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The Cochrane Database of Systematic... Feb 2021Dementia is a progressive syndrome characterised by deterioration in memory, thinking and behaviour, and by impaired ability to perform daily activities. Two classes of... (Review)
Review
BACKGROUND
Dementia is a progressive syndrome characterised by deterioration in memory, thinking and behaviour, and by impaired ability to perform daily activities. Two classes of drug - cholinesterase inhibitors (donepezil, galantamine and rivastigmine) and memantine - are widely licensed for dementia due to Alzheimer's disease, and rivastigmine is also licensed for Parkinson's disease dementia. These drugs are prescribed to alleviate symptoms and delay disease progression in these and sometimes in other forms of dementia. There are uncertainties about the benefits and adverse effects of these drugs in the long term and in severe dementia, about effects of withdrawal, and about the most appropriate time to discontinue treatment.
OBJECTIVES
To evaluate the effects of withdrawal or continuation of cholinesterase inhibitors or memantine, or both, in people with dementia on: cognitive, neuropsychiatric and functional outcomes, rates of institutionalisation, adverse events, dropout from trials, mortality, quality of life and carer-related outcomes.
SEARCH METHODS
We searched the Cochrane Dementia and Cognitive Improvement Group's Specialised Register up to 17 October 2020 using terms appropriate for the retrieval of studies of cholinesterase inhibitors or memantine. The Specialised Register contains records of clinical trials identified from monthly searches of a number of major healthcare databases, numerous trial registries and grey literature sources.
SELECTION CRITERIA
We included all randomised, controlled clinical trials (RCTs) which compared withdrawal of cholinesterase inhibitors or memantine, or both, with continuation of the same drug or drugs.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed citations and full-text articles for inclusion, extracted data from included trials and assessed risk of bias using the Cochrane risk of bias tool. Where trials were sufficiently similar, we pooled data for outcomes in the short term (up to 2 months after randomisation), medium term (3-11 months) and long term (12 months or more). We assessed the overall certainty of the evidence for each outcome using GRADE methods.
MAIN RESULTS
We included six trials investigating cholinesterase inhibitor withdrawal, and one trial investigating withdrawal of either donepezil or memantine. No trials assessed withdrawal of memantine only. Drugs were withdrawn abruptly in five trials and stepwise in two trials. All participants had dementia due to Alzheimer's disease, with severities ranging from mild to very severe, and were taking cholinesterase inhibitors without known adverse effects at baseline. The included trials randomised 759 participants to treatment groups relevant to this review. Study duration ranged from 6 weeks to 12 months. There were too few included studies to allow planned subgroup analyses. We considered some studies to be at unclear or high risk of selection, performance, detection, attrition or reporting bias. Compared to continuing cholinesterase inhibitors, discontinuing treatment may be associated with worse cognitive function in the short term (standardised mean difference (SMD) -0.42, 95% confidence interval (CI) -0.64 to -0.21; 4 studies; low certainty), but the effect in the medium term is very uncertain (SMD -0.40, 95% CI -0.87 to 0.07; 3 studies; very low certainty). In a sensitivity analysis omitting data from a study which only included participants who had shown a relatively poor prior response to donepezil, inconsistency was reduced and we found that cognitive function may be worse in the discontinuation group in the medium term (SMD -0.62; 95% CI -0.94 to -0.31). Data from one longer-term study suggest that discontinuing a cholinesterase inhibitor is probably associated with worse cognitive function at 12 months (mean difference (MD) -2.09 Standardised Mini-Mental State Examination (SMMSE) points, 95% CI -3.43 to -0.75; moderate certainty). Discontinuation may make little or no difference to functional status in the short term (SMD -0.25, 95% CI -0.54 to 0.04; 2 studies; low certainty), and its effect in the medium term is uncertain (SMD -0.38, 95% CI -0.74 to -0.01; 2 studies; very low certainty). After 12 months, discontinuing a cholinesterase inhibitor probably results in greater functional impairment than continuing treatment (MD -3.38 Bristol