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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 -
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 -
The Lancet. Neurology Dec 2021The efficacy of amantadine in the symptomatic treatment of patients with Parkinson's disease, discovered serendipitously more than 50 years ago, has stood the test of... (Review)
Review
The efficacy of amantadine in the symptomatic treatment of patients with Parkinson's disease, discovered serendipitously more than 50 years ago, has stood the test of time and the drug is still commonly used by neurologists today. Its pharmacological actions are unique in combining dopaminergic and glutamatergic properties, which account for its dual effect on parkinsonian signs and symptoms and levodopa-induced dyskinesias. Furthermore, amantadine has additional and less well-defined pharmacological effects, including on anticholinergic and serotonergic activity. Evidence from randomised controlled trials over the past 5 years has confirmed the efficacy of amantadine to treat levodopa-induced dyskinesias in patients with Parkinson's disease, and clinical studies have also provided support for its potential to reduce motor fluctuations. Other uses of amantadine, such as in the treatment of drug-induced parkinsonism, atypical parkinsonism, Huntington's disease, or tardive dyskinesia, lack a strong evidence base. Future trials should examine its role in the management of motor and non-motor symptoms in patients with early Parkinson's disease and those with other movement disorders.
Topics: Amantadine; Antiparkinson Agents; Dyskinesia, Drug-Induced; Humans; Levodopa; Parkinson Disease
PubMed: 34678171
DOI: 10.1016/S1474-4422(21)00249-0 -
Brain Injury Feb 2020This comprehensive review discusses clinical studies of patients following brain injuries (traumatic, acquired, or stroke), who have been treated with amantadine or... (Review)
Review
This comprehensive review discusses clinical studies of patients following brain injuries (traumatic, acquired, or stroke), who have been treated with amantadine or memantine. Both amantadine and memantine are commonly used in the acute rehabilitation setting following brain injuries, despite their lack of FDA-approval for neuro-recovery. Given the broad utilization of such agents, there is a need to review the evidence supporting this common off-label prescribing. The purpose of this review is to describe the mechanisms of action for memantine and amantadine, as well as to complete a comprehensive review of the clinical uses of these agents. We included 119 original, clinical research articles from NCBI Medline, published before 2019. We focused on the domains of neuroplasticity, functional recovery, motor recovery, arousal, fatigue, insomnia, behavior, agitation, and cognition. Most of the existing research supporting the use of amantadine and memantine in recovery from brain injuries was done in very small populations, limiting the significance of conclusions. While most studies are positive; small effect sizes are usually reported, or populations are subject to bias. Furthermore, evidence is so limited that this review includes research regarding both acute and chronic acquired brain injury populations. Fortunately, reported short-term side effects generally are modest, and stop soon after amantadine/memantine is discontinued. However, responses are inconsistent, and the phenotype of responders remains elusive.
Topics: Amantadine; Brain Injuries; Humans; Memantine; Neuronal Plasticity; Off-Label Use; Recovery of Function
PubMed: 32078407
DOI: 10.1080/02699052.2020.1723697 -
The American Journal of Psychiatry May 2023Trichotillomania and skin-picking disorder are underrecognized and often disabling conditions in which individuals repeatedly pull at their hair or pick at their skin,... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Trichotillomania and skin-picking disorder are underrecognized and often disabling conditions in which individuals repeatedly pull at their hair or pick at their skin, leading to noticeable hair loss or tissue damage. To date there is a severe paucity of evidence-based treatments for these conditions. In this study, the authors sought to determine whether memantine, a glutamate modulator, is more effective than placebo in reducing hair-pulling and skin-picking behavior.
METHODS
One hundred adults with trichotillomania or skin-picking disorder (86 women; mean age, 31.4 years [SD=10.2]) were enrolled in a double-blind trial of memantine (dosing range, 10-20 mg/day) or placebo for 8 weeks. Participants were assessed with measures of pulling and picking severity. Outcomes were examined using a linear mixed-effects model. The prespecified primary outcome measure was treatment-related change on the NIMH Trichotillomania Symptom Severity Scale, modified to include skin picking.
RESULTS
Compared with placebo, memantine treatment was associated with significant improvements in scores on the NIMH scale, Sheehan Disability Scale, and Clinical Global Impressions severity scale in terms of treatment-by-time interactions. At study endpoint, 60.5% of participants in the memantine group were "much or very much improved," compared with 8.3% in the placebo group (number needed to treat=1.9). Adverse events did not differ significantly between the treatment arms.
CONCLUSIONS
This study found that memantine treatment resulted in statistically significant reductions in hair pulling and skin-picking symptoms compared with placebo, with relatively high efficacy (based on number needed to treat), and was well tolerated. The glutamate system may prove to be a beneficial target in the treatment of compulsive behaviors.
