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JAMA Oct 2019Worldwide, 47 million people live with dementia and, by 2050, the number is expected to increase to 131 million. (Review)
Review
IMPORTANCE
Worldwide, 47 million people live with dementia and, by 2050, the number is expected to increase to 131 million.
OBSERVATIONS
Dementia is an acquired loss of cognition in multiple cognitive domains sufficiently severe to affect social or occupational function. In the United States, Alzheimer disease, one cause of dementia, affects 5.8 million people. Dementia is commonly associated with more than 1 neuropathology, usually Alzheimer disease with cerebrovascular pathology. Diagnosing dementia requires a history evaluating for cognitive decline and impairment in daily activities, with corroboration from a close friend or family member, in addition to a thorough mental status examination by a clinician to delineate impairments in memory, language, attention, visuospatial cognition such as spatial orientation, executive function, and mood. Brief cognitive impairment screening questionnaires can assist in initiating and organizing the cognitive assessment. However, if the assessment is inconclusive (eg, symptoms present, but normal examination findings), neuropsychological testing can help determine whether dementia is present. Physical examination may help identify the etiology of dementia. For example, focal neurologic abnormalities suggest stroke. Brain neuroimaging may demonstrate structural changes including, but not limited to, focal atrophy, infarcts, and tumor, that may not be identified on physical examination. Additional evaluation with cerebrospinal fluid assays or genetic testing may be considered in atypical dementia cases, such as age of onset younger than 65 years, rapid symptom onset, and/or impairment in multiple cognitive domains but not episodic memory. For treatment, patients may benefit from nonpharmacologic approaches, including cognitively engaging activities such as reading, physical exercise such as walking, and socialization such as family gatherings. Pharmacologic approaches can provide modest symptomatic relief. For Alzheimer disease, this includes an acetylcholinesterase inhibitor such as donepezil for mild to severe dementia, and memantine (used alone or as an add-on therapy) for moderate to severe dementia. Rivastigmine can be used to treat symptomatic Parkinson disease dementia.
CONCLUSIONS AND RELEVANCE
Alzheimer disease currently affects 5.8 million persons in the United States and is a common cause of dementia, which is usually accompanied by other neuropathology, often cerebrovascular disease such as brain infarcts. Causes of dementia can be diagnosed by medical history, cognitive and physical examination, laboratory testing, and brain imaging. Management should include both nonpharmacologic and pharmacologic approaches, although efficacy of available treatments remains limited.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Excitatory Amino Acid Antagonists; Humans; Memantine; Neuroimaging; Neuropsychological Tests
PubMed: 31638686
DOI: 10.1001/jama.2019.4782 -
International Journal of Environmental... Mar 2022Flu is a serious health, medical, and economic problem, but no therapy is yet available that has satisfactory results and reduces the occurrence of these problems.... (Review)
Review
Flu is a serious health, medical, and economic problem, but no therapy is yet available that has satisfactory results and reduces the occurrence of these problems. Nearly 20 years after the registration of the previous therapy, baloxavir marboxil, a drug with a new mechanism of action, recently appeared on the market. This is a promising step in the fight against the influenza virus. This article presents the possibilities of using all available antiviral drugs specific for influenza A and B. We compare all currently recommended anti-influenza medications, considering their mechanisms of action, administration, indications, target groups, effectiveness, and safety profiles. We demonstrate that baloxavir marboxil presents a similar safety and efficacy profile to those of drugs already used in the treatment of influenza. Further research on combination therapy is highly recommended and may have promising results.
