Nootropic Agents

促智剂
  • 文章类型: Journal Article
    背景:医学生中滥用处方精神兴奋剂(PPs)的现象越来越多,承受高度压力的人,尤其是因为苛刻和竞争激烈的教育环境。
    目的:调查比利时医学生的这一现象,以确定误用的危险因素。
    方法:我们从2023年3月7日至2023年4月3日使用在线问卷进行了横断面研究。在文献综述和专家咨询的基础上,编制了一份半定量问卷,包括感知压力量表(PSS-10)和五大量表(BFI-10)。问卷对323名最后一年的医学生(其中61.9%的人回答)进行了调查,而对325名二年级学生和205名一年级学生进行了比较(回答率为36.9%和18.5%,分别)。使用Jamovi(2.3.21版)进行描述性和双变量分析。
    结果:多年来,PPs的使用有所增加。在最后一年,12.6%的人报告说他们已经使用PPs来提高他们的认知能力,3.6%的人目前正在使用它们。各种危险因素与PPs的滥用有关,包括缺乏意识,寻求感觉,其他物质使用,高压力水平,社会影响力,课程高标准感知,以及对物质使用缺乏伦理关注。
    结论:这项研究表明,超过十分之一的学生在学习期间至少使用过PPs,这主要可以通过挑战医学教育背景和人格特质来解释。应实施量身定制的预防策略。
    BACKGROUND: The misuse of prescription psychostimulants (PPs) is growing among medical students, who are subject to high levels of stress, not least because of a demanding and competitive educational environment.
    OBJECTIVE: To investigate this phenomenon among medical students in Belgium to identify misuse risk factors.
    METHODS: We conducted a cross-sectional study using an online questionnaire from 7 march 2023 to 3 April 2023. A semi-quantitative questionnaire based on a literature review and consultation with experts was drawn up, including the Perceived Stress Scale (PSS-10) and the Big Five Inventory (BFI-10). The questionnaire was administered to 323 final-year medical students (61.9% of whom responded) and comparatively to 325 second-to-last-year students and 205 first-year students (response rate was 36.9% and 18.5%, respectively). Descriptive and bivariate analyses were performed with Jamovi (version 2.3.21).
    RESULTS: Use of PPs increased over the years. In the final year, 12.6% reported that they had already used PPs to improve their cognitive performance, and 3.6% were currently using them. Various risk factors were associated with the misuse of PPs, including lack of consciousness, sensation-seeking, other substances use, high stress levels, social influence, curriculum high standards perception, and lack of ethical concern regarding the substance use.
    CONCLUSIONS: This study showed that more than one in ten final-year students have used PPs at least once during their studies, which can be explained mainly by challenging medical education context and personality traits. Tailored preventive strategies should be implemented.
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  • 文章类型: Journal Article
    背景:胆酸胆碱(α-甘油基磷酸胆碱)是一种磷脂,包括胆碱,这增加了乙酰胆碱的释放。ASCOMALVA审判,多奈哌齐和甘磷酸胆碱的组合,减缓阿尔茨海默病的认知能力下降。这项研究旨在通过将多奈哌齐与目前在韩国使用的其他促智药组合来复制这种效果。
    方法:119例符合使用多奈哌齐的认知功能减退患者,迷你精神状态检查(MMSE)得分为26分或更低,被分配到:单独的多奈哌齐(DO);多奈哌齐和羟磷酸胆碱(DN);多奈哌齐和乙酰左旋肉碱(DA);或多奈哌齐和银杏叶提取物(DG)。认知评估,如MMSE,临床痴呆评级,阿尔茨海默病评估量表-认知子量表(ADAS-Cog),和阿尔茨海默病评估量表-非认知子量表在基线时间点的第12周和第24周进行.