Activities of Daily Living Scale (BADLS) points, 95% CI -6.67 to -0.10; one study; moderate certainty). Discontinuation may be associated with a worsening of neuropsychiatric symptoms over the short term and medium term, although we cannot exclude a minimal effect (SMD - 0.48, 95% CI -0.82 to -0.13; 2 studies; low certainty; and SMD -0.27, 95% CI -0.47 to -0.08; 3 studies; low certainty, respectively). Data from one study suggest that discontinuing a cholinesterase inhibitor may result in little to no change in neuropsychiatric status at 12 months (MD -0.87 Neuropsychiatric Inventory (NPI) points; 95% CI -8.42 to 6.68; moderate certainty). We found no clear evidence of an effect of discontinuation on dropout due to lack of medication efficacy or deterioration in overall medical condition (odds ratio (OR) 1.53, 95% CI 0.84 to 2.76; 4 studies; low certainty), on number of adverse events (OR 0.85, 95% CI 0.57 to 1.27; 4 studies; low certainty) or serious adverse events (OR 0.80, 95% CI 0.46 to 1.39; 4 studies; low certainty), and on mortality (OR 0.75, 95% CI 0.36 to 1.55; 5 studies; low certainty). Institutionalisation was reported in one trial, but it was not possible to extract data for the groups relevant to this review.
AUTHORS' CONCLUSIONS
This review suggests that discontinuing cholinesterase inhibitors may result in worse cognitive, neuropsychiatric and functional status than continuing treatment, although this is supported by limited evidence, almost all of low or very low certainty. As all participants had dementia due to Alzheimer's disease, our findings are not transferable to other dementia types. We were unable to determine whether the effects of discontinuing cholinesterase inhibitors differed with baseline dementia severity. There is currently no evidence to guide decisions about discontinuing memantine. There is a need for further well-designed RCTs, across a range of dementia severities and settings. We are aware of two ongoing registered trials. In making decisions about discontinuing these drugs, clinicians should exercise caution, considering the evidence from existing trials along with other factors important to patients and their carers.
Topics: Activities of Daily Living; Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Humans; Memantine; Parkinson Disease; Quality of Life; Rivastigmine
PubMed: 35608903
DOI: 10.1002/14651858.CD009081.pub2 -
Cancer Medicine May 2023Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including... (Review)
Review
BACKGROUND
Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including quality of life and survival. This systematic review aimed to identify and describe interventions used to ameliorate (improve) or prevent cognitive impairments in adults with brain tumours.
METHODS
We performed a literature search of the Ovid MEDLINE, PsychINFO and PsycTESTS databases from commencement until September 2021.
RESULTS
In total, 9998 articles were identified by the search strategy; an additional 14 articles were identified through other sources. Of these, 35 randomised and nonrandomised studies were deemed to meet the inclusion/exclusion criteria of our review and were subsequently included for evaluation. A range of interventions were associated with positive effects on cognition, including pharmacological agents such as memantine, donepezil, methylphenidate, modafinil, ginkgo biloba and shenqi fuzheng, and nonpharmacological interventions such as general and cognitive rehabilitation, working memory training, Goal Management Training, aerobic exercise, virtual reality training combined with computer-assisted cognitive rehabilitation, hyperbaric oxygen therapy and semantic strategy training. However, most identified studies had a number of methodological limitations and were judged to be at moderate-to-high risk of bias. In addition, it remains unclear whether and to what extent the identified interventions lead to durable cognitive benefits after cessation of the intervention.
CONCLUSION
The 35 studies identified in this systematic review have indicated potential cognitive benefits for a number of pharmacological and nonpharmacological interventions in patients with brain tumours. Study limitations were identified and further studies should focus on improved study reporting, methods to reduce bias and minimise participant drop-out and withdrawal where possible, and consider standardisation of methods and interventions across studies. Greater collaboration between centres could result in larger studies with standardised methods and outcome measures, and should be a focus of future research in the field.
