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Acta Neuropathologica Communications Jun 2024The relationship between amyloidosis and vasculature in cognitive impairment and Alzheimer's disease (AD) pathogenesis is increasingly acknowledged. We conducted a...
The relationship between amyloidosis and vasculature in cognitive impairment and Alzheimer's disease (AD) pathogenesis is increasingly acknowledged. We conducted a quantitative and topographic assessment of retinal perivascular amyloid plaque (AP) distribution in individuals with both normal and impaired cognition. Using a retrospective dataset of scanning laser ophthalmoscopy fluorescence images from twenty-eight subjects with varying cognitive states, we developed a novel image processing method to examine retinal peri-arteriolar and peri-venular curcumin-positive AP burden. We further correlated retinal perivascular amyloidosis with neuroimaging measures and neurocognitive scores. Our study unveiled that peri-arteriolar AP counts surpassed peri-venular counts throughout the entire cohort (P < 0.0001), irrespective of the primary, secondary, or tertiary vascular branch location, with a notable increase among cognitively impaired individuals. Moreover, secondary branch peri-venular AP count was elevated in the cognitively impaired (P < 0.01). Significantly, peri-venular AP count, particularly in secondary and tertiary venules, exhibited a strong correlation with clinical dementia rating, Montreal cognitive assessment score, hippocampal volume, and white matter hyperintensity count. In conclusion, our exploratory analysis detected greater peri-arteriolar versus peri-venular amyloidosis and a marked elevation of amyloid deposition in secondary branch peri-venular regions among cognitively impaired subjects. These findings underscore the potential feasibility of retinal perivascular amyloid imaging in predicting cognitive decline and AD progression. Larger longitudinal studies encompassing diverse populations and AD-biomarker confirmation are warranted to delineate the temporal-spatial dynamics of retinal perivascular amyloid deposition in cognitive impairment and the AD continuum.
Topics: Humans; Male; Female; Aged; Cognitive Dysfunction; Hippocampus; Atrophy; Amyloidosis; Aged, 80 and over; Retrospective Studies; Middle Aged; Plaque, Amyloid; Retinal Diseases; Retinal Vessels; Ophthalmoscopy
PubMed: 38943220
DOI: 10.1186/s40478-024-01810-2 -
Nutrition & Metabolism Jun 2024Conflicting findings regarding the impact of High protein intake during the early phase in critically ill patients have been reported. Therefore, we aimed to assess the...
BACKGROUND
Conflicting findings regarding the impact of High protein intake during the early phase in critically ill patients have been reported. Therefore, we aimed to assess the influence of higher early protein intake on the prognosis of critically ill patients.
METHODS
This randomized controlled trial involved 173 critically ill patients who stayed in the Intensive Care Unit/Emergency ICU (ICU/EICU) for at least 7 days. The Low group (n = 87) and High group (n = 86) received protein supplementation of 0.8 g/kg.d and 1.5 g/kg.d, respectively, within 1-3 days of enteral nutrition (EN) initiation, with both groups transitioning to 1.5 g/kg.d on the 4th day. The serum prealbumin (PA), blood urea nitrogen/creatinine, and rectus femoris muscle thickness and cross-sectional area of all patients was measured on the 1th, 3rd, 5th, 7th day, and the day of ICU/EICU discharge.
RESULTS
Patients in both Low and High groups showed no significant differences in age, APACHE II scores, or other demographic and baseline characteristics. There were also no significant differences in the primary outcome (28-day mortality rate) and secondary outcomes (incidence rate of refeeding syndrome and EN tolerance score) between the two groups. However, the Low group exhibited a significantly higher 28-day mortality rate (HR = 2.462, 95% CI: 1.021-5.936, P = 0.045) compared to High group, as determined by Cox proportional hazards models incorporating the time factor. The High group exhibited significantly shorter durations of mechanical ventilation and ICU stay compared to the Low group. Serum PA levels were higher, and rectus femoris muscle atrophy rates were lower in the High group. Furthermore, for septic patients, high protein intake significantly reduced the 28-day mortality rate despite a small sample size (n = 34).
CONCLUSIONS
Our study indicates that increasing early protein intake to 1.5 g/kg.d may be safe and help improve the nutritional status and prognosis of critically ill patients.
TRIAL REGISTRATION
This study was registered with the Chinese Clinical Trial Registry (ChiCTR2000039997, https://www.chictr.org.cn/ ).
PubMed: 38943189
DOI: 10.1186/s12986-024-00818-8 -
Die Anaesthesiologie Jun 2024
PubMed: 38942900
DOI: 10.1007/s00101-024-01430-4 -
Cell Death & Disease Jun 2024Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the...
Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment.
Topics: Aging; Obesity; Animals; Gene Expression Profiling; Glycolysis; Male; Mice; Mice, Inbred C57BL; Muscle Fibers, Skeletal; Transcriptome; Muscle Fibers, Slow-Twitch; Humans
PubMed: 38942747
DOI: 10.1038/s41419-024-06851-y -
Neuroimaging Clinics of North America Aug 2024Multiple sclerosis (MS) is increasingly understood not only as a white matter disease but also involving both the deep and cortical gray matter (GM). GM pathology in... (Review)
Review
Multiple sclerosis (MS) is increasingly understood not only as a white matter disease but also involving both the deep and cortical gray matter (GM). GM pathology in people with MS (pwMS) includes the presence of lesions, leptomeningeal inflammation, atrophy, altered iron concentration, and microstructural changes. Studies using 7T and 3T MR imaging with optimized protocols established that GM damage is a principal driver of disease progression in pwMS. Future work is needed to incorporate the assessment of these GM imaging biomarkers into the clinical workup of pwMS and the assessment of treatment efficacy.
Topics: Humans; Multiple Sclerosis; Gray Matter; Magnetic Resonance Imaging; Neuroimaging; Brain
PubMed: 38942527
DOI: 10.1016/j.nic.2024.03.007 -
Neurobiology of Disease Jun 2024Anorexia nervosa (AN) is an eating disorder (ED) that has seen an increase in its incidence in the last thirty years. Compared to other psychosomatic disorders, ED can...
Anorexia nervosa (AN) is an eating disorder (ED) that has seen an increase in its incidence in the last thirty years. Compared to other psychosomatic disorders, ED can be responsible for many major medical complications, moreover, in addition to the various systemic impairments, patients with AN undergo morphological and physiological changes affecting the cerebral cortex. Through immunohistochemical studies on portions of postmortem human brain of people affected by AN and healthy individuals, and western blot studies on leucocytes of young patients and healthy controls, this study investigated the role in the afore-mentioned processes of altered redox state. The results showed that the brain volume reduction in AN could be due to an increase in the rate of cell death, mainly by apoptosis, in which mitochondria, main cellular organelles affected by a decreased dietary intake, and a highly compromised intracellular redox balance, may play a pivotal role.
PubMed: 38942323
DOI: 10.1016/j.nbd.2024.106580 -
Experimental Neurology Jun 2024Traumatic brain injury (TBI) leads to changes in the neural circuitry of the hippocampus that result in chronic learning and memory deficits. However, effective...
Traumatic brain injury (TBI) leads to changes in the neural circuitry of the hippocampus that result in chronic learning and memory deficits. However, effective therapeutic strategies to ameliorate these chronic learning and memory impairments after TBI are limited. Two pharmacological targets for enhancing cognition are nicotinic acetylcholine receptors (nAChRs) and GABA receptors (GABARs), both of which regulate hippocampal network activity to form declarative memories. A promising compound, 522-054, both allosterically enhances α7 nAChRs and inhibits α5 subunit-containing GABARs. Administration of 522-054 enhances long-term potentiation (LTP) and cognitive functioning in non-injured animals. In this study, we assessed the effects of 522-054 on hippocampal synaptic plasticity and learning and memory deficits in the chronic post-TBI recovery period. Adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury or sham surgery. At 12 wk after injury, we assessed basal synaptic transmission and LTP at the Schaffer collateral-CA1 synapse of the hippocampus. Bath application of 522-054 to hippocampal slices reduced deficits in basal synaptic transmission and recovered TBI-induced impairments in LTP. Moreover, treatment of animals with 522-054 at 12 wk post-TBI improved cue and contextual fear memory and water maze acquisition and retention without a measurable effect on cortical or hippocampal atrophy. These results suggest that dual allosteric modulation of α7 nAChR and α5 GABAR signaling may be a potential therapy for treating cognitive deficits during chronic recovery from TBI.
PubMed: 38942266
DOI: 10.1016/j.expneurol.2024.114879 -
Ageing Research Reviews Jun 2024Dementia, a prevalent condition in the United States, affecting millions of individuals and their families, underscores the importance of healthy cognitive ageing, which...