    结果:在第12周,DN组MMSE评分增加3.52%,而DO组增加了1.36%。在DA+DG组中,下降了2.17%。在第24周,DO组MMSE评分增加1.07%,DN组增加1.61%,DA+DG组下降5.71%。DO组ADAS-Cog下降0.9%,而DN组在第12周时提高了13.9%。在第24周,ADAS-Cog在DN组中显示改善18.5%,而DO组则提高了9.4%。阿尔茨海默病评估量表-非认知子量表在第12周和第24周也显示DN组比DO组有更好的表现。
    结论:胆碱alfoscerate在认知和非认知领域都表现出额外的认知改善,支持ASCOMALVA试验的结果。
    BACKGROUND: Choline alfoscerate (alpha-glycerylphosphorylcholine) is a phospholipid that includes choline, which increases the release of acetylcholine. The ASCOMALVA trial, a combination of donepezil and choline alfoscerate, slowed cognitive decline in Alzheimer disease. This study aims to replicate the effect by combining donepezil with other nootropics currently used in South Korea.
    METHODS: The 119 patients with cognitive decline who were eligible to use donepezil, with an mini-mental state examination (MMSE) score of 26 or less, were assigned to: donepezil alone (DO); donepezil and choline alfoscerate (DN); donepezil and acetyl-l-carnitine (DA); or donepezil and ginkgo biloba extract (DG). Cognitive evaluations such as MMSE, clinical dementia rating, Alzheimer disease assessment scale-cognitive subscale (ADAS-Cog), and Alzheimer disease assessment scale-noncognitive subscale were performed at the 12th and 24th weeks from the baseline time point.
    RESULTS: At the 12th week, the MMSE score increased 3.52% in the DN group, whereas it increased by 1.36% in the DO group. In the DA + DG group, it decreased by 2.17%. At the 24th week, the MMSE score showed an increase of 1.07% in the DO group and 1.61% in the DN group, but decreased by 5.71% in the DA + DG group. ADAS-Cog decreased by 0.9% in the DO group, while it improved by 13.9% in the DN group at the 12th week. At the 24th week, ADAS-Cog showed improvement in the DN group by 18.5%, whereas it improved by 9.4% in the DO group. Alzheimer disease assessment scale-noncognitive subscale also revealed better performance in the DN group than in the DO group at the 12th and 24th weeks.
    CONCLUSIONS: Choline alfoscerate exhibits additional cognitive improvement in both cognitive and noncognitive domains, supporting the findings of the ASCOMALVA trial.
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  • 文章类型: Journal Article
    背景:缺乏抗痴呆药物(ADDs)的最新时间趋势分析。这项研究的目的是使用真实世界数据评估痴呆症患者的ADD发生率(IR)。
    方法:来自英国/CPRD-GOLD(2007-20)的初级保健数据(国家/数据库),西班牙/SIDIAP(2010-20)和荷兰/IPCI(2008-20),标准化为通用数据模型。
    方法:队列研究。参与者:年龄≥40岁的痴呆患者,既往数据≥1年。随访:直到研究期结束,转移出集水区,利伐斯的明死亡或事故处方,加兰他敏,多奈哌齐或美金刚.其他变量:年龄/性别,痴呆的类型,合并症.统计数据:总体和年度年龄/性别IR,95%的置信区间,每100,000人年(IR每105PY(95CI))。
    结果:我们在UK/CPRD-GOLD中确定了总共(抗痴呆症患者/痴呆症患者)41,024/110,642,西班牙/SIDIAP为51667/134927,荷兰/IPCI为2088/17559。在英国,从2007年(30,829(28,891-32,862))到2010年(17,793(17,083-18,524)),然后增加到2019年(31,601(30,483至32,749)),并在2020年减少(24,067(23,021-25,148))。在西班牙,从2010年(51003(49199-52855))到2020年(14571(14109-15043)),ADD的IR(每105日元(95CI))下降了72%。在荷兰,从2009年(21,151(14,967-29,031))到2020年(4763(4176-5409)),ADD的IR(每105日元(95CI))下降了77%。年龄≥65-79岁的受试者和男性(在英国和荷兰)更频繁地开始ADD。
    结论:痴呆的治疗仍然高度异质性。迫切需要在痴呆症患者的药理管理方面达成进一步共识。
    An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data.
    Primary care data (country/database) from the UK/CPRD-GOLD (2007-20), Spain/SIDIAP (2010-20) and the Netherlands/IPCI (2008-20), standardised to a common data model.
