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Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives.Alzheimer's & Dementia : the Journal of... Jun 2024Alzheimer's disease (AD) is a neurodegenerative disease that involves multiple systems in the body. Numerous recent studies have revealed bidirectional crosstalk between... (Review)
Review
Alzheimer's disease (AD) is a neurodegenerative disease that involves multiple systems in the body. Numerous recent studies have revealed bidirectional crosstalk between the brain and bone, but the interaction between bone and brain in AD remains unclear. In this review, we summarize human studies of the association between bone and brain and provide an overview of their interactions and the underlying mechanisms in AD. We review the effects of AD on bone from the aspects of AD pathogenic proteins, AD risk genes, neurohormones, neuropeptides, neurotransmitters, brain-derived extracellular vesicles (EVs), and the autonomic nervous system. Correspondingly, we elucidate the underlying mechanisms of the involvement of bone in the pathogenesis of AD, including bone-derived hormones, bone marrow-derived cells, bone-derived EVs, and inflammation. On the basis of the crosstalk between bone and the brain, we propose potential strategies for the management of AD with the hope of offering novel perspectives on its prevention and treatment. HIGHLIGHTS: The pathogenesis of AD, along with its consequent changes in the brain, may involve disturbing bone homeostasis. Degenerative bone disorders may influence the progression of AD through a series of pathophysiological mechanisms. Therefore, relevant bone intervention strategies may be beneficial for the comprehensive management of AD.
PubMed: 38824621
DOI: 10.1002/alz.13864 -
Parkinsonism & Related Disorders May 2024Parkinson's disease (PD) presents with decreased heart rate variability (HRV) from its early stages. However, most of its evidence originates from HRV measurements in...
INTRODUCTION
Parkinson's disease (PD) presents with decreased heart rate variability (HRV) from its early stages. However, most of its evidence originates from HRV measurements in parasympathetic dominant states. In this study, we aimed to examine whether HRV in sympathetic dominant states during the head-up tilt table test (HUT) serves as a marker of autonomic dysfunction in PD and isolated REM sleep behavior disorder (iRBD).
METHODS
We retrospectively assessed 102 patients with PD, 10 patients with iRBD, and 43 healthy controls. We then measured the coefficient of variation of RR intervals as an HRV parameter in sympathetic dominant states (CVRR-S) and parasympathetic dominant states (CVRR-P). Furthermore, we evaluated parameters of cardiac autonomic function, including HUT and the heart-to-mediastinum (H/M) ratio of cardiac metaiodobenzylguanidine scintigraphy.
RESULTS
Patients with iRBD and PD at Hoehn and Yahr stage I exhibited a significantly decreased CVRR-S compared to healthy controls (controls vs. iRBD vs. PD; 1.82 ± 0.64 % vs. 1.13 ± 0.41 % vs. 1.15 ± 0.51 %, p < 0.001), although no further deterioration was observed in PD at more severe Hoehn and Yahr stages. CVRR-S showed a significant correlation with the H/M ratio in PD (r = 0.51, p < 0.001). Additionally, receiver operating characteristic (ROC) analysis revealed a larger area under the ROC curve in CVRR-S compared to that in CVRR-P for discriminating PD or iRBD from healthy controls.
CONCLUSION
HRV in sympathetic dominant states shows the potential to be a marker of autonomic dysfunction in iRBD and early-stage PD, aiding in early diagnosis and patient stratification.