Topics: Adult; Humans; Quality of Life; Cognitive Dysfunction; Cognition; Cognition Disorders; Brain Neoplasms
PubMed: 36880363
DOI: 10.1002/cam4.5760 -
Frontiers in Aging Neuroscience 2023To conduct a meta-analysis of the effectiveness and safety of ginkgo biloba preparations combined with donepezil hydrochloride vs. donepezil for the treatment of...
OBJECTIVE
To conduct a meta-analysis of the effectiveness and safety of ginkgo biloba preparations combined with donepezil hydrochloride vs. donepezil for the treatment of Alzheimer's disease (AD).
METHODS
Three English databases (Cochrane Library, PubMed, EMBASE), and four Chinese databases [the China National Knowledge Infrastructure (CKNI), the Chinese Biomedical Literature database (CBM), the Chongqing VIP database, and WANFANG DATA)] were manually searched for literature published from the respective dates of inception of the databases to December 2022. The randomized controlled trials (RCTs) of ginkgo biloba preparations with donepezil hydrochloride vs. donepezil for the treatment of AD were included. Relevant literature was screened, and the data in the included studies were extracted for quality assessment according to the Risk of bias tool. The RevMan 5.3 software was used for meta-analysis.
RESULTS
A total of 1,642 participants were enrolled in the 18 RCTs. Of these, 842 were in the experimental group (ginkgo biloba preparations combined with donepezil hydrochloride) and 800 were in the control group (donepezil). The overall methodological quality of the included RCTs is poor due to the high risks of blindness and allocation concealment. The meta-analysis results showed statistically significant differences in several outcomes including Risk Ratio (RR) in change for clinical effectiveness rate (1.23, 95% CI 1.13, 1.34, < 0.00001), mean difference (MD) in change for Mini-Mental State Examination score (3.02, 95% CI 2.14, 3.89, < 0.00001), Activity of Daily Living Scale score (-4.56, 95% CI -5.09, -4.03, < 0.00001), Hasegawa Dementia Scale score (2.04, 95% CI 1.74, 2.34, < 0.00001), Montreal Cognitive Assessment score (2.38, 95% CI 0.72, 4.06, = 0.005), between the experimental and control groups. But there is no statistically significant difference in change for adverse reaction (0.91, 95% CI 0.58, 1.42, = 0.69).
CONCLUSION
Ginkgo biloba preparations plus donepezil can improve clinical effectiveness rate and vocabulary memory outcomes. However, more relevant high-quality RCTs are needed in the future to validate these results.
SYSTEMATIC REVIEW REGISTRATION
Identifier CRD42022378970.
PubMed: 36960422
DOI: 10.3389/fnagi.2023.1124710 -
The Cochrane Database of Systematic... Nov 2022Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of... (Review)
Review
BACKGROUND
Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of pharmacological and non-pharmacological treatment of cognitive deficits in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 12, 2014.
OBJECTIVES
To assess the effectiveness of interventions for preventing or ameliorating cognitive deficits in adults treated with cranial irradiation.
SEARCH METHODS
For this review update we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, Embase via Ovid, and PsycInfo via Ovid to 12 September 2022.
SELECTION CRITERIA
We included randomised controlled (RCTs) trials that evaluated pharmacological or non-pharmacological interventions in cranial irradiated adults, with objective cognitive functioning as a primary or secondary outcome measure.
DATA COLLECTION AND ANALYSIS
Two review authors (MK, JD) independently extracted data from selected studies and carried out a risk of bias assessment. Cognitive function, fatigue and mood outcomes were reported. No data were pooled.
