Epizodická paměť a její porucha jsou jedním z ukazatelů vyšší pravděpodobnosti vývoje Alzheimerovy choroby mezi staršími zdravými lidmi a pacienty s mírnou kognitivní poruchou (MCI). Poruchy jsou definující charakteristikou pro amnestický typ MCI s paměťovými poruchami, bez jiných kognitivních problémů a se zachovanými aktivitami běžného života. Podle současných teoretických přístupů zahrnuje epizodická paměť časovou a prostorovou komponentu. Tato studie ověřovala hypotézu, že tyto dvě komponenty jsou v rozdílné míře ovlivněné nepaměťovými kognitivními funkcemi a také v rozdílné míře reflektované v současných klinických testech epizodické paměti. Použili jsme nově vyvinutý počítačový test paměti epizodického typu, rozlišující časovou a prostorovou komponentu a porovnali výsledky v tomto testu u kontrolní skupiny zdravých lidí a tří skupin pacientů s MCI: neamnestické MCI, amnestické MCI jednoa vícedoménové. Postiženi v testu byli pacienti s amnestickou MCI a překvapivě pacienti s neamnestickou MCI byli postiženi v paměti pro pořadí obrázků. Naše výsledky ukazují, že použité standardní testy epizodické paměti postrádají časovou komponentu, což můžže vézt k neschopnosti zaznamenat paměťový deficit u některých pacientů.
Episodic memory and its impairment is one of the markers of higher probability of progression to Alzheimer disease (AD) among healthy elderly population and among patients with mild cognitive impairment (MCI). The impairment is a defining characteristic for amnestic type of MCI with memory dysfunction but normal other cognitive functions and intact activities of daily life. According to the current theoretical concepts, episodic memory includes temporal and spatial component. The aim of this study was to verify the hypothesis, that these two components of episodic memory are to a different degree influenced by non-memory cognitive functions and also to a different degree reflected in current clinically used episodic memory tests. We used a novel episodic-like memory test for human, distinguishing the temporal and spatial component, and compared results in this test of a group of healthy subjects and three groups of MCI patients: nonamnestic MCI, amnestic MCI single-domain and amnestic MCI multi-domain. Both amnestic MCI groups were impaired in the test. Surprisingly, the group of naMCI patients was impaired in the recall of temporal order of pictures. Our results show that the routinely used standard episodic memory tests lack the temporal component, potentially leading to failure of noticing memory impairment in some subjects.
- MeSH
- Alzheimerova nemoc diagnóza MeSH
- financování organizované MeSH
- kognitivní poruchy diagnóza klasifikace MeSH
- kongresy jako téma MeSH
- lidé MeSH
- neuropsychologické testy normy statistika a číselné údaje MeSH
- poruchy paměti diagnóza klasifikace MeSH
- regresní analýza MeSH
- rozpomínání klasifikace účinky léků MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
Objectives: To review available evidence of pharmacological and non-pharmacological treatment for MCI and analyse information and limitations in national and international guidelines.Methods: Experts from several European countries conducted a qualitative review of the literature on MCI and treatments for MCI, as well as respective chapters in national and international guidelines on dementia/MCI. Psychotherapeutic/psychosocial treatments were excluded from the review.Results: Consensus diagnostic criteria for MCI are available, making early recognition and accurate classification of MCI subtypes possible. MCI can be identified in a primary care setting. Further corroboration and differential diagnosis should be done at specialist level. Mixed pathologies are the rule in MCI, thus a multi-target treatment approach is a rational strategy. Promising evidence has been generated for multi-domain interventions. Limited evidence is available for different pharmacological classes that have been investigated in MCI clinical trials (e.g. acetylcholinesterase inhibitors). EGb 761® improved symptoms in some clinical trials; it is the only pharmacological treatment recommended in existing guidelines for the symptomatic treatment of MCI.Conclusions: MCI is recognised as an important treatment target and some recent national guidelines have considered symptomatic treatment recommendations for MCI. However, more needs to be done, especially at an international level.
