towards distinct onconeural antigens is the hallmark of paraneoplastic neurological diseases (PNDs). Stable formation of immunoglobulin (Ig) G antibodies to particular onconeural antigens occurs in the majority of cases, whereas persistent coexistence of antibodies specific for multiple onconeural antigens is a relatively rare phenomenon of certain malignant tumors like small cell lung cancer (SCLC). We here describe onconeural antigen spreading in a 70-year-old Caucasian male with PND due to SCLC. Onconeural antigen spreading may be promoted by two mutually non-exclusive mechanisms: (i) a switch of antigen expression pattern of the underlying tumor tissue as a result of a mutagenic process caused by the cancer itself and (ii) a self-propagated paraneoplastic immune response with persistent neuronal destruction, liberation, processing and presentation of intracellular neural antigens. This illustrates a potential dissociation between peripheral anti-tumoral immunity and central anti-neural immunity during the course of PND.
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http://dx.doi.org/10.1093/omcr/omy034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037119PMC
July 2018

Amygdala enlargement and emotional responses in (autoimmune) temporal lobe epilepsy.

Sci Rep 2018 06 22;8(1):9561. Epub 2018 Jun 22.

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

Temporal lobe epilepsy with amygdala enlargement (TLE-AE) is increasingly recognized as a distinct adult electroclinical syndrome. However, functional consequences of morphological alterations of the amygdala in TLE-AE are poorly understood. Here, two emotional stimulation designs were employed to investigate subjective emotional rating and skin conductance responses in a sample of treatment-naïve patients with suspected or confirmed autoimmune TLE-AE (n = 12) in comparison to a healthy control group (n = 16). A subgroup of patients completed follow-up measurements after treatment. As compared to healthy controls, patients with suspected or confirmed autoimmune TLE-AE showed markedly attenuated skin conductance responses and arousal ratings, especially pronounced for anxiety-inducing stimuli. The degree of right amygdala enlargement was significantly correlated with the degree of autonomic arousal attenuation. Furthermore, a decline of amygdala enlargement following prompt aggressive immunotherapy in one patient suffering from severe confirmed autoimmune TLE-AE with a very recent clinical onset was accompanied by a significant improvement of autonomic responses. Findings suggest dual impairments of autonomic and cognitive discrimination of stimulus arousal as hallmarks of emotional processing in TLE-AE. Emotional responses might, at least partially, recover after successful treatment, as implied by first single case data.
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http://dx.doi.org/10.1038/s41598-018-27914-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015084PMC
June 2018

Distinguishing neurocognitive deficits in adult patients with NP-C from early onset Alzheimer's dementia.

Orphanet J Rare Dis 2018 06 5;13(1):91. Epub 2018 Jun 5.

Department of Neurology, University Hospital of Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany.

Background: Niemann-Pick disease type C (NP-C) is a rare, progressive neurodegenerative disease caused by mutations in the NPC1 or the NPC2 gene. Neurocognitive deficits are common in NP-C, particularly in patients with the adolescent/adult-onset form. As a disease-specific therapy is available, it is important to distinguish clinically between the cognitive profiles in NP-C and primary dementia (e.g., early Alzheimer's disease; eAD).

Methods: In a prospective observational study, we directly compared the neurocognitive profiles of patients with confirmed NP-C (n = 7) and eAD (n = 15). All patients underwent neurocognitive assessment using dementia screening tests (mini-mental status examination [MMSE] and frontal assessment battery [FAB]) and an extensive battery of tests assessing verbal memory, visuoconstructive abilities, visual memory, executive functions and verbal fluency.

Results: Overall cognitive impairment (MMSE) was significantly greater in eAD vs. NP-C (p = 0.010). The frequency of patients classified as cognitively 'impaired' was also significantly greater in eAD vs. NP-C (p = 0.025). Patients with NP-C showed relatively preserved verbal memory, but frequent impairment in visual memory, visuoconstruction, executive functions and in particular, verbal fluency. In the eAD group, a wider profile of more frequent and more severe neurocognitive deficits was seen, primarily featuring severe verbal and visual memory deficits along with major executive impairment. Delayed verbal memory recall was a particularly strong distinguishing factor between the two groups.

Conclusion: A combination of detailed yet easy-to-apply neurocognitive tests assessing verbal memory, executive functions and verbal fluency may help distinguish NP-C cases from those with primary dementia due to eAD.
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http://dx.doi.org/10.1186/s13023-018-0833-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989447PMC
June 2018

Diagnostic Value of Diffusion Tensor Imaging and Positron Emission Tomography in Early Stages of Frontotemporal Dementia.

J Alzheimers Dis 2018 ;63(1):239-253

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

Background: Due to suboptimal sensitivity and specificity of structural and molecular neuroimaging tools, the diagnosis of behavioral variant frontotemporal dementia (bvFTD) remains challenging.

Objective: Investigation of the sensitivity of diffusion tensor imaging (DTI) and fluorodeoxyglucose positron emission tomography (FDG-PET) to detect cerebral alterations in early stages of bvFTD despite inconspicuous conventional MRI.

