Cognitive and neuropsychological functions have been impaired at high altitude and the effects depend on altitude and duration of stay. However, the neurobiological mechanism of this impairment is poorly understood especially exposure to different duration. Aim of the present study was to investigate the changes of behavior, biochemistry and morphology after exposure to different duration of hypobaric hypoxia. The rats were exposed continuously to a simulated high altitude of 6100m for 3, 7, 14 and 21 days in an animal decompression chamber. Spatial reference memory was tested by Morris water maze. The oxidative stress markers like free radicals, NO, lipid peroxidation, LDH activity and antioxidant systems like GSH, GSSG, GPx, GR, SOD were estimated from cortex, hippocampus and striatum. The morphological changes, neurodegeneration, DNA fragmentation and mode of cell death have also been studied. It was observed that the spatial reference memory was significantly affected after exposure to hypobaric hypoxia. Increased oxidative stress markers along with decreased effectiveness of antioxidant system were also observed in hypoxia-exposed animals. Further pyknotic, shrunken, tangle-like neurons were observed in all these regions after hypoxia and neurodegeneration, DNA fragmentation and apoptosis were also observed in all the three regions. But after 21 days of exposure, the spatial memory was improved along with improvement of antioxidant activities. Our result suggests that the apoptotic death may be involved in HA-induced memory impairment and after 7 days of exposure the effect was more pronounced but after 21 days of exposure recovery was observed.

&lt;b&gt;<i>Introduction:</i>&lt;/b&gt; Dementia is a chronic disease with a variable prevalence throughout the world; however, this could be higher at high-altitude populations. We aimed to summarize the prevalence of cognitive impairment and dementia in older adults living at high altitude. &lt;b&gt;<i>Methods:</i>&lt;/b&gt; We searched in PubMed, Medline, Scopus, Web of Science, and Embase and included the studies published from inception to July 20, 2020, with no language restriction, which reported the frequency of cognitive impairment or dementia in older adults living at high-altitude populations. Random-effects meta-analyses were performed to calculate the overall prevalence and 95% confidence intervals (95% CI) of cognitive impairment and dementia. The risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS) adapted for cross-sectional studies. &lt;b&gt;<i>Results:</i>&lt;/b&gt; Six studies were included (3,724 participants), and 5 of the 6 included studies were carried out in Latin America. The altitude ranged from 1,783 to 3,847 m, the proportion of women included varied from 38.7 to 65.6%, and the proportion of participants with elementary or illiterate educational level ranged from 71.7 to 97.6%. The overall prevalence of cognitive impairment was 22.0% (95% CI: 8–40, <i>I</i>²: 99%), and the overall prevalence of dementia was 11.0% (95% CI: 6–17, <i>I</i>²: 92%). In a subgroup analysis according to the instrument used to evaluate cognitive impairment, the prevalence of cognitive impairment was 21.0% (95% CI: 5–42, <i>I</i>²: 99%) in the MMSE group while the prevalence was 29.0% (95% CI: 0–78) in the non-MMSE group. &lt;b&gt;<i>Conclusions:</i>&lt;/b&gt; The prevalence of cognitive impairment and dementia in older adults living at high altitude is almost twice the number reported in some world regions.

Tau pathology and vascular dysfunction are important contributors to Alzheimer's disease (AD), but vascular-tau associations and their effects on cognition are poorly understood. We investigated these associations in male and female humans by conducting voxelwise comparisons between cerebral blood flow (CBF) and tau positron emission tomography (PET) images in independent discovery [cognitively normal (CN), 19; mild cognitive impairment (MCI) risk, 43; MCI, 6] and replication (CN,73; MCI, 45; AD, 20) cohorts. In a subgroup, we assessed relationships between tau and soluble platelet-derived growth factor β (sPDGFRβ), a CSF marker of pericyte injury. We tested whether CBF/sPDGFRβ-tau relationships differed based on Montreal Cognitive Assessment (MoCA) global cognition performance, or based on amyloid burden. Mediation analyses assessed relationships among CBF/sPDGFRβ, tau, and cognition. Negative CBF-tau correlations were observed predominantly in temporal-parietal regions. In the replication cohort, early negative CBF-tau correlations increased in spatial extent and in strength of correlation with increased disease severity. Stronger CBF-tau and sPDGFRβ-tau correlations were observed in participants with greater amyloid burden and lower MoCA scores. Importantly, when stratifying by amyloid status, stronger CBF-tau relationships in individuals with lower MoCA scores were driven by amyloid participants. Tau PET was a significant mediator CBF/sPDGFRβ-MoCA relationships in numerous regions. Our results demonstrate vascular-tau associations across the AD spectrum and suggest that early vascular-tau associations are exacerbated in the presence of amyloid, consistent with a two-hit model of AD on cognition. Combination treatments targeting vascular health, as well as amyloid-β and tau levels, may preserve cognitive function more effectively than single-target therapies. Emerging evidence demonstrates a role for vascular dysfunction as a significant contributor to Alzheimer's pathophysiology. However, associations between vascular dysfunction and tau pathology, and their effects on cognition remain poorly understood. Multimodal neuroimaging data from two independent cohorts were analyzed to provide novel evidence of associations between cerebral blood flow (CBF), an MRI measure of vascular health, and tau pathology using PET. CBF-tau associations were related to cognition and driven in part by amyloid burden. Soluble platelet-derived growth factor β, an independent CSF vascular biomarker, confirmed vascular-tau associations in a subgroup analysis. These results suggest that combination treatments targeting vascular health, amyloid-β, and tau levels may more effectively preserve cognitive function than single-target therapies.Copyright © 2020 the authors.