    Cohort study. Participants: dementia patients ≥40 years old with ≥1 year of previous data. Follow-up: until the end of the study period, transfer out of the catchment area, death or incident prescription of rivastigmine, galantamine, donepezil or memantine. Other variables: age/sex, type of dementia, comorbidities. Statistics: overall and yearly age/sex IR, with 95% confidence interval, per 100,000 person-years (IR per 105 PY (95%CI)).
    We identified a total of (incident anti-dementia users/dementia patients) 41,024/110,642 in UK/CPRD-GOLD, 51,667/134,927 in Spain/SIDIAP and 2,088/17,559 in the Netherlands/IPCI.In the UK, IR (per 105 PY (95%CI)) of ADD decreased from 2007 (30,829 (28,891-32,862)) to 2010 (17,793 (17,083-18,524)), then increased up to 2019 (31,601 (30,483 to 32,749)) and decrease in 2020 (24,067 (23,021-25,148)). In Spain, IR (per 105 PY (95%CI)) of ADD decreased by 72% from 2010 (51,003 (49,199-52,855)) to 2020 (14,571 (14,109-15,043)). In the Netherlands, IR (per 105 PY (95%CI)) of ADD decreased by 77% from 2009 (21,151 (14,967-29,031)) to 2020 (4763 (4176-5409)). Subjects aged ≥65-79 years and men (in the UK and the Netherlands) initiated more frequently an ADD.
    Treatment of dementia remains highly heterogeneous. Further consensus in the pharmacological management of patients living with dementia is urgently needed.
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  • 文章类型: Journal Article
    白细胞弹性蛋白酶是炎症的标志物。以前,发现患者精神障碍的严重程度与血浆弹性蛋白酶样活性有关.在体外实验中分析了各种亲神经药物对白细胞弹性蛋白酶活性的影响。我们揭示了苯并二氮卓类镇静剂地西泮和溴代氢氯苯基苯并二氮卓类和免疫调节剂氨基二氢噻嗪二酮和双氯芬酸对健康供体和纯人类中性粒细胞弹性蛋白酶的血浆弹性蛋白酶样活性的抑制作用。抗精神病药物氯丙嗪和阿利马嗪,以及促智药长春西汀以剂量依赖性方式增加弹性蛋白酶样活性。氯丙嗪和长春西汀的激活作用,但不是阿利马嗪,在中性粒细胞弹性蛋白酶中复制。我们假设这些药物可以在精神障碍的复杂治疗中影响炎症反应的发展。
    Leukocyte elastase is a marker of inflammation. Previously, a relationship was found between the severity of mental disorders in patients and elastase-like activity of blood plasma. The effect of various neurotropic drugs on leukocyte elastase activity was analyzed in an in vitro experiment. We revealed an inhibitory effect of the benzodiazepine tranquilizers diazepam and bromodihydrochlorophenylbenzodiazepine and immunomodulators aminodihydrophthalazinedione and diclofenac on the plasma elastase-like activity of healthy donors and pure human neutrophil elastase. The antipsychotics chlorpromazine and alimemazine, as well as the nootropic vinpocetine increased elastase-like activity in a dose-dependent manner. The activating effect of chlorpromazine and vinpocetine, but not alimemazine, was reproduced in neutrophil elastase. We hypothesized that these drugs can affect the development of inflammatory reactions in the complex therapy of mental disorders.
