Alzheimerova choroba (AD) je od svého počátku spojena s poruchou prostorové navigace. Vyvíjí se pravděpodobně několik let před klinickými projevy. Klinicky se AD projevuje nejdříve kognitivními poruchami bez omezení běžného života pacienta. Toto stádium se nazývá mírná kognitivní porucha (MCI) a rozlišení toho, jaký vzorec kognitivního postižení se váže s pozdějším vznikem AD, je důležitým cílem současného výzkumu. V tomto článku informujeme o našich experimentech týkajících se prostorové navigace u MCI. Test skrytého cíle vyvinutý v naší laboratoři je analogií Morrisova vodního bludiště a hodnotí dva typy navigace: alocentrickou, používající vzdálené orientační body, a egocentrickou, používající současnou polohu subjektu. Pacienti s amnestickou MCI se zdají být v tomto testu postiženi a vzorec jejich postižení v jednotlivých subtestech je závislý na typu MCI. Vyšetření prostorové navigace může být užitečné pro dlouhodobé sledování vývoje choroby a hodnocení rizika vývoje AD u presymptomatických pacientů.
Alzheimer's disease (AD) is from its start associated with spatial disorientation. The disease probably develops in the brain s everal years before clinical manifestation. Clinically, it starts by cognitive impairment without any restriction of the daily life of the patients. This stage is called mild cognitive impairment (MCI), and distinction of which pattern of cognitive impairment is connected wi th later development of the Alzheimer's disease is an important objective for current medicine. In this article we report about our expe riments concerning spatial navigation in MCI. Hidden Goal Task developed in our lab is a real space analogue of Morris water maze and e valuates two modes of spatial navigation: allocentric, using distal orientation cues, and egocentric, using current subject position. Am nestic MCI patients seem to be impaired in this test and the pattern of their impairment in individual subtests is dependent on the type o f MCI. Spatial navigation assessment can be useful for longitudinal monitoring of the disease progression or evaluation of pre-symptom atic individuals at risk of AD.
- MeSH
- Alzheimer Disease complications psychology MeSH
- Maze Learning physiology MeSH
- Research Support as Topic MeSH
- Financing, Organized MeSH
- Hippocampus physiology MeSH
- Cognition Disorders etiology psychology MeSH
- Humans MeSH
- Neurocognitive Disorders etiology complications psychology MeSH
- Orientation physiology MeSH
- Spatial Behavior physiology MeSH
- Psychological Tests standards statistics & numerical data MeSH
- Check Tag
- Humans MeSH
Prostorová orientace je schopnost určování a udržování trasy z jednoho místa do druhého. V průběhu fyziologického stárnutí dochází k postupnému mírnému zhoršování prostorové orientace. Nicméně výrazné postižení prostorové orientace může být první známkou počínající Alzheimerovy choroby, ještě před plným rozvojem syndromu demence, ve stadiu mírné kognitivní poruchy. Především pacienti, kteří mají velmi vysoké riziko rozvoje Alzheimerovy choroby, pacienti s mírnou kognitivní poruchou s postižením paměti hipokampálního typu projevující se poruchou ukládání a vybavování informací mají výrazně porušenu prostorovou orientaci podobného charakteru jako pacienti s lehkou Alzheimerovou chorobou. Testování prostorové orientace u starší populace a vývoj počítačových testů pro rutinní klinické použití tedy představují nejen možnost dále prozkoumat tuto kognitivní doménu, ale zejména možnost velmi časné diagnostiky Alzheimerovy choroby. Jelikož velká část základního výzkumu kognice a preklinického zkoušení kognitiv u laboratorních zvířat je prováděna testy prostorové kognice, má výzkum prostorové orientace u lidí velký význam i z hlediska translačního výzkumu.
Spatial navigation is a process of determining and maintaining a course or trajectory from one place to another. There is a mild progressive decline of spatial navigation in the course of physiological ageing. Nevertheless, severe spatial navigation deficit might be the first sign of incipient Alzheimer's disease at the stage of mild cognitive impairment, before the full dementia syndrome develops. Patients with mild cognitive impairment with memory deficit of hippocampal type, manifested by encoding and retrieval impairment, are at very high risk of Alzheimer's disease. These patients have the same pattern of spatial navigation impairment as patients with mild Alzheimer's disease. Spatial navigation testing in older patients and a development of computerized tests for routine clinical use thus represent a possibility to further investigate this cognitive domain as well as an opportunity of an early diagnosis of Alzheimer's disease. Spatial navigation in humans is of great significance for translational research as spatial navigation tests form a major part of basic cognitive research and are also used in preclinical testing of cognitive drugs in laboratory animals.
