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Psychiatry Research Jan 2021Geriatric patients with dementia frequently present with agitation, aggression, psychosis, and other behavioral and psychological symptoms of dementia (BPSD). We present... (Meta-Analysis)
Meta-Analysis
Geriatric patients with dementia frequently present with agitation, aggression, psychosis, and other behavioral and psychological symptoms of dementia (BPSD). We present an update of our previously published algorithms for the use of psychopharmacologic agents in these patients taking into account more recent studies and findings in meta-analyses, reviews, and other published algorithms. We propose three algorithms: BPSD in an emergent, urgent, and non-urgent setting. In the emergent setting when intramuscular (IM) administration is necessary, the first-line recommendation is for olanzapine (since IM aripiprazole, previously favored, is no longer available) and haloperidol injection is the second choice, followed by possible consideration of an IM benzodiazepine. In the urgent setting, the first line would be oral second-generation antipsychotics (SGAs) aripiprazole and risperidone. Perhaps next could be then prazosin, and lastly electroconvulsive therapy is a consideration. There are risks associated with these agents, and adverse effects can be severe. Dosing strategies, discontinuation considerations, and side effects are discussed. In the non-emergent setting, medications are proposed for use in the following order: trazodone, donepezil and memantine, antidepressants such as escitalopram and sertraline, SGAs, prazosin, and carbamazepine. Other options with less support but potential future promise are discussed.
Topics: Academic Medical Centers; Aged; Algorithms; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Citalopram; Dementia; Electroconvulsive Therapy; Haloperidol; Humans; Olanzapine; Psychopharmacology; Risperidone
PubMed: 33340800
DOI: 10.1016/j.psychres.2020.113641 -
Journal of Sleep Research Aug 2021Suboptimal sleep causes cognitive decline and probably accelerates Alzheimer's Disease (AD) progression. Several sleep interventions have been tested in established AD... (Review)
Review
Suboptimal sleep causes cognitive decline and probably accelerates Alzheimer's Disease (AD) progression. Several sleep interventions have been tested in established AD dementia cases. However early intervention is needed in the course of AD at Mild Cognitive Impairment (MCI) or mild dementia stages to help prevent decline and maintain good quality of life. This systematic review aims to summarize evidence on sleep interventions in MCI and mild AD dementia. Seven databases were systematically searched for interventional studies where ≥ 75% of participants met diagnostic criteria for MCI/mild AD dementia, with a control group and validated sleep outcome measures. Studies with a majority of participants diagnosed with Moderate to Severe AD were excluded. After removal of duplicates, 22,133 references were returned in two separate searches (August 2019 and September 2020). 325 full papers were reviewed with 18 retained. Included papers reported 16 separate studies, total sample (n = 1,056), mean age 73.5 years. 13 interventions were represented: Cognitive Behavioural Therapy - Insomnia (CBT-I), A Multi-Component Group Based Therapy, A Structured Limbs Exercise Programme, Aromatherapy, Phase Locked Loop Acoustic Stimulation, Transcranial Stimulation, Suvorexant, Melatonin, Donepezil, Galantamine, Rivastigmine, Tetrahydroaminoacridine and Continuous Positive Airway Pressure (CPAP). Psychotherapeutic approaches utilising adapted CBT-I and a Structured Limbs Exercise Programme each achieved statistically significant improvements in the Pittsburgh Sleep Quality Index with one study reporting co-existent improved actigraphy variables. Suvorexant significantly increased Total Sleep Time and Sleep Efficiency whilst reducing Wake After Sleep Onset time. Transcranial Stimulation enhanced cortical slow oscillations and spindle power during daytime naps. Melatonin significantly reduced sleep latency in two small studies and sleep to wakefulness transitions in a small sample. CPAP demonstrated efficacy in participants with Obstructive Sleep Apnoea. Evidence to support other interventions was limited. Whilst new evidence is emerging, there remains a paucity of evidence for sleep interventions in MCI and mild AD highlighting a pressing need for high quality experimental studies exploring alternative sleep interventions.
Topics: Alzheimer Disease; Cognitive Dysfunction; Humans; Quality of Life; Sleep
PubMed: 33289311
DOI: 10.1111/jsr.13229 -
Journal of Alzheimer's Disease : JAD 2020A critical strategy in the management of Alzheimer's disease (AD) is optimizing the effects of currently available pharmacologic therapies such as citicoline (CC).