PubMed: 38823170
DOI: 10.1016/j.parkreldis.2024.107020 -
Journal of Psychiatric Practice May 2024Serotonin (5-HT) syndrome (SS) consists of changes in mental status as well as autonomic and neuromuscular changes. Though not well understood, serotonergic pathways... (Review)
Review
Serotonin (5-HT) syndrome (SS) consists of changes in mental status as well as autonomic and neuromuscular changes. Though not well understood, serotonergic pathways have been implicated in the mechanism of action of electroconvulsive therapy (ECT). Ketamine has been used as an induction agent in ECT and as therapy for treatment-resistant depression. Utilizing a case report and literature review, we explored the underlying serotonergic mechanisms of ECT and ketamine by which a syndrome of serotonin toxicity may be precipitated. We describe the case of a 72-year-old woman who developed recurrent SS on 2 occasions in similar circumstances involving the administration of ketamine for ECT. In our literature review, we found 5 cases in which SS was associated with ECT and 1 case linking ketamine to SS. There is emerging evidence that the mechanism of ECT involves 5-HT1A and 5-HT2A receptors, the same receptors that are involved in SS. ECT can transiently increase the permeability of the blood-brain barrier, leading to increased levels of antidepressants in the brain. ECT can, therefore, enhance 5-HT transmission and the likelihood of SS in the presence of serotonergic agents. The effect of ketamine on 5-HT transmission is mediated by the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. Ketamine increases α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid activity in the medial prefrontal cortex, which leads to downstream 5-HT release through glutamate. Through this mechanism, ketamine can increase 5-HT transmission, leading to SS. To our knowledge, this is the only case report of recurrent SS with concurrent use of ECT and ketamine. As ketamine is frequently used in ECT and many patients undergoing ECT are on serotonergic medications, it is important to recognize ketamine as a potential risk factor for SS. There is no evidence for added efficacy when combining ECT and ketamine. Thus, one should proceed with caution when combining these treatments. The burgeoning use of ketamine in ambulatory settings makes it necessary to elucidate the risks, which we discuss further. More research is needed into the mechanisms of ketamine and ECT, specifically how the combination of these treatments influence 5-HT levels.
Topics: Humans; Ketamine; Female; Electroconvulsive Therapy; Aged; Serotonin Syndrome; Depressive Disorder, Major; Recurrence; Depressive Disorder, Treatment-Resistant
PubMed: 38819248
DOI: 10.1097/PRA.0000000000000787 -
International Journal of Medical... 2024Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) leads to coronavirus disease-2019 (COVID-19) which can cause severe cardiovascular complications including... (Review)
Review
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) leads to coronavirus disease-2019 (COVID-19) which can cause severe cardiovascular complications including myocardial injury, arrhythmias, acute coronary syndrome and others. Among these complications, arrhythmias are considered serious and life-threatening. Although arrhythmias have been associated with factors such as direct virus invasion leading to myocardial injury, myocarditis, immune response disorder, cytokine storms, myocardial ischemia/hypoxia, electrolyte abnormalities, intravascular volume imbalances, drug interactions, side effects of COVID-19 vaccines and autonomic nervous system dysfunction, the exact mechanisms of arrhythmic complications in patients with COVID-19 are complex and not well understood. In the present review, the literature was extensively searched to investigate the potential mechanisms of arrhythmias in patients with COVID-19. The aim of the current review is to provide clinicians with a comprehensive foundation for the prevention and treatment of arrhythmias associated with long COVID-19.
Topics: Humans; COVID-19; Arrhythmias, Cardiac; SARS-CoV-2
PubMed: 38818469
DOI: 10.7150/ijms.94578 -
Neurology India Mar 2024
Topics: Humans; Autonomic Nervous System Diseases; Flushing; Hypohidrosis
PubMed: 38817189
DOI: 10.4103/neurol-india.Neurol-India-D-24-00157 -
Movement Disorders : Official Journal... May 2024Cerebrovascular activity is not only crucial to optimal cerebral perfusion, but also plays an important role in the glymphatic clearance of interstitial waste, including... (Review)
Review
Cerebrovascular activity is not only crucial to optimal cerebral perfusion, but also plays an important role in the glymphatic clearance of interstitial waste, including α-synuclein. This highlights a need to evaluate how cerebrovascular activity is altered in Lewy body diseases. This review begins by discussing how vascular risk factors and cardiovascular autonomic dysfunction may serve as upstream or direct influences on cerebrovascular activity. We then discuss how patients with Lewy body disease exhibit reduced and delayed cerebrovascular activity, hypoperfusion, and reductions in measures used to capture cerebrospinal fluid flow, suggestive of a reduced capacity for glymphatic clearance. Given the lack of an existing framework, we propose a model by which these processes may foster α-synuclein aggregation and neuroinflammation. Importantly, this review highlights several avenues for future research that may lead to treatments early in the disease course, prior to neurodegeneration. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
PubMed: 38817039
DOI: 10.1002/mds.29867 -
Muscle & Nerve May 2024The diagnostic evaluation of a peripheral neuropathy includes testing for the presence of monoclonal gammopathy, which can be found in about 10% of patients with...
