Publications
282 results found
Riso L, Kaaks R, Kühn T, et al., 2019, General and abdominal adiposity and the risk of parkinson's disease.A prospective chort study, Parkinsonism and Related Disorders, Vol: 62, Pages: 98-104, ISSN: 1353-8020
IntroductionDue to demographic change, an increase in the frequency of Parkinson's disease (PD) patients is expected in the future and, thus, the identification of modifiable risk factors is urgently needed. We aimed to examine the associations of body mass index (BMI) and waist circumference (WC) with incident PD.MethodsIn 13 of the 23 centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a total of 734 incident cases of PD were identified between 1992 and 2012 with a mean follow-up of 12 years. Cox proportional hazards regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). We modelled anthropometric variables as continuous and categorical exposures and performed subgroup analyses by potential effect modifiers including sex and smoking.ResultsWe found no association between BMI, WC and incident PD, neither among men nor among women. Among never and former smokers, BMI and waist circumference were also not associated with PD risk. For male smokers, however, we observed a statistically significant inverse association between BMI and PD risk (HR 0.51, 95%CI: 0.30, 0.84) and the opposite for women, i.e. a significant direct association of BMI (HR 1.79, 95%CI: 1.04, 3.08) and waist circumference (HR 1.64, 95%CI: 1.03, 2.61) with risk of PD.ConclusionOur data revealed no association between excess weight and PD risk but a possible interaction between anthropometry, sex and smoking.
Perneczky R, 2019, Dementia prevention and reserve against neurodegenerative disease, DIALOGUES IN CLINICAL NEUROSCIENCE, Vol: 21, Pages: 53-60, ISSN: 1294-8322
- Author Web Link
- Cite
- Citations: 12
Perneczky R, 2019, Dementia treatment versus prevention, DIALOGUES IN CLINICAL NEUROSCIENCE, Vol: 21, Pages: 43-51, ISSN: 1294-8322
- Author Web Link
- Cite
- Citations: 14
Perneczky R, Kempermann G, Korczyn AD, et al., 2019, Translational research on reserve against neurodegenerative disease: consensus report of the International Conference on Cognitive Reserve in the Dementias and the Alzheimer's Association Reserve, Resilience and Protective Factors Professional Interest Area working groups, BMC MEDICINE, Vol: 17, ISSN: 1741-7015
- Author Web Link
- Cite
- Citations: 53
Rauchmann B-S, Schneider-Axmann T, Alexopoulos P, et al., 2019, CSF soluble TREM2 as a measure of immune response along the Alzheimer's disease continuum, NEUROBIOLOGY OF AGING, Vol: 74, Pages: 182-190, ISSN: 0197-4580
- Author Web Link
- Cite
- Citations: 41
Udeh-Momoh C, Price G, Ropacki M, et al., 2019, Prospective Evaluation of Cognitive Health and Related Factors in Elderly at Risk for Developing Alzheimer’s Dementia: A Longitudinal Cohort study, The Journal of Prevention of Alzheimer's Disease, ISSN: 2274-5807
Alexopoulos P, Thierjung N, Economou P, et al., 2019, Plasma Levels of Soluble AβPPβ as a Biomarker for Alzheimer's Disease with Dementia, JOURNAL OF ALZHEIMERS DISEASE, Vol: 69, Pages: 83-90, ISSN: 1387-2877
- Author Web Link
- Cite
- Citations: 1
Beyer L, Schnabel J, Kazmierczak P, et al., 2019, Neuronal injury biomarkers for assessment of the individual cognitive reserve in clinically suspected Alzheimer's disease, NEUROIMAGE-CLINICAL, Vol: 24, ISSN: 2213-1582
- Author Web Link
- Cite
- Citations: 13
Brugnolo A, De Carli F, Pagani M, et al., 2019, Head-to-Head Comparison among Semi-Quantification Tools of Brain FDG-PET to Aid the Diagnosis of Prodromal Alzheimer's Disease, JOURNAL OF ALZHEIMERS DISEASE, Vol: 68, Pages: 383-394, ISSN: 1387-2877
- Author Web Link
- Cite
- Citations: 11
Prokopenko I, Miyakawa G, Zheng B, et al., 2019, Alzheimer's disease pathology explains association between dementia with Lewy bodies and APOE-ε4/TOMM40 long poly-T repeat allele variants., Alzheimers & Dementia, Vol: 5, Pages: 814-824, ISSN: 1552-5260
Introduction: The role of TOMM40-APOE 19q13.3 region variants is well documented in Alzheimer's disease (AD) but remains contentious in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). Methods: We dissected genetic profiles within the TOMM40-APOE region in 451 individuals from four European brain banks, including DLB and PDD cases with/without neuropathological evidence of AD-related pathology and healthy controls. Results: TOMM40-L/APOE-ε4 alleles were associated with DLB (OR TOMM40 -L = 3.61; P value = 3.23 × 10-9; OR APOE -ε4 = 3.75; P value = 4.90 × 10-10) and earlier age at onset of DLB (HR TOMM40 -L = 1.33, P value = .031; HR APOE -ε4 = 1.46, P value = .004), but not with PDD. The TOMM40-L/APOE-ε4 effect was most pronounced in DLB individuals with concomitant AD pathology (OR TOMM40 -L = 4.40, P value = 1.15 × 10-6; OR APOE -ε4 = 5.65, P value = 2.97 × 10-8) but was not significant in DLB without AD. Meta-analyses combining all APOE-ε4 data in DLB confirmed our findings (ORDLB = 2.93, P value = 3.78 × 10-99; ORDLB+AD = 5.36, P value = 1.56 × 10-47). Discussion: APOE-ε4/TOMM40-L alleles increase susceptibility and risk of earlier DLB onset, an effect explained by concomitant AD-related pathology. These findings have important implications in future drug discovery and development efforts in DLB.