- MeSH
- Alzheimerova nemoc diagnóza farmakoterapie terapie MeSH
- kognitivní dysfunkce klasifikace diagnóza farmakoterapie terapie MeSH
- konsensus MeSH
- lidé MeSH
- mezinárodní spolupráce * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- směrnice pro lékařskou praxi jako téma * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
INTRODUCTION: The diagnosis of mild cognitive impairment (MCI) refers to cognitive impairment not meeting dementia criteria. A survey among members of the American Association of Neurology (AAN) showed that MCI was considered a useful diagnosis. Recently, research criteria have been proposed for the diagnosis of Alzheimer's disease (AD) in MCI based on AD biomarkers (prodromal AD/MCI due to AD). The aim of this study was to investigate the attitudes of clinicians in Europe on the clinical utility of MCI and prodromal AD/MCI due to AD criteria. We also investigated whether the prodromal AD/MCI due to AD criteria impacted management of MCI patients. METHODS: An online survey was performed in 2015 among 102 members of the European Academy of Neurology (EAN) and the European Alzheimer's Disease Consortium (EADC). Questions were asked on how often criteria were used, how they were operationalized, how they changed patient management, and what were considered advantages and limitations of MCI and prodromal AD/MCI due to AD. The questionnaire consisted of 47 questions scored on a Likert scale. RESULTS: Almost all respondents (92%) used the MCI diagnosis in clinical practice. Over 80% of the EAN/EADC respondents found a MCI diagnosis useful because it helped to label the cognitive problem, involve patients in planning for the future, and start risk reduction activities. These findings were similar to those reported in the AAN survey. Research criteria for prodromal AD/MCI due to AD were used by 68% of the EAN/EADC respondents. The most common reasons to use the criteria were increased certainty of diagnosis (86%), increased possibilities to provide counseling (51%), facilitation of follow-up planning (48%), start of medical intervention (49%), and response to patients' wish for a diagnosis (41%). Over 70% of the physicians considered that a diagnosis of prodromal AD/MCI due to AD had an added value over the MCI diagnosis. CONCLUSIONS: The diagnostic criteria of MCI and prodromal AD/MCI due to AD are commonly used among EAN/EADC members. The prodromal AD/MCI due to AD were considered clinically useful and impacted patient management and communication.
- MeSH
- Alzheimerova nemoc diagnóza MeSH
- kognitivní dysfunkce diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- neurologie MeSH
- postoj zdravotnického personálu * MeSH
- prodromální symptomy MeSH
- průzkumy a dotazníky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
Transcranial direct current stimulation combined with cognitive training (tDCS-cog) represents a promising approach to combat cognitive decline among healthy older adults and patients with mild cognitive impairment (MCI). In this 5-day-long double-blinded randomized trial, we investigated the impact of intensified tDCS-cog protocol involving two trains of stimulation per day on working memory (WM) enhancement in 35 amnestic and multidomain amnestic MCI patients. Specifically, we focused to improve WM tasks relying on top-down attentional control and hypothesized that intensified tDCS would enhance performance of visual object matching task (VOMT) immediately after the stimulation regimen and at a 1-month follow-up. Secondarily, we explored whether the stimulation would augment online visual working memory training. Using fMRI, we aimed to elucidate the neural mechanisms underlying the intervention effects by analyzing BOLD activations during VOMT. Our main finding revealed no superior after-effects of tDCS-cog over the sham on VOMT among individuals with MCI as indicated by insignificant immediate and long-lasting after-effects. Additionally, the tDCS-cog did not enhance online training as predicted. The fMRI analysis revealed brain activity alterations in right insula that may be linked to tDCS-cog intervention. In the study we discuss the insignificant behavioral results in the context of the current evidence in tDCS parameter space and opening the discussion of possible interference between trained cognitive tasks.
