Impaired spatial navigation is early marker of Alzheimer's disease (AD). We examined ability of self- and informant-reported navigation questionnaires to discriminate between clinically and biomarker-defined participants, and associations of questionnaires with navigation performance, regional brain atrophy, AD biomarkers, and biomarker status. 262 participants (cognitively normal, with subjective cognitive decline, amnestic mild cognitive impairment [aMCI], and mild dementia) and their informants completed three navigation questionnaires. Navigation performance, magnetic resonance imaging volume/thickness of AD-related brain regions, and AD biomarkers were measured. Informant-reported questionnaires distinguished between cognitively normal and impaired participants, and amyloid-β positive and negative aMCI. Lower scores were associated with worse navigation performance, greater atrophy in AD-related brain regions, and amyloid-β status. Self-reported questionnaire scores did not distinguish between the groups and were weakly associated with navigation performance. Other associations were not significant. Informant-reported navigation questionnaires may be a screening tool for early AD reflecting atrophy of AD-related brain regions and AD pathology.

• Klíčová slova
• Clinical neuroscience, Disease, Neuroscience,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Spatial navigation impairment is a promising cognitive marker of Alzheimer's disease (AD) that can reflect the underlying pathology. OBJECTIVES: We assessed spatial navigation performance in AD biomarker positive older adults with amnestic mild cognitive impairment (AD aMCI) vs. those AD biomarker negative (non-AD aMCI), and examined associations between navigation performance, MRI measures of brain atrophy, and cerebrospinal fluid (CSF) biomarkers. METHODS: A total of 122 participants with AD aMCI (n = 33), non-AD aMCI (n = 31), mild AD dementia (n = 28), and 30 cognitively normal older adults (CN) underwent cognitive assessment, brain MRI (n = 100 had high-quality images for volumetric analysis) and three virtual navigation tasks focused on route learning (body-centered navigation), wayfinding (world-centered navigation) and perspective taking/wayfinding. Cognitively impaired participants underwent CSF biomarker assessment [amyloid-β1-42, total tau, and phosphorylated tau181 (p-tau181)] and amyloid PET imaging (n = 47 and n = 45, respectively), with a subset having both (n = 19). RESULTS: In route learning, AD aMCI performed worse than non-AD aMCI (p < 0.001), who performed similarly to CN. In wayfinding, aMCI participants performed worse than CN (both p ≤ 0.009) and AD aMCI performed worse than non-AD aMCI in the second task session (p = 0.032). In perspective taking/wayfinding, aMCI participants performed worse than CN (both p ≤ 0.001). AD aMCI and non-AD aMCI did not differ in conventional cognitive tests. Route learning was associated with parietal thickness and amyloid-β1-42, wayfinding was associated with posterior medial temporal lobe (MTL) volume and p-tau181 and perspective taking/wayfinding was correlated with MRI measures of several brain regions and all CSF biomarkers. CONCLUSION: AD biomarker positive and negative older adults with aMCI had different profiles of spatial navigation deficits that were associated with posterior MTL and parietal atrophy and reflected AD pathology.

• Klíčová slova
• allocentric navigation, egocentric navigation, entorhinal cortex, hippocampus, neurodegeneration, precuneus, retrosplenial cortex, tauopathies,
• Publikační typ
• časopisecké články MeSH

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 learning and the wayfinding/perspective-taking task, respectively. In addition, a primacy effect was present in the wayfinding/perspective-taking task in the CN older adults. More effective spatial navigation was associated with better memory and executive functions. The results demonstrate that a realistic and ecologically valid spatial navigation test suite can reveal different aspects of visuospatial processing in typical and atypical aging.

• Klíčová slova
• Alzheimer’s disease, mild cognitive impairment, navigation strategies, perspective taking, route learning, spatial navigation, visuospatial functions, wayfinding,
• Publikační typ
• časopisecké články 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.