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  • 文章类型: Journal Article
    背景:阿尔茨海默病(AD)是一种神经退行性疾病,其特征是认知能力逐渐丧失(痴呆),是主要的公共卫生问题。这里,我们的目的是研究罗莎·达马塞纳精油(RDEO)对东莨菪碱引起的健忘症大鼠模型学习和记忆功能的影响,以及乙酰胆碱酯酶(AChE)活性的变化,M1毒蕈碱乙酰胆碱受体(mAChR)表达,和脑源性神经营养因子(BDNF)在提取的脑组织中的水平。
    方法:对照,健忘症(东pol碱,1mg/kg/i.p.)和治疗(RDEO,100μL/kg/p.o.或加兰他敏,1.5mg/kg/i.p.)组进行Morris水迷宫和新物体识别测试。通过ELISA测定AChE活性,蛋白质印迹法测定m1mAChR和BDNF浓度变化。此外,使用计算工具,人M1mAChR被建模为活性构象,RDEO的主要成分停靠在该受体上。
    结果:根据我们的行为测试,RDEO能够减轻体内由东莨菪碱引起的学习和记忆障碍。我们的体外实验表明,观察到的积极作用与健忘大鼠大脑中AChE活性的降低以及M1mAChR和BDNF水平的增加密切相关。我们还在计算机环境中证明了RDEO的主要成分,特别是香茅醇,香叶醇,还有nerol,可以有利地容纳在活性状态人M1mAChR的变构结合袋中,并主要通过氢键和烷基-π相互作用锚定在这里。
    结论:我们的研究结果为未来针对AD患者的基于RDEO的药物产品开发提供了坚实的实验基础。
    BACKGROUND: Alzheimer\'s disease (AD) is a neurodegenerative condition characterized by gradual loss of cognitive abilities (dementia) and is a major public health problem. Here, we aimed at investigating the effects of Rosa damascena essential oil (RDEO) on learning and memory functions in a rat model of amnesia induced by scopolamine, as well as on changes in acetylcholinesterase (AChE) activity, M1 muscarinic acetylcholine receptor (mAChR) expression, and brain-derived neurotrophic factor (BDNF) levels in the extracted brain tissues.
    METHODS: The control, amnesia (scopolamine, 1 mg/kg/i.p.) and treatment (RDEO, 100 μL/kg/p.o. or galantamine, 1.5 mg/kg/i.p.) groups were subjected to Morris water maze and new object recognition tests. AChE activity was assayed by ELISA, and M1 mAChR and BDNF concentration changes were determined by western blotting. Also, using computational tools, human M1 mAChR was modeled in an active conformation, and the major components of RDEO were docked onto this receptor.
    RESULTS: According to our behavioral tests, RDEO was able to mitigate the learning and memory impairments caused by scopolamine in vivo. Our in vitro assays showed that the observed positive effects correlated well with a decrease in AChE activity and an increase in M1 mAChR and BDNF levels in amnestic rat brains. We also demonstrated in an in silico setting that the major components of RDEO, specifically -citronellol, geraniol, and nerol, could be accommodated favorably within the allosteric binding pocket of active-state human M1 mAChR and anchored here chiefly by hydrogen-bonding and alkyl-π interactions.
    CONCLUSIONS: Our findings offer a solid experimental foundation for future RDEO-based medicinal product development for patients suffering from AD.
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  • 文章类型: Journal Article
    所提出的研究坚持一定的方法,以确保用于分析cerrophenoxine药物的技术是可持续的和绿色的。必须强调的是,最近开发的几种工具被用作环境可持续性和适用性的潜在指标。本研究提出了一种新颖且完全创新的方法,该方法利用超灵敏的荧光光谱法来检测Centrophenoxine(CPX)药物。本研究采用的方法包括一步一步的利用,一罐,和直接荧光光谱技术,在药物的验证和评估中被发现是有效和环境可持续的。简单地说,当CPX和赤藓红B试剂在酸性环境中组合时,立即产生高共振瑞利散射产物。观察到灵敏度极限在15-47ngmL-1的范围内,而线性被评估为在50-2000ngmL-1的范围内。通过分析去甲苯丙胺-赤藓红B复合物,确定了系统所有可修改参数的最佳设置。此外,该系统证明符合国际协调理事会(ICH)规范,没有遇到任何问题。然后根据最近的不同环境安全测量指标对建议的过程进行评级,以了解其对环境的影响。幸运的是,利用绿色/红色/蓝色(RGB12)设计结合生态和功能元素的WAC标准也称赞当前的分析技术为白色。此外,采用新的适用性评估工具(BAGI)来评估计划方法在分析化学领域的实用性。
