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Early stages of neurodegenerative diseases and their diagnosis using experimental cognitive tests with a specific focus on spatial cognition
Laczó, Martina ; Laczó, Jan (advisor) ; Telenský, Petr (referee) ; Hocko Fajnerová, Iveta (referee)
Early stages of neurodegenerative diseases and their diagnosis using experimental cognitive tests with a specific focus on spatial navigation Abstract This dissertation thesis is focused on early and differential diagnosis of Alzheimer's disease (AD) using experimental cognitive tests. AD starts as a preclinical stage, progresses to the mild cognitive impairment (MCI) and eventually to the dementia stage. It is crucial to diagnose AD very early to slow down its progression. However, the use of specific AD biomarkers, such as amyloid and tau positron emission tomography and cerebrospinal fluid (CSF) biomarkers, is very limited. Experimental spatial navigation and spatial pattern separation tests, unlike conventional cognitive tests, may have a strong diagnostic potential as they depend on brain regions affected early in AD. The first study in a virtual environment showed preference for word-centered navigation in cognitively normal older adults, while participants with early AD preferred body- centered strategy to compensate for neurodegeneration. Using a virtual navigation test, the second study showed different profiles of navigation impairment in MCI participants with AD and other (i.e., non-AD) etiologies and demonstrated that navigation assessment differentiated AD from non-AD participants. Various...
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Diagnostic markers in patients in early stage of multiple sclerosis
Hynčicová, Eva ; Laczó, Jan (advisor) ; Horáček, Jiří (referee) ; Taláb, Radomír (referee)
The aims of the thesis were to assess diagnostic markers for monitoring of the disease progression in patients with clinically isolated syndrome (CIS) and laboratory markers of efficacy of the interferon beta (IFNß) therapy. This thesis includes 4 studies. The first study was focused on evaluation of cognitive impairment and its structural correlates in patients with CIS. Using comprehensive neuropsychological testing and brain magnetic resonance imaging (MRI) with volumetric analyses we found cognitive impairment in 18-37 % of CIS patients in almost all cognitive domains. Brain volume was reduced predominantly in fronto- temporal regions and the thalamus. Next, visuo-spatial impairment was associated with lower white matter volume in patients with CIS. The two other studies evaluated neuropsychiatric symptoms, life satisfaction, health-related quality of life and their mutual relationships. In addition, one of these two studies evaluated structural correlates of neuropsychiatric symptoms on brain MRI. Using a battery of specific questionnaires, we demonstrated depressive symptoms and anxiety in patients with CIS, lower life satisfaction, lower health-related quality of life and close mutual relationships. The quality of life was associated more with cognitive functioning than with disability in...
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Early diagnostic of mnestic disorders in neurodegenerative diseases
Laczó, Jan ; Bojar, Martin (advisor) ; Jirák, Roman (referee) ; Mareš, Jan (referee) ; Rektorová, Irena (referee)
The ageing of the world's population means that the number of people with dementia, especially Alzheimer's disease (AD), will dramatically increase. That's why there is now a great effort to detect the presence of AD in its earliest predementia stages, in the stage of mild cognitive impairment (MCI), and particularly to identify individuals with amnestic syndrome of the hippocampal type (Ha-MCI - preclinical AD). The aim of our studies was to reveal whether spatial navigation testing could serve as an early biomarker of AD - whether spatial navigation is impaired early in patients with MCI, especially in Ha-MCI patients. We used the human analogue of the Morris water maze, the Hidden Goal Task (HGT), which is designed t! o separate two different modes of navigation, egocentric (body- centred, hippocampus independent) and allocentric (world-centred, hippocampus dependent), using a real space navigation setting called the Blue Velvet Arena (BVA), fully enclosed cylindrical arena, as well as a computer version of the BVA. Our results suggest that spatial navigation is impaired already in patients with amnestic MCI, who are more likely to progress to AD, especially in those with amnestic syndrome of the hippocampal type. The Ha-MCI patients presented severe spatial navigation impairment similar to that seen in...
