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Objectives Endothelial dysfunction (ED) has been linked to the pathogenesis of cerebral small vessel disease (SVD). We aimed to assess ED and cerebrovascular reactivity (CVR) in the patients with a diverse manifestation of SVD, with similar and extensive white matter lesions (WMLs, modified Fazekas scale grade ≥2), compared with a control group (CG) without the MRI markers of SVD, matched for age, gender, hypertension, diabetes, and to evaluate the change of CVR following 24 months. Methods We repeatedly measured the vasomotor reactivity reserve (VMRr) and breath-holding index (BHI) of the middle cerebral artery (MCA) by the transcranial Doppler ultrasound (TCD) techniques in 60 subjects above 60 years with a history of lacunar stroke (LS), vascular dementia (VaD), or parkinsonism (VaP) (20 in each group), and in 20 individuals from a CG. Results The mean age, frequency of the main vascular risk factors, and sex distribution were similar in the patients with the SVD groups and a CG. The VMRr and the BHI were more severely impaired at baseline (respectively, 56.7 ± 18% and 0.82 ± 0.39) and at follow-up (respectively, 52.3 ± 16.7% and 0.71 ± 0.38) in the patients with SVD regardless of the clinical manifestations (ANOVA, p > 0.1) than in the CG (respectively, baseline VMRr 77.2 ± 15.6%, BHI 1.15 ± 0.47, p 0.1). Conclusions This study provided evidence that the change in CVR measures is detectable over a 24-month period in patients with different clinical manifestations of SVD. Compared with the patients in CG with similar atherothrombotic risk factors, all the CVR measures (BMRr and BHI) significantly declined over time in the subjects with SVD. The reduction in CVR was not related to the SVD radiological progression.Background The promotion of healthy aging is one of the major challenges for healthcare systems in current times. The present study investigates the effects of a standardized physical activity intervention for older adults on cognitive capacity, self-reported health, fear of falls, balance, leg strength and gait under consideration of movement biography, sleep duration, and current activity behavior. Methods This single-blinded, randomized controlled trial included 49 community-dwelling older adults (36 women; 82.9 ± 4.5 years of age (Mean [M] ± SD); intervention group = 25; control group = 24). Movement biography, sleep duration, cognitive capacity, self-reported health status, and fear of falls were assessed by means of questionnaires. Leg strength, gait, and current activity levels were captured using a pressure plate, accelerometers, and conducting the functional-reach and chair-rising-test. The multicomponent intervention took place twice a week for 45 min and lasted 16 weeks. Sub-cohorts of different slination with adequate sleep duration appears to provide combinable beneficial effects for cognitive capacity in older adults. Trainability of gait, fear of falls, and flexibility seems to be affected by movement biography and current physical activity levels. Trial registration This study was registered at the DRKS (German Clinical Trials Register) on November 11, 2020 with the corresponding trial number DRKS00020472.The current pilot study aimed to test the gains of working memory (WM) training, both at the short- and long-term, at a behavioral level, and by examining the electrophysiological changes induced by training in resting-state EEG activity among older adults. The study group included 24 older adults (from 64 to 75 years old) who were randomly assigned to a training group (TG) or an active control group (ACG) in a double-blind, repeated-measures experimental design in which open eyes, resting-state EEG recording, followed by a WM task, i.e., the Categorization Working Memory Span (CWMS) task, were collected before and after training, as well as at a 6-month follow-up session. At the behavioral level, medium to large Cohen's d effect sizes was found for the TG in immediate and long-term gains in the WM criterion task, as compared with small gains for the ACG. Regarding intrusion errors committed in the CWMS, an index of inhibitory control representing a transfer effect, results showed that medium to large effect sizes for immediate and long-term gains emerged for the TG, as compared to small effect sizes for the ACG. Spontaneous high-beta/alpha ratio analyses in four regions of interest (ROIs) revealed no pre-training group differences. Significantly greater TG anterior rates, particularly in the left ROI, were found after training, with frontal oscillatory responses being correlated with better post-training CWMS performance in only the TG. The follow-up analysis showed similar results, with greater anterior left high-beta/alpha rates among TG participants. Follow-up frontal high-beta/alpha rates in the right ROI were correlated with lower CWMS follow-up intrusion errors in only the TG. The present findings are further evidence of the efficacy of WM training in enhancing the cognitive functioning of older adults and their frontal oscillatory activity. Overall, these results suggested that WM training also can be a promising approach toward fostering the so-called functional cortical plasticity in aging.Objective To explore the frequency, evolution, associated factors, and risk factors of fatigue over 3-year of prospective follow-up in a cohort of patients with early Parkinson's disease (PD). Methods A total of 174 PD patients in the early stage were enrolled and quantitively assessed motor and non-motor symptoms using comprehensive scales including the Fatigue Severity Scale (FSS) annually. Each subject was categorized as PD with and without fatigue based on a cut-off mean value of 4 using FSS. The generalized estimating equation (GEE) was utilized to investigate the