    The proposed research adheres to a certain methodology to ensure that the technique used for analyzing the centrophenoxine drug is sustainable and green. It is important to highlight that several tools that have been recently developed were utilized as potential indicators of environmental sustainability and applicability. The present research presents a novel and entirely innovative method utilizing ultrasensitive spectrofluorimetry for the detection of centrophenoxine (CPX) drug. The employed methodology in this study involved the utilization of one-step, one-pot, and direct spectrofluorimetric technique, which was found to be both efficient and environmentally sustainable in the validation and assessment of the drug. Simply, when CPX and erythrosine B reagent were combined in an acidic environment, the highly resonance Rayleigh scattering product was immediately produced. The sensitivity limits were observed to be within the range of 15-47 ng mL-1, whereas the linearity was assessed to be in the range of 50-2000 ng mL-1. The optimal settings for all modifiable parameters of the system were ascertained through an analysis of centrophenoxine-erythrosine B complexes. Moreover, the system demonstrated compliance with International Council for Harmonization (ICH) specifications without encountering any issues. The suggested process was then rated on different recent environmental safety measuring metrics to see how good it was for the environment. Fortunately, the WAC standards that combine ecological and functional elements utilizing the Green/Red/Blue (RGB 12) design also acclaimed the current analytical technique as a white one. Additionally, a new applicability evaluation tool (BAGI) was employed to estimate the practicability of the planned method in the analytical chemistry field.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    背景:目前使用多奈哌齐治疗路易体痴呆(DLB)相关症状的证据有限。我们对DLB患者使用多奈哌齐的三项随机对照试验进行了荟萃分析,以研究多奈哌齐在简易精神状态检查(MMSE)中的总体疗效。神经精神量表(NPI),和临床医生基于访谈的变化加照顾者输入印象(CIBIC加)。
    方法:使用安慰剂或10mg多奈哌齐的312例患者的数据进行了荟萃分析。MMSE的总体平均得分差异,估计从基线到第12周的NPI-2和NPI-10及其95%置信区间(CI)。ForCIBIC-plus,从7分的成绩转变为二分结果(改善/无改善),估计比值比(OR)及其95%CI.使用随机效应模型,异质性使用Cochrane的Q检验和I2统计量进行评估。
    结果:怀疑NPI-2(P<0.05;I2=87.2%)和NPI-10(P<0.05;I2=67.7%)存在异质性,而未怀疑MMSE(P=0.23;I2=32.4%)和CIBIC-plus(P=0.26;I2=19.8%)。多奈哌齐组的总体平均MMSE评分差异(平均差异:1.50;95%CI,0.67-2.34)和从基线到第12周改善CIBIC-plus的总体几率(OR:2.20;95%CI,1.13-4.26)高于安慰剂组。
    结论:我们的荟萃分析结果表明多奈哌齐对DLB患者认知障碍的总体疗效和总体临床状况。
    BACKGROUND: Current evidence for the management of symptoms associated with dementia with Lewy bodies (DLB) using donepezil is limited. We conducted a meta-analysis of three randomised controlled trials of donepezil in patients with DLB to investigate the overall efficacy of donepezil on Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), and Clinician\'s Interview-Based Impression of Change-plus Caregiver Input (CIBIC-plus).
    METHODS: A meta-analysis was performed using the data of 312 patients administered placebo or 10 mg donepezil. Overall mean score differences for MMSE, NPI-2, and NPI-10 from baseline to week 12 and their 95% confidence intervals (CI) were estimated. For CIBIC-plus, which was transformed from a seven-point grade to a dichotomous outcome (improvements/no improvements), odds ratio (OR) and its 95% CI were estimated. Random-effects models were used, and heterogeneity was evaluated using the Cochrane\'s Q test and I2 statistic.
    RESULTS: Heterogeneity was suspected for NPI-2 (P < 0.05; I2 = 87.2%) and NPI-10 (P < 0.05; I2 = 67.7%) while it was not suspected for MMSE (P = 0.23; I2 = 32.4%) and CIBIC-plus (P = 0.26; I2 = 19.8%). The overall mean MMSE score difference (mean difference: 1.50; 95% CI, 0.67-2.34) and the overall odds of improving CIBIC-plus (OR: 2.20; 95% CI, 1.13-4.26) from baseline to week 12 were higher in the donepezil group than in the placebo group.
    CONCLUSIONS: Results of our meta-analysis indicated overall efficacy of donepezil on cognitive impairment and global clinical status in patients with DLB.