BACKGROUND
A critical strategy in the management of Alzheimer's disease (AD) is optimizing the effects of currently available pharmacologic therapies such as citicoline (CC).
OBJECTIVE
The purpose of this study was to determine the effects of CC as adjunct therapy to cholinesterase inhibitors (AChEI) in the treatment of AD.
METHODS
We identified relevant studies by electronic search until April 2020. We considered studies with a comparator group that enrolled elderly patients with a diagnosis of AD and employed CC as an adjunct therapy to AChEIs compared to AChEI monotherapy or comparisons of different AChEIs combined with CC. Methodological quality assessment was done using the Newcastle-Ottawa Scale.
RESULTS
Out of 149 articles identified, two retrospective cohort studies involving 563 elderly patients affected with AD were included. After 3 months and 9 months, better Mini-Mental Status Examination scores were observed in the "AChEIs + CC" group versus "AChEIs alone" group. CC combined with donepezil may be better in improving cognition than when combined with rivastigmine. No significant difference was noted in terms of activities of daily living (ADL) and instrumental-ADL. Neuropsychiatric Inventory and Geriatric Depression Scale-short form scores appeared to be lower in the combination treatment versus monotherapy. The adverse events of combined treatment were self-limiting and included occasional excitability, gastric intolerance, and headache.
CONCLUSION
Limited evidence from pooled data of two observational studies suggests that CC used in adjunct with AChEIs in the treatment of AD was well-tolerated and showed improvement in cognition, mood, and behavioral symptoms compared to treating with AChEIs alone.
Topics: Alzheimer Disease; Case-Control Studies; Cognition; Cytidine Diphosphate Choline; Drug Therapy, Combination; Humans; Nootropic Agents; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32538854
DOI: 10.3233/JAD-200378 -
Drugs & Aging Jul 2020Deprescribing is of particular importance in older adults with limited life expectancy since this population group is highly susceptible to the potential harms of...
BACKGROUND
Deprescribing is of particular importance in older adults with limited life expectancy since this population group is highly susceptible to the potential harms of inappropriate medications.
OBJECTIVE
This systematic review aimed to explore attitudes towards deprescribing among older adults with limited life expectancy and their relatives.
METHODS
A systematic literature review was conducted in the MEDLINE and EMBASE databases from inception to October 2019. Inclusion criteria were studies specifically describing attitudes towards deprescribing among older adults (≥ 65 years) with limited life expectancy and/or their relatives regardless of study type. Results were analyzed, inspired by the Joanna Briggs Institute's method for synthesis of qualitative data.
RESULTS
A total of 842 studies were identified and screened; 84 were full-text assessed for eligibility and 7 were ultimately included. Two studies investigated the attitudes of older adults with limited life expectancy and their relatives towards deprescribing of statins and donepezil, respectively, while the five remaining studies related to attitudes towards deprescribing in general. Four main themes were identified: (1) the well-being of older adults with limited life expectancy; (2) involvement of older adults and their relatives in deprescribing; (3) the role of health care professionals in deprescribing; and (4) medication-related factors affecting deprescribing. Within each of these themes, several subthemes were identified.
CONCLUSIONS
Attitudes towards deprescribing among older adults with limited life expectancy and their relatives vary and highlight several barriers and enablers to the deprescribing process. Several of these factors must be addressed to successfully implement deprescribing initiatives in this patient group.
Topics: Aged; Deprescriptions; Donepezil; Family; Health Knowledge, Attitudes, Practice; Health Personnel; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Life Expectancy; Professional Role
PubMed: 32537682
DOI: 10.1007/s40266-020-00774-x -
Frontiers in Pharmacology 2020Pharmacological treatments play a significant role in treating mild to moderate Alzheimer's disease (AD), but the optimal doses of various drugs used for these...
BACKGROUND
Pharmacological treatments play a significant role in treating mild to moderate Alzheimer's disease (AD), but the optimal doses of various drugs used for these treatments are unknown. Our study compared the efficacy, acceptability, and safety of different doses of pharmacological treatments for mild to moderate AD.