• Klíčová slova
• Allocentric, Cognition, Egocentric, Lesion load, MRI, Neuropsychology, Volumetry, Voxel-based morphometry,
• MeSH
• kognice MeSH
• kognitivní dysfunkce * MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• prostorová navigace * MeSH
• roztroušená skleróza * diagnostické zobrazování   MeSH
• vnímání prostoru MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The apolipoprotein E (APOE) ɛ4 allele is associated with episodic memory and spatial navigation deficits. The brain-derived neurotrophic factor (BDNF) Met allele may further worsen memory impairment in APOEɛ4 carriers but its role in APOEɛ4-related spatial navigation deficits has not been established. OBJECTIVE: We examined influence of APOE and BDNF Val66Met polymorphism combination on spatial navigation and volumes of selected navigation-related brain regions in cognitively unimpaired (CU) older adults and those with amnestic mild cognitive impairment (aMCI). METHODS: 187 participants (aMCI [n = 116] and CU [n = 71]) from the Czech Brain Aging Study were stratified based on APOE and BDNF Val66Met polymorphisms into four groups: ɛ4-/BDNFVal/Val, ɛ4-/BDNFMet, ɛ4+/BDNFVal/Val, and ɛ4+/BDNFMet. The participants underwent comprehensive neuropsychological examination, brain MRI, and spatial navigation testing of egocentric, allocentric, and allocentric delayed navigation in a real-space human analogue of the Morris water maze. RESULTS: Among the aMCI participants, the ɛ4+/BDNFMet group had the least accurate egocentric navigation performance (p < 0.05) and lower verbal memory performance than the ɛ4-/BDNFVal/Val group (p = 0.007). The ɛ4+/BDNFMet group had smaller hippocampal and entorhinal cortical volumes than the ɛ4-/BDNFVal/Val (p≤0.019) and ɛ4-/BDNFMet (p≤0.020) groups. Among the CU participants, the ɛ4+/BDNFMet group had less accurate allocentric and allocentric delayed navigation performance than the ɛ4-/BDNFVal/Val group (p < 0.05). CONCLUSION: The combination of APOEɛ4 and BDNF Met polymorphisms is associated with more pronounced egocentric navigation impairment and atrophy of the medial temporal lobe regions in individuals with aMCI and less accurate allocentric navigation in CU older adults.

• Klíčová slova
• Alzheimer’s disease, Morris water maze, apolipoproteins E, brain-derived neurotrophic factor, entorhinal cortex, episodic memory, gene polymorphism, magnetic resonance imaging, mild cognitive impairment, spatial navigation,
• MeSH
• apolipoprotein E4 genetika   MeSH
• kognitivní dysfunkce genetika   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozkový neurotrofický faktor genetika   MeSH
• polymorfismus genetický MeSH
• prostorová navigace fyziologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• apolipoprotein E4 MeSH
• BDNF protein, human MeSH Prohlížeč
• mozkový neurotrofický faktor MeSH

PURPOSE: Identification of demographic, physical/physiological, lifestyle and genetic factors contributing to the onset of dementia, specifically Alzheimer disease (AD), and implementation of novel methods for early diagnosis are important to alleviate prevalence of dementia globally. The Czech Brain Aging Study (CBAS) is the first large, prospective study to address these issues in Central/Eastern Europe by enrolling non-demented adults aged 55+ years, collecting a variety of personal and biological measures and tracking cognitive function over time. PARTICIPANTS: The CBAS recruitment was initiated in 2011 from memory clinics at Brno and Prague University Hospitals, and by the end of 2018, the study included 1228 participants. Annual follow-ups include collection of socioeconomic, lifestyle and personal history information, neurology, neuropsychology, laboratory, vital sign and brain MRI data. In a subset, biomarker assessment (cerebrospinal fluid (CSF) and amyloid positron emission tomography) and spatial navigation were performed. Participants were 69.7±8.1 years old and had 14.6±3.3 years of education at baseline, and 59% were women. By the end of 2018, 31% finished three and more years of follow-up; 9% converted to dementia. Apolipoprotein E status is available from 95% of the participants. The biological sample bank linked to CBAS database contained CSF, serum and DNA. FINDINGS TO DATE: Overall, the findings, mainly from cross-sectional analyses, indicate that spatial navigation is a promising marker of early AD and that it can be distinguished from other cognitive functions. Specificity of several standard memory tests for early AD pathology was assessed with implications for clinical practice. The relationship of various lifestyle factors to cognition and brain atrophy was reported. FUTURE PLANS: Recruitment is ongoing with secured funding. Longitudinal data analyses are currently being conducted. Proposals for collaboration on specific data from the database or biospecimen, as well as collaborations with similar cohort studies to increase sample size, are welcome. Study details are available online (www.cbas.cz).

• Klíčová slova
• dementia, epidemiology, mental health,
• MeSH
• Alzheimerova nemoc epidemiologie   MeSH
• demence epidemiologie   MeSH
• hodnocení rizik MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• ochranné faktory MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

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 tests Amunet. LI-MCI performed worse than the CN and LI-NonMCI groups on egocentric and delayed spatial navigation subtests. LI-MCI patients have spatial navigation deficits. The microstructural abnormalities in diffuse brain regions, including hippocampus, uncinate fasciculus and other brain regions may contribute to the spatial navigation impairment in LI-MCI patients at follow-up.

