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Associations of morphometric and metabolic biomarkers with cognitive impairment in Alzheimer's disease and Lewy body dementias
Nedelská, Zuzana ; Hort, Jakub (advisor) ; Nevrlý, Martin (referee) ; Dušek, Petr (referee)
Associations of morphometric and metabolic biomarkers with cognitive impairment in Alzheimer's disease and Lewy body dementias Abstract Dementia has become one of the major health care and socio-economic challenges. Alzheimer's disease (AD) is the most common dementia whereas dementia with Lewy bodies (DLB) is the second most common neurodegenerative after AD. However, both dementias exist in a quite heterogeneous contiua that can overlap with each other. Approaches that allow for the identification of individuals at risk of developing AD in preclinical or prodromal stages are of major interest to apply the symptomatic and newly introduced biological therapies and non- pharmacological interventions that are more effective early on. Similar efforts are undertaken in the DLB field although no causal treatment for DLB is available yet. A prerequisite for an efficacious and targeted intervention is a selection of individuals who would benefit the most from this intervention. This process includes the timely and accurate diagnosis, differential diagnosis, prognostication, and management of treatable comorbidities. This dissertation has two parts. Part one is an overview of AD and DLB. The second part summarizes author's research work. The main research aims corroborated in this thesis are three-fold: First, to...
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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...
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Early diagnosis of memory disorders in neurodegenerative disease
Kadlecová, Alexandra ; Hort, Jakub (advisor) ; Stuchlík, Aleš (referee) ; Vymazal, Josef (referee)
lncreased incidence and prevalence of dementi a syndrome is related to ageing of the population. The most common cause of dementia is Alzheimer disease (AD), which represents serious health, social and economical burden to the society. Current diagnostic criteria and research of AD tend to make a diagnosis of AD at the earliest stages or the disease, when the likelihood to influence the course ofthe disease is the highest and extension of the period with high quality of life can be expected. AD begins by impairment or mediotemporal structures - amygdala and hippocampus. Atrophy in these critical brain structures is well detectable before the onset of dementia syndrome and can be manifested by Hrst clinical symptoms. Presented PhD thesis deals with detection of these early signs of AD - spatial disorientation, emotional agnosia and behavioural disturbances or patients with mild cognitive impairrnent, the condition understood as prodromal stage of AD. Powered by TCPDF (www.tcpdf.org)
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Neurosonological markers of cognitive decline progression in patients with dementia
Soukupová Urbanová, Barbora ; Hort, Jakub (advisor) ; Školoudík, David (referee) ; Horáček, Jiří (referee)
Alzheimer's disease represents an important socio-economic problem worldwide. Its complex and not entirely clear pathophysiological mechanisms are subject of intensive research with the aim to identify the affected individuals very soon in the disease process and to find efficacious prevention or treatment. According to recent knowledge, a multifactorial microangiopathy plays a role in the disease development. Probably both traditional vascular risk factors as well as mechanisms linked to neurodegeneration with amyloid accumulation are the factors involved. This work presents a summary of up to date knowledge about Alzheimer's disease vascular risk factors, signs of vascular impairment on brain imaging and possible interactions of vascular and neurodegenerative pathophysiological pathways. It focuses on the neurosonological signs of brain vascular impairment and presents own outcomes in this research area. Using cross-sectional and longitudinal design, the study demonstrates functional impairment of brain microcirculation in patients with various cerebrovascular burdens and various degrees of cognitive decline and it identifies the most appropriate neurosonological parameter in the prediction of cognitive decline progression. On the same study sample it explores the association of other vascular...