METHODS
Randomized controlled trials (RCTs) were identified by searching the PubMed, EMBASE, and Cochrane Library databases (all RCTs published from the date of inception of the databases until September 19, 2019). Trials comparing the efficacy, acceptability, and safety of pharmacological interventions involving donepezil, galantamine, rivastigmine, memantine, huperzine A, and extract EGb761, alone or in combination, were identified. The primary outcomes were efficacy, acceptability, and safety.
RESULTS
Our meta-analysis included 37 studies involving 14,705 participants. In terms of improving cognitive function, galantamine 32 mg, galantamine 24 mg, donepezil 5 mg, and donepezil 10 mg were more effective than other interventions, with the surface under the cumulative ranking curve (SUCRA) values of 93.2, 75.5, 73.3, and 65.6%, respectively. According to the SUCRA values, EGb761 240 mg was considered to be the optimal intervention in terms of both acceptability and safety. With regard to clinical global impression, rivastigmine 12 mg had the highest probability of being ranked first (83.7%). The rivastigmine 15 cm patch (SUCRA = 93.7%) may be the best choice for daily living. However, there were no interventions that could significantly improve neuropsychiatric symptoms, compared with the placebo.
CONCLUSIONS
Different doses of the tested pharmacological interventions yielded benefits with regard to cognition, acceptability, safety, function, and clinical global impressions, but not effective behaviors.
PubMed: 32528296
DOI: 10.3389/fphar.2020.00778 -
Neurological Sciences : Official... Oct 2020Improvement of cognitive function may be desirable for healthy individuals and clinically beneficial for those with cognitive impairment such as from Alzheimer's disease... (Review)
Review
INTRODUCTION
Improvement of cognitive function may be desirable for healthy individuals and clinically beneficial for those with cognitive impairment such as from Alzheimer's disease (AD) or mild cognitive impairment (MCI). The aim of this systematic review is to investigate the cognitive effects of oral saffron intake, in patients with MCI/AD and/or in non-demented individuals, by following the PRISMA guidelines.
METHODS
We performed a literature search on MedLine, Cochrane library, and ClinicalTrials.gov to identify randomized controlled trials (RCTs) investigating the effects of oral saffron administration in patients with MCI/AD and/or in non-demented individuals.
RESULTS
Five studies (enrolling 325 individuals) met our inclusion criteria. Four studies included patients with MCI/AD, and one study included cognitively normal individuals. Saffron was well-tolerated in all groups. Regarding cognitively impaired patients, scores on Alzheimer's Disease Assessment Scale-cognitive subscale or Mini mental state examination were significantly better when saffron was compared with placebo and did not differ significantly when saffron was compared with donepezil or memantine. Saffron effects on functional status were similar with its effects on cognition.
CONCLUSIONS
Saffron was shown to be equally effective to common symptomatic drugs for MCI/AD and resulted in no difference in the incidence of side effects, when compared with placebo or drugs. The promising results should be seen cautiously, since the evidence was derived from studies with potentially high risk of bias (ROB). RCTs with larger sample sizes and low ROB are required to definitively assess the potential role of saffron as an MCI/AD treatment.
Topics: Alzheimer Disease; Cognition; Cognitive Dysfunction; Crocus; Donepezil; Humans
PubMed: 32445136
DOI: 10.1007/s10072-020-04427-0 -
Frontiers in Aging Neuroscience 2020The effects of acupuncture on Alzheimer's disease (AD) outcomes remain controversial. The aim of this review was to evaluate the effectiveness and safety of acupuncture...