• Klíčová slova
• Gerotarget, diffusion tensor imaging, lacunar infarction, mild cognitive impairment, spatial navigation,
• MeSH
• anizotropie MeSH
• bílá hmota diagnostické zobrazování   patofyziologie   MeSH
• difuzní magnetická rezonance * MeSH
• kognice * MeSH
• kognitivní dysfunkce diagnostické zobrazování   patofyziologie   psychologie   MeSH
• lakunární cévní mozková příhoda diagnostické zobrazování   patofyziologie   psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• prostorové chování * MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• vnímání prostoru * MeSH
• zobrazování difuzních tenzorů * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Identification of famous landmarks (FLI), famous faces (FFI) and recognition of facial emotions (FER) is affected early in the course of Alzheimer's disease (AD). FFI, FER and FLI may represent domain specific tasks relying on activation of distinct regions of the medial temporal lobe, which are affected successively during the course of AD. However, the data on FFI and FER in MCI are controversial and FLI domain remains almost unexplored. OBJECTIVES: To determine whether and how are these three specific domains impaired in head to head comparison of patients with amnestic MCI (aMCI) single domain (SD-aMCI) and multiple domain (MD-aMCI). We propose that FLI might be most reliable in differentiating SD-aMCI, which is considered to be an earlier stage of AD pathology spread out, from the controls. PATIENTS AND METHODS: A total of 114 patients, 13 with single domain (SD-aMCI) and 30 with multiple domains (MD-aMCI), 29 with mild AD and 42 controls underwent standard neurological and neuropsychological evaluations as well as tests of FLI, FER and FFI. RESULTS: Compared to the control group, AD subjects performed worse on FFI (p = 0.020), FER (p<0.001) and FLI (p<0.001), MD-aMCI group had significantly worse scores only on FLI (p = 0.002) and approached statistical significance on FER (0.053). SD-aMCI group performed significantly worse only on FLI (p = 0.028) compared to controls. CONCLUSIONS: Patients with SD-aMCI had an isolated impairment restricted to FLI, while patients with MD-aMCI showed impairment in FLI as well as in FER. Patients with mild dementia due to AD have more extensive impairment of higher visual perception. The results suggest that FLI testing may contribute to identification of patients at risk of AD. We hypothesize that clinical examination of all three domains might reflect the spread of the disease from transentorhinal cortex, over amygdala to fusiform gyrus.

• MeSH
• Alzheimerova nemoc diagnóza   psychologie   MeSH
• emoce MeSH
• kognitivní dysfunkce * MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• rozpoznávání (psychologie) MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spánkový lalok patologie   MeSH
• výraz obličeje MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Although the memory impairment is a hallmark of Alzheimer's disease (AD), AD has also been characterized by spatial disorientation, which is present from its early stages. Spatial disorientation in AD manifests itself in getting lost in familiar and unfamiliar places and have been characterized more specifically using spatial navigation tests in both real space and virtual environments as an impairment in multiple spatial abilities, including allocentric and egocentric navigation strategies, visuo-spatial perception, or selection of relevant information for successful navigation. Patients suffering mild cognitive impairment (MCI), who are at a high risk of development of dementia, show impairment in a subset of these abilities, mainly connected with allocentric and egocentric processing. While spatial disorientation in typical AD patients probably reflects neurodegenerative changes in medial and posterior temporal, parietal, and frontal lobes, and retrosplenial cortex, the impairment of spatial navigation in MCI seem to be connected mainly with the medial temporal and also parietal brain changes. In this review, we will summarize the signs of brain disease in most MCI and AD patients showing in various tasks of spatial memory and navigation.

• Klíčová slova
• Alzheimer’s disease, brain changes, mild cognitive impairment, spatial disorientation, spatial navigation,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Older age is associated with changes in the brain, including the medial temporal lobe, which may result in mild spatial navigation deficits, especially in allocentric navigation. The aim of the study was to characterize the profile of real-space allocentric (world-centered, hippocampus-dependent) and egocentric (body-centered, parietal lobe dependent) navigation and learning in young vs. older adults, and to assess a possible influence of gender. We recruited healthy participants without cognitive deficits on standard neuropsychological testing, white matter lesions or pronounced hippocampal atrophy: 24 young participants (18-26 years old) and 44 older participants stratified as participants 60-70 years old (n = 24) and participants 71-84 years old (n = 20). All underwent spatial navigation testing in the real-space human analog of the Morris Water Maze, which has the advantage of assessing separately allocentric and egocentric navigation and learning. Of the eight consecutive trials, trials 2-8 were used to reduce bias by a rebound effect (more dramatic changes in performance between trials 1 and 2 relative to subsequent trials). The participants who were 71-84 years old (p < 0.001), but not those 60-70 years old, showed deficits in allocentric navigation compared to the young participants. There were no differences in egocentric navigation. All three groups showed spatial learning effect (p' s ≤ 0.01). There were no gender differences in spatial navigation and learning. Linear regression limited to older participants showed linear (β = 0.30, p = 0.045) and quadratic (β = 0.30, p = 0.046) effect of age on allocentric navigation. There was no effect of age on egocentric navigation. These results demonstrate that navigation deficits in older age may be limited to allocentric navigation, whereas egocentric navigation and learning may remain preserved. This specific pattern of spatial navigation impairment may help differentiate normal aging from prodromal Alzheimer's disease.

• Klíčová slova
• Alzheimer’s disease, aging, allocentric navigation, egocentric navigation, gender, hippocampus, spatial learning, spatial navigation,
• Publikační typ
• časopisecké články MeSH