The diagnostic evaluation of a peripheral neuropathy includes testing for the presence of monoclonal gammopathy, which can be found in about 10% of patients with peripheral neuropathy. Our role, as physicians, is to determine whether the neuropathy is directly related to the gammopathy or whether the co-occurrence of these two disorders is purely coincidental. The evaluating physician needs to be familiar with the different types of neuropathies associated with monoclonal gammopathies, their clinical and electrodiagnostic characteristics, and their appropriate diagnostic evaluation and management. Testing for monoclonal protein disorders includes serum protein electrophoresis (SPEP) and immunofixation of blood, and in some cases of urine, as well as measurement of free light chains and quantitative immunoglobulins. Specific antibody testing is directed by paraprotein type and neuropathy phenotype. Patients with abnormal free light chains in association with sensory and autonomic neuropathy should be evaluated for AL amyloidosis. When a lambda monoclonal protein is identified together with a clinical phenotype of chronic inflammatory demyelinating neuropathy (CIDP), a diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS) syndrome should be considered. Patients with IgM paraprotein associated neuropathy should be assessed for distal acquired demyelinating sensorimotor (DADS) neuropathy, with or without anti myelin associated glycoprotein (MAG) antibody or CANOMAD syndrome. In many cases, a monoclonal gammopathy of uncertain significance (MGUS) is incidental and unrelated to the neuropathy. Collaboration with oncology is critical in evaluating patients with monoclonal proteins to assess for underlying plasma cell neoplasms or B cell lymphomas.
PubMed: 38816958
DOI: 10.1002/mus.28164 -
Scientific Reports May 2024Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition...
Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition referred to as "syndrome T". Peripheral neuropathy, described in untreated thyroid disease, could be a contributing mechanism. We analysed autonomic and somatosensory function in 29 patients with AIT and treated hypothyroidism and 27 healthy volunteers. They underwent heart rate variability (HRV) analysis and quantitative sensory testing (n = 28), comprising 13 parameters of small and large nerve fibre function and pain thresholds. Autonomic cardiovascular function was assessed in rest, deep respiration and orthostasis. Additionally, biomarkers for autoimmunity and thyroid function were measured. Anxiety, depression and QoL were assessed using validated questionnaires. 36% of the patients showed at least one sign of somatosensory small or large fibre dysfunction. 57% presented with mild hyperalgesia to at least one stimulus. Several markers of autonomic function and some detection thresholds were related to the antibody titres. Anxiety, depression scores and QoL correlated to antibody titres and HRV measures. Autonomic and somatosensory dysfunction indicate that in treated hypothyroidism and AIT a subgroup of patients suffers from neuropathic symptoms leading to impaired QoL. Additionally, mild hyperalgesia as a possible sensitisation phenomenon should be considered a target for symptomatic treatment.