Topics: Antiviral Agents; Enzyme Inhibitors; Humans; Influenza, Human; Neuraminidase; Pyridones
PubMed: 35270708
DOI: 10.3390/ijerph19053018 -
International Journal of... 2021Antiviral drugs are a class of medicines particularly used for the treatment of viral infections. Drugs that combat viral infections are called antiviral drugs. Viruses... (Review)
Review
Antiviral drugs are a class of medicines particularly used for the treatment of viral infections. Drugs that combat viral infections are called antiviral drugs. Viruses are among the major pathogenic agents that cause number of serious diseases in humans, animals and plants. Viruses cause many diseases in humans, from self resolving diseases to acute fatal diseases. Developing strategies for the antiviral drugs are focused on two different approaches: Targeting the viruses themselves or the host cell factors. Antiviral drugs that directly target the viruses include the inhibitors of virus attachment, inhibitors of virus entry, uncoating inhibitors, polymerase inhibitors, protease inhibitors, inhibitors of nucleoside and nucleotide reverse transcriptase and the inhibitors of integrase. The inhibitors of protease (ritonavir, atazanavir and darunavir), viral DNA polymerase (acyclovir, tenofovir, valganciclovir and valacyclovir) and of integrase (raltegravir) are listed among the Top 200 Drugs by sales during 2010s. Still no effective antiviral drugs are available for many viral infections. Though, there are a couple of drugs for herpesviruses, many for influenza and some new antiviral drugs for treating hepatitis C infection and HIV. Action mechanism of antiviral drugs consists of its transformation to triphosphate following the viral DNA synthesis inhibition. An analysis of the action mechanism of known antiviral drugs concluded that they can increase the cell's resistance to a virus (interferons), suppress the virus adsorption in the cell or its diffusion into the cell and its deproteinisation process in the cell (amantadine) along with antimetabolites that causes the inhibition of nucleic acids synthesis. This review will address currently used antiviral drugs, mechanism of action and antiviral agents reported against COVID-19.
Topics: Animals; Antiviral Agents; COVID-19; Drug Therapy, Combination; Host-Pathogen Interactions; Humans; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 33726557
DOI: 10.1177/20587384211002621 -
Journal of Parkinson's Disease 2023The pathophysiology of Parkinson's disease (PD) tremor remains incompletely understood and there is a lack of clinical trials specifically addressing its pharmacological... (Review)
Review
The pathophysiology of Parkinson's disease (PD) tremor remains incompletely understood and there is a lack of clinical trials specifically addressing its pharmacological treatment. Levodopa is the most efficacious drug for most patients and should be used as primary approach to control troublesome tremor. While the efficacy of oral dopamine agonists on PD tremor has been demonstrated in controlled trials, there is no evidence of greater antitremor efficacy compared to levodopa. The magnitude of the antitremor effect of anticholinergics is generally lower than that of levodopa. Due to their adverse effects, anticholinergics have a limited role in selected young and cognitively intact patients. Propranolol may improve resting and action tremor and may be considered as an adjunct in patients with insufficient tremor response to levodopa and this also applies to clozapine, despite its unfavorable adverse effect profile. Treating motor fluctuations with MAO-B and COMT inhibitors, dopamine agonists, amantadine, or on-demand treatments such as subcutaneous or sublingual apomorphine and inhaled levodopa as well as with continuous infusions of levodopa or apomorphine will improve off period tremor episodes. For patients with drug-refractory PD tremor despite levodopa optimization deep brain stimulation and focused ultrasound are first-line considerations. Surgery can also be highly effective for the treatment medication-refractory tremor in selected patients without motor fluctuations. The present review highlights the clinical essentials of parkinsonian tremor, critically examines available trial data on the effects of medication and surgical approaches and provides guidance for the choice of treatments to control PD tremor in clinical practice.
Topics: Humans; Parkinson Disease; Levodopa; Tremor; Dopamine Agonists; Antiparkinson Agents; Apomorphine; Cholinergic Antagonists
PubMed: 36847017
DOI: 10.3233/JPD-225060 -
Ideggyogyaszati Szemle Nov 2021In aging societies, the morbidity and mortality of dementia is increasing at a significant rate, thereby imposing burden on healthcare, economy and the society as well.... (Review)
Review
In aging societies, the morbidity and mortality of dementia is increasing at a significant rate, thereby imposing burden on healthcare, economy and the society as well. Patients' and caregivers' quality of life and life expectancy are greatly determined by the early diagnosis and the initiation of available symptomatic treatments. Cholinesterase inhibitors and memantine have been the cornerstones of Alzheimer's therapy for approximately two decades and over the years, more and more experience has been gained on their use in non-Alzheimer's dementias too. The aim of our work was to provide a comprehensive summary about the use of cholinesterase inhibitors and memantine for the treatment of Alzheimer's and non-Alzheimers's dementias.
