|
|
The effect of amyloid beta on viability of selected neuropathogens: challenging the infectious hypothesis of Alzheimer disease
Vosála, Ondřej ; Macháček, Tomáš (advisor) ; Černý, Jan (referee)
Alzheimer's disease is the leading cause of dementia worldwide, affecting millions of individuals. Researchers have identified amyloid beta (A ) as the primary agent responsible for neuropathogenicity, but the factors triggering its overproduction remain uncertain. An relatively new theory, known as the infectious hypothesis, sheds light on this phenomenon by associating the excess production of A with its potential role as an antimicrobial peptide-an element of the innate immune response against neuroinfections. This hypothesis posits a transition from acute physiological overproduction during neuroinfection to a chronically dysregulated and pathological process targeting both pathogens and neural tissue. So far, experimental evidence supporting this theory has been primarily obtained through studies involving viruses or bacteria. Aim of this study was to investigate the role of multicellular pathogens in stimulating A overproduction and, on the other hand, A role in elimination of such infections. Toxocara canis was chosen as a main model of neuropathogenic parasite. Although successful infections were achieved in BALB/c mice, there was no observable increase in A production even after 16 weeks of infection. To further challenge the survivability of Toxocara larvae in increased A concentration in...
|
|
|
Mitophagy biomarkers in the continuum of Alzheimer's disease
Katonová, Alžbeta ; Veverová, Kateřina (advisor) ; Bohačiaková, Dáša (referee)
The findings of recent years have shown that impaired mitophagy is involved in the pathophysiology of Alzheimer's disease (AD) and other neurodegenerative diseases. Studies on brain biopsies of AD patients, cellular and animal models of AD show that age-dependent decline in mitophagy is a significant contributor to AD pathology, and that the levels of mitophagy proteins are altered. However, whether these changes are reflected in the biofluids of individuals with AD, and whether mitophagy proteins could be potential biomarkers of AD, is unknown.The aim of the diploma thesis was to compare the level of mitophagy markers in blood serum and cerebrospinal fluid (CSF) of patients in various stages of AD with cognitively healthy controls (CU) and determine its relationship to the degree of cognitive impairment and standard Alzheimer's biomarkers (amyloid beta (Ab42), total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau181)). We have shown that mitophagy is impaired in individuals with AD, manifested by increased levels of PINK1 and BNIP3L (activators of mitophagy) and decreased levels of TFEB (master regulator of lysosomal biogenesis) compared to CU. Moreover, these changes were associated with more advanced AD pathology, manifested by increased AD biomarker positivity and cognitive...
|
|
|
Perception of dementia by professional carers
Osúchová, Veronika ; Hasmanová Marhánková, Jaroslava (advisor) ; Numerato, Dino (referee)
This diploma thesis is focused on professional carers, who are trained experts employed in specialised institutions that take care about more than one person with dementia in one group. The professional carers are under pressure during this time and there is a certain tension between reaching the maximal possible high quality care and growing number of clients in institutions specialised in dementia and dementia discourse, in which framework especially negative connotations are highlighted. It is just an approach of the carers that plays an important role in this issue. The work with dementia discourse and dealing with the above mentioned issue from the side of carers has a considerable impact on functioning, health condition and quality of life of individuals with dementia. Their dealing with the issue can influence strongly and steer the running an institution and the quality of life of such an institution clients. A difficult situation of professional carers also influences the carers themselves, their concepts of this illness and concepts of their own ageing. This diploma thesis is aimed at an analysis how the pictures of dementia are constructed by professional carers who take care about clients with various forms of dementia in the long term. In the framework of this thesis, their subjective...
|
|
|
Communication disorders of people with Alzheimer's disease
Bláhová, Natálie ; Korandová, Zuzana (advisor) ; Horynová, Jana (referee)
The topic of the thesis Communication disorders of people with Alzhiemer's disease is focused on the analysis of the manifestations of impaired communication ability of people with Alzheimer's disease. The bachelor thesis is divided into theoretical and practical part. The theoretical part consists of two chapters. In the firts chapter, entitled Theoretical Background, the term communication is discussed, as well as the concept of dementia. Other subsections discuss cognitive-communication disorders and manifestiations of impaired communication ability of people with dementia. Speech and language process deficits in individual language levels are also listed here. The second chapter deals with neurodegenerative disease. It is followed by a subchapter related to Alzheimer's disease and subsequently clarifies the topic of the burden placed on family caregivers. The practical part presents an analysis of a research investigation that was carried out in the Clementas home for the elderly in Janovice nad Úhlavou. A presentation of the Clementas Center is also included in the bachelor's thesis. The research sample consisted of tree clients of this home. The practical part was based on observing the participants, using indicative diagnostic tools and the clients' health documentation. Furthermore, the...
|
|
|
Neuropsychiatric and cognitive aspects of early stages of Alzheimer's disease and other neurodegenerative disorders in late-life
Matušková, Veronika ; Vyhnálek, Martin (advisor) ; Kopeček, Miloslav (referee) ; Mitterová, Kristína (referee)
Neuropsychiatric and cognitive aspects of early stages of Alzheimer's disease and other neurodegenerative disorders in late-life Abstract The early diagnosis of Alzheimer's disease (AD) is currently focused on the stages preceding the dementia syndrome, i.e. the preclinical stage and the mild cognitive impairment (MCI) stage. However, the detection of AD using specific biomarkers of beta amyloid and tau protein is limited in clinical practice and often costly or invasive. Therefore, the detection of early clinical signs of AD continues to be invaluable. The aim of this dissertation is to contribute to the early diagnosis of AD by examining specific cognitive markers as well as neuropsychiatric symptoms (NPS), which have so far received little research and clinical attention. The first study introduces criteria for what is termed mild behavioral impairment (MBI), a syndrome analogous to mild cognitive impairment (MCI) describing new-onset and persistent NPS in older adults, and maps MBI symptoms across the cognitive spectrum with the Mild Behavioral Impairment Checklist (MBI-C), translated and adapted in this study. The second study shows that the severity of MBI-C symptoms, particularly impulse dyscontrol and decreased motivation in non-demented older adults, is associated with lower volume or thickness of...