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The Utility of Spatial Navigation and Metabolic Biomarkers in Early and Differential Diagnosis of Neurodegenerative Diseases
Cerman, Jiří ; Laczó, Jan (advisor) ; Roth, Jan (referee) ; Kopeček, Miloslav (referee)
Alzheimer's disease (AD) is the most common neurodegenerative disease leading to dementia and represents a significant socio-economic problem. Currently, only symptomatic treatment of AD is possible and the development of new causal therapy faces a number of difficulties, which are inter alia related to identifying early stages and the possibilities of differential diagnosis of specific neurodegenerative diseases. Therefore, in recent years, methods that are easily available and able to reliably identify individuals at risk of developing AD already at preclinical and prodromal stages are of particular interest. The work presents a basic overview of the current knowledge about neurodegenerative diseases and especially AD and extends the knowledge in this area. The main goals of the thesis are to map out the potential contribution of spatial navigation testing as a new experimental method, which is suitable for early diagnosis and differential diagnosis of advanced stages of neurodegenerative diseases, and to evaluate the benefits of metabolic biomarker testing in clinical practice. In the early stages of neurodegenerative diseases, the work focuses primarily on the evaluation of impairment of a specific type of spatial navigation - path integration in patients with AD and also on subjective spatial...
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Sensory and sensitive dysfunctions in neurodegenerative disorders of the basal ganglia.
Kopal, Aleš ; Roth, Jan (advisor) ; Baláž, Marek (referee) ; Laczó, Jan (referee)
Complex functions of the basal ganglia are affected by numerous sensory and sensitive stimuli. In our studies, we investigated parameters of sense of smell and vision in neurodegenerative diseases of the basal ganglia - Parkinson's disease (PD) and Huntington's disease (HD). In the first study, we use Odourized Markers Test (OMT) to determine its applicability in PD patients, and to determine whether it distinguishes olfactory disorders between neurodegenerative and other disorders. Results show that OMT is applicable for PD patients and comparable to Sniffin' Sticks as it demonstrates gains of lower scores in PD patients compared to healthy subjects, but they do not differentiate other etiology of olfactory disorders. In the next study, we tested the pleasantness of odor stimulants in PD patients using New test of odor pleasantness (NTOP). We investigated suitability and validity of its use. We found that PD patients had lower odor rating score compared to healthy group correlated with Sniffin' Sticks and OMT. In the following study, we examined whether PD patients with visual hallucinations (PDH+) have structural retinal changes measured by optical coherence tomography (OCT) and functional retinal changes examined by 2,5% contrast sensitivity test compared to PD patients without hallucinations...
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The Utility of Spatial Navigation and Metabolic Biomarkers in Early and Differential Diagnosis of Neurodegenerative Diseases
Cerman, Jiří ; Laczó, Jan (advisor) ; Roth, Jan (referee) ; Kopeček, Miloslav (referee)
Alzheimer's disease (AD) is the most common neurodegenerative disease leading to dementia and represents a significant socio-economic problem. Currently, only symptomatic treatment of AD is possible and the development of new causal therapy faces a number of difficulties, which are inter alia related to identifying early stages and the possibilities of differential diagnosis of specific neurodegenerative diseases. Therefore, in recent years, methods that are easily available and able to reliably identify individuals at risk of developing AD already at preclinical and prodromal stages are of particular interest. The work presents a basic overview of the current knowledge about neurodegenerative diseases and especially AD and extends the knowledge in this area. The main goals of the thesis are to map out the potential contribution of spatial navigation testing as a new experimental method, which is suitable for early diagnosis and differential diagnosis of advanced stages of neurodegenerative diseases, and to evaluate the benefits of metabolic biomarker testing in clinical practice. In the early stages of neurodegenerative diseases, the work focuses primarily on the evaluation of impairment of a specific type of spatial navigation - path integration in patients with AD and also on subjective spatial...