- MeSH
- Alzheimer Disease diagnosis physiopathology MeSH
- Financing, Organized MeSH
- Cognitive Dysfunction diagnosis physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Spatial Behavior physiology MeSH
- Aging physiology pathology MeSH
- Space Perception physiology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Publication type
- Review MeSH
AIMS: To find out whether neuropsychiatric comorbidity (comMCI) influences spatial navigation performance in amnestic mild cognitive impairment (aMCI). METHODS: We recruited aMCI patients with (n = 21) and without (n = 21) neuropsychiatric comorbidity or alcohol abuse, matched for global cognitive impairment and cognitively healthy elderly participants (HE, n = 22). They completed the Mini-Mental State Examination and a virtual Hidden Goal Task in egocentric, allocentric, and delayed recall subtests. RESULTS: In allocentric navigation, aMCI and comMCI performed significantly worse than HE and similarly to each other. Although aMCI performed significantly worse at egocentric navigation than HE, they performed significantly better than patients with comMCI. CONCLUSIONS: Despite the growing burden of dementia and the prevalence of neuropsychiatric symptoms in the elderly population, comMCI remains under-studied. Since trials often assess "pure" aMCI, we may underestimate patients' navigation and other deficits. This finding emphasizes the importance of taking account of the cognitive effects of psychiatric disorders in aMCI.
- MeSH
- Amnesia epidemiology psychology MeSH
- Cognitive Dysfunction epidemiology psychology MeSH
- Comorbidity MeSH
- Humans MeSH
- Spatial Navigation * MeSH
- Spatial Memory MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Detection of incipient Alzheimer disease (AD) pathophysiology is critical to identify preclinical individuals and target potentially disease-modifying therapies towards them. Current neuroimaging and biomarker research is strongly focused in this direction, with the aim of establishing AD fingerprints to identify individuals at high risk of developing this disease. By contrast, cognitive fingerprints for incipient AD are virtually non-existent as diagnostics and outcomes measures are still focused on episodic memory deficits as the gold standard for AD, despite their low sensitivity and specificity for identifying at-risk individuals. This Review highlights a novel feature of cognitive evaluation for incipient AD by focusing on spatial navigation and orientation deficits, which are increasingly shown to be present in at-risk individuals. Importantly, the navigation system in the brain overlaps substantially with the regions affected by AD in both animal models and humans. Notably, spatial navigation has fewer verbal, cultural and educational biases than current cognitive tests and could enable a more uniform, global approach towards cognitive fingerprints of AD and better cognitive treatment outcome measures in future multicentre trials. The current Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed AD and identifies research gaps and future research priorities.
- MeSH
- Alzheimer Disease diagnosis physiopathology MeSH
- Biomarkers * MeSH
- Humans MeSH
- Prodromal Symptoms * MeSH
- Spatial Navigation physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- MeSH
- Alzheimer Disease pathology MeSH
- Hippocampus pathology physiology MeSH
- Cognitive Dysfunction pathology MeSH
- Humans MeSH
- Spatial Navigation * MeSH
- Aging * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Editorial MeSH
BACKGROUND: Cognitive deficits are common in early multiple sclerosis (MS), however, spatial navigation changes and their associations with brain pathology remain poorly understood. OBJECTIVE: To characterize the profile of spatial navigation changes in two main navigational strategies, egocentric (self-centred) and allocentric (world-centred), and their associations with demyelinating and neurodegenerative changes in early MS. METHODS: Participants with early MS after the first clinical event (n = 51) and age-, gender- and education-matched controls (n = 42) underwent spatial navigation testing in a real-space human analogue of the Morris water maze task, comprehensive neuropsychological assessment, and MRI brain scan with voxel-based morphometry and volumetric analyses. RESULTS: The early MS group had lower performance in the egocentric (p = 0.010), allocentric (p = 0.004) and allocentric-delayed (p = 0.038) navigation tasks controlling for age, gender and education. Based on the applied criteria, lower spatial navigation performance was present in 26-29 and 33-41% of the participants with early MS in the egocentric and the allocentric task, respectively. Larger lesion load volume in cortical, subcortical and cerebellar regions (ß ≥ 0.29; p ≤ 0.032) unlike brain atrophy was associated with less accurate allocentric navigation performance. CONCLUSION: Lower spatial navigation performance is present in up to 41% of the participants with early MS. Demyelinating lesions in early MS may disrupt neural network forming the basis of allocentric navigation.