Methods: Thirty patients with early stages of bvFTD underwent a detailed neuropsychological examination, cerebral 3T MRI with DTI analysis, and FDG-PET. After 12 months of follow-up, all patients finally fulfilled the diagnosis of bvFTD. Individual FDG-PET data analyses showed that 20 patients exhibited a "typical" pattern for bvFTD with bifrontal and/or temporal hypometabolism (bvFTD/PET+), and that 10 patients showed a "non-typical"/normal pattern (bvFTD/PET-). DTI data were compared with 42 healthy controls in an individual and voxel-based group analysis. To examine the clinical relevance of the findings, associations between pathologically altered voxels of DTI or FDG-PET results and behavioral symptoms were estimated by linear regression analyses.

Results: DTI voxel-based group analyses revealed microstructural degeneration in bifrontal and bitemporal areas in bvFTD/PET+ and bvFTD/PET- groups. However, when comparing the sensitivity of individual DTI data analysis with FDG-PET, DTI appeared to be less sensitive. Neuropsychological symptoms were considerably related to neurodegeneration within frontotemporal areas identified by DTI and FDG-PET.

Conclusion: DTI seems to be an interesting tool for detection of functionally relevant neurodegenerative alterations in early stages of bvFTD, even in bvFTD/PET- patients. However, at a single subject level, it seems to be less sensitive than FDG-PET. Thus, improvement of individual DTI analysis is necessary.
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http://dx.doi.org/10.3233/JAD-170224DOI Listing
August 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

NMDAR encephalitis: passive transfer from man to mouse by a recombinant antibody.

Ann Clin Transl Neurol 2017 11 3;4(11):768-783. Epub 2017 Oct 3.

Department of Neurology Medical Faculty Heinrich Heine University Düsseldorf Düsseldorf Germany.

Objective: Autoimmune encephalitis is most frequently associated with anti-NMDAR autoantibodies. Their pathogenic relevance has been suggested by passive transfer of patients' cerebrospinal fluid (CSF) in mice in vivo. We aimed to analyze the intrathecal plasma cell repertoire, identify autoantibody-producing clones, and characterize their antibody signatures in recombinant form.

Methods: Patients with recent onset typical anti-NMDAR encephalitis were subjected to flow cytometry analysis of the peripheral and intrathecal immune response before, during, and after immunotherapy. Recombinant human monoclonal antibodies (rhuMab) were cloned and expressed from matching immunoglobulin heavy- (IgH) and light-chain (IgL) amplicons of clonally expanded intrathecal plasma cells (cePc) and tested for their pathogenic relevance.

Results: Intrathecal accumulation of B and plasma cells corresponded to the clinical course. The presence of cePc with hypermutated antigen receptors indicated an antigen-driven intrathecal immune response. Consistently, a single recombinant human GluN1-specific monoclonal antibody, rebuilt from intrathecal cePc, was sufficient to reproduce NMDAR epitope specificity in vitro. After intraventricular infusion in mice, it accumulated in the hippocampus, decreased synaptic NMDAR density, and caused severe reversible memory impairment, a key pathogenic feature of the human disease, in vivo.

Interpretation: A CNS-specific humoral immune response is present in anti-NMDAR encephalitis specifically targeting the GluN1 subunit of the NMDAR. Using reverse genetics, we recovered the typical intrathecal antibody signature in recombinant form, and proved its pathogenic relevance by passive transfer of disease symptoms from man to mouse, providing the critical link between intrathecal immune response and the pathogenesis of anti-NMDAR encephalitis as a humorally mediated autoimmune disease.
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http://dx.doi.org/10.1002/acn3.444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682115PMC
November 2017

Relevance of raised cerebrospinal fluid monocyte levels in patients with frontotemporal dementia.

Neurobiol Aging 2018 02 13;62:45-52. Epub 2017 Oct 13.

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

Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder. The contribution of the immune system to its pathogenesis remains incompletely understood. In this study, we performed comprehensive immune cell profiling in the cerebrospinal fluid (CSF) and peripheral blood of patients with FTD. Thirty-two patients with behavioral variant frontotemporal dementia and 25 patients with primary progressive aphasia were included and compared to 14 healthy elderly controls. All patients underwent neuropsychological examination, magnetic resonance imaging, voxel-based diffusion tensor imaging, and peripheral blood and CSF immune cell profiling by multiparameter flow cytometry. The percentage of CSF monocytes was significantly increased specifically in patients with primary progressive aphasia. The proportion of monocytes in the CSF of the total FTD patient group directly correlated with semantic language impairment and microstructural temporal lesions. Increased intrathecal numbers of monocytes suggest a specific response of the innate immune system in a subset of patients with FTD. The findings are of clinical relevance since monocyte levels in the CSF were correlated with typical neuropsychological deficits and microstructural patterns of temporal degeneration.
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http://dx.doi.org/10.1016/j.neurobiolaging.2017.09.032DOI Listing
February 2018

Distinct cognitive impairments in different disease courses of multiple sclerosis-A systematic review and meta-analysis.