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Diagnostic markers in patients in early stage of multiple sclerosis
Hynčicová, Eva ; Laczó, Jan (advisor) ; Horáček, Jiří (referee) ; Taláb, Radomír (referee)
The aims of the thesis were to assess diagnostic markers for monitoring of the disease progression in patients with clinically isolated syndrome (CIS) and laboratory markers of efficacy of the interferon beta (IFNß) therapy. This thesis includes 4 studies. The first study was focused on evaluation of cognitive impairment and its structural correlates in patients with CIS. Using comprehensive neuropsychological testing and brain magnetic resonance imaging (MRI) with volumetric analyses we found cognitive impairment in 18-37 % of CIS patients in almost all cognitive domains. Brain volume was reduced predominantly in fronto- temporal regions and the thalamus. Next, visuo-spatial impairment was associated with lower white matter volume in patients with CIS. The two other studies evaluated neuropsychiatric symptoms, life satisfaction, health-related quality of life and their mutual relationships. In addition, one of these two studies evaluated structural correlates of neuropsychiatric symptoms on brain MRI. Using a battery of specific questionnaires, we demonstrated depressive symptoms and anxiety in patients with CIS, lower life satisfaction, lower health-related quality of life and close mutual relationships. The quality of life was associated more with cognitive functioning than with disability in...
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Immunosuppression in active multiple sclerosis: combination treatment with interferon beta and azathioprine and fingolimod monotherapy
Tichá, Veronika ; Kubala Havrdová, Eva (advisor) ; Vymazal, Josef (referee) ; Laczó, Jan (referee)
Introduction: Addition of a second drug used to be a strategy to achieve clinical stabilization of multiple sclerosis in many patients with on-going activity despite monotherapy. Modern immunosuppressive drugs used in monotherapy exert more specific mode of action. Methods: This retrospective observational study evaluated 5-year data from 85 patients with active multiple sclerosis despite monotherapy with either interferon beta or azathioprine, who received add-on azathioprine or interferon beta, respectively. In a subgroup of 23 patients 10- year data were analysed. In a second part of the study, a group of 126 patients switched either from interferon beta or glatiramer acetate to fingolimod was followed-up for one after the change of their treatment and a in a subgroup of 53 patients the 2-year data were assessed. Clinical (relapse frequency, disability) parameters were compared preceding and following the addition of second drug or the switch of treatment. Laboratory results and potential serious adverse events were evaluated in a group of patients with combination therapy. Results: The add-on treatment triggered a drop in annualised relapse rate by approximately 1.5 points sustained over 5 and 10 years. No effect on disability was observed. Simultaneously, white blood cell and lymphocyte counts...
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Early diagnostic of mnestic disorders in neurodegenerative diseases
Laczó, Jan ; Bojar, Martin (advisor) ; Jirák, Roman (referee) ; Mareš, Jan (referee) ; Rektorová, Irena (referee)
The ageing of the world's population means that the number of people with dementia, especially Alzheimer's disease (AD), will dramatically increase. That's why there is now a great effort to detect the presence of AD in its earliest predementia stages, in the stage of mild cognitive impairment (MCI), and particularly to identify individuals with amnestic syndrome of the hippocampal type (Ha-MCI - preclinical AD). The aim of our studies was to reveal whether spatial navigation testing could serve as an early biomarker of AD - whether spatial navigation is impaired early in patients with MCI, especially in Ha-MCI patients. We used the human analogue of the Morris water maze, the Hidden Goal Task (HGT), which is designed t! o separate two different modes of navigation, egocentric (body- centred, hippocampus independent) and allocentric (world-centred, hippocampus dependent), using a real space navigation setting called the Blue Velvet Arena (BVA), fully enclosed cylindrical arena, as well as a computer version of the BVA. Our results suggest that spatial navigation is impaired already in patients with amnestic MCI, who are more likely to progress to AD, especially in those with amnestic syndrome of the hippocampal type. The Ha-MCI patients presented severe spatial navigation impairment similar to that seen in...
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