Objective: Headache and memory impairment are the primary clinical symptoms of chronic mountain sickness (CMS). In this study, we used voxel-based morphometry (VBM) and the amplitude of the low-frequency fluctuation method (ALFF) based on blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) to identify changes in the brain structure and function caused by CMS.

Tau pathology and vascular dysfunction are important contributors to Alzheimer's disease (AD), but vascular-tau associations and their effects on cognition are poorly understood. We investigated these associations in male and female humans by conducting voxelwise comparisons between cerebral blood flow (CBF) and tau positron emission tomography (PET) images in independent discovery [cognitively normal (CN), 19; mild cognitive impairment (MCI) risk, 43; MCI, 6] and replication (CN,73; MCI, 45; AD, 20) cohorts. In a subgroup, we assessed relationships between tau and soluble platelet-derived growth factor β (sPDGFRβ), a CSF marker of pericyte injury. We tested whether CBF/sPDGFRβ-tau relationships differed based on Montreal Cognitive Assessment (MoCA) global cognition performance, or based on amyloid burden. Mediation analyses assessed relationships among CBF/sPDGFRβ, tau, and cognition. Negative CBF-tau correlations were observed predominantly in temporal-parietal regions. In the replication cohort, early negative CBF-tau correlations increased in spatial extent and in strength of correlation with increased disease severity. Stronger CBF-tau and sPDGFRβ-tau correlations were observed in participants with greater amyloid burden and lower MoCA scores. Importantly, when stratifying by amyloid status, stronger CBF-tau relationships in individuals with lower MoCA scores were driven by amyloid participants. Tau PET was a significant mediator CBF/sPDGFRβ-MoCA relationships in numerous regions. Our results demonstrate vascular-tau associations across the AD spectrum and suggest that early vascular-tau associations are exacerbated in the presence of amyloid, consistent with a two-hit model of AD on cognition. Combination treatments targeting vascular health, as well as amyloid-β and tau levels, may preserve cognitive function more effectively than single-target therapies. Emerging evidence demonstrates a role for vascular dysfunction as a significant contributor to Alzheimer's pathophysiology. However, associations between vascular dysfunction and tau pathology, and their effects on cognition remain poorly understood. Multimodal neuroimaging data from two independent cohorts were analyzed to provide novel evidence of associations between cerebral blood flow (CBF), an MRI measure of vascular health, and tau pathology using PET. CBF-tau associations were related to cognition and driven in part by amyloid burden. Soluble platelet-derived growth factor β, an independent CSF vascular biomarker, confirmed vascular-tau associations in a subgroup analysis. These results suggest that combination treatments targeting vascular health, amyloid-β, and tau levels may more effectively preserve cognitive function than single-target therapies.Copyright © 2020 the authors.

The aim of the present study was to investigate cerebral microstructural alterations after single short-term mountain climbing. Voxel-based morphometry (VBM) analysis of gray matter (GM) and white matter (WM) volumes and Tract-Based Spatial Statistics (TBSS) analysis of WM fractional anisotropy (FA) based on MRI images were carried out on 14 mountaineers before and after mountain climbing (6206 m). In addition, verbal and spatial 'two-back' tasks and serial reaction time task were also tested. No significant changes were detected in total and regional volumes of GM, WM, and cerebral spinal fluid after mountain climbing. Significant decreased FA values were found in the bilateral corticospinal tract, corpus callosum (anterior and posterior body, splenium), reticular formation of dorsal midbrain, left superior longitudinal fasciculus, right posterior cingulum bundles, and left middle cerebellar peduncle. In all the above regions, the radial diffusivity values tended to increase, except in the left superior longitudinal fasciculus the change was statistically significant. There were no significant changes in the two cognitive tests after mountain climbing. These findings indicate that short-term high-altitude exposure leads to disturbances mainly in cerebral WM, showing compromised fiber microstructural integrity, which may clarify the mechanisms underlining some cognitive and motor deficits tested previously.

