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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 -
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 -
Annals of Internal Medicine Sep 2019Alzheimer disease (AD) and other dementia syndromes are becoming more common; an estimated 5.5 million adults aged 65 years or older are living with AD in the United... (Review)
Review
Alzheimer disease (AD) and other dementia syndromes are becoming more common; an estimated 5.5 million adults aged 65 years or older are living with AD in the United States. It is important for primary care physicians to gain knowledge in this field because most community-dwelling older adults receive their care from them. This article discusses the latest findings in approaches to prevent cognitive decline as well as dementia screening, diagnosis, and treatment. Approaches to address quality of life for persons with dementia and their caregivers are also discussed.
Topics: Aged; Caregivers; Central Nervous System Agents; Cholinesterase Inhibitors; Dementia; Diagnosis, Differential; Humans; Mass Screening; Memantine; Practice Guidelines as Topic; Quality of Life
PubMed: 31476229
DOI: 10.7326/AITC201909030 -
Brain and Behavior Nov 2020Alzheimer's disease (AD) is a degenerative brain disease that progresses over time, heavily burdening patients, families, and aging societies worldwide. Memantine and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Alzheimer's disease (AD) is a degenerative brain disease that progresses over time, heavily burdening patients, families, and aging societies worldwide. Memantine and donepezil are frequently used in its treatment, both as monotherapy and in combination. This multiple treatment comparison meta-analysis assessed the efficacy of these regimens and placebo in the management of AD.
METHODS
We searched PubMed, Embase, the Cochrane Library, and Wanfang Med Online and China National Knowledge Infrastructure for English and Chinese publications from the first records to 17 April 2020. Two investigators scanned articles for placebo-controlled trials of memantine and donepezil alone and in combination. We extracted data on the following outcomes: cognition, global assessment, daily activities, neuropsychiatric symptoms, adverse events, and the acceptability and cost of these treatment regimens.
RESULTS
Of 936 records screened, we included 54 trials in this analysis. The combination therapy was more effective in improving cognition (mean difference (MD)-5.01, 95% credible interval (95% Crl) -10.73 to 0.86 in the Alzheimer's Disease Assessment Scale-Cognitive Subscale; MD 9.61, 95% Crl 2.29 to 16.97 in the Severe Impairment Battery), global assessment (MD -2.88, 95% Crl -6.04 to 0.40), daily activities (MD 13.06, 95% Crl -34.04 to 58.92), and neuropsychiatric symptoms (MD -6.84, 95% Crl -10.62 to -2.82) compared with placebo. Memantine was more acceptable than placebo (MD 0.93, 95% Crl 0.69 to 1.22).
CONCLUSIONS
Memantine plus donepezil showed superior outcomes for cognition, global assessment, daily activities, and neuropsychiatric symptoms, but lower acceptability than monotherapy and placebo. Combination therapy may be more cost-effective, because memantine slows the progression of AD.
Topics: Alzheimer Disease; China; Donepezil; Humans; Memantine; Network Meta-Analysis
PubMed: 32914577
DOI: 10.1002/brb3.1831 -
The Journal of Neuropsychiatry and... 2022In this review, the authors explored the clinical features of frontotemporal dementia (FTD), focusing on treatment. The clinical features of FTD are unique, with... (Review)
Review
In this review, the authors explored the clinical features of frontotemporal dementia (FTD), focusing on treatment. The clinical features of FTD are unique, with disinhibition, apathy, loss of empathy, and compulsions common. Motor changes occur later in the illness. The two major proteins that aggregate in the brain with FTD are tau and TDP-43, whereas a minority of patients aggregate FET proteins, primarily the FUS protein. Genetic causes include mutations in , , and . There are no medications that can slow FTD progression, although new therapies for the genetic forms of FTD are moving into clinical trials. Once a diagnosis is made, therapies should begin, focusing on the family and the patient. In the setting of FTD, families experience a severe burden associated with caregiving, and the clinician should focus on alleviating this burden. Advice around legal and financial issues is usually helpful. Careful consideration of environmental changes to cope with abnormal behaviors is essential. Most compounds that have been used to treat dementia of the Alzheimer's disease type are not effective in FTD, and cholinesterase inhibitors and memantine should be avoided. Although the data are scant, there is some evidence that antidepressants and second-generation antipsychotics may help individual patients.
Topics: C9orf72 Protein; Cholinesterase Inhibitors; DNA-Binding Proteins; Frontotemporal Dementia; Humans; Memantine; Mutation; RNA-Binding Protein FUS
PubMed: 35578801
DOI: 10.1176/appi.neuropsych.21060166 -
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 -
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 -
Cognitive and Behavioral Neurology :... Dec 2021Behavioral and psychological symptoms of dementia (BPSD) are common in individuals with Alzheimer disease (AD). Donepezil and memantine are both widely used for the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Behavioral and psychological symptoms of dementia (BPSD) are common in individuals with Alzheimer disease (AD). Donepezil and memantine are both widely used for the treatment of moderate AD.
OBJECTIVE
To evaluate the effects of donepezil and memantine in relieving BPSD in individuals with moderate AD.
METHOD
We conducted a prospective, randomized, 6-month clinical trial involving 85 individuals with moderate AD divided into two groups: group 1 (n = 42) was treated with donepezil; group 2 (n = 43) was treated with memantine. We used the Neuropsychiatric Inventory (NPI) to assess the prevalence and severity of BPSD at baseline and after 6 months of treatment with donepezil or memantine.
RESULTS
The two groups' baseline characteristics, including age, sex, mean length of education, and disease duration, were comparable, as were their baseline Mini-Mental State Examination scores. The NPI Total score improved from baseline to month 6 in both groups (P < 0.0001). Analyses of the NPI subdomains revealed that both donepezil treatment and memantine treatment produced statistically significant improvement in all of the NPI domains except euphoria and apathy, for which no improvement was observed after memantine treatment. Both treatments were well tolerated, with mostly mild and transient adverse effects.
CONCLUSION
Specific drugs for AD, including donepezil and memantine, may be effective in treating BPSD in individuals with moderate AD, with a favorable safety profile.
Topics: Alzheimer Disease; Behavioral Symptoms; Donepezil; Humans; Indans; Memantine; Piperidines; Prospective Studies; Treatment Outcome
PubMed: 34851866
DOI: 10.1097/WNN.0000000000000285 -
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