- MeSH
- Cognition MeSH
- Cognitive Dysfunction * MeSH
- Humans MeSH
- Neuropsychological Tests MeSH
- Spatial Navigation * MeSH
- Multiple Sclerosis * diagnostic imaging MeSH
- Space Perception MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Během stárnutí a při vývoji Alzheimerovy choroby (AD) se objevují poruchy prostorově navigace pravděpodobně spojené se změnami ve funkci hipokampu, čelního laloku a dalších mozkových struktur. U člověka zahrnují změny schopností navigace v prostoru v důsledku stárnutí jak prostorové, tak neprostorové strategie. Tyto změny jsou vysvětlovány omezením kognitivní kapacity, horší výkonností pracovní paměti, neefektivními prostorovými strategiemi nebo deficitem v použití alocentrické kognitivní mapy. U starších lidí byly popsány subjektivní potíže s navigací a vyhýbání se neznámým místům a cestám. Vážné poruchy prostorové orientace neslučující se samostatným životem jsou často popisovány u pacientů s AD a problémy s navigací v prostoru byly popsány i u pacientů s mírnou kognitivní poruchou. Desorientace u pacientů a AD může být vysvětlena pomocí deficitu ve složitějším vnímání, jako je vnímání optického toku, pomocí deficitu v prostorové paměti nebo pomocí obou. Tento přehled shrnuje nejdůležitější poznatky z literatury se zaměřením na neurální základy kognitivních změn a na možnosti časné detekce a vývoje AD pomocí vyšetření schopností navigace v prostoru.
Age dependent and Alzheimer's disease (AD) related deficits in spatial learning and memory are thought to be based on alterations in the hippocampus, frontal cortex and other brain structures which develop during aging and progression of AD. In human, the age related changes in spatial navigation comprise deficits in both route and place learning. These deficits have been explained by limits in cognitive capacity, working memory deficit, inefficient search strategies or deficits in allocentric cognitive mapping. Self -perceived deficits in navigation and behavioral patterns to avoid unfamiliar routes and places were described in elderly individuals. Dis abling topographic disorientation that interferes with independent living can be observed in many AD patients and difficulties with sp atial navigation were found even in patients with mild cognitive impairment. The disorientation in AD can be explained by higher orde r perceptual deficits including impaired visual motion processing and/or spatial memory deficits. The review will cover the current literature while focusing on the neural basis of the cognitive changes and the possibility of early detection and prediction of AD progres sion by spatial navigation abilities assessment.
- MeSH
- Alzheimer Disease etiology physiopathology MeSH
- Financing, Organized MeSH
- Hippocampus physiology MeSH
- Humans MeSH
- Neurocognitive Disorders etiology physiopathology MeSH
- Orientation MeSH
- Memory Disorders etiology physiopathology MeSH
- Aging physiology pathology MeSH
- Space Perception physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Alzheimerova nemoc je od svého počátku spojena s dezorientací v prostoru. Ve většině případů je předcházena mírnou kognitivní poruchou, jejíž podtypy s různou predikcí dalšího vývoje se rozlišují pomocí testů zaměřených na paměť a další kognitivní domény Pomocí testu jednoduché navigace v reálném prostoru i na obrazovce počítače jsme porovnávali postižení pacientů s mírnou kognitivní poruchou ve standardních kognitivních testech a v prostorové navigaci. Navigační test probíhal v laboratoři prostorové navigace, zvané Blue Velvet Arena, v Nemocnici Motol. Test jednoduché navigace vyšetřuje tři módy prostorové navigace: navigaci na značku, alocentrickou navigaci, používající vzdálený orientační bod, a egocentrickou navigaci, používající současnou polohu subjektu. Zjistili jsme, že standardní kognitivní testy nepředpovídaly úspěšnost v navigačních testech a prostorová navigace může tak představovat nezávislou kognitivní doménu.