Structural network damage is a potentially important mechanism by which cerebral small vessel disease (SVD) can cause cognitive impairment. As a central hub of the structural network, the role of thalamus in SVD-related cognitive impairments remains unclear. We aimed to determine the associations between the structural alterations of thalamic subregions and cognitive impairments in SVD.In this cross-sectional study, 205 SVD participants without thalamic lacunes from the third follow-up (2020) of the prospective RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort), which was initiated in 2006, Nijmegen, were included. Cognitive functions included processing speed, executive function, and memory. Probabilistic tractography was performed from thalamus to 6 cortical regions, followed by connectivity-based thalamic segmentation to assess each thalamic subregion volume and connectivity (measured by mean diffusivity [MD] of the connecting white matter tracts) with the cortex. Least absolute shrinkage and selection operator regression analysis was conducted to identify the volumes or connectivity of the total thalamus and 6 thalamic subregions that have the strongest association with cognitive performance. Linear regression and mediation analyses were performed to test the association of least absolute shrinkage and selection operator-selected thalamic subregion volume or MD with cognitive performance, while adjusting for age and education.We found that higher MD of the thalamic-motor tract was associated with worse processing speed (β=-0.27; <0.001), higher MD of the thalamic-frontal tract was associated with worse executive function (β=-0.24; =0.001), and memory (β=-0.28; <0.001), respectively. The mediation analysis showed that MD of thalamocortical tracts mediated the association between corresponding thalamic subregion volumes and the cognitive performances in 3 domains.Our results suggest that the structural alterations of thalamus are linked to cognitive impairment in SVD, largely depending on the damage pattern of the white matter tracts connecting specific thalamic subregions and cortical regions.

Reductions in prefrontal oxygenation near maximal exertion may limit exercise performance by impairing executive functions that influence the decision to stop exercising; however, whether deoxygenation also occurs in motor regions that more directly affect central motor drive is unknown. Multichannel near-infrared spectroscopy was used to compare changes in prefrontal, premotor, and motor cortices during exhaustive exercise. Twenty-three subjects performed two sequential, incremental cycle tests (25 W/min ramp) during acute hypoxia [79 Torr inspired Po2 (PiO2)] and normoxia (117 Torr PiO2) in an environmental chamber. Test order was balanced, and subjects were blinded to chamber pressure. In normoxia, bilateral prefrontal oxygenation was maintained during low- and moderate-intensity exercise but dropped 9.0 ± 10.7% (mean ± SD, P &lt; 0.05) before exhaustion (maximal power = 305 ± 52 W). The pattern and magnitude of deoxygenation were similar in prefrontal, premotor, and motor regions ( R2 &gt; 0.94). In hypoxia, prefrontal oxygenation was reduced 11.1 ± 14.3% at rest ( P &lt; 0.01) and fell another 26.5 ± 19.5% ( P &lt; 0.01) at exhaustion (maximal power = 256 ± 38 W, P &lt; 0.01). Correlations between regions were high ( R2 &gt; 0.61), but deoxygenation was greater in prefrontal than premotor and motor regions ( P &lt; 0.05). Prefrontal, premotor, and motor cortex deoxygenation during high-intensity exercise may contribute to an integrative decision to stop exercise. The accelerated rate of cortical deoxygenation in hypoxia may hasten this effect.

The study of individuals at high-altitude (HA) exposure provides an important opportunity for unraveling physiological and psychological mechanism of brain underlying hypoxia condition. However, this has rarely been assessed longitudinally. We aim to explore the cognitive and cerebral microstructural alterations after chronic HA exposure. We recruited 49 college freshmen who immigrated to Tibet and followed up for 2 years. Control group consisted of 49 gender and age-matched subjects from sea level. Neuropsychological tests were also conducted to determine whether the subjects' cognitive function had changed in response to chronic HA exposure. Surface-based cortical and subcortical volumes were calculated from structural magnetic resonance imaging data, and tract-based spatial statistics (TBSS) analysis of white matter (WM) fractional anisotropy (FA) based on diffusion weighted images were performed. Compared to healthy controls, the high-altitude exposed individuals showed significantly lower accuracy and longer reaction times in memory tests. Significantly decreased gray matter volume in the caudate region and significant FA changes in multiple WM tracts were observed for HA immigrants. Furthermore, differences in subcortical volume and WM integration were found to be significantly correlated with the cognitive changes after 2 years' HA exposure. Cognitive functions such as working memory and psychomotor function were found to be impaired during chronic HA. Differences of brain subcortical volumes and WM integration between HA and sea-level participants indicated potential impairments in the brain structural modifications and microstructural integrity of WM tracts after HA exposure.© 2019 Wiley Periodicals, Inc.