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Předkladana guidelines pro Diagnostiku a lecbu Alzheimerovy choroby vychazeji z mediciny založene na důkazech. Jednotlive vědecke prace jsou hodnoceny podle sily důkazů, kterou přinaseji od I – nejpřesvědcivějsich až po IV – nejslabsi. Na... more
Předkladana guidelines pro Diagnostiku a lecbu Alzheimerovy choroby vychazeji z mediciny založene na důkazech. Jednotlive vědecke prace jsou hodnoceny podle sily důkazů, kterou přinaseji od I – nejpřesvědcivějsich až po IV – nejslabsi. Na zakladě těchto důkazů je pak poskytnuto doporuceni A – ucinne, B – pravděpodobně ucinne, C – možna ucinne. Jedna se o revizi předchozich doporucených postupů publikovaných v roce 2007. Nově jsou diskutovany biomarkery Alzheimerovy choroby – vysetřeni mozkomisniho moku, magneticka rezonance a dalsi zobrazovaci metody a nove poznatky z neuropsychologie. V oblasti lecby je kritickemu hodnoceni podrobena řada farmak uživaných v Ceske republice, pro jejichž ucinnost nejsou dostatecne důkazy.
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Age-related spatial navigation decline is more pronounced in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia. We used a realistic-looking virtual navigation test suite to analyze different aspects of... more
Age-related spatial navigation decline is more pronounced in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia. We used a realistic-looking virtual navigation test suite to analyze different aspects of visuospatial processing in typical and atypical aging. A total of 219 older adults were recruited from the Czech Brain Aging Study cohort. Cognitively normal older adults (CN; n = 78), patients with amnestic MCI (n = 75), and those with mild AD dementia (n = 66) underwent three navigational tasks, cognitive assessment, and brain MRI. Route learning and wayfinding/perspective-taking tasks distinguished the groups as performance and learning declined and specific visuospatial strategies were less utilized with increasing cognitive impairment. Increased perspective shift and utilization of non-specific strategies were associated with worse task performance across the groups. Primacy and recency effects were observed across the groups in the route learnin...
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Vascular cognitive impairment (VCI) is the second most common cause of cognitive deficit after Alzheimer’s disease. Since VCI patients represent an important target population for prevention, an ongoing effort has been made to elucidate... more
Vascular cognitive impairment (VCI) is the second most common cause of cognitive deficit after Alzheimer’s disease. Since VCI patients represent an important target population for prevention, an ongoing effort has been made to elucidate the pathogenesis of this disorder. In this review, we summarize the information from animal models on the molecular changes that occur in the brain during a cerebral vascular insult and ultimately lead to cognitive deficits in VCI. Animal models cannot effectively represent the complex clinical picture of VCI in humans. Nonetheless, they allow some understanding of the important molecular mechanisms leading to cognitive deficits. VCI may be caused by various mechanisms and metabolic pathways. The pathological mechanisms, in terms of cognitive deficits, may span from oxidative stress to vascular clearance of toxic waste products (such as amyloid beta) and from neuroinflammation to impaired function of microglia, astrocytes, pericytes, and endothelial ...
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ALZ-801 is an oral, small-molecule inhibitor of beta amyloid (Aβ) oligomer formation in clinical development for Alzheimer's disease (AD). ALZ-801 is a prodrug of tramiprosate with improved pharmacokinetic properties and... more
ALZ-801 is an oral, small-molecule inhibitor of beta amyloid (Aβ) oligomer formation in clinical development for Alzheimer's disease (AD). ALZ-801 is a prodrug of tramiprosate with improved pharmacokinetic properties and gastrointestinal tolerability. During clinical studies, we discovered that the primary metabolite of tramiprosate and its prodrug ALZ-801, 3-sulfopropanoic acid (3-SPA), is an endogenous molecule in the human brain and present in the cerebrospinal fluid (CSF) of patients with AD and other neurodegenerative brain diseases. The objectives of this research were to (1) identify and confirm the presence of 3-SPA in CSF samples from elderly, drug-naïve patients with memory deficits; (2) quantify the levels of 3-SPA in the CSF of patients with AD from tramiprosate phase III North American (NA) trial; (3) evaluate the in vitro anti-Aβ42 oligomer activity of 3-SPA; and (4) characterize the pharmacokinetics and brain-penetration properties of 3-SPA. Lumbar CSF samples fro...