Alzheimer's disease is from its start associated with a spatial disorientation. In most cases it's preceded with the mild cogni tive impairment, which subtypes of different expected outcomes of the disease are distinguished by psychology tests focused on memory and other cognitive do- mains. Using a simple navigation test in a real space and on a computer monitor we compared the deficits in patients with mild cognitive im- pairment in standard cognitive tests and in spatial navigation. The navigation test was performed in a spatial cognition labora tory, called Blue Velvet Arena, placed in Teaching Hospital Motol. The simple navigation task evaluates three modes of spatial navigation: cued, using proximal orientation cue, allocentric, using distal orientation cue, and egocentric, using current subject position. Our preliminary res ults suggest that standard cognitive test did not predict the results in spatial navigation tests and spatial navigation can therefore represent an independent co- gnitive domain.
- Keywords
- mírná kognitivní porucha, prostorová orientace,
- MeSH
- Alzheimer Disease diagnosis MeSH
- Dementia MeSH
- Financing, Organized MeSH
- Cognition Disorders diagnosis MeSH
- Humans MeSH
- Neuropsychological Tests standards statistics & numerical data MeSH
- Orientation MeSH
- Memory MeSH
- Computer Simulation utilization MeSH
- Cues MeSH
- Spatial Memory MeSH
- Spatial Behavior MeSH
- Psychomotor Performance MeSH
- Statistics as Topic MeSH
- Case-Control Studies MeSH
- Space Perception MeSH
- Visual Perception MeSH
- Check Tag
- Humans MeSH
BACKGROUND: Subjective cognitive decline (SCD) may serve as a symptomatic indicator for preclinical Alzheimer's disease; however, SCD is a heterogeneous entity regarding clinical progression. We aimed to investigate whether spatial navigation could reveal subcortical structural alterations and the risk of progression to objective cognitive impairment in SCD individuals. METHODS: One hundred and eighty participants were enrolled: those with SCD (n = 80), normal controls (NCs, n = 77), and mild cognitive impairment (MCI, n = 23). SCD participants were further divided into the SCD-good (G-SCD, n = 40) group and the SCD-bad (B-SCD, n = 40) group according to their spatial navigation performance. Volumes of subcortical structures were calculated and compared among the four groups, including basal forebrain, thalamus, caudate, putamen, pallidum, hippocampus, amygdala, and accumbens. Topological properties of the subcortical structural covariance network were also calculated. With an interval of 1.5 years ± 12 months of follow-up, the progression rate to MCI was compared between the G-SCD and B-SCD groups. RESULTS: Volumes of the basal forebrain, the right hippocampus, and their respective subfields differed significantly among the four groups (p < 0.05, false discovery rate corrected). The B-SCD group showed lower volumes in the basal forebrain than the G-SCD group, especially in the Ch4p and Ch4a-i subfields. Furthermore, the structural covariance network of the basal forebrain and right hippocampal subfields showed that the B-SCD group had a larger Lambda than the G-SCD group, which suggested weakened network integration in the B-SCD group. At follow-up, the B-SCD group had a significantly higher conversion rate to MCI than the G-SCD group. CONCLUSION: Compared to SCD participants with good spatial navigation performance, SCD participants with bad performance showed lower volumes in the basal forebrain, a reorganized structural covariance network of subcortical nuclei, and an increased risk of progression to MCI. Our findings indicated that spatial navigation may have great potential to identify SCD subjects at higher risk of clinical progression, which may contribute to making more precise clinical decisions for SCD individuals who seek medical help.
Spatial navigation (SN) impairment is present early in Alzheimer's disease (AD). We tested whether SN performance, self-centered (egocentric) and world-centered (allocentric), was distinguishable from performance on established cognitive functions-verbal and nonverbal memory, executive and visuospatial function, attention/working memory, and language function. 108 older adults (53 cognitively normal [CN] and 55 with amnestic mild cognitive impairment [aMCI]) underwent neuropsychological examination and real-space navigation testing. Subset (n = 63) had automated hippocampal volumetry. In a factor analysis, allocentric and egocentric navigation tasks loaded highly onto the same factor with low loadings on other factors comprising other cognitive functions. In linear regression, performance on other cognitive functions was not, or was only marginally, associated with spatial navigation performance in CN or aMCI groups. After adjustment for age, gender, and education, right hippocampal volume explained 26% of the variance in allocentric navigation in aMCI group. In conclusion, spatial navigation, a known cognitive marker of early AD, may be distinguished from other cognitive functions. Therefore, its assessment along with other major cognitive functions may be highly beneficial in terms of obtaining a comprehensive neuropsychological profile.
- MeSH
- Hippocampus diagnostic imaging pathology MeSH
- Cognition physiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Memory physiology MeSH
- Spatial Navigation physiology MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Aging pathology psychology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