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Memory and cognitive coordination impairment in rat models of neuropsychiatric diseases
Vojtěchová, Iveta ; Stuchlík, Aleš (advisor) ; Syka, Josef (referee) ; Hort, Jakub (referee)
The memory and spatial navigation are extremely important brain functions for humans, but they are often the question of life and death for animals. In humans, memory can be disrupted by various neuropsychiatric disorders. The patients suffering from Alzheimer's dementia (AD) have impaired working and long-term memory, spatial navigation, higher cognitive functions and social memory. The deficit of cognitive coordination (the skill to recognize the relevancy of incoming information) and disorientation belong to the symptomatology of schizophrenia. Intelectual disability appears in some patients with autism spectrum disorder. Unfortunately, it is not possible to cure these disorders efficiently because the etiology is not known in the majority of patients. The causes leading to development of these disorders could be revealed using animal models. This thesis contributes to the characterization of the cognitive skills disruptions - as well as other behavioral alterations - in selected rat models of AD (transgenic McGill rat, non-transgenic Samaritan rat) and schizophrenia (lipopolysaccharide model of early postnatal, or prenatal, bacterial infection). The thesis also discusses the validity and limitations of these models. Our results showed a severe deficit of spatial navigation, learning and...
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Clinical variability of rare dementias: manifestations and possible reasons
Tesař, Adam ; Rusina, Robert (advisor) ; Baláž, Marek (referee) ; Hort, Jakub (referee)
Clinical variants of dementia are limiting their diagnosis and can leads to underdiagnosing or substitution of two different diseases with the same symptomatology. The aim of this study is a better understanding of a factors involved in the clinical variability of rare dementias. Progressive supranuclear palsy and Gerstmann-Sträussler-Scheinker syndrome caused by mismatch mutation P102L in Prion protein are used as model diseases. In this thesis, we firstly demonstrate the influence of the distribution of neuropathology and its spread on the clinical phenotype of the disease. Although a single neurodegenerative disease increases the risk of neurodegenerative comorbidity, this other neuropathology does not affect the phenotypic presentation of the primary disease. Monogenetically inherited proteinopathies can have a different clinical subtype, which is not only conditioned by causal protein polymorphisms, but can be influenced by the wild type allele of causal protein. A more accurate understanding of the symptomatic variability in dementias will allow a better focus of a drug studies and, in the future a treatment, but it will also lead to a better understanding of the pathogenesis of neurodegenerative diseases. Keywords: dementia, Progressive supranuclear palsy, Gerstmann-Sträussler-Scheinker...
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Age dependent decrease of cerebro-vascular reactivity and its impact on brain parenchyme integrity
Peisker, Tomáš ; Kalvach, Pavel (advisor) ; Zvěřina, Eduard (referee) ; Hort, Jakub (referee)
Summary: Sufficient vasodilatory and vasoconstrictive reactivity of cerebral arterioles is an important prerequisite for adequate capillary perfusion. To appreciate its capacity during aging and to elucidate its impact on parenchymal integrity we undertook a correlation using ultrasonography and brain MRI. Sixty healthy persons with no stenoses in carotid and vertebral arteries were examined by transcranial doppler ultrasonography (TCD) to assess middle cerebral artery mean flow velocities (MFV) et rest, after 30 sec apnea and after 90 sec hyperventilation. Young persons, N=20, mean age 24,8 (20- 32) were compared with middle aged, N=20, 54,8 (40-63) and elderly, N=20, 76,2 (69-84). A cohort of 40 elderly persons, mean age 68,4 (57-85) were evaluated also by MRI using FLAIR and T2-weighted sequences. Their extent of leukoaraiosis measured by the Fazekas scale was correlated with their vasoregulatory capacity. Results: The steady state mean flow velocity (MFV) in young persons, 71 cm/sec, decreases to 48,1 and to 44,9 cm/sec in the middle and the old aged. The postapnoic vasodilatation in young persons accelerates the MCA blood velocity by 41,7%, while in middle and old age only by 37,9 and 32,7% respectively. The MCA deceleration post hyperventilation by 49,8% in young people decreases to 37,8% and to 29,7%...