Topics: Alzheimer Disease; Caregivers; Cholinesterase Inhibitors; Humans; Memantine; Quality of Life
PubMed: 34856086
DOI: 10.18071/isz.74.0379 -
International Journal of Molecular... Nov 2022Guillain-Barré syndrome (GBS) is a rare immune-mediated acute polyradiculo-neuropathy that typically develops after a previous gastrointestinal or respiratory... (Review)
Review
Guillain-Barré syndrome (GBS) is a rare immune-mediated acute polyradiculo-neuropathy that typically develops after a previous gastrointestinal or respiratory infection. This narrative overview aims to summarise and discuss current knowledge and previous evidence regarding triggers and pathophysiology of GBS. A systematic search of the literature was carried out using suitable search terms. The most common subtypes of GBS are acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). The most common triggers of GBS, in three quarters of cases, are previous infections. The most common infectious agents that cause GBS include , , and cytomegalovirus. is responsible for about a third of GBS cases. GBS due to is usually more severe than that due to other causes. Clinical presentation of GBS is highly dependent on the structure of pathogenic lipo-oligosaccharides (LOS) that trigger the innate immune system via Toll-like-receptor (TLR)-4 signalling. AIDP is due to demyelination, whereas in AMAN, structures of the axolemma are affected in the nodal or inter-nodal space. In conclusion, GBS is a neuro-immunological disorder caused by autoantibodies against components of the myelin sheath or axolemma. Molecular mimicry between surface structures of pathogens and components of myelin or the axon is one scenario that may explain the pathophysiology of GBS.
Topics: Humans; Amantadine; Autoantibodies; Axons; Campylobacter jejuni; Guillain-Barre Syndrome
PubMed: 36430700
DOI: 10.3390/ijms232214222 -
Journal of Clinical Oncology : Official... Apr 2020Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition.
METHODS
This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine. The primary end point was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests. Secondary end points included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported symptom burden.
RESULTS
Between July 2015 and March 2018, 518 patients were randomly assigned. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% 40.4%; = .01) and learning and memory at 6 months (11.5% 24.7% [ = .049] and 16.4% 33.3% [ = .02], respectively). Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue ( = .04), less difficulty with remembering things ( = .01), and less difficulty with speaking ( = .049) and using imputed data, less interference of neurologic symptoms in daily activities ( = .008) and fewer cognitive symptoms ( = .01).
CONCLUSION
HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.
Topics: Antiparkinson Agents; Brain Neoplasms; Chemoradiotherapy; Cognition; Cognition Disorders; Female; Hippocampus; Humans; Male; Memantine; Middle Aged; Progression-Free Survival; Proportional Hazards Models; Quality of Life; Radiation Injuries; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated
PubMed: 32058845
DOI: 10.1200/JCO.19.02767 -
The Lancet. Neurology Jan 2021Methylphenidate, modafinil, and amantadine are commonly prescribed medications for alleviating fatigue in multiple sclerosis; however, the evidence supporting their...
BACKGROUND
Methylphenidate, modafinil, and amantadine are commonly prescribed medications for alleviating fatigue in multiple sclerosis; however, the evidence supporting their efficacy is sparse and conflicting. Our goal was to compare the efficacy of these three medications with each other and placebo in patients with multiple sclerosis fatigue.
METHODS
In this randomised, placebo-controlled, four-sequence, four-period, crossover, double-blind trial, patients with multiple sclerosis who reported fatigue and had a Modified Fatigue Impact Scale (MFIS) score of more than 33 were recruited at two academic multiple sclerosis centres in the USA. Participants received oral amantadine (up to 100 mg twice daily), modafinil (up to 100 mg twice daily), methylphenidate (up to 10 mg twice daily), or placebo, each given for up to 6 weeks. All patients were intended to receive all four study medications, in turn, in one of four different sequences with 2-week washout periods between medications. A biostatistician prepared a concealed allocation schedule, stratified by site, randomly assigning a sequence of medications in approximately a 1:1:1:1 ratio, in blocks of eight, to a consecutive series of numbers. The statistician and pharmacists had no role in assessing the participants or collecting data, and the participants, caregivers, and assessors were masked to allocation. The primary outcome measure was the MFIS measured while taking the highest tolerated dose at week 5 of each medication period, analysed by use of a linear mixed-effect regression model. This trial is registered with ClinicalTrials.gov, NCT03185065 and is closed.
