Your search for: 'author:("Hortobágyi, Tibor")' has returned 5 results. (0.015s) Save search

Authors: Görlach, Christoph | Hortobágyi, Tibor | Hortobágyi, Szabolcs | Benyó, Zoltán

Article Type: Research Article

Abstract: Purpose: The aim of the present study was to assess the effects of neuronal nitric oxide synthase (NOS I) inhibitors and a combination of NOS I and NOS II inhibitors on lesion volume after experimental brain injury. Methods: Cold lesion of the brain was induced by application of a precooled (.... 78 °C) copper cylinder to the intact dura of the rat for 6 s. Brains were removed 24 h after the injury and lesion volume determined using the triphenyltetrazolium-chloride method. Results: The specific NOS I inhibitor 3-bromo-7-nitroindazole (Br-7-NI) reduced lesion volume significantly by 21 % compared with the vehicle …control. In contrast, 7-nitroindazole had no effect on lesion volume. When aminoguanidine, a specific NOS II inhibitor, was adminis-tered after Br-7-NI, lesion volume was significantly reduced but not significantly more than with either compound alone. Conclusion: Brain injury after cold lesion is partly mediated by NOS I activity and can be attenuated successfully with Br-7-NI, while coin-hibition of NOS II does not improve the outcome significantly. Show more

Keywords: Nitric oxide synthase, NOS I, NOS II, 3-bromo-7-nitroindazole, 7-nitroindazole, aminoguanidine, cold brain injury, rat

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 2-3, pp. 71-76, 2000

Authors: Skogseth, Ragnhild | Hortobágyi, Tibor | Soennesyn, Hogne | Chwiszczuk, Luiza | Ffytche, Dominic | Rongve, Arvid | Ballard, Clive | Aarsland, Dag

Article Type: Research Article

Abstract: Background: The first consensus criteria for dementia with Lewy bodies (DLB) published in 1996 were revised in 2005, partly because the original clinical criteria had suboptimal sensitivity. Few studies have assessed the accuracy of the 2005 criteria applied prospectively in newly diagnosed patients who have been followed longitudinally. Objective: To explore the correlation between clinical and pathological diagnoses in patients with DLB and Parkinson’s disease with dementia (PDD). Methods: From a prospective referral cohort study with enriched recruitment of patients with DLB and PDD, we included the first 56 patients coming to autopsy. Patients had mild dementia at inclusion and …were followed annually until death with standardized clinical assessments. Pathological assessment was performed blind to clinical information according to standardized protocols and consensus criteria for DLB. Results: 20 patients received a pathological diagnosis of Lewy body disease; the corresponding clinical diagnoses were probable DLB (n  = 11), PDD (n  = 5), probable (n  = 2) or possible (n  = 2) Alzheimer’s disease (AD). Of 14 patients with a clinical diagnosis of probable DLB, 11 had DLB/PDD and 3 had AD at pathology. One patient with clinically possible DLB fulfilled criteria for pathological AD. Sensitivity, specificity, positive predictive value, and negative predictive values for probable DLB were 73%, 93%, 79%, and 90%. Conclusion: Our findings suggest that the international clinical consensus criteria for DLB perform reasonably well. However, false positive and false negative diagnoses still occur, indicating that the criteria need to be improved, that biomarkers may be needed, and that neuropathological feedback is vital to improve accuracy. Show more

Keywords: Autopsy, dementia, diagnosis, Lewy body disease, neuropathology, Parkinson’s disease

DOI: 10.3233/JAD-170274

Citation: Journal of Alzheimer's Disease, vol. 59, no. 4, pp. 1139-1152, 2017

Authors: Giil, Lasse Melvaer | Solvang, Stein-Erik Hafstad | Giil, Malin Melvaer | Hellton, Kristoffer H. | Skogseth, Ragnhild Eide | Vik-Mo, Audun Osland | Hortobágyi, Tibor | Aarsland, Dag | Nordrehaug, Jan Erik

Article Type: Research Article

Abstract: Background: Epidemiological studies link serum potassium (K+ ) to cognitive performance, but whether cognitive prognosis in dementia is related to K+ levels is unknown. Objective: To determine if K+ levels predict cognitive prognosis in dementia and if this varies according to diagnosis or neuropathological findings. Methods: This longitudinal cohort study recruited 183 patients with mild Alzheimer’s disease or Lewy body dementia (LBD). Serum K+ and eGFR were measured at baseline and medications which could affect K+ registered. The Mini-Mental State Examination (MMSE) was measured annually over 5 years, and mortality registered. Association between K+ and √(30 -MMSE) was estimated overall, …and according to diagnosis (joint model). Associations between MMSE-decline and K+ were assessed in two subgroups with neuropathological examination (linear regression) or repeated measurements of K+ over 3 years (mixed model). Results: Serum K+ at baseline was associated with more errors on MMSE over time (Estimate 0.18, p  = 0.003), more so in LBD (p  = 0.048). The overall association and LBD interaction were only significant in the 122 patients not using K+ relevant medication. Repeated K+ measures indicated that the association with MMSE errors over time was due to a between-person effect (p  < 0.05, n  = 57). The association between the annual MMSE decline was stronger in patients with autopsy confirmed LBD and more α -synuclein pathology (all: p  < 0.05, n  = 41). Conclusion: Higher serum K+ predicts poorer cognitive prognosis in demented patients not using medications which affect K+ , likely a between-person effect seen mainly in LBD. Show more

