BACKGROUND: Spatial navigation deficits are early symptoms of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for AD. This study investigated effects of APOE genotype on spatial navigation in biomarker-defined individuals with amnestic mild cognitive impairment (aMCI) and associations of AD biomarkers and atrophy of AD-related brain regions with spatial navigation. METHODS: 107 participants, cognitively normal older adults (CN, n = 48) and aMCI individuals stratified into AD aMCI (n = 28) and non-AD aMCI (n = 31) groups, underwent cognitive assessment, brain MRI, and spatial navigation assessment using the Virtual Supermarket Test with egocentric and allocentric tasks and a self-report questionnaire. Cerebrospinal fluid (CSF) biomarkers (amyloid-β1-42, phosphorylated tau181 and total tau) and amyloid PET imaging were assessed in aMCI participants. RESULTS: AD aMCI participants had the highest prevalence of APOE ε4 carriers and worst allocentric navigation. CSF levels of AD biomarkers and atrophy in AD-related brain regions were associated with worse allocentric navigation. Between-group differences in spatial navigation and associations with AD biomarkers and regional brain atrophy were not influenced by APOE genotype. Self-reported navigation ability was similar across groups and unrelated to spatial navigation performance. CONCLUSIONS: These findings suggest that allocentric navigation deficits in aMCI individuals are predominantly driven by AD pathology, independent of APOE genotype. This highlights the role of AD pathology as measured by biomarkers, rather than genetic status, as a major factor in navigational impairment in aMCI, and emphasizes the assessment of spatial navigation as a valuable tool for early detection of AD.

• Klíčová slova
• Allocentric navigation, Amyloid-β, Egocentric navigation, Entorhinal cortex, Hippocampus, Tau protein,
• MeSH
• Alzheimerova nemoc * genetika   mozkomíšní mok   diagnostické zobrazování   komplikace   patofyziologie   patologie   MeSH
• amyloidní beta-protein mozkomíšní mok   MeSH
• apolipoprotein E4 * genetika   MeSH
• apolipoproteiny E * genetika   MeSH
• atrofie MeSH
• biologické markery mozkomíšní mok   MeSH
• genotyp MeSH
• kognitivní dysfunkce * genetika   mozkomíšní mok   diagnostické zobrazování   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   diagnostické zobrazování   MeSH
• neuropsychologické testy MeSH
• peptidové fragmenty mozkomíšní mok   MeSH
• pozitronová emisní tomografie MeSH
• prostorová navigace * fyziologie   MeSH
• proteiny tau mozkomíšní mok   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
• Názvy látek
• amyloid beta-protein (1-42) MeSH Prohlížeč
• amyloidní beta-protein MeSH
• apolipoprotein E4 * MeSH
• apolipoproteiny E * MeSH
• biologické markery MeSH
• peptidové fragmenty MeSH
• proteiny tau MeSH

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: 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.

• Klíčová slova
• Basal forebrain, Progression risk, Spatial navigation, Structural covariance network, Subjective cognitive decline,
• MeSH
• Alzheimerova nemoc * komplikace   MeSH
• kognitivní dysfunkce * psychologie   MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• progrese nemoci MeSH
• prostorová navigace * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Dementia syndrome is one of the most devastating conditions in older adults. As treatments to stop neurodegeneration become available, accurate and timely diagnosis will increase in importance. One issue is that cognitive performance sometimes does not match the corresponding level of neuropathology, affecting diagnostic accuracy. Cognitive reserve (CR), which can preserve cognitive function despite underlying neuropathology, explains at least some variability in cognitive performance. We examined the influence of CR proxies (education and occupational position) on the relationship between hippocampal or total gray matter volume and cognition. METHODS: We used data from the Czech Brain Aging Study. Participants were clinically confirmed to be without dementia (n = 457, including subjective cognitive decline and amnestic mild cognitive impairment) or with dementia syndrome (n = 113). RESULTS: For participants without dementia, higher education magnified the associations between (a) hippocampal volume and executive control (b = 0.09, p = 0.033), (b) total gray matter volume and language (b = 0.12, p < 0.001), and (c) total gray matter volume and memory (b = 0.08, p = 0.018). Similarly, higher occupational position magnified the association between total gray matter volume and (a) attention/working memory (b = 0.09, p = 0.009), (b) language (b = 0.13, p = 0.002), and (c) memory (b = 0.10, p = 0.013). For participants with dementia, the associations between hippocampal (b = -0.26, p = 0.024) and total gray matter (b = -0.28, p = 0.024) volume and visuospatial skills decreased in magnitude with higher education. CONCLUSION: We found that the association between brain volume and cognitive performance varies based on CR, with greater CR related to a stronger link between brain volume and cognition before, and a weaker link after, dementia diagnosis.