The effects of acupuncture on Alzheimer's disease (AD) outcomes remain controversial. The aim of this review was to evaluate the effectiveness and safety of acupuncture for the treatment of AD. PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, Chinese BioMedical Literature Database, VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, and Wanfang Data were searched to identify relevant randomized controlled trials from inception to January 19, 2019. Data were extracted and evaluated by two authors independently. The data analysis was conducted using R (version 3.6.0) and RStudio (version 1.2.1335) software. Thirty trials involving 2,045 patients were included. Acupuncture plus drug therapy may have been more beneficial for general cognitive function in AD patients than drug therapy alone (short-term treatment: MD, mean difference = 1.94, 95% CI: 1.11, 2.77; < 0.01; medium-term treatment: = 4.41, 95% CI: 1.83, 7.00; < 0.01). People who received acupuncture plus drug therapy attained higher ADL (Activities of Daily Living) scores than patients who received drug therapy alone for medium-term treatment duration ( = -2.14; 95% CI: -3.69, -0.59; < 0.01). However, there is no statistically significant difference in subgroup effect on MMSE (Mini-mental Status Examination) and ADLs ( > 0.05) when comparing acupuncture treatment with drug therapy (such as Donepezil hydrochloride, Nimodipine, or Yizhijiannao), or acupuncture plus drug therapy (such as Donepezil hydrochloride, Dangguishaoyaosan, or Jiannaosan) with drug therapy alone. There was also no significant difference in general cognitive function, ADLs, or incidence of adverse events between acupuncture treatment and drug therapy ( > 0.05). This review indicates that acupuncture plus drug therapy may have a more beneficial effect for AD patients than drug therapy alone on general cognitive function in the short and medium term and on ADLs in the medium term. Acupuncture alone may not have superior effects compared with drug therapy on global cognitive function, ADLs, and incidence of adverse events. Duration of treatment may not modify the effect of acupuncture in comparison with drug therapy. Additional large-scale and high-quality clinical trials are needed.
PubMed: 32435187
DOI: 10.3389/fnagi.2020.00098 -
Medicine May 2020The aim of this systematic review was to evaluate the effect of therapies for cognitive impairment on patients' perceived cognitive function in breast cancer survivors...
OBJECTIVE
The aim of this systematic review was to evaluate the effect of therapies for cognitive impairment on patients' perceived cognitive function in breast cancer survivors with chemotherapy-related cognitive impairment.
METHOD
A literature search of PubMed, Embase, and the Cochrane Library was conducted up to April 2019. Search terms included breast cancer, chemotherapy, and cognitive impairment.
RESULT
Six randomized controlled trials with a total of 305 patients were included in this review. A total of 6 randomized controlled trials using various treatments (Tibetan sound meditation, donepezil, memory and attention adaptation training, aerobic exercise, acupuncture, Qigong) for chemotherapy-related cognitive impairment met the eligibility criteria and were included. This review showed that meditative interventions (Tibetan sound meditation, Qigong) and cognitive therapy (memory and attention adaptation training) may partially improve some aspects of patients' perceived (self-reported) cognitive functioning, particularly patients' perceived cognitive impairment and ability.
CONCLUSION
In this systematic review, the results showed that meditative interventions (Tibetan sound meditation, Qigong) and cognitive therapy (memory and attention adaptation training) may be optional therapies. We hope to have more randomized controlled trials to support this result in the future.
Topics: Antineoplastic Agents; Breast Neoplasms; Cancer Survivors; Cognitive Behavioral Therapy; Cognitive Dysfunction; Female; Humans; Meditation; Randomized Controlled Trials as Topic
PubMed: 32384481
DOI: 10.1097/MD.0000000000020092 -
JAMA Feb 2020Early identification of cognitive impairment may improve patient and caregiver health outcomes.
IMPORTANCE
Early identification of cognitive impairment may improve patient and caregiver health outcomes.
OBJECTIVE
To systematically review the test accuracy of cognitive screening instruments and benefits and harms of interventions to treat cognitive impairment in older adults (≥65 years) to inform the US Preventive Services Task Force.
DATA SOURCES
MEDLINE, PubMed, PsycINFO, and Cochrane Central Register of Controlled Trials through January 2019, with literature surveillance through November 22, 2019.
STUDY SELECTION
Fair- to good-quality English-language studies of cognitive impairment screening instruments, and pharmacologic and nonpharmacologic treatments aimed at persons with mild cognitive impairment (MCI), mild to moderate dementia, or their caregivers.
DATA EXTRACTION AND SYNTHESIS
Independent critical appraisal and data abstraction; random-effects meta-analyses and qualitative synthesis.
MAIN OUTCOMES AND MEASURES
Sensitivity, specificity; patient, caregiver, and clinician decision-making; patient function, quality of life, and neuropsychiatric symptoms; caregiver burden and well-being.
