Efficacy and Safety of Psychostimulants for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Abstract Introduction Several reports of the effectiveness of the use of psychostimulants for the treatment of Alzheimer’s disease (AD) are available. Methods A systematic review and meta-analysis was conducted including double-blind, randomized, placebo-controlled trials. Outcomes were the improvement of apathy scales score (primary), mini-mental state examination (MMSE) score, activities of daily living scale score, Zarit burden interview score, all-cause discontinuation, discontinuation due to adverse events, and incidence of at least 1 adverse event. Results Three methylphenidate studies and 1 modaﬁnil study were identified (n=156). Results from combined psychostimulants were superior to placebo in the improvement of apathy scales score (standardized mean differences [SMD]=−0.63 (−1.22, −0.04), p=0.04, all studies) and the MMSE score (SMD=−0.58 (−1.14, −0.02), p=0.04, 3 methylphenidate studies). The modaﬁnil study was excluded from the meta-analysis for the improvement of apathy scales score; therefore, the effect size increased (SMD=−0.82 (−1.43, −0.20), p=0.009). However, no significant differences were observed in terms of other outcomes, including safety outcomes between the treatment groups. Discussion Methylphenidate would be effective in treating apathy and cognitive impairment in AD patients.

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Effect of antihypertensive drugs on cognition and behavioral symptoms of patients with Alzheimer’s disease: A meta-analysis

Current Pharmaceutical Biotechnology ◽

10.2174/1386207323666201211101720 ◽

2020 ◽

Vol 21 ◽

Author(s):

Roja Rahimi ◽

Shekoufeh Nikfar ◽

Masoud Sadeghi ◽

Mohammad Abdollahi ◽

Reza Heidary Moghaddam ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Randomized Clinical Trials ◽

Antihypertensive Drugs ◽

Meta Analysis ◽

Behavioral Symptoms ◽

Cochrane Library ◽

Mean Differences ◽

Global Impression Of Change ◽

State Examination

Background: It has been found that there is a link between hypertension and elevated risk of Alzheimer’s disease (AD). Herein, a meta-analysis based on randomized clinical trials (RCTs) was used to assess the effect of antihypertensive drugs on cognition and behavioral symptoms of AD patients. Method: The three databases – PubMed/Medline, Scopus, and Cochrane Library- were searched up to March 2020. The quality of the studies included in the meta-analysis was evaluated by the Jadad score. Clinical Global Impression of Change (CGIC) included in two studies, Mini-Mental State Examination (MMSE) included in three studies, and Neuropsychiatric Inventory (NPI) in three studies were the main outcomes in this systematic review. Results: Out of 1506 studies retrieved in the databases, 5 RCTs included and analyzed in the meta-analysis. The pooled mean differences of CGIC, MMSE, and NPI in patients with AD receiving antihypertensive drugs compared to placebo was -1.76 with (95% CI = -2.66 to -0.86; P=0.0001), 0.74 (95% CI = 0.20 to 1.28; P= 0.007), and -9.49 (95% CI = -19.76 to 0.79; P = 0.07), respectively. Conclusion: The findings of the present meta-analysis show that antihypertensive drugs may improve cognition and behavioral symptoms of patients with AD. However, more well-designed RCTs with similar drugs are needed to achieve more conclusive results.

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The Associations of Plasma/Serum Carotenoids with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Journal of Alzheimer s Disease ◽

10.3233/jad-210384 ◽

2021 ◽

pp. 1-12

Author(s):

Mingyue Qu ◽

Hanxu Shi ◽

Kai Wang ◽

Xinggang Wang ◽

Nan Yu ◽

...