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The impact of brain-derived neurotrophic factor (BDNF) gene polymorphism and BDNF levels for prediction, diagnosis and follow-up of cognitive deficit in neurodegenerative diseases
Čechová, Kateřina ; Hort, Jakub (advisor) ; Telenský, Petr (referee) ; Rektorová, Irena (referee)
Alzheimer's disease (AD) is a slowly progressing neurodegenerative disease characterized by an extracellular accumulation of senile plaques and intracellular neurofibrillary tangles. Apart from these hallmarks, AD is very heterogeneous, especially at the age of onset and the rate of progression. Genetic polymorphisms are key modulators influencing these factors. One of them is a polymorphism for the Brain-derived neurotrophic factor (BDNF), a neurotrophin involved in the synaptic plasticity in the hippocampus and medial temporal lobe structures, areas primarily affected in AD. The thesis aimed to investigate the effect of BDNF Va66Met polymorphism together with the main genetic risk factor for sporadic AD, Apolipoprotein E (APOE) polymorphism, on cognitive functions and structural brain changes. We have shown that the combination of risk alleles BDNF Met and APOE ɛ4 is associated with more severe impairment in episodic memory, egocentric orientation and smaller volumes of medial temporal lobe structures in individuals with amnestic mild cognitive impairment (aMCI), and allocentric orientation in cognitively unimpaired individuals compared to non-carriers. These findings suggest that carriers of the combination of BDNF Met and APOE ɛ4 have a higher risk of progression to more severe disease stages,...
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Cognitive Impairment in Parkinson's Disease
Bezdíček, Ondřej ; Růžička, Evžen (advisor) ; Papežová, Hana (referee) ; Hort, Jakub (referee)
Cognitive impairment is considered as essential feature of non-motor symptoms in Parkinson's disease (PD). It is a result of underlying pathological processes in the brain of PD patients and it leads to decreased quality of life. In this thesis an analysis of the structure and profile of cognitive impairment is presented with special emphasis on executive functions and memory. We take diagnostic entities developed for the description of PD cognitive spectrum such as mild cognitive impairment (PD-MCI) and dementia (PD-D) as examples of heterogeneity and different severity of cognitive impairment in PD. However, neuropsychological methods in Czech version that would measure these diagnotic units were not adequatly validated. In the experimental part we test a hypothesis, if gait disorder with falls in PD is interconnected with cognitive impairment, and if PD-fallers have more severe cognitive deficit than PD-non-fallers. On the basis of nine validity or normative data studies we show psychometric properties and clinical utility of several basic neuropsychological methods in the Czech population for memory (Rey Auditory Verbal Learning Test, California Verbal Learning Test, Second Edition, Memory For Intentions Screening Test and Enhanced Cued Recall Test), sustained attention and executive functions...
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The impact of brain-derived neurotrophic factor (BDNF) gene polymorphism and BDNF levels for prediction, diagnosis and follow-up of cognitive deficit in neurodegenerative diseases
Čechová, Kateřina ; Hort, Jakub (advisor) ; Telenský, Petr (referee) ; Rektorová, Irena (referee)
Alzheimer's disease (AD) is a slowly progressing neurodegenerative disease characterized by an extracellular accumulation of senile plaques and intracellular neurofibrillary tangles. Apart from these hallmarks, AD is very heterogeneous, especially at the age of onset and the rate of progression. Genetic polymorphisms are key modulators influencing these factors. One of them is a polymorphism for the Brain-derived neurotrophic factor (BDNF), a neurotrophin involved in the synaptic plasticity in the hippocampus and medial temporal lobe structures, areas primarily affected in AD. The thesis aimed to investigate the effect of BDNF Va66Met polymorphism together with the main genetic risk factor for sporadic AD, Apolipoprotein E (APOE) polymorphism, on cognitive functions and structural brain changes. We have shown that the combination of risk alleles BDNF Met and APOE ɛ4 is associated with more severe impairment in episodic memory, egocentric orientation and smaller volumes of medial temporal lobe structures in individuals with amnestic mild cognitive impairment (aMCI), and allocentric orientation in cognitively unimpaired individuals compared to non-carriers. These findings suggest that carriers of the combination of BDNF Met and APOE ɛ4 have a higher risk of progression to more severe disease stages,...
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