MAIN RESULTS
Eight studies met the inclusion criteria and were included in this updated review. Six were from the original version of the review, and two more were added when the search was updated. Nineteen further studies were assessed as part of this update but did not fulfil the inclusion criteria. Of the eight included studies, four studies investigated "prevention" of cognitive problems (during radiotherapy and follow-up) and four studies investigated "amelioration" (interventions to treat cognitive impairment as a late complication of radiotherapy). There were five pharmacological studies (two studies on prevention and three in amelioration) and three non-pharmacological studies (two on prevention and one in amelioration). Due to differences between studies in the interventions being evaluated, a meta-analysis was not possible. Studies in early radiotherapy treatment phase (five studies) Pharmacological studies in the "early radiotherapy treatment phase" were designed to prevent or ameliorate cognitive deficits and included drugs used in dementia (memantine) and fatigue (d-threo-methylphenidate hydrochloride). Non-pharmacological studies in the "early radiotherapy treatment phase" included a ketogenic diet and a two-week cognitive rehabilitation and problem-solving programme. In the memantine study, the primary cognitive outcome of memory at six months did not reach significance, but there was significant improvement in overall cognitive function compared to placebo, with similar adverse events across groups. The d-threo-methylphenidate hydrochloride study found no statistically significant difference between arms, with few adverse events. The study of a calorie-restricted ketogenic diet found no effect, although a lower than expected calorie intake in the control group complicates interpretation of the results. The study investigating the utility of a rehabilitation program did not carry out a statistical comparison of cognitive performance between groups. Studies in delayed radiation or late effect phase (four studies) The "amelioration" pharmacological studies to treat cognitive complications of radiotherapy included drugs used in dementia (donepezil) or psychostimulants (methylphenidate and modafinil). Non-pharmacological measures included cognitive rehabilitation and problem solving (Goal Management Training). These studies included patients with cognitive problems at entry who had "stable" brain cancer. The donepezil study did not find an improvement in the primary cognitive outcome of overall cognitive performance, but did find improvement in an individual test of memory, compared to placebo; adverse events were not reported. A study comparing methylphenidate with modafinil found improvements in cognitive function in both the methylphenidate and modafinil arms; few adverse events were reported. Another study comparing two different doses of modafinil combined treatment arms and found improvements across all cognitive tests, however, a number of adverse events were reported. Both studies were limited by a small sample size. The Goal Management Training study suggested a benefit of the intervention, a behavioural intervention that combined mindfulness and strategy training, on executive function and processing speed. There were a number of limitations across studies and few were without high risks of bias.
AUTHORS' CONCLUSIONS
In this update, limited additional evidence was found for the treatment or amelioration of cognitive deficits in adults treated with cranial irradiation. As concluded in the original review, there is supportive evidence that memantine may help prevent cognitive deficits for adults with brain metastases receiving cranial irradiation. There is supportive evidence that donepezil, methylphenidate and modafinil may have a role in treating cognitive deficits in adults with brain tumours who have been treated with cranial irradiation; patient withdrawal affected the statistical power of these studies. Further research that tries to minimise the withdrawal of consent, and subsequently reduce the requirement for imputation procedures, may offer a higher certainty of evidence. There is evidence from only a single small study to support non-pharmacological interventions in the amelioration of cognitive deficits. Further research is required.
Topics: Adult; Humans; Modafinil; Donepezil; Memantine; Quality of Life; Cognitive Dysfunction; Cranial Irradiation; Cognition; Methylphenidate; Brain Neoplasms; Fatigue; Dementia
PubMed: 36427235
DOI: 10.1002/14651858.CD011335.pub3 -
Medicine Oct 2022Gunao-Yizhi decoction has the effects of supplementing intelligence, strengthening marrow, resolving phlegm, and reducing turbidity. It is clinically used for the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gunao-Yizhi decoction has the effects of supplementing intelligence, strengthening marrow, resolving phlegm, and reducing turbidity. It is clinically used for the treatment of vascular dementia (VaD). However, there is still a lack of systematic evaluation of its efficacy and safety. This review conducted a systematic review of the current evidence on the efficacy and safety of Gunao-Yizhi decoction combined with donepezil for VaD.
METHODS
China National Knowledge Infrastructure (CNKI), Wanfang database (Wanfang), Chinese Science and Technology Periodical Database (VIP), China Biology Medicine disc (CBM), MEDLINE, EMBASE, and Cochrane Library were searched for randomized controlled trials on Gunao-Yizhi decoction combined with donepezil for VaD. RevMan 5.3 software was used for data analysis.