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Research Interests: Epidemiology, Neuroimaging, Dementia, Magnetic Resonance Imaging, Developmental neuroscience, and 10 moreHealth Policy, Medicine, Differential Diagnosis, Clinical Neurology, Clinical Sciences, Cellular and Molecular Neuroscience, Mental Health and Psychiatry Nursing, Neurosciences, Dementia With Lewy Bodies, and Geriatrics and Gerontology
Impairment of spatial navigation (SN) skills is one of the features of the Alzheimer’s disease (AD) already at the stage of mild cognitive impairment (MCI). We used a computer-based battery of spatial navigation tests to measure the SN... more
Impairment of spatial navigation (SN) skills is one of the features of the Alzheimer’s disease (AD) already at the stage of mild cognitive impairment (MCI). We used a computer-based battery of spatial navigation tests to measure the SN performance in 22 MCI patients as well as 21 normal controls (NC). In order to evaluate intrinsic activity in the subcortical regions that may play a role in SN, we measured ALFF, fALFF, and ReHo derived within 14 subcortical regions. We observed reductions of intrinsic activity in MCI patients. We also demonstrated that the MCI versus NC group difference can modulate activity-behavior relationship, that is, the correlation slopes between ReHo and allocentric SN task total errors were significantly different between NC and MCI groups in the right hippocampus (interaction F=4.44, p=0.05), pallidum (F=8.97, p=0.005), and thalamus (F=5.95, p=0.02), which were negative in NC (right hippocampus, r=−0.49; right pallidum, r=−0.50; right thalamus, r=−0.45; al...
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Cerebrospinal fluid collection by lumbar puncture (LP) is performed in the diagnostic workup of several neurological brain diseases. Reluctance to perform the procedure is among others due to a lack of standards and guidelines to minimize... more
Cerebrospinal fluid collection by lumbar puncture (LP) is performed in the diagnostic workup of several neurological brain diseases. Reluctance to perform the procedure is among others due to a lack of standards and guidelines to minimize the risk of complications, such as post-LP headache or back pain. We provide consensus guidelines for the LP procedure to minimize the risk of complications. The recommendations are based on (1) data from a large multicenter LP feasibility study (evidence level II-2), (2) systematic literature review on LP needle characteristics and post-LP complications (evidence level II-2), (3) discussion of best practice within the Joint Programme Neurodegenerative Disease Research Biomarkers for Alzheimer's disease and Parkinson's Disease and Biomarkers for Multiple Sclerosis consortia (evidence level III). Our consensus guidelines address contraindications, as well as patient-related and procedure-related risk factors that can influence the developmen...
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Subjective cognitive complaints (SCCs) may be an early marker of prodromal Alzheimer's disease. Using a 10-item yes/no SCCs questionnaire (Le Questionnaire de Plainte Cognitive [QPC]), we evaluated the prevalence and distribution of... more
Subjective cognitive complaints (SCCs) may be an early marker of prodromal Alzheimer's disease. Using a 10-item yes/no SCCs questionnaire (Le Questionnaire de Plainte Cognitive [QPC]), we evaluated the prevalence and distribution of SCCs in cognitively healthy Czech older adults and examined total score and specific QPC items in relation to depressive symptomology and cognitive performance. A sample of 340 cognitively healthy older community-dwelling volunteers aged 60 or older from the third wave of the longitudinal project National Normative Study of Cognitive Determinants of Healthy Aging, who underwent a comprehensive neuropsychological assessment and completed the QPC and the 15-item Geriatric Depression Scale (GDS-15). Regression analysis was controlled for age when GDS-15 was the outcome and for age and GDS-15 with cognitive domains as the outcome. 71% reported 1 + SCCs, with prevalence of individual complaints ranging from 4% to 40%. The number of SCCs was associated wit...