- MeSH
- dorsolaterální prefrontální kortex MeSH
- dvojitá slepá metoda MeSH
- kognitivní dysfunkce * terapie MeSH
- krátkodobá paměť fyziologie MeSH
- lidé MeSH
- mozek diagnostické zobrazování MeSH
- prefrontální mozková kůra fyziologie MeSH
- přímá transkraniální stimulace mozku * metody MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
OBJECTIVE: We investigated the association between APOE ε4 status and spatial navigation in patients with amnestic mild cognitive impairment (aMCI) and assessed the role of hippocampal volume in this association. METHOD: Participants were 74 patients with clinically confirmed aMCI (33 APOE ε4 noncarriers, 26 heterozygous, and 15 homozygous ε4 carriers). Body-centered (egocentric) and world-centered (allocentric) spatial navigation in a computerized human analogue of the Morris Water Maze was assessed. Brain MRI with subsequent automated hippocampal volumetry was included. RESULTS: Groups were similar in neuropsychological profile. Controlling for age, sex, education, and free memory recall, the APOE ε4 carriers performed more poorly on all spatial navigation subtasks (ps < .05). APOE ε4 homozygotes performed worse than heterozygotes (p = .021). Right hippocampal volume accounted for the differences in allocentric and delayed subtasks (ps > .05), but not in the egocentric subtask (p < .001). CONCLUSIONS: Using an easy-to-use, computer-based tool to assess spatial navigation, we found spatial navigation deficits to worsen in a dose-dependent manner as a function of APOE ε4 status. This was at least partially due to differences in right hippocampal volume.
- MeSH
- amnézie komplikace genetika patologie MeSH
- apolipoprotein E4 genetika MeSH
- funkční lateralita MeSH
- hipokampus patologie MeSH
- kognitivní dysfunkce komplikace genetika patologie MeSH
- lidé MeSH
- neuropsychologické testy MeSH
- počítače MeSH
- prostorová navigace fyziologie MeSH
- prostorové učení fyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Alzheimer's disease (AD) is the most frequent cause of dementia. Misfolded protein pathological hallmarks of AD are brain deposits of amyloid-β (Aβ) plaques and phosphorylated tau neurofibrillary tangles. However, doubts about the role of Aβ in AD pathology have been raised as Aβ is a common component of extracellular brain deposits found, also by in vivo imaging, in non-demented aged individuals. It has been suggested that some individuals are more prone to Aβ neurotoxicity and hence more likely to develop AD when aging brains start accumulating Aβ plaques. Here, we applied genome-wide transcriptomic profiling of lymphoblastoid cells lines (LCLs) from healthy individuals and AD patients for identifying genes that predict sensitivity to Aβ. Real-time PCR validation identified 3.78-fold lower expression of RGS2 (regulator of G-protein signaling 2; P=0.0085) in LCLs from healthy individuals exhibiting high vs low Aβ sensitivity. Furthermore, RGS2 showed 3.3-fold lower expression (P=0.0008) in AD LCLs compared with controls. Notably, RGS2 expression in AD LCLs correlated with the patients' cognitive function. Lower RGS2 expression levels were also discovered in published expression data sets from postmortem AD brain tissues as well as in mild cognitive impairment and AD blood samples compared with controls. In conclusion, Aβ sensitivity phenotyping followed by transcriptomic profiling and published patient data mining identified reduced peripheral and brain expression levels of RGS2, a key regulator of G-protein-coupled receptor signaling and neuronal plasticity. RGS2 is suggested as a novel AD biomarker (alongside other genes) toward early AD detection and future disease modifying therapeutics.
- MeSH
- Alzheimerova nemoc diagnóza genetika patologie MeSH
- amyloidní beta-protein genetika MeSH
- amyloidní plaky genetika patologie MeSH
- buněčné linie MeSH
- časná diagnóza MeSH
- celogenomová asociační studie * MeSH
- data mining * MeSH
- exprese genu genetika MeSH
- fenotyp MeSH
- genetické asociační studie MeSH
- genetické markery genetika MeSH
- lidé MeSH
- mozek patologie MeSH
- neurofibrilární klubka genetika patologie MeSH
- proteiny RGS genetika MeSH
- senioři MeSH
- stanovení celkové genové exprese * MeSH
- výpočetní biologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