RESULTS
Twelve studies were obtained, including 1036 patients. Compared with donepezil alone, meta-analysis showed that Gunao-Yizhi decoction combined with donepezil could improve clinical efficacy, mini-mental state examination (MMSE) score, Hasegawa dementia scale (HDS), increase the level of superoxide dismutase (SOD) in serum, and reduce the level of malonaldehyde dismutas (MDA) in serum. The GRADE system was adopted to evaluate the outcome index. Clinical efficiency and the MMSE score were evaluated as very-low-quality evidence. HDS score, serum SOD level, and serum MDA level were evaluated as low-quality evidence.
CONCLUSION
Gunao-Yizhi decoction combined with donepezil has a significant prevalence in the treatment of vascular dementia, with no increase in adverse events. Gunao-Yizhi decoction can be recommended for routine use in the treatment of VaD.
Topics: Dementia, Vascular; Donepezil; Drugs, Chinese Herbal; Humans; Malondialdehyde; Superoxide Dismutase
PubMed: 36221397
DOI: 10.1097/MD.0000000000030971 -
Frontiers in Neuroscience 2023Prior research has shown mixed results regarding the effectiveness of combining donepezil and traditional Chinese medicine (TCM) to treat mild cognitive impairment... (Review)
Review
OBJECTIVE
Prior research has shown mixed results regarding the effectiveness of combining donepezil and traditional Chinese medicine (TCM) to treat mild cognitive impairment (MCI). In light of this, our study aims to examine the efficacy and safety of this treatment approach for patients with MCI.
METHODS
We conducted a comprehensive search of various databases, including Medline ( PubMed), Cochrane, Embase, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wanfang Database from their inception to November 16, 2022. The selection of studies, risk of bias assessment, and data extraction were carried out independently by two authors. The statistical analysis was performed using STATA.
RESULTS
Our meta-analysis included a total of 35 studies with 2,833 patients, published between 2008 and 2022, with intervention durations ranging from 4 weeks to 12 months. However, most of the studies had a high risk of detection bias. Our findings indicated that the combination of donepezil and TCM significantly improved the Montreal Cognitive Assessment (MoCA) score (weighted mean difference [WMD] = 2.79, 95% confidence interval [CI]: 1.82 to 3.75) and the Barthel Index score (WMD = 9.20, 95% CI: 5.39 to 13.00) compared to donepezil alone. However, subgroup analyses showed that the MoCA score did not increase significantly in patients with MCI resulting from cerebrovascular disease (WMD = 1.47, 95% CI: -0.02 to 2.96).
CONCLUSION
The combination of donepezil and TCM may have a more positive effect on cognitive function and activities of daily living in patients with MCI compared to the use of donepezil alone. However, due to the limited quality of the studies included in our analysis, these findings should be interpreted with caution.
PubMed: 37476835
DOI: 10.3389/fnins.2023.1206491 -
Clinics (Sao Paulo, Brazil) 2024Summarize the evidence on drug therapies for obstructive sleep apnea. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Summarize the evidence on drug therapies for obstructive sleep apnea.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed, Embase, Scopus, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched on February 17th, 2023. A search strategy retrieved randomized clinical trials comparing the Apnea-Hypopnea Index (AHI) in pharmacotherapies. Studies were selected and data was extracted by two authors independently. The risk of bias was assessed using the Cochrane Risk of Bias tool. RevMan 5.4. was used for data synthesis.
RESULTS
4930 articles were obtained, 68 met inclusion criteria, and 29 studies (involving 11 drugs) were combined in a meta-analysis. Atomoxetine plus oxybutynin vs placebo in AHI mean difference of -7.71 (-10.59, -4.83) [Fixed, 95 % CI, I2 = 50 %, overall effect: Z = 5.25, p < 0.001]. Donepezil vs placebo in AHI mean difference of -8.56 (-15.78, -1.33) [Fixed, 95 % CI, I2 = 21 %, overall effect: Z = 2.32, p = 0.02]. Sodium oxybate vs placebo in AHI mean difference of -5.50 (-9.28, -1.73) [Fixed, 95 % CI, I2 = 32 %, overall effect: Z = 2.86, p = 0.004]. Trazodone vs placebo in AHI mean difference of -12.75 (-21.30, -4.19) [Fixed, 95 % CI, I2 = 0 %, overall effect: Z = 2.92, p = 0.003].