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Deep gray matter structures are associated with memory and other important functions that are impaired in Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, systematic characterization of the subregional atrophy... more
Deep gray matter structures are associated with memory and other important functions that are impaired in Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, systematic characterization of the subregional atrophy and deformations in these structures in AD and MCI still need more investigations. In this article, we combined complex volumetry- and vertex-based analysis to investigate the pattern of subregional structural alterations in deep gray matter structures and its association with global clinical scores in AD (n = 30) and MCI patients (n = 30), compared to normal controls (NCs, n = 30). Among all seven pairs of structures, the bilateral hippocampi and nucleus accumbens showed significant atrophy in AD compared with NCs (p < 0.05). But only the subregional atrophy in the dorsal-medial part of the left hippocampus, the ventral part of right hippocampus, and the left nucleus accumbens, the posterior part of the right nucleus accumbens correlated with the ...
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Lacunar cerebral infarction (LI) is one of risk factors of vascular dementia and correlates with progression of cognitive impairment including the executive functions. However, little is known on spatial navigation impairment and its... more
Lacunar cerebral infarction (LI) is one of risk factors of vascular dementia and correlates with progression of cognitive impairment including the executive functions. However, little is known on spatial navigation impairment and its underlying microstructural alteration of white matter in patients with LI and with or without mild cognitive impairment (MCI). Our aim was to investigate whether the spatial navigation impairment correlated with the white matter integrity in LI patients with MCI (LI-MCI). Thirty patients with LI were included in the study and were divided into LI-MCI (n=17) and non MCI (LI-Non MCI) groups (n=13) according neuropsychological tests.The microstructural integrity of white matter was assessed by calculating a fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI) scans. The spatial navigation accuracy, separately evaluated as egocentric and allocentric, was assessed by a computerized human analogue of the Morris Water Maze t...
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Communication is very important for people to be successfully integrated into social environment and make and maintain relationship. Particularly, language difficulties lead to social exclusion of the people affected with Alzheimer's... more
Communication is very important for people to be successfully integrated into social environment and make and maintain relationship. Particularly, language difficulties lead to social exclusion of the people affected with Alzheimer's disease (AD) and contribute to a significant decrease in the quality of their life and also have a big impact on their family members who in most cases become their caregivers who need to communicate with their loved ones in order to meet their needs. Therefore, the goal of this study is to describe language impairments in the individual phases of AD and discuss their improvement with respect to AD on the basis of literature review. The authors of this article use traditional research methods in order to achieve the goal set mentioned earlier. First, a method of literature review of available sources describing language impairments in the individual phases of AD is exploited. Second, to show how informal caregivers and relevant drugs can successfull...
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The basal forebrain degenerates in Alzheimer's disease (AD) and this process is believed to contribute to the cognitive decline observed in AD patients. Impairment in spatial navigation is an early feature of the disease but whether... more
The basal forebrain degenerates in Alzheimer's disease (AD) and this process is believed to contribute to the cognitive decline observed in AD patients. Impairment in spatial navigation is an early feature of the disease but whether basal forebrain dysfunction in AD is responsible for the impaired navigation skills of AD patients is not known. Our objective was to investigate the relationship between basal forebrain volume and performance in real space as well as computer-based navigation paradigms in an elderly cohort comprising cognitively normal controls, subjects with amnestic mild cognitive impairment and those with AD. We also tested whether basal forebrain volume could predict the participants' ability to perform allocentric- vs. egocentric-based navigation tasks. The basal forebrain volume was calculated from 1.5 T magnetic resonance imaging (MRI) scans, and navigation skills were assessed using the human analog of the Morris water maze employing allocentric, egocent...
