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Abstract Background Mild behavioral impairment (MBI) has been commonly reported in early Alzheimer’s disease (AD) but rarely using biomarker-defined samples. It is also unclear whether genetic polymorphisms influence MBI in such individuals. We thus aimed to examine the association between the cognitive status of participants (amnestic mild cognitive impairment (aMCI-AD) vs cognitively normal (CN) older adults) and MBI severity. Within aMCI-AD, we further examined the association between APOE and BDNF risk genetic polymorphisms and MBI severity. Methods We included 62 aMCI-AD participants and 50 CN older adults from the Czech Brain Aging Study. The participants underwent neurological, comprehensive neuropsychological examination, APOE and BDNF genotyping, and magnetic resonance imaging. MBI was diagnosed with the Mild Behavioral Impairment Checklist (MBI-C), and the diagnosis was based on the MBI-C total score ≥ 7. Additionally, self-report instruments for anxiety (the Beck Anxiety Inventory) and depressive symptoms (the Geriatric Depression Scale-15) were administered. The participants were stratified based on the presence of at least one risk allele in genes for APOE (i.e., e4 carriers and non-carriers) and BDNF (i.e., Met carriers and non-carriers). We used linear regressions to examine the associations. Results MBI was present in 48.4% of the aMCI-AD individuals. Compared to the CN, aMCI-AD was associated with more affective, apathy, and impulse dyscontrol but not social inappropriateness or psychotic symptoms. Furthermore, aMCI-AD was related to more depressive but not anxiety symptoms on self-report measures. Within the aMCI-AD, there were no associations between APOE e4 and BDNF Met and MBI-C severity. However, a positive association between Met carriership and self-reported anxiety appeared. Conclusions MBI is frequent in aMCI-AD and related to more severe affective, apathy, and impulse dyscontrol symptoms. APOE and BDNF polymorphisms were not associated with MBI severity separately; however, their combined effect warrants further investigation.

IntroductionChoroid plexus (CP)-related mechanisms have been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease. In this pilot study, we aimed to elucidate the association between longitudinal changes in CP volume, sex and cognitive impairment.MethodsWe assessed longitudinal changes in CP volume in a cohort of n = 613 subjects across n = 2,334 datapoints from ADNI 2 and ADNI-GO, belonging to cognitively unimpaired (CN), stable mild cognitive impairment (MCI), clinically diagnosed Alzheimer’s disease dementia (AD) or convertor (to either AD or MCI) subgroups. CP volume was automatically segmented and used as a response variable in linear mixed effect models with random intercept clustered by patient identity. Temporal effects of select variables were assessed by interactions and subgroup analyses.ResultsWe found an overall significant increase of CP volume in time (14.92 mm3 per year, 95% confidence interval, CI (11.05, 18.77), p

BackgroundSpatial navigation impairment is a promising cognitive marker of Alzheimer’s disease (AD) that can reflect the underlying pathology.ObjectivesWe 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.MethodsA 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).ResultsIn 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.ConclusionAD 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.

Aim: The aim of this cytogenetic study is to confirm the significance of chromosome 3 loss (monosomy 3) and of the gain of chromosome 8 as prognostic markers in histopathological samples of enucleated eyes with uveal melanoma in the Czech population. Methods: This is a retrospective study of 52 enucleated eyes. Chromosome 3 and 8 status were tested by CISH, and in a few samples FISH was used. The correlation between monosomy 3 and gain of chromosome 8 and clinical features (histopathological type, size of the tumour) were evaluated. A follow up for the detection of metastases was conducted in all patients. The statistical significance of chromosomal abnormalities as a prognostic factor for the development of metastases was calculated. Results: There were 52 patients, 27 men (51.9%) and 25 women (48.1%) enrolled in our study group. The mean age was 63 ± 14 years. Loss of the one copy of chromosome 3 (monosomy 3) was detected in 26 (50.0%) patients, monosomy 8 was present in 34.6% of patients with monosomy 3. After 5 years there were no metastases in 82% of patients without monosomy 3 as opposed to 40% of patients with monosomy 3. We confirmed a statistically significant association between progression free survival (PFS) and the presence of monosomy 3 (P=0.017). The association between PFS and gain of chromosome 8 was significant as well (0.010). Conclusions: Our data showed the association of progression-free survival with the presence of monosomy 3 in uveal melanomas. We provided a good prognostic value of monosomy 3 in uveal melanoma.