associated factors, and the stepwise binary logistic regression model was performed to explore the predictors. Results The frequency of fatigue was slightly changed (ranging from 35.1 to 40.4%) during the 3-year follow-up. The changed pattern of the frequency of fatigue was similar to that of anxiety. Fatigue was significantly associated with nocturnal sleep disorders (B 2.446, P less then 0.001), high Hamilton Anxiety Rating Scale (HAMA) score (B 1.072, P = 0.011), and high Unified PD Rating Scale (UPDRS) III score (B 1.029, P = 0.003) over time. High UPDRS III score [odds ratio (OR) 1.051, P = 0.015] at baseline increased the risk of developing fatigue after 1-year; high LEDD (OR 1.002, P = 0.037) increased the risk of developing fatigue after 2-year; and high LEDD (OR 1.003, P = 0.049) and high HAMA score (OR 1.077, P = 0.042) increased the risk of developing fatigue after 3-year. Conclusion Our present study provided evidence of the longitudinal evolution of fatigue in patients with early PD and help clinical management of fatigue.Proteinaceous inclusions, called Lewy bodies (LBs), are used as a pathological hallmark for Parkinson's disease (PD). Recent studies suggested a prion-like spreading mechanism for α-synucleinopathy where early neuropathological deposits occur, among others, in the olfactory bulb (OB) and amygdala. LBs contain insoluble α-synuclein and many other ubiquitinated proteins, suggesting a role of protein degradation system failure in PD pathogenesis. Therefore, we wanted to study the effects of a proteasomal inhibitor, lactacystin, on the aggregability and transmissibility of α-synuclein in the OB and amygdala. We performed injections of lactacystin in the OB and amygdala of wild-type mice. Motor behavior, markers of neuroinflammation, α-synuclein, and dopaminergic integrity were assessed by immunohistochemistry. Overall, there were no differences in the number of neurons and α-synuclein expression in these regions following injection of lactacystin into either the OB or amygdala. Microglial and astroglial labeling appeared to be correlated with surgery-induced inflammation or local effects of lactacystin. Consistent with the behavior and pathological findings, there was no loss of dopaminergic cell bodies in the substantia nigra and terminals in the striatum. Our data showed that long-term lactacystin injections in extra nigrostriatal regions may not mimic spreading aspects of PD and reinforce the special vulnerability of dopaminergic neurons of the substantia nigra pars compacta (SNc).Aphasia is characterized by the disability of spontaneous conversation, listening, understanding, retelling, naming, reading, or writing. However, the neural mechanisms of language damage after stroke are still under discussion. This study aimed to investigate the global and nodal characterization of the functional networks in patients with aphasic stroke based on resting-state functional MRI (fMRI). DT-061 price Twenty-four right-handed patients with aphasia after stroke and 19 healthy controls (HC) underwent a 3-TfMRI scan. A whole-brain large-scale functional connectivity network was then constructed based on Power's atlas of 264 functional regions of interest, and the global and nodal topological properties of these networks were analyzed using graph theory approaches. The results showed that patients with aphasia had decreased in small-worldness (sigma), normalized clustering coefficient (gamma), and local efficiency (E loc) values. Furthermore, E loc was positively correlated with language ability, retelling, naming, and listening comprehension in patients with aphasia. Patients with aphasia also had decreased nodal degree and decreased nodal efficiency in the left postcentral gyrus, central opercular cortex, and insular cortex. Our results suggest that the global and local topology attributes were altered by injury in patients with aphasic stroke. We argue that the local efficiency of brain networks might be used as a potential indicator of basic speech function in patients with aphasia.Objectives To compare gray matter microstructural characteristics of higher-order olfactory regions among older adults with and without hyposmia. Methods Data from the Brief Smell Identification Test (BSIT) were obtained in 1998-99 for 265 dementia-free adults from the Health, Aging, and Body Composition study (age at BSIT 74.9 ± 2.7; 62% White; 43% male) who received 3T diffusion tensor imaging in 2006-08 [Interval of time mean (SD) 8.01 years (0.50)], Apolipoprotein (ApoEε4) genotypes, and repeated 3MS assessments until 2011-12. Cognitive status (mild cognitive impairment, dementia, normal cognition) was adjudicated in 2011-12. Hyposmia was defined as BSIT ≤ 8. Microstructural integrity was quantified by mean diffusivity (MD) in regions of the primary olfactory cortex amygdala, orbitofrontal cortex (including olfactory cortex, gyrus rectus, the orbital parts of the superior, middle, and inferior frontal gyri, medial orbital part of the superior frontal gyrus), and hippocampus. Multivariable regression models were adjusted for total brain atrophy, demographics, cognitive status, and ApoEε4 genotype. Results Hyposmia in 1998-99 (n = 57, 21.59%) was significantly associated with greater MD in 2006-08, specifically in the orbital part of the middle frontal gyrus, and amygdala, on the right [adjusted beta (p value) 0.414 (0.01); 0.527 (0.01); respectively]. Conclusion Older adults with higher mean diffusivity in regions important for olfaction are more likely to have hyposmia up to ten years prior. Future studies should address whether hyposmia can serve as an early biomarker of brain microstructural abnormalities for older adults with a range of cognitive functions, including those with normal cognition.

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