CONCLUSION
The combination of noradrenergic and antimuscarinic drugs shows promising results. Identifying endotypes may be the key to future drug therapies for obstructive sleep apnea. Moreover, studies with longer follow-up assessing the safety and sustained effects of these treatments are needed.
PROSPERO REGISTRATION NUMBER
CRD42022362639.
Topics: Humans; Sleep Apnea, Obstructive; Atomoxetine Hydrochloride; Donepezil; Norepinephrine
PubMed: 38341903
DOI: 10.1016/j.clinsp.2024.100330 -
Journal of Alzheimer's Disease : JAD 2023Choline alphoscerate (alpha glyceryl phosphorylcholine, α-GPC) is a choline-containing phospholipid used as a medicine or nutraceutical to improve cognitive function... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Choline alphoscerate (alpha glyceryl phosphorylcholine, α-GPC) is a choline-containing phospholipid used as a medicine or nutraceutical to improve cognitive function impairment occurring in neurological conditions including adult-onset dementia disorders. Despite its 1985 marketing authorization, there are still discrepancies between countries regarding its approval as a prescription medicine and discussions about its effectiveness.
OBJECTIVE
This study aimed to evaluate the efficacy of the α-GPC compound for treating cognitive impairment in patients with adult-onset neurological disorders.
METHODS
Relevant studies were identified by searching PubMed, Web of Science, and Embase. Studies that evaluated the effects of α-GPC alone or in combination with other compounds on adult-onset cognitive impairment reporting cognition, function, and behavior were considered. We assessed the risk of bias of selected studies using the Cochrane risk of bias tool.
RESULTS
A total of 1,326 studies and 300 full-text articles were screened. We included seven randomized controlled trials (RCTs) and one prospective cohort study that met our eligibility criteria. We found significant effects of α-GPC in combination with donepezil on cognition [4 RCTs, mean difference (MD):1.72, 95% confidence interval (CI): 0.20 to 3.25], functional outcomes [3 RCTs, MD:0.79, 95% CI: 0.34 to 1.23], and behavioral outcomes [4 RCTs; MD: -7.61, 95% CI: -10.31 to -4.91]. We also observed that patients who received α-GPC had significantly better cognition than those who received either placebo or other medications [MD: 3.50, 95% CI: 0.36 to 6.63].
CONCLUSION
α-GPC alone or in combination with donepezil improved cognition, behavior, and functional outcomes among patients with neurological conditions associated with cerebrovascular injury.