ObjectivesMild behavioral impairment (MBI) is a syndrome describing late-onset persistent neuropsychiatric symptoms (NPS) in non-demented older adults. Few studies to date have investigated the associations of MBI with structural brain changes. Our aim was to explore structural correlates of NPS in a non-demented memory clinic sample using the Mild Behavioral Impairment Checklist (MBI-C) that has been developed to measure MBI.MethodsOne hundred sixteen non-demented older adults from the Czech Brain Aging Study with subjective cognitive concerns were classified as subjective cognitive decline (n = 37) or mild cognitive impairment (n = 79). Participants underwent neurological and neuropsychological examinations and brain magnetic resonance imaging (MRI) (1.5 T). The Czech version of the MBI-C was administered to participants’ informants. Five a priori selected brain regions were measured, namely, thicknesses of the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and entorhinal cortex (ERC) and volume of the hippocampus (HV), and correlated with MBI-C total and domain scores.ResultsEntorhinal cortex was associated with MBI-C total score (rS = −0.368, p < 0.001) and with impulse dyscontrol score (rS = −0.284, p = 0.002). HV was associated with decreased motivation (rS = −0.248, p = 0.008) and impulse dyscontrol score (rS = −0.240, p = 0.011).ConclusionNeuropsychiatric symptoms, particularly in the MBI impulse dyscontrol and motivation domains, are associated with medial temporal lobe atrophy in a clinical cohort of non-demented older adults. This study supports earlier involvement of temporal rather than frontal regions in NPS manifestation. Since these regions are typically affected early in the course of Alzheimer’s disease (AD), the MBI-C may potentially help further identify individuals at-risk of developing AD dementia.

Aim. A retrospective evaluation of the results of treatment of myopic choroidal neovascularization (mCNV) with intravitreal injections of ranibizumab in a pro re nata (PRN) regimen in three groups of patients distributed according to axial length. Methods. The paper presents a retrospective multicenter study carried out with the cooperation of several Departments of Ophthalmology in the Czech Republic. The study included 60 eyes of 60 patients suffering from mCNV, divided according to axial length into three groups. The first group consisted of 20 patients with an axial length of the eyes shorter than 28 mm (Group 1), the second group included 27 patients with axial lengths ranging from 28 mm to 29.81 mm (Group 2), and 13 patients had axial lengths longer than 30 mm (Group 3). All patients were first administered 3 initial intravitreal ranibizumab injections at monthly intervals (loading phase), and other injections were administered according to a PRN treatment regimen. Patients were evaluated before treatment and then at intervals of 3, 6, 9, and 12 months. The effect of ranibizumab treatment on the functional and morphological parameters of the affected eye was evaluated. Results. The average baseline BCVA ± SD in Group 1 was 52.6 ± 12.5 letters of ETDRS optotypes, and at the end of the one-year follow-up, it was 63.3 ± 11.8 letters. The average baseline of CRT ± SD in this group was 377.4 ± 80.0 μm, and in the 12th month, it was 311.1 ± 63.7 μm. The average baseline BCVA ± SD in Group 2 was 50.2 ± 9.0 ETDRS letters, and at the end of the follow-up, it was 60 ± 12.4 letters. The average baseline of CRT ± SD in Group 2 was 391.2 ± 85.2 μm, and in the 12th month, it was 323.9 ± 91.2 μm. In Group 3, the average baseline of BCVA was 48.5 ± 14.5 ETDRS letters, and at the end of the one-year follow-up, it was 55.7 ± 16.1 letters. The average baseline CRT ± SD for Group 3 was 342.1 ± 94.9 μm, and after 12 months, it was 287.8 ± 88.4 μm. An improvement of BCVA by ≥15 letters of ETDRS optotypes was achieved by 3 patients of 20 (15%) in Group 1, by 5 patients of 27 (18.5%) in Group 2, and by 3 patients of 13 (23.1%) in Group 3. All these changes were statistically significant in comparison with the input values p

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.

Despite the rising global burden of stroke and its socio-economic implications, the neuroimaging predictors of subsequent cognitive impairment are still poorly understood. We address this issue by studying the relationship of white matter integrity assessed within ten days after stroke and patients' cognitive status one year after the attack. Using diffusion-weighted imaging, we apply the Tract-Based Spatial Statistics analysis and construct individual structural connectivity matrices by employing deterministic tractography. We further quantify the graph-theoretical properties of individual networks. The Tract-Based Spatial Statistic did identify lower fractional anisotropy as a predictor of cognitive status, although this effect was mostly attributable to the age-related white matter integrity decline. We further observed the effect of age propagating into other levels of analysis. Specifically, in the structural connectivity approach we identified pairs of regions significantly correlated with clinical scales, namely memory, attention, and visuospatial functions. However, none of them persisted after the age correction. Finally, the graph-theoretical measures appeared to be more robust towards the effect of age, but still were not sensitive enough to capture a relationship with clinical scales. In conclusion, the effect of age is a dominant confounder especially in older cohorts, and unless appropriately addressed, may falsely drive the results of the predictive modelling.

Abstract To identify knowledge gaps regarding new‐onset agitation and impulsivity prior to onset of cognitive impairment or dementia the International Society to Advance Alzheimer's Research and Treatment Neuropsychiatric Syndromes (NPS) Professional Interest Area conducted a scoping review. Extending a series of reviews exploring the pre‐dementia risk syndrome Mild Behavioral Impairment (MBI), we focused on late‐onset agitation and impulsivity (the MBI impulse dyscontrol domain) and risk of incident cognitive decline and dementia. This scoping review of agitation and impulsivity pre‐dementia syndromes summarizes the current biomedical literature in terms of epidemiology, diagnosis and measurement, neurobiology, neuroimaging, biomarkers, course and prognosis, treatment, and ongoing clinical trials. Validations for pre‐dementia scales such as the MBI Checklist, and incorporation into longitudinal and intervention trials, are needed to better understand impulse dyscontrol as a risk factor for mild cognitive impairment and dementia.