• Klíčová slova
• MRI, attention/working memory, executive control, language, visuospatial skills,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The ability to understand emotions is often disturbed in patients with cognitive impairments. Right temporal lobe structures play a crucial role in emotional processing, especially the amygdala, temporal pole (TP), superior temporal sulcus (STS), and anterior cingulate (AC). Those regions are affected in early stages of Alzheimer´s disease (AD). The aim of our study was to evaluate emotional prosody recognition (EPR) in participants with amnestic mild cognitive impairment (aMCI) due to AD, AD dementia patients, and cognitively healthy controls and to measure volumes or thickness of the brain structures involved in this process. In addition, we correlated EPR score to cognitive impairment as measured by MMSE. The receiver operating characteristic (ROC) analysis was used to assess the ability of EPR tests to differentiate the control group from the aMCI and dementia groups. METHODS: Eighty-nine participants from the Czech Brain Aging Study: 43 aMCI due to AD, 36 AD dementia, and 23 controls, underwent Prosody Emotional Recognition Test. This experimental test included the playback of 25 sentences with neutral meaning each recorded with different emotional prosody (happiness, sadness, fear, disgust, anger). Volume of the amygdala and thickness of the TP, STS, and rostral and caudal parts of AC (RAC and CAC) were measured using FreeSurfer algorithm software. ANCOVA was used to evaluate EPR score differences. ROC analysis was used to assess the ability of EPR test to differentiate the control group from the aMCI and dementia groups. The Pearson's correlation coefficients were calculated to explore relationships between EPR scores, structural brain measures, and MMSE. RESULTS: EPR was lower in the dementia and aMCI groups compared with controls. EPR total score had high sensitivity in distinguishing between not only controls and patients, but also controls and aMCI, controls and dementia, and aMCI and dementia. EPR decreased with disease severity as it correlated with MMSE. There was a significant positive correlation of EPR and thickness of the right TP, STS, and bilateral RAC. CONCLUSIONS: EPR is impaired in AD dementia and aMCI due to AD. These data suggest that the broad range of AD symptoms may include specific deficits in the emotional sphere which further complicate the patient's quality of life.

• Klíčová slova
• Alzheimer´s disease, Emotion recognition, Mild cognitive impairment, Prosody, Superior temporal sulcus, Temporal pole,
• MeSH
• Alzheimerova nemoc * diagnóza   psychologie   MeSH
• emoce MeSH
• kognitivní dysfunkce * diagnóza   psychologie   MeSH
• kvalita života MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• rozpoznávání (psychologie) MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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

Individuals with subjective cognitive decline (SCD) are at higher risk of incipient Alzheimer's disease (AD). Spatial navigation (SN) impairments in AD dementia and mild cognitive impairment patients have been well-documented; however, studies investigating SN deficits in SCD subjects are still lacking. This study aimed to explore whether basal forebrain (BF) and entorhinal cortex (EC) atrophy contribute to spatial disorientation in the SCD stage. In total, 31 SCD subjects and 24 normal controls were enrolled and administered cognitive scales, a 2-dimensional computerized SN test, and structural magnetic resonance imaging (MRI) scanning. We computed the differences in navigation distance errors and volumes of BF subfields, EC, and hippocampus between the SCD and control groups. The correlations between MRI volumetry and navigation distance errors were also calculated. Compared with the controls, the SCD subjects performed worse in both egocentric and allocentric navigation. The SCD group showed volume reductions in the whole BF (p < 0.05, uncorrected) and the Ch4p subfield (p < 0.05, Bonferroni corrected), but comparable EC and hippocampal volumes with the controls. In the SCD cohort, the allocentric errors were negatively correlated with total BF (r = -0.625, p < 0.001), Ch4p (r = -0.625, p < 0.001), total EC (r = -0.423, p = 0.031), and left EC volumes (r = -0.442, p = 0.024), adjusting for age, gender, years of education, total intracranial volume, and hippocampal volume. This study demonstrates that SN deficits and BF atrophy may be promising indicators for the early detection of incipient AD patients. The reduced BF volume, especially in the Ch4p subfield, may serve as a structural basis for allocentric disorientation in SCD subjects independent of hippocampal atrophy. Our findings may have further implications for the preclinical diagnosis and intervention for potential AD patients.

• Klíčová slova
• allocentric, basal forebrain, entorhinal cortex, spatial navigation, subjective cognitive decline,
• Publikační typ
• časopisecké články 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

• Klíčová slova
• Alzheimer’s disease, aging, basal forebrain, hippocampus, spatial navigation,
• MeSH
• Alzheimerova nemoc patologie   MeSH
• hipokampus patologie   fyziologie   MeSH
• kognitivní dysfunkce patologie   MeSH
• lidé MeSH
• prostorová navigace * MeSH
• stárnutí * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• úvodníky MeSH