Topics: Adult; Humans; Female; Trichotillomania; Memantine; Double-Blind Method; Glutamates
PubMed: 36856701
DOI: 10.1176/appi.ajp.20220737 -
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 -
JAMA Internal Medicine May 2024Dementia affects 10% of those 65 years or older and 35% of those 90 years or older, often with profound cognitive, behavioral, and functional consequences. As the baby... (Review)
Review
IMPORTANCE
Dementia affects 10% of those 65 years or older and 35% of those 90 years or older, often with profound cognitive, behavioral, and functional consequences. As the baby boomers and subsequent generations age, effective preventive and treatment strategies will assume increasing importance.
OBSERVATIONS
Preventive measures are aimed at modifiable risk factors, many of which have been identified. To date, no randomized clinical trial data conclusively confirm that interventions of any kind can prevent dementia. Nevertheless, addressing risk factors may have other health benefits and should be considered. Alzheimer disease can be treated with cholinesterase inhibitors, memantine, and antiamyloid immunomodulators, with the last modestly slowing cognitive and functional decline in people with mild cognitive impairment or mild dementia due to Alzheimer disease. Cholinesterase inhibitors and memantine may benefit persons with other types of dementia, including dementia with Lewy bodies, Parkinson disease dementia, vascular dementia, and dementia due to traumatic brain injury. Behavioral and psychological symptoms of dementia are best treated with nonpharmacologic management, including identifying and mitigating the underlying causes and individually tailored behavioral approaches. Psychotropic medications have minimal evidence of efficacy for treating these symptoms and are associated with increased mortality and clinically meaningful risks of falls and cognitive decline. Several emerging prevention and treatment strategies hold promise to improve dementia care in the future.
CONCLUSIONS AND RELEVANCE
Although current prevention and treatment approaches to dementia have been less than optimally successful, substantial investments in dementia research will undoubtedly provide new answers to reducing the burden of dementia worldwide.
Topics: Aged; Humans; Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Memantine; Risk Factors; Aged, 80 and over
PubMed: 38436963
DOI: 10.1001/jamainternmed.2023.8522 -
The Journal of Trauma and Acute Care... Mar 2022Traumatic brain injury is a global burden. We aimed to perform a meta-analysis to determine the efficacy of amantadine for cognitive performance after traumatic brain... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Traumatic brain injury is a global burden. We aimed to perform a meta-analysis to determine the efficacy of amantadine for cognitive performance after traumatic brain injury.
METHODS
The systematic review was prospectively registered on the International Prospective Register of Systematic Reviews website under the registration number CRD42017080044. We used Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to report the steps of meta-analysis. The search included electronic databases (PubMed, PsycINFO, Embase, Cochrane Library databases, CENTRAL, ProQuest and ClinicalTrials.gov trial registry). Critical care medicine journals and clinical neurology specialty were searched using www.scimagojr.com. There was no publication date restriction. Two authors assessed studies' relevance and extracted data. Studies were assessed for quality using the Cochrane risk of bias tool. Data were analyzed using Comprehensive Meta-analysis Program versions 2.0 and 3.0.
RESULTS
Twenty-six studies out of 3,440 records were included in the systematic review, of which only 14 clinical trials and 6 observational studies were included in the meta-analysis. Amantadine significantly enhanced the cognitive function relative to control group (mean difference [MD], 0.50; 95% confidence interval [CI], 0.33-0.66; p < 0.001, 16 studies, 1,127 participants, low certainty evidence). Consistent significant difference in favor of amantadine relative to control group was found (MD of 0.79 [95% CI, 0.34-1.24], very low certainty evidence, for cohort studies vs. MD of 0.40 [95% CI, 0.25-0.56], moderate certainty evidence, for RCTS). Starting amantadine in the first week after TBI had a significant effect on improving cognitive function (MD, 0.97; 95% CI, 0.45-1.49; 16 studies, 1,127 participants, low certainty). Amantadine showed a better effect when administered for less than 1 month (MD, 0.83; 95% CI, 0.56-1.11; low certainty) and to patients below 18 years of age (MD, 0.66; 95% CI, 0.32-0.99; low certainty) or to patients with less severe traumatic brain injury (MD, 0.40; 95% CI, 0.18-0.62; low certainty). No statistically significant difference existed between amantadine and the control concerning the adverse events (OR, 1.74; 95% CI, 0.88-3.44; p = 0.11, moderate certainty). Metaregression of the different clinical parameters, which are onset of treatment, age, and severity of traumatic brain injury, showed a statistically significant relation between onset of treatment and the effect size of amantadine. The relation between the other two parameters and the effect size of amantadine showed a marginal statistical significance.
CONCLUSION
Amantadine may improve the cognitive function when used after TBI. Further research with high validity is needed to reach a solid conclusion about the use of amantadine in traumatic brain injury.
LEVEL OF EVIDENCE
Systematic review/meta-analysis, level III.
Topics: Amantadine; Brain Injuries, Traumatic; Dopamine Agents; Humans
PubMed: 34284464
DOI: 10.1097/TA.0000000000003363 -
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