Topics: Humans; Donepezil; Glycerylphosphorylcholine; Cognitive Dysfunction; Cognition Disorders; Cognition; Randomized Controlled Trials as Topic
PubMed: 36683513
DOI: 10.3233/JAD-221189 -
Pharmaceuticals (Basel, Switzerland) Jan 2022Alzheimer's disease (AD) is a leading progressive neurodegenerative disease worldwide, and its treatment is a challenging clinical problem. This review was conducted to... (Review)
Review
Alzheimer's disease (AD) is a leading progressive neurodegenerative disease worldwide, and its treatment is a challenging clinical problem. This review was conducted to evaluate the efficacy and safety of herbal medicine for AD treatment. The PubMed, CENTRAL, EMBASE, CNKI, OASIS, KTKP, and CiNii databases were searched until June 2020 for randomized controlled trials (RCTs) on herbal medicine for AD, and a meta-analysis of 57 RCTs was conducted. For cognitive function, herbal medicine significantly improved the Mini-Mental State Examination (MMSE) and AD Assessment Scale-Cognitive Subscale (ADAS-cog) scores compared with conventional medicine. The MMSE scores showed no significant difference between the groups treated with herbal medicine and donepezil; however, herbal medicine significantly lowered the ADAS-cog score. Acori Graminei Rhizoma-containing and Cnidii Rhizoma-containing herbal medicine significantly improved the MMSE and ADAS-cog scores compared with conventional medicine. Ginseng Radix-containing herbal medicine showed a positive, but not statistically significant, tendency toward improving the MMSE score compared with conventional medicine. Herbal medicine with conventional medicine significantly improved the MMSE, ADAS-cog, and Montreal Cognitive Assessment (MoCA) scores compared with conventional medicine, and herbal medicine with donepezil also significantly improved these scores compared with donepezil. Acori Graminei Rhizoma or Cnidii Rhizoma-containing herbal medicine with conventional medicine significantly improved the MMSE and ADAS-cog scores compared with conventional medicine. Ginseng Radix-containing herbal medicine + conventional medicine significantly improved the MMSE score, but not the ADAS-cog score, compared with conventional medicine. For behavioral and psychological symptoms of dementia, the Neuropsychiatry Inventory (NPI) score was not significantly different between herbal and conventional medicines. Herbal medicine with conventional medicine significantly improved the NPI and Behavioral Pathology in Alzheimer's Disease Rating Scale scores compared with conventional medicine. The NPI score showed no significant difference between the groups treated with herbal medicine and placebo. Furthermore, herbal medicine with conventional medicine significantly lowered plasma amyloid beta levels compared with conventional medicine alone. Herbal medicine, whether used alone or as an adjuvant, may have beneficial effects on AD treatment. However, owing to the methodological limitations and high heterogeneity of the included studies, concrete conclusions cannot be made.
PubMed: 35215287
DOI: 10.3390/ph15020174 -
Frontiers in Neuroscience 2022The mainstay of therapy for many neurodegenerative dementias still relies on acetylcholinesterase inhibitors (AChEI); however, there is debate on various aspects of such...
BACKGROUND
The mainstay of therapy for many neurodegenerative dementias still relies on acetylcholinesterase inhibitors (AChEI); however, there is debate on various aspects of such treatment. A huge body of literature exists on possible predictors of response, but a comprehensive review is lacking. Therefore, our aim is to perform a systematic review of the predictors of response to AChEI in neurodegenerative dementias, providing a categorization and interpretation of the results.
METHODS
We conducted a systematic review of the literature up to December 31, 2021, searching five different databases and registers, including studies on rivastigmine, donepezil, and galantamine, with clearly defined criteria for the diagnosis of dementia and the response to AChEI therapy. Records were identified through the string: . The results were presented narratively.
RESULTS
We identified 1,994 records in five different databases; after exclusion of duplicates, title and abstract screening, and full-text retrieval, 122 studies were finally included.
DISCUSSION
The studies show high heterogeneity in duration, response definition, drug dosage, and diagnostic criteria. Response to AChEI seems associated with correlates of cholinergic deficit (hallucinations, fluctuating cognition, substantia innominate atrophy) and preserved cholinergic neurons (faster alpha on REM sleep EEG, increased anterior frontal and parietal lobe perfusion after donepezil); white matter hyperintensities in the cholinergic pathways have shown inconsistent results. The K-variant of butyrylcholinesterase may correlate with better response in late stages of disease, while the role of polymorphisms in other genes involved in the cholinergic system is controversial. Factors related to drug availability may influence response; in particular, low serum albumin (for donepezil), CYP2D6 variants associated with reduced enzymatic activity and higher drug doses are the most consistent predictors, while AChEI concentration influence on clinical outcomes is debatable. Other predictors of response include faster disease progression, lower serum cholesterol, preserved medial temporal lobes, apathy, absence of concomitant diseases, and absence of antipsychotics. Short-term response may predict subsequent cognitive response, while higher education might correlate with short-term good response (months), and long-term poor response (years). Age, gender, baseline cognitive and functional levels, and APOE relationship with treatment outcome is controversial.
PubMed: 36203811
DOI: 10.3389/fnins.2022.998224