Keyword(s):

Systematic Review ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Meta Analysis ◽

Scoring Systems ◽

Serum Levels ◽

Epidemiological Studies ◽

Pooled Analysis ◽

Protective Effects ◽

Mean Differences

Background: Multiple lines of evidence indicate protective effects of carotenoids in Alzheimer’s disease (AD). However, previous epidemiological studies reported inconsistent results regarding the associations between carotenoids levels and the risk of AD. Objective: Our study aims to evaluate the associations of six major members of carotenoids with the occurrence of AD by conducting a systematic review and meta-analysis. Methods: Following PRISMA guidelines, a comprehensive literature search of PubMed, Web of Science, Ebsco, and PsycINFO databases was conducted, and the quality of each included studies was evaluated by a validated scoring systems. Standardized mean differences (SMD) with 95%confidence intervals (CI) were determined by using a random effects model. Heterogeneity was evaluated by I2 statistics. Publication bias was detected using funnel plots and Egger’s test. Results: Sixteen studies, with 10,633 participants were included. Pooled analysis showed significantly lower plasma/serum levels of lutein (SMD = –0.86, 95%CI: –1.67 to –0.05, p = 0.04) and zeaxanthin (SMD = –0.59; 95%CI: –1.12 to –0.06, p = 0.03) in patients with AD versus cognitively intact controls, while α-carotene (SMD = 0.21, 95%CI: –0.68 to 0.26, p = 0.39), β-carotene (SMD = 0.04, 95%CI: –0.57 to 0.65, p = 0.9), lycopene (SMD = –0.12, 95%CI: –0.96 to 0.72, p = 0.78), and β-cryptoxanthin (SMD = –0.09, 95%CI: –0.83 to 0.65, p = 0.81) did not achieve significant differences. Conclusion: Of six major members of carotenoids, only lutein and zeaxanthin concentrations in plasma/serum were inversely related to the risk of AD. More high-quality longitudinal studies are needed to verify these findings.

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Efficacy of Donepezil on Behavioral Symptoms in Patients With Moderate to Severe Alzheimer's Disease

International Psychogeriatrics ◽

10.1017/s104161020200858x ◽

2002 ◽

Vol 14 (4) ◽

pp. 389-404 ◽

Cited By ~ 144

Author(s):

◽

Serge Gauthier ◽

Howard Feldman ◽

Jane Hecker ◽

Bruno Vellas ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Motor Behavior ◽

Controlled Trial ◽

Behavioral Symptoms ◽

Double Blind ◽

Significant Treatment ◽

Treatment Groups ◽

Effect Of Treatment ◽

State Examination

Objective: This subanalysis of a large, double-blind, placebo-controlled trial examined the prevalence of behavioral symptoms in moderate to severe Alzheimer's disease (AD), and the effect of treatment with donepezil. Methods: Two hundred ninety patients with moderate to severe AD (standardized Mini-Mental State Examination scores 5–17) were randomized to receive 24 weeks of once-daily doses of donepezil 5 mg/day for 28 days, and 10 mg/day thereafter per the clinician's judgment (n = 144), or placebo (n = 146). The outcome measure of interest was the 12-item Neuropsychiaric Inventory (NPI). Results: Baseline demographics were similar between the treatment groups. Least squares mean (± SE) baseline NPI 12-item total scores were 19.55 ± 1.48 and 19.30 ± 1.45, respectively. At baseline, the most common symptoms were apathy/indifference (67%), aberrant motor behavior (53%), depression/dysphoria (52%), anxiety (49%), and agitation/aggression (45%). NPI individual item change from baseline scores at Week 24 using a last observation carried forward (LOCF) analysis showed benefits with donepezil treatment compared with placebo for all items, with significant treatment differences for depression/dysphoria, anxiety, and apathy/indifference (p < .05). Symptoms present at baseline that improved significantly for donepezil- compared with placebo-treated patients at Week 24 LOCF included anxiety, apathy/indifference, and irritability/lability (p < .05). When patients who were not receiving psychoactive medications at baseline were analyzed separately, significant improvements in NPI 12-item total score were observed with donepezil compared with placebo at most visits and at Week 24 LOCF (p < .05). Conclusions: Behavioral symptoms of the magnitude observed in this moderate to severe AD population improved with donepezil.

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