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  • 文章类型: Journal Article
    背景:多奈哌齐已在日本被批准用于治疗路易体痴呆(DLB),其临床试验表明其对认知障碍的有益作用。这项IV期研究通过关注12周双盲期的全球临床状况来评估多奈哌齐的疗效。
    方法:将可能患有DLB的患者随机分配到安慰剂组(n=79)或10mg多奈哌齐组(n=81)。主要终点是全球临床状态的变化,使用临床医生基于访谈的变化印象加照顾者输入(CIBIC-plus)进行评估。我们还评估了四个CIBIC-plus域(一般情况,认知功能,行为,和日常生活活动)以及使用迷你精神状态检查(MMSE)和神经精神量表(NPI)测量的认知障碍以及行为和神经精神症状的变化,分别。
    结果:尽管多奈哌齐的优势在全球临床状态中没有显示,在认知领域检测到显著的有利效应(P=0.006).在事后分析中调整后,多奈哌齐组的MMSE评分有所改善(MMSE平均差异,1.4(95%置信区间(CI),0.42-2.30),P=0.004)。两组NPI的改善相似(NPI-2:-0.2(95%CI,-1.48至1.01),P=0.710;NPI-10:0.1(95%CI,-3.28至3.55),P=0.937)。
    结论:结果支持观察到10mg多奈哌齐改善DLB患者的认知功能具有临床意义。全球临床状态的评估可能会受到本研究中招募的轻度至中度DLB患者的影响。没有发现新的安全问题。
    BACKGROUND: Donepezil has been approved in Japan for the treatment of dementia with Lewy bodies (DLB) based on clinical trials showing its beneficial effects on cognitive impairment. This phase IV study evaluated the efficacy of donepezil by focusing on global clinical status during a 12-week double-blind phase.
    METHODS: Patients with probable DLB were randomly assigned to the placebo (n = 79) or 10 mg donepezil (n = 81) groups. The primary endpoint was changes in global clinical status, assessed using the Clinician\'s Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). We also assessed four CIBIC-plus domains (general condition, cognitive function, behaviour, and activities of daily living) and changes in cognitive impairment and behavioural and neuropsychiatric symptoms measured using the Mini-Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI), respectively.
    RESULTS: Although donepezil\'s superiority was not shown in the global clinical status, a significant favourable effect was detected in the cognitive domain (P = 0.006). MMSE scores improved in the donepezil group after adjustments in post hoc analysis (MMSE mean difference, 1.4 (95% confidence interval (CI), 0.42-2.30), P = 0.004). Improvements in NPIs were similar between the groups (NPI-2: -0.2 (95% CI, -1.48 to 1.01), P = 0.710; NPI-10: 0.1 (95% CI, -3.28 to 3.55), P = 0.937).
    CONCLUSIONS: The results support the observation that the efficacy of 10 mg donepezil in improving cognitive function is clinically meaningful in DLB patients. The evaluation of global clinical status might be affected by mild to moderate DLB patients enrolled in this study. No new safety concerns were detected.
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  • 文章类型: Journal Article
    目的:本综述的目的是确定用于治疗患有神经认知障碍的老年人的关键药物类别。
    结果:临床因素在这些治疗痴呆症的药物种类的处方中起着至关重要的作用。处方趋势的变化取决于老年人中常见的医学和精神病学合并症的存在,并且基于对合并症和痴呆症药物治疗之间潜在相互作用的考虑。目前存在六种药物类别来解决痴呆症的神经认知方面,具有不同的药代动力学和药效学特征。我们在本报告中回顾了这六个类别,并提供了有关这些药物使用的临床见解。虽然有文献研究老年人群痴呆的个别药物治疗方案的安全性和有效性,对于这些药物在临床实践中的具体使用,需要进一步的研究提供更明确的指导.
    The purpose of this review is to identify key classes of medications that are used for the treatment of older adults with neurocognitive disorders.
    Clinical factors play a critical role in the prescribing of these medication classes for the treatment of dementia. The variation in prescribing trends is determined by the presence of medical and psychiatric comorbidities commonly occurring in older adults and is based on the consideration of potential interactions between pharmacotherapies for the comorbidities and for the dementia. Six medication classes currently exist to address the neurocognitive aspect of dementia, with varying pharmacokinetic and pharmacodynamic profiles. We review these six classes in this report and provide a provision of clinical insights regarding the use of these agents. While literature exists on the safety and efficacy of individual medication options for the treatment of dementia in the older adult population, further research is needed to provide clearer guidance regarding the specific use of these agents in clinical practice.
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