Neurosci Biobehav Rev 2017 Dec 8;83:568-578. Epub 2017 Sep 8.

Department of Statistics, Faculty of Psychology, University of Münster, Germany. Electronic address:

Cognitive impairment (CI) is common and debilitating in patients with multiple sclerosis. However, little is known about how different disease courses affect CI, impeding prognosis and disease management. Here, we contrasted the magnitude and profile of CI measured with standardized neuropsychological tests in patients with primary progressive multiple sclerosis (PPMS) against relapsing-remitting multiple sclerosis (RRMS) while considering potentially confounding demographic and clinical differences. Systematic literature review and meta-analysis was performed finding 47 eligible studies (N=4460 patients). Effect-sizes for 12 cognitive domains were calculated as Hedges' g. Results indicated more severe CI overall (g=-0.37, p<.001) and in each single cognitive domain (g=-0.28 to -0.65, p<.001) in patients with PPMS despite comparable degrees of fatigue and depression. Moderator analyses revealed that these differences were not fully attributable to clinical heterogeneity between disease courses (e.g., age, disability). Particularly verbal learning and memory differentiated PPMS and RRMS independent from demographic differences. Results imply that, previously under-recognized, PPMS patients display severe degrees of CI and need more specialized disease management than RRMS patients.
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http://dx.doi.org/10.1016/j.neubiorev.2017.09.005DOI Listing
December 2017

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

Treating refractory post-herpetic anti--methyl-d-aspartate receptor encephalitis with rituximab.

Oxf Med Case Reports 2017 Jul 3;2017(7):omx034. Epub 2017 Jul 3.

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

Herpes simplex virus-1 has been identified as the trigger factor in certain cases of NMDA-receptor autoimmune encephalitis. We report on a 67-year-old female patient, who was severely affected by post-herpetic NMDA-receptor autoimmune encephalitis. Her symptoms did not improve under methylprednisolone pulse therapy and plasma exchange under acyclovir prophylaxis. She received protein A immunoadsorption and a long-term immunosuppression with rituximab. Under treatment, activated T-cells as well as B- and plasma cells decreased in peripheral blood and cerebrospinal fluid, and anti-NMDA-R IgG titers in serum and cerebrospinal fluid declined with near complete cessation of intrathecal autoantibody synthesis. The patient regained near complete independence and profoundly improved on formal neuropsychological assessment. Despite reduction of antiviral defense through of lowered activated T cells and concomitantly decreasing HSV-specific IgG antibodies, no evidence of viral reactivation was detected.
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http://dx.doi.org/10.1093/omcr/omx034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495011PMC
July 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

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

Intact action segmentation in Parkinson's disease: Hypothesis testing using a novel computational approach.

Neuropsychologia 2015 Nov 30;78:29-40. Epub 2015 Sep 30.

Department of Neurology, University Hospital Cologne, Cologne, Germany; Biological Psychology, Department of Psychology, Westfälische-Wilhelms Universität Münster, Münster, Germany.

Action observation is known to trigger predictions of the ongoing course of action and thus considered a hallmark example for predictive perception. A related task, which explicitly taps into the ability to predict actions based on their internal representations, is action segmentation; the task requires participants to demarcate where one action step is completed and another one begins. It thus benefits from a temporally precise prediction of the current action. Formation and exploitation of these temporal predictions of external events is now closely associated with a network including the basal ganglia and prefrontal cortex. Because decline of dopaminergic innervation leads to impaired function of the basal ganglia and prefrontal cortex in Parkinson's disease (PD), we hypothesised that PD patients would show increased temporal variability in the action segmentation task, especially under medication withdrawal (hypothesis 1). Another crucial aspect of action segmentation is its reliance on a semantic representation of actions. There is no evidence to suggest that action representations are substantially altered, or cannot be accessed, in non-demented PD patients. We therefore expected action segmentation judgments to follow the same overall patterns in PD patients and healthy controls (hypothesis 2), resulting in comparable segmentation profiles. Both hypotheses were tested with a novel classification approach. We present evidence for both hypotheses in the present study: classifier performance was slightly decreased when it was tested for its ability to predict the identity of movies segmented by PD patients, and a measure of normativity of response behaviour was decreased when patients segmented movies under medication-withdrawal without access to an episodic memory of the sequence. This pattern of results is consistent with hypothesis 1. However, the classifier analysis also revealed that responses given by patients and controls create very similar action-specific patterns, thus delivering evidence in favour hypothesis 2. In terms of methodology, the use of classifiers in the present study allowed us to establish similarity of behaviour across groups (hypothesis 2). The approach opens up a new avenue that standard statistical methods often fail to provide and is discussed in terms of its merits to measure hypothesised similarities across study populations.
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http://dx.doi.org/10.1016/j.neuropsychologia.2015.09.034DOI Listing
November 2015