Dementia, a prevalent condition in the United States, affecting millions of individuals and their families, underscores the importance of healthy cognitive ageing, which involves maintaining cognitive function and mental wellness as individuals grow older, promoting overall well-being and quality of life. Our original research study investigates the correlation between lifestyle factors and brain atrophy in individuals with mild cognitive impairment (MCI) or Alzheimer's disease (AD), as well as healthy older adults. Conducted over six months in West Texas, the research involved 20 participants aged 62-87. Findings reveal that sleep deprivation in MCI subjects and AD patients correlate with posterior cingulate cortex, hippocampal atrophy and total brain volume, while both groups exhibit age-related hippocampal volume reduction. Notably, fruit/vegetable intake negatively correlates with certain brain regions' volume, emphasizing the importance of diet. Lack of exercise is associated with reduced brain volume and hippocampal atrophy, underlining the cognitive benefits of physical activity. The study underscores lifestyle's significant impact on cognitive health, advocating interventions to promote brain health and disease prevention, particularly in MCI/AD cases. While blood profile data showed no significant results regarding cognitive decline, the study underscores the importance of lifestyle modifications in preserving cognitive function.
PubMed: 38942198
DOI: 10.1016/j.arr.2024.102397 -
Journal of the Neurological Sciences Jun 2024Brain and cortical atrophy play crucial roles in supporting the clinical diagnosis of Alzheimer's disease (AD). This study hypothesized that the ratios of brain or...
BACKGROUND
Brain and cortical atrophy play crucial roles in supporting the clinical diagnosis of Alzheimer's disease (AD). This study hypothesized that the ratios of brain or cortical volume to subcortical gray matter structure volumes are potential imaging markers for cognitive alterations in AD dementia and amnestic mild cognitive impairment (aMCI).
METHODS
Seventy-seven subjects diagnosed with AD dementia or aMCI underwent baseline neuropsychological testing, 2-year follow-up cognitive assessments, and high-resolution T1-weighted MRI scans. Total brain/cortical volume and subcortical gray matter structure volumes were automatically segmented and measured. Univariate and multiple linear regression analyses were conducted to determine the associations between volumetric ratios and interval changes in cognitive scores.
RESULTS
The ratio of cortical volume to caudate volume showed the most significant association with changes in MoCA (B = 0.132, SE = 0.042, p = 0.002), MMSE (B = 0.140, SE = 0.040, p = 0.001), and CDR-SOB (B = -0.013, SE = 0.005, p = 0.007) scores over the 2-year follow-up period. These associations remained significant after adjusting for various covariates. Similar associations were observed for the ratios of cortical volume to putamen and globus pallidum volumes.
CONCLUSIONS
The cortex-to-caudate volume ratio is significantly associated with cognitive decline in AD dementia and aMCI. This ratio may serve as a useful biomarker for monitoring disease progression and predicting cognitive outcomes. Our findings highlight the importance of considering the relative atrophy of cortical and subcortical structures in understanding AD pathology.
PubMed: 38941706
DOI: 10.1016/j.jns.2024.123113 -
Medicine Jun 2024This article aims to analyze the prevalence of sarcopenia among the elderly in Guizhou Province, China, and its association with human immunodeficiency virus (HIV)... (Observational Study)
Observational Study
This article aims to analyze the prevalence of sarcopenia among the elderly in Guizhou Province, China, and its association with human immunodeficiency virus (HIV) infection. This cross-sectional study included 377 patients aged 60 and above in Guiyang Public Health Treatment Center from December 2022 to October 2023, including 231 patients in the community clinic and 146 HIV-infected individuals. According to the Asian Working Group for Sarcopenia 2019 Consensus to diagnose sarcopenia. Logistic regression was used to explore association between sarcopenia and HIV, and stratified by sex and age group. The prevalence of sarcopenia in the non-HIV infection elderly in Guizhou Province was 7.8% (21.3% in males and 5.5% in females), and the prevalence of sarcopenia in HIV-infected individuals was 29.5% (33.3% in males and 13.2% in females), with a statistically significant difference between HIV groups (χ2 = 30.946, P < .001). After control of gender, age, body mass index, body fat percentage, hypertension, diabetes, taking statins, smoking status, medium to high-intensity physical activity, whether childhood poverty, and parents died young, HIV infection was significantly associated with sarcopenia in the elderly (odds ratio = 4.635, 95% confidence interval = 1.920-11.188, P = .001). The results of stratified regression were similar to the main results. The prevalence of sarcopenia in the elderly population in China was severe. HIV infection was a risk factor for sarcopenia. It is urgent to establish a prevention and treatment system for sarcopenia in the elderly population, especially for elderly HIV-infected male.
Topics: Humans; Male; Female; Sarcopenia; China; HIV Infections; Prevalence; Cross-Sectional Studies; Aged; Middle Aged; Risk Factors; Aged, 80 and over
PubMed: 38941377
DOI: 10.1097/MD.0000000000038532