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Several recent studies have indicated that white matter is affected in Alzheimer's disease (AD). Diffusion tensor imaging is a tool by which the white matter microstructure can be examined in vivo, and might offer a possibility for... more
Several recent studies have indicated that white matter is affected in Alzheimer's disease (AD). Diffusion tensor imaging is a tool by which the white matter microstructure can be examined in vivo, and might offer a possibility for the identification of the pattern of white matter disintegration in AD. In the current analysis, we made use of a novel model-free analysis approach of linked independent component analysis to identify a motif of diffusion parameter alterations exemplifying AD. Analysis of the diffusion data of 16 AD patients and 17 age-matched healthy subjects revealed six independent components, two of which demonstrated differences between the patients and controls. Component #0 was dominated by axial diffusivity, but significant alterations in fractional anisotropy and mean and radial diffusivity were also detected. Alterations were found in regions of crossing of major white matter pathways, such as forceps, corona radiate, and superior longitudinal fascicle, as ...
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There are differences in organizing randomized controlled trials (RCTs) across Europe. Clinical trials on Alzheimer's disease are frequently performed in Western, Central, and Eastern Europe. The Czech Republic and Romania are... more
There are differences in organizing randomized controlled trials (RCTs) across Europe. Clinical trials on Alzheimer's disease are frequently performed in Western, Central, and Eastern Europe. The Czech Republic and Romania are referred to in this chapter to represent several specific issues that can occur within RCTs. Both countries offer a very good infrastructure within the public health system as well as university hospitals and private practices with huge experience in performing RCTs. There are differences, however, in contracting, investigators' motivation, site selection, and qualification for performing RCTs. Organizing RCTs on Alzheimer's disease represents a specific field in which these differences are reflected.
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Patients with Alzheimer's disease (AD) frequently have difficulties with spatial orientation in their day-to-day life. Although AD is typically preceded by amnestic mild cognitive impairment (MCI), spatial navigation has not yet been... more
Patients with Alzheimer's disease (AD) frequently have difficulties with spatial orientation in their day-to-day life. Although AD is typically preceded by amnestic mild cognitive impairment (MCI), spatial navigation has not yet been studied in MCI. Sixty-five patients were divided into five groups: probable AD ( n = 21); MCI, further classified as amnestic MCI single domain ( n = 11); amnestic MCI multiple domain ( n = 18), or nonamnestic MCI ( n = 7), and subjective memory complaints ( n = 8). These patients, together with a group of healthy control subjects ( n = 26), were tested by using a four-subtests task that required them to locate an invisible goal inside a circular arena. Each subtest began with an overhead view of the arena showed on a computer monitor. This was followed by a real navigation inside of the actual space, an enclosed arena 2.9 m in diameter. Depending on the subtest, the subjects could use the starting position and/or cues on the wall for navigation. Th...
Research Interests: Spatial Memory, Cognition, Multidisciplinary, Space perception, Humans, and 14 moreFemale, Amnesia, Male, Aged, Middle Aged, Spatial Orientation, Short Term Memory, Spatial navigation, Biological markers, Disease Progression, Memory Disorders, Alzheimer Disease, Cognition disorders, and Neuropsychological Tests
Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among these individuals, deterioration in spatial navigation, manifested by poor... more
Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among these individuals, deterioration in spatial navigation, manifested by poor hippocampus-dependent allocentric navigation, may occur well before the clinical onset of dementia. Our aim was to determine whether allocentric spatial navigation impairment would be proportional to right hippocampal volume loss irrespective of general brain atrophy. We also contrasted the respective spatial navigation scores of the real-space human Morris water maze with its corresponding 2D computer version. We included 42 cognitively impaired patients with either amnestic mild cognitive impairment ( n = 23) or mild and moderate AD ( n = 19), and 14 cognitively intact older controls. All participants underwent 1.5T MRI brain scanning with subsequent automatic measurement of the total brain and hippocampal (right and left) volumes. Allocentric spatial navigation wa...
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... V roce 2007 byla vydána ao tři roky později aktu-alizována evropská doporučení pro diagnostiku ... 7. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR JR, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC,... more
... V roce 2007 byla vydána ao tři roky později aktu-alizována evropská doporučení pro diagnostiku ... 7. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR JR, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P ...