FINDINGS
Between Oct 4, 2017, and Feb 27, 2019, of 169 patients screened, 141 patients were enrolled and randomly assigned to one of four medication administration sequences: 35 (25%) patients to the amantadine, placebo, modafinil, and methylphenidate sequence; 34 (24%) patients to the placebo, methylphenidate, amantadine, and modafinil sequence; 35 (25%) patients to the modafinil, amantadine, methylphenidate, and placebo sequence; and 37 (26%) patients to the methylphenidate, modafinil, placebo, and amantadine sequence. Data from 136 participants were available for the intention-to-treat analysis of the primary outcome. The estimated mean values of MFIS total scores at baseline and the maximal tolerated dose were as follows: 51·3 (95% CI 49·0-53·6) at baseline, 40·6 (38·2-43·1) with placebo, 41·3 (38·8-43·7) with amantadine, 39·0 (36·6-41·4) with modafinil, and 38·6 (36·2-41·0) with methylphenidate (p=0·20 for the overall medication effect in the linear mixed-effect regression model). As compared with placebo (38 [31%] of 124 patients), higher proportions of participants reported adverse events while taking amantadine (49 [39%] of 127 patients), modafinil (50 [40%] of 125 patients), and methylphenidate (51 [40%] of 129 patients). Three serious adverse events occurred during the study (pulmonary embolism and myocarditis while taking amantadine, and a multiple sclerosis exacerbation requiring hospital admission while taking modafinil).
INTERPRETATION
Amantadine, modafinil, and methylphenidate were not superior to placebo in improving multiple sclerosis fatigue and caused more frequent adverse events. The results of this study do not support an indiscriminate use of amantadine, modafinil, or methylphenidate for the treatment of fatigue in multiple sclerosis.
FUNDING
Patient-Centered Outcomes Research Institute.
Topics: Adult; Amantadine; Central Nervous System Stimulants; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Fatigue; Female; Humans; Male; Methylphenidate; Middle Aged; Modafinil; Multiple Sclerosis; Outcome Assessment, Health Care; Severity of Illness Index
PubMed: 33242419
DOI: 10.1016/S1474-4422(20)30354-9 -
International Journal of Molecular... Sep 2023In an ever-increasing aged world, Alzheimer's disease (AD) represents the first cause of dementia and one of the first chronic diseases in elderly people. With 55... (Review)
Review
In an ever-increasing aged world, Alzheimer's disease (AD) represents the first cause of dementia and one of the first chronic diseases in elderly people. With 55 million people affected, the WHO considers AD to be a disease with public priority. Unfortunately, there are no final cures for this pathology. Treatment strategies are aimed to mitigate symptoms, i.e., acetylcholinesterase inhibitors (AChEI) and the N-Methyl-D-aspartate (NMDA) antagonist Memantine. At present, the best approaches for managing the disease seem to combine pharmacological and non-pharmacological therapies to stimulate cognitive reserve. Over the last twenty years, a number of drugs have been discovered acting on the well-established biological hallmarks of AD, deposition of β-amyloid aggregates and accumulation of hyperphosphorylated tau protein in cells. Although previous efforts disappointed expectations, a new era in treating AD has been working its way recently. The Food and Drug Administration (FDA) gave conditional approval of the first disease-modifying therapy (DMT) for the treatment of AD, aducanumab, a monoclonal antibody (mAb) designed against Aβ plaques and oligomers in 2021, and in January 2023, the FDA granted accelerated approval for a second monoclonal antibody, Lecanemab. This review describes ongoing clinical trials with DMTs and non-pharmacological therapies. We will also present a future scenario based on new biomarkers that can detect AD in preclinical or prodromal stages, identify people at risk of developing AD, and allow an early and curative treatment.
Topics: United States; Humans; Aged; Alzheimer Disease; Acetylcholinesterase; Amyloid beta-Peptides; Memantine; Antibodies, Monoclonal
PubMed: 37762203
DOI: 10.3390/ijms241813900