Grimmer T, Goldhardt O, Yakushev I, et al., 2019, Associations of Neprilysin Activity in CSF with Biomarkers for Alzheimer's Disease, NEURODEGENERATIVE DISEASES, Vol: 19, Pages: 43-50, ISSN: 1660-2854
- Author Web Link
- Cite
- Citations: 6
Beyer L, Schnabel J, Kazmierczak P, et al., 2018, Neuronal Injury Biomarkers for Assessment of Cognitive Reserve in Alzheimer's Disease, 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), Publisher: SPRINGER, Pages: S228-S229, ISSN: 1619-7070
Zhang M, Ferrari R, Tartaglia MC, et al., 2018, A <i>C6orf10/LOC101929163</i> locus is associated with age of onset in <i>C9orf72</i> carriers, BRAIN, Vol: 141, Pages: 2895-2907, ISSN: 0006-8950
- Author Web Link
- Cite
- Citations: 30
Beyer L, Meyer-Wilmes J, Schoenecker S, et al., 2018, Left Temporal Hypometabolism in FDG-PET underlines Cognitive Reserve Hypothesis in Frontotemporal Dementia, 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), Publisher: SPRINGER, Pages: S408-S408, ISSN: 1619-7070
Schulz J, Takousis P, Wohlers I, et al., 2018, Systematic meta-analyses of small RNA profiling studies identify differentially expressed microRNAs in Parkinson's disease, 50th European-Society-of-Human-Genetics (ESHG) Conference, Publisher: NATURE PUBLISHING GROUP, Pages: 409-410, ISSN: 1018-4813
Häckert J, Falkai P, Perneczky R, et al., 2018, [The speechless patient]., MMW Fortschr Med, Vol: 160, Pages: 53-56
Alexopoulos P, Gleixner L-S, Werle L, et al., 2018, Plasma levels of soluble amyloid precursor protein β in symptomatic Alzheimer's disease, EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, Vol: 268, Pages: 519-524, ISSN: 0940-1334
- Author Web Link
- Cite
- Citations: 6
Calsolaro V, Mayers J, Fan Z, et al., 2018, Evaluation of novel astrocyte marker [11C]BU99008 PET in Alzheimer’s disease: a Dementia Platform U.K. experimental medicine study, Alzheimer's and Dementia, Vol: 14, Pages: P842-P843, ISSN: 1552-5260
Fan Z, Calsolaro V, Mayers J, et al., 2018, Relationship between astrocyte activation using [11C]BU99008 PET, glucose metabolism and amyloid in Alzheimer’s disease: a Dementia Platform UK experimental medicine study, Alzheimer's and Dementia, Vol: 14, Pages: P1640-P1640, ISSN: 1552-5260
Beyer L, Meyer-Wilmes J, Schönecker S, et al., 2018, Clinical Routine FDG-PET Imaging of Suspected Progressive Supranuclear Palsy and Corticobasal Degeneration: A Gatekeeper for Subsequent Tau-PET Imaging?, Frontiers in Neurology, Vol: 9, ISSN: 1664-2295
Background: F-18-fluordeoxyglucose positron emission tomography (FDG-PET) is widely used for discriminative diagnosis of tau-positive atypical parkinsonian syndromes (T+APS). This approach now stands to be augmented with more specific tau tracers. Therefore, we retrospectively analyzed a large clinical routine dataset of FDG-PET images for evaluation of the strengths and limitations of stand-alone FDG-PET. Methods: A total of 117 patients (age 68.4 ± 11.1 y) underwent an FDG-PET exam. Patients were followed clinically for a minimum of one year and their final clinical diagnosis was recorded. FDG-PET was rated visually (positive/negative) and categorized as high, moderate or low likelihood of T+APS and other neurodegenerative disorders. We then calculated positive and negative predictive values (PPV/NPV) of FDG-PET readings for the different subgroups relative to their final clinical diagnosis. Results: Suspected diagnoses were confirmed by clinical follow-up (≥1 y) for 62 out of 117 (53%) patients. PPV was excellent when FDG-PET indicated a high likelihood of T+APS in combination with low to moderate likelihood of another neurodegenerative disorder. PPV was distinctly lower when FDG-PET indicated only a moderate likelihood of T+APS or when there was deemed equal likelihood of other neurodegenerative disorder. NPV of FDG-PET with a low likelihood for T+APS was high. Conclusions: FDG-PET has high value in clinical routine evaluation of suspected T+APS, gaining satisfactory differential diagnosis in two thirds of the patients. One third of patients would potentially profit from further evaluation by more specific radioligands, with FDG-PET serving gatekeeper function for the more expensive methods.