Topics: Humans; Female; Male; Middle Aged; Adult; Autonomic Nervous System; Quality of Life; Thyroiditis, Autoimmune; Heart Rate; Hypothyroidism; Thyroxine; Aged; Somatosensory Disorders; Anxiety
PubMed: 38811750
DOI: 10.1038/s41598-024-63158-w -
Translational Psychiatry May 2024Empirically supported treatments for posttraumatic stress disorder (PTSD) exist, but research suggests these therapies are less effective, acceptable, and feasible to... (Randomized Controlled Trial)
Randomized Controlled Trial
Empirically supported treatments for posttraumatic stress disorder (PTSD) exist, but research suggests these therapies are less effective, acceptable, and feasible to deliver to active duty service members (SMs) compared to civilians. Stellate ganglion block (SGB) procedure, in which a local anesthetic is injected around the cervical sympathetic chain or stellate ganglion to temporarily inhibit sympathetic nervous activity, is gaining popularity as an alternative PTSD treatment in military settings. However, it is unknown whether certain PTSD symptoms are more responsive to SGB than others. The current study involved a secondary analysis of data collected from a previous randomized controlled trial of SGB compared to sham (normal saline) injection (N = 113 SMs). PTSD symptoms were assessed via clinical interview and self-report at baseline and 8 weeks post-SGB or sham. Logistic regression analyses showed that the marked alterations in arousal and reactivity PTSD symptom cluster demonstrated the greatest symptom severity reductions after SGB, relative to sham. The reexperiencing cluster also showed pronounced response to SGB in clinician-rated but not self-reported outcomes. Post-hoc item-level analyses suggested that arousal and reactivity cluster findings were driven by reductions in hypervigilance, concentration difficulties, and sleep disturbance, whereas clinician-rated reexperiencing cluster findings were driven by reductions in physiological reactions to trauma cues, emotional reactions to trauma cues, and intrusions. Our findings align with a burgeoning literature positioning SGB as a potential novel or adjunctive PTSD treatment. Results could guide future hypothesis-driven research on mediators of therapeutic change during SGB for PTSD symptoms in SMs.
Topics: Humans; Stress Disorders, Post-Traumatic; Stellate Ganglion; Male; Adult; Female; Autonomic Nerve Block; Military Personnel; Treatment Outcome; Middle Aged; Arousal; Young Adult; Self Report
PubMed: 38811568
DOI: 10.1038/s41398-024-02926-8 -
JACC. Cardiovascular Interventions May 2024Fasting before coronary procedures is currently recommended to reduce complications despite the lack of scientific evidence. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Fasting before coronary procedures is currently recommended to reduce complications despite the lack of scientific evidence.
OBJECTIVES
The TONIC (Comparison Between Fasting and No Fasting Before Interventional Coronary Intervention on the Occurrence of Adverse Events) noninferiority trial investigated the safety and comfort of a nonfasting strategy (ad libitum food and drinks) vs traditional fasting (>6 hours for solid food and liquids) before coronary procedures.
METHODS
In this monocentric, prospective, single-blind randomized controlled trial, 739 patients undergoing coronary procedures were included and randomized to a fasting or a nonfasting strategy. Emergency procedures were excluded. The primary endpoint was a composite of vasovagal reaction, hypoglycemia (defined by blood sugar ≤0.7 g/L), and isolated nausea and/or vomiting. Noninferiority margin was 4%. Secondary endpoints were contrast-induced nephropathy and patients' satisfaction.
RESULTS
Among the 739 procedures (697 elective and 42 semiurgent), 517 angiographies, and 222 angioplasties (including complex and high-risk procedures) were performed. The primary endpoint occurred in 30 of 365 nonfasting patients (8.2%) vs 37 of 374 fasting patients (9.9%), demonstrating noninferiority (absolute between-group difference, -1.7%; 1-sided 95% CI upper limit: 1.8%). No food-related adverse event occurred, and contrast-related acute kidney injuries were similar between groups. Overall, procedure satisfaction and perceived pain were similar in both groups, but nonfasting patients reported less hunger and thirst (P < 0.01). In case of redo coronary procedures, most patients (79%) would choose a nonfasting strategy.
CONCLUSIONS
The TONIC randomized trial demonstrates the noninferiority of a nonfasting strategy to the usual fasting strategy for coronary procedures regarding safety, while improving patients' comfort.
Topics: Humans; Fasting; Male; Female; Prospective Studies; Single-Blind Method; Middle Aged; Treatment Outcome; Aged; Time Factors; Risk Factors; Patient Satisfaction; Percutaneous Coronary Intervention; Coronary Angiography; Hypoglycemia; Syncope, Vasovagal; Blood Glucose; Coronary Artery Disease; Risk Assessment
PubMed: 38811102
DOI: 10.1016/j.jcin.2024.03.033