|
|
|
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...
|
|
|
Comparison of outreach social and health care services for people with dementia in the Czech Republic and the Netherlands
Rooijakkers, Jitka ; Povolná, Pavla (advisor) ; Mertl, Jiří (referee)
The master thesis deals with the quality of care provided to people with dementia and their informal carers. The aim is to compare health care and social services for this group of patients in two countries - the Czech Republic and the Netherlands. The first part defines the dementia syndrome, its diagnosis, symptoms, treatment and management of dementia. This is followed by the topic of palliative and hospice care and euthanasia The thesis also includes the concept of long-term care, which is purposely limited in this thesis to only that part which is provided either by a health service provider or by a social service in the patient's/service user's home environment. The next section refers to laws, regulations and policy documents that relate to the topic of care for people with dementia. The last part of the theoretical definition of this thesis describes the health and social service system in the Netherlands, including reference to strategic documents that shape the care of people with dementia and their informal carers. The empirical part includes the elaboration and analysis of qualitative research, which I conducted through interviews directly with informal carers.
|
|
|
Advanced neuroimaging methods and their use in evaluation of structural changes of the brain and their cognitive correlates in early diagnosis of neurodegenerative disorders
Lerch, Ondřej ; Hort, Jakub (advisor) ; Rusina, Robert (referee) ; Dušek, Petr (referee)
Advanced neuroimaging methods and their use in evaluation of structural changes of the brain and their cognitive correlates in early diagnosis of neurodegenerative disorders Abstract Neurodegenerative diseases are a heterogeneous group of diseases characterized by the loss of specific neuronal populations caused by the deposition of pathologically altered proteins into the brain tissue. The structural corelate of these pathological changes is a brain atrophy. The most common neurodegenerative disease is Alzheimer's disease (AN). The cholinergic deficit, caused by atrophy of the basal telencephalon (BF), and atrophy of the medial temporal lobe (MTL) are among the hallmarks of AN. Recent advances in imaging methods and image processing techniques have made it possible to measure atrophy at the level of substructures. The aim of this dissertation was to evaluate the potential utility of imaging methods in the assessment of structural changes and their cognitive correlates in the early diagnosis of neurodegeneration, in particular to evaluate the utility of segmentation of the BF nuclei and MTL substructures in the early and differential diagnosis of AN, their mutual relationships and cognitive correlates. We confirmed that differences in atrophy of individual BF and MTL substructures may be utilized in the...
|
|
|
Biofluid biomarkers of Alzheimer's disease and Lewy body disease and their relationship with cognitive and structural markers
Jurášová, Vanesa ; Veverová, Kateřina (advisor) ; Chmátalová, Zuzana (referee)
The diagnosis of Alzheimer's disease is based on the determination of specific proteins in cerebrospinal fluid (CSF) or their imaging using positron emission tomography. Both methods are invasive and can expose the patient to risk and discomfort. Blood biomarkers, therefore, represent hope for early diagnosis and monitoring of individuals at increased risk of developing Alzheimer's disease. The diploma thesis aimed to determine biomarkers in blood using the ultrasensitive Simoa TM (Single molecular assay) technology and to verify their relationship to the values in CSF. The second aim was to track the relationship between blood biomarkers and cognitive markers of Alzheimer's disease. We demonstrated a positive relationship between serum, plasma, and CSF p-tau 181 concentrations. A negative correlation was observed between the concentrations of p-tau 181 in blood and the results of the MMSE test, which is considered a standard cognitive assessment tool. These findings suggest that plasma and serum p-tau 181 may greatly help the clinical identification of neurodegenerative diseases in primary care. The negative correlation of plasma and serum p-tau 181 with MMSE test results suggests that blood p-tau 181 could be used in population-based studies to detect individuals at high risk of developing...
|
|
|
LC-MS/MS study of phase one in vitro biotransformation of potential drugs against Alzheimer's disease
Kuřátková, Aneta ; Kučera, Radim (advisor) ; Váňová, Nela (referee)
No treatment that would completely stop the progression of Alzheimer's disease has not been found yet. Recently used tacrine showed good results in the treatment of Alzheimer's disease, however long-term use led to chronic hepatotoxicity due to its metabolites. This master thesis deals with the compound 7-phenoxytacrine, one of the promising tacrine derivatives, which is one of the candidates for potential use in the therapy of Alzheimer's disease. Due to the formation of hepatotoxic metabolites of tacrine after the biotransformation in human liver, it appears necessary to identify the emerging metabolites of 7-phenoxytacrine molecule. Within this master's thesis in vitro biotransformation study of 7-phenoxytacrine using human liver microsomes was performed. High performance liquid chromatography with tandem mass spectrometry was used to determine the parent substance and the seventeen 7-phenoxytacrine metabolites. The analytical method showed the formation of six monohydroxylated and eleven dehydroxylated metabolites of 7-phenoxytacrine. Thus, we concluded that hydroxylation is the major metabolic reaction after in vitro microsomal biotransformation. In addition to the identification of metabolites, a quantification and microsomal stability study, including the determination of the amount of...
|
guest ::