Alexopoulos P, Thierjung N, Grimmer T, et al., 2018, Cerebrospinal fluid BACE1 activity and sAβPPβ as biomarker candidates of Alzheimer's Disease, Dementia and Geriatric Cognitive Disorders, Vol: 45, Pages: 152-161, ISSN: 1420-8008
BACKGROUND/AIMS: The utility of β-site amyloid-β precursor protein (AβPP) cleaving enzyme 1 (BACE1) activity and soluble AβPP β (sAβPPβ) levels in cerebrospinal fluid (CSF) in detecting Alzheimer's disease (AD) is still elusive. METHODS: BACE1 activity and sAβPPβ concentration were measured in patients with AD dementia (n = 56) and mild cognitive impairment (MCI) due to AD (n = 76) with abnormal routine AD CSF markers, in patients with MCI with normal CSF markers (n = 39), and in controls without preclinical AD (n = 48). In a subsample with available 18F-fluorodeoxyglucose positron emission tomography (FDG PET) data, ordinal regression models were employed to compare the contribution of BACE1 and sAβPPβ to correct diagnostic classification to that of FDG PET. RESULTS: BACE1 activity was significantly higher in patients with MCI due to AD compared to both controls and patients with MCI with normal CSF markers. sAβPPβ did not differ between any of the studied groups. Interestingly, BACE1 activity was not found to be inferior to FDG PET as predictive covariate in differentiating between the diagnostic groups. CONCLUSIONS: Further studies using biomarker-underpinned diagnoses are warranted to shed more light on the potential diagnostic utility of BACE1 activity as AD biomarker candidate in MCI.
Beyer L, Meyer-Wilmes J, Schonecker S, et al., 2018, Impact of cognitive reserve in frontotemporal dementia illustrated by FDG-PET, Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI), Publisher: SOC NUCLEAR MEDICINE INC, ISSN: 0161-5505
Bonham LW, Karch CM, Fan CC, et al., 2018, CXCR4 involvement in neurodegenerative diseases., Transl Psychiatry, Vol: 8
Neurodegenerative diseases likely share common underlying pathobiology. Although prior work has identified susceptibility loci associated with various dementias, few, if any, studies have systematically evaluated shared genetic risk across several neurodegenerative diseases. Using genome-wide association data from large studies (total n = 82,337 cases and controls), we utilized a previously validated approach to identify genetic overlap and reveal common pathways between progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), Parkinson's disease (PD) and Alzheimer's disease (AD). In addition to the MAPT H1 haplotype, we identified a variant near the chemokine receptor CXCR4 that was jointly associated with increased risk for PSP and PD. Using bioinformatics tools, we found strong physical interactions between CXCR4 and four microglia related genes, namely CXCL12, TLR2, RALB, and CCR5. Evaluating gene expression from post-mortem brain tissue, we found that expression of CXCR4 and microglial genes functionally related to CXCR4 was dysregulated across a number of neurodegenerative diseases. Furthermore, in a mouse model of tauopathy, expression of CXCR4 and functionally associated genes was significantly altered in regions of the mouse brain that accumulate neurofibrillary tangles most robustly. Beyond MAPT, we show dysregulation of CXCR4 expression in PSP, PD, and FTD brains, and mouse models of tau pathology. Our multi-modal findings suggest that abnormal signaling across a 'network' of microglial genes may contribute to neurodegeneration and may have potential implications for clinical trials targeting immune dysfunction in patients with neurodegenerative diseases.