RESULTS
The review included 287 studies with more than 280 000 older adults. One randomized clinical trial (RCT) (n = 4005) examined the direct effect of screening for cognitive impairment on patient outcomes, including potential harms, finding no significant differences in health-related quality of life at 12 months (effect size, 0.009 [95% CI, -0.063 to 0.080]). Fifty-nine studies (n = 38 531) addressed the accuracy of 49 screening instruments to detect cognitive impairment. The Mini-Mental State Examination was the most-studied instrument, with a pooled sensitivity of 0.89 (95% CI, 0.85 to 0.92) and specificity of 0.89 (95% CI, 0.85 to 0.93) to detect dementia using a cutoff of 23 or less or 24 or less (15 studies, n = 12 796). Two hundred twenty-four RCTs and 3 observational studies including more than 240 000 patients or caregivers addressed the treatment of MCI or mild to moderate dementia. None of the treatment trials were linked with a screening program; in all cases, participants were persons with known cognitive impairment. Medications approved to treat Alzheimer disease (donepezil, galantamine, rivastigmine, and memantine) improved scores on the ADAS-Cog 11 by 1 to 2.5 points over 3 months to 3 years. Psychoeducation interventions for caregivers resulted in a small benefit for caregiver burden (standardized mean difference, -0.24 [95% CI, -0.36 to -0.13) over 3 to 12 months. Intervention benefits were small and of uncertain clinical importance.
CONCLUSIONS AND RELEVANCE
Screening instruments can adequately detect cognitive impairment. There is no empirical evidence, however, that screening for cognitive impairment improves patient or caregiver outcomes or causes harm. It remains unclear whether interventions for patients or caregivers provide clinically important benefits for older adults with earlier detected cognitive impairment or their caregivers.
Topics: Aged; Caregivers; Cognitive Dysfunction; Dementia; Early Diagnosis; Humans; Independent Living; Mass Screening; Neuropsychological Tests; Practice Guidelines as Topic; Sensitivity and Specificity
PubMed: 32096857
DOI: 10.1001/jama.2019.22258 -
European Journal of Clinical... Dec 2019To study the strength of the evidence on efficacy, safety and acceptability of cholinesterase inhibitors (ChEI) and memantine for Alzheimer's disease (AD); and to... (Meta-Analysis)
Meta-Analysis
Study of the strength of the evidence and the redundancy of the research on pharmacological treatment for Alzheimer's disease: a cumulative meta-analysis and trial sequential analysis.
PURPOSE
To study the strength of the evidence on efficacy, safety and acceptability of cholinesterase inhibitors (ChEI) and memantine for Alzheimer's disease (AD); and to determine the number of redundant post-authorisation trials.
METHODS
A cumulative meta-analysis with a trial sequential analysis (TSA) was performed. Primary outcomes were cognitive function assessed with ADAS-cog or SIB scales, discontinuation due to adverse events (AE) and discontinuation for any reason. The redundancy of post-authorisation clinical trials was studied by determining the novel aspects of each study on patient, intervention, comparator and trial outcome characteristics. Two criteria of futile trial (lenient and strict) were used.
RESULTS
A total of 63 randomised clinical trials (RCTs) (16,576 patients) were included. It was conclusive that neither ChEI nor memantine achieved clinically significant improvement in cognitive function. In relation to safety, there was sufficient evidence to conclude that donepezil caused a clinically relevant increase on dropouts due to AE whereas the evidence was inconclusive for the remaining interventions. Regarding acceptability, it was conclusive that no ChEI improved treatment discontinuation while it was uncertain for memantine. The proportion of redundant trials was 5.6% with the lenient criteria and 42.6% with the strict one.
CONCLUSIONS
The evidence is conclusive that ChEI and memantine do not achieve clinically significant symptomatic improvement in AD while the acceptability of ChEI is unsatisfactory. Although evidence on the safety of pharmacological interventions for AD and acceptability of memantine is inconclusive, no further RCTs are needed as their efficacy is not clinically relevant. Redundant trials were identified but their number depends on the criteria of futility used.
Topics: Activities of Daily Living; Alzheimer Disease; Cholinesterase Inhibitors; Cognition; Evidence-Based Medicine; Humans; Memantine; Randomized Controlled Trials as Topic
PubMed: 31435707
DOI: 10.1007/s00228-019-02742-w