Keywords: α-synuclein, Alzheimer’s disease, cognitive decline, kalium, Lewy body dementia, Mini-Mental State Examination, MMSE-decline, potassium, prognosis

DOI: 10.3233/JAD-181131

Citation: Journal of Alzheimer's Disease, vol. 68, no. 1, pp. 239-253, 2019

Authors: Alghamdi, Amani | Vallortigara, Julie | Howlett, David R. | Broadstock, Martin | Hortobágyi, Tibor | Ballard, Clive | Thomas, Alan J. | O’Brien, John T. | Aarsland, Dag | Attems, Johannes | Francis, Paul T. | Whitfield, David R.

Article Type: Research Article

Abstract: Lewy body dementia is the second most common neurodegenerative dementia and is pathologically characterized by α-synuclein positive cytoplasmic inclusions, with varying amounts of amyloid-β (Aβ) and hyperphosphorylated tau (tau) aggregates in addition to synaptic loss. A dysfunctional ubiquitin proteasome system (UPS), the major proteolytic pathway responsible for the clearance of short lived proteins, may be a mediating factor of disease progression and of the development of α-synuclein aggregates. In the present study, protein expression of a key component of the UPS, the RPT6 subunit of the 19S regulatory complex was determined. Furthermore, the main proteolytic-like (chymotrypsin- and PGPH-) activities have …also been analyzed. The middle frontal (Brodmann, BA9), inferior parietal (BA40), and anterior cingulate (BA24) gyrus’ cortex were selected as regions of interest from Parkinson’s disease dementia (PDD, n  = 31), dementia with Lewy bodies (DLB, n  = 44), Alzheimer’s disease (AD, n  = 16), and control (n  = 24) brains. Clinical and pathological data available included the MMSE score. DLB, PDD, and AD were characterized by significant reductions of RPT6 (one-way ANOVA, p  < 0.001; Bonferroni post hoc test) in prefrontal cortex and parietal cortex compared with controls. Strong associations were observed between RPT6 levels in prefrontal, parietal cortex, and anterior cingulate gyrus and cognitive impairment (p  = 0.001, p  = 0.001, and p  = 0.008, respectively). These findings highlight the involvement of the UPS in Lewy body dementia and indicate that targeting the UPS may have the potential to slow down or reduce the progression of cognitive impairment in DLB and PDD. Show more

Keywords: Alzheimer’s disease, amyloid-beta, cognitive impairment, dementia with Lewy bodies, Parkinson’s disease with dementia, RPT6, tau, ubiquitin proteasome system

DOI: 10.3233/JAD-160946

Citation: Journal of Alzheimer's Disease, vol. 57, no. 2, pp. 373-386, 2017

Authors: Vallortigara, Julie | Whitfield, David | Quelch, William | Alghamdi, Amani | Howlett, David | Hortobágyi, Tibor | Johnson, Mary | Attems, Johannes | O’Brien, John T. | Thomas, Alan | Ballard, Clive G. | Aarsland, Dag | Francis, Paul T.

Article Type: Research Article

Abstract: Alpha-synuclein (α -syn) aggregations are the key pathological hallmark of dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), but are also frequently present in Alzheimer’s disease (AD). Much remains unknown about the role of α -syn in the synapse and the wider role of synaptic dysfunction in these dementias. Changes in concentrations of key ‘SNAP (Soluble N-ethylmaleimide Sensitive Factor Attachment Protein) Receptor’ (SNARE) proteins as a consequence of alterations in the aggregation state of α -syn may contribute to synaptic dysfunction in patients with DLB, PDD, and AD and result in impaired cognition. We have studied a large …cohort (n  = 130) of autopsy confirmed DLB, PDD, AD, and control brains. Using semi-quantitative western blotting, we have demonstrated significant changes across the diagnostic groups of DLB, PDD, and AD in the SNARE and vesicle proteins syntaxin, Munc18, VAMP2, and monomeric α -syn in the prefrontal cortex, with a significant reduction of Munc18 in AD patients (p  <  0.001). This correlated to the final MMSE score before death (p  = 0.016). We also identified a significant negative correlation between the duration of dementia and the levels of the binding partners VAMP2 (p  = 0.0004) and monomeric α -syn (p  = 0.0002). Our findings may indicate that an upregulation of SNARE complex related proteins occurs in the early stages of disease as an attempt at compensating for failing synapses, prior to widespread deposition of pathological α -syn. Show more

Keywords: Alpha-synuclein, Alzheimer’s disease, dementia with lewy bodies, munc18, Parkinson’s disease dementia, SNARE process, synaptic dysfunction, VAMP2

DOI: 10.3233/JAD-150707

Citation: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 101-110, 2016