Franzmeier N, Düzel E, Jessen F, et al., 2018, Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease, Brain, Vol: 141, Pages: 1186-1200, ISSN: 1460-2156
Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer's disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer's disease, 55 controls from the Dominantly Inherited Alzheimer's Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer's disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer's disease and cerebrospinal fluid tau levels in sporadic Alzheimer's disease cases. In both autosomal dominant and sporadic Alzheimer's disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer's disease, a significant left frontal cortex connectivity × estimated years of onset
Perneczky R, 2018, Population-based approaches to Alzheimer's disease prevention., Biomarkers for Alzheimer’s Disease Drug Development, Editors: Perneczky, Publisher: Springer, Pages: 15-29
Progress in prevention and treatment of Alzheimer's disease (AD) and dementia is hampered by the restricted understanding of the biological and environmental causes underlying pathophysiology. It is widely accepted that certain genetic factors are associated with AD and a number of lifestyle and other environmental characteristics have also been linked to dementia risk. However, interactions between genes and the environment are not yet well understood, and coordinated global action is required to utilize existing cohorts and other resources effectively and efficiently to identify new avenues for dementia prevention. This chapter provides a brief summary of current research on risk and protective factors and opportunities and challenges in relation to population-based approaches are discussed.
Skrobot OA, Black SE, Chen C, et al., 2018, Progress toward standardized diagnosis of vascular cognitive impairment: Guidelines from the Vascular Impairment of Cognition Classification Consensus Study, ALZHEIMERS & DEMENTIA, Vol: 14, Pages: 280-292, ISSN: 1552-5260
- Author Web Link
- Cite
- Citations: 171
Broce I, Karch CM, Wen N, et al., 2018, Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies., PLoS Med, Vol: 15
BACKGROUND: Converging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD). Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed. METHODS AND FINDINGS: Using large genome-wide association studies (GWASs) (total n = 192,886 cases and controls) and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with FTD-related disorders-namely, FTD, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS)-and 1 or more immune-mediated diseases including Crohn disease, ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), and psoriasis. We found up to 270-fold genetic enrichment between FTD and RA, up to 160-fold genetic enrichment between FTD and UC, up to 180-fold genetic enrichment between FTD and T1D, and up to 175-fold genetic enrichment between FTD and CeD. In contrast, for CBD and PSP, only 1 of the 6 immune-mediated diseases produced genetic enrichment comparable to that seen for FTD, with up to 150-fold genetic enrichment between CBD and CeD and up to 180-fold enrichment between PSP and RA. Further, we found minimal enrichment between ALS and the immune-mediated diseases tested, with the highest levels of enrichment between ALS and RA (up to 20-fold). For FTD, at a conjunction false discovery rate < 0.05 and after excluding SNPs in linkage disequilibrium, we found that 8 of the 15 identified loci mapped to the human leukocyte antigen (HLA) region on Chromosome (Chr) 6. We also found novel candidate FTD susceptibility loci within LRRK2 (leucine rich repeat kinase 2), TBKBP1 (TBK1 binding protein 1), and PGBD5
Perneczky R, Alexopoulos P, 2018, Soluble Amyloid Precursor Proteins in Blood: Methods and Challenges, BIOMARKERS FOR PRECLINICAL ALZHEIMER'S DISEASE, Editors: Perneczky, Publisher: HUMANA PRESS INC, Pages: 179-187, ISBN: 978-1-4939-7673-7
- Author Web Link
- Cite
- Citations: 1
Perneczky R, 2018, Biomarkers for Preclinical Alzheimer's Disease Preface, BIOMARKERS FOR PRECLINICAL ALZHEIMER'S DISEASE, Editors: Perneczky, Publisher: HUMANA PRESS INC, Pages: VII-VII, ISBN: 978-1-4939-7673-7
Perneczky R, 2018, Biomarkers for Alzheimer's Disease Drug Development Preface, BIOMARKERS FOR ALZHEIMER'S DISEASE DRUG DEVELOPMENT, Editors: Perneczky, Publisher: HUMANA PRESS INC, Pages: V-V, ISBN: 978-1-4939-7703-1
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.