scholarly journals Measuring serum oestradiol in women with Alzheimer's disease: the importance of the sensitivity of the assay method

2003 ◽  
pp. 67-72 ◽  
Author(s):  
E Hogervorst ◽  
J Williams ◽  
M Combrinck ◽  
A David Smith
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Robust Regression ◽  
Meta Analysis ◽  
Hormone Replacement ◽  
Assay Method ◽  
Sensitive Assay ◽  
Significant Difference ◽  
Low Levels ◽  
The Difference

OBJECTIVE: Oestrogens could be protective against the development of Alzheimer's disease (AD) but reports on oestrogen levels in AD have been conflicting. DESIGN AND METHODS: A meta-analysis using robust regression was carried out to assess whether the sensitivity of the assays of past studies had affected the reported level of total oestradiol. We had also measured total oestradiol in women with AD (n=66) and controls (n=62) not using hormone replacement therapy. We used two assays for total oestradiol to assess the difference between sensitive (radioimmunoassay with a specific rabbit antibody: 3 pmol/l) and relatively insensitive (immunoassay: 37 pmol/l) assays. RESULTS: Meta-analysis using robust regression indicated that insensitive assays gave higher levels of total oestradiol when many samples fall below the level of sensitivity of the method. Earlier reports of low levels of total oestradiol in AD might be explained by this phenomenon, since total oestradiol levels (using the sensitive assay) in our controls were one third of those reported in the earlier studies. Using the sensitive assay we found that women with AD had significantly (P<0.01) higher levels (26+/-13 pmol/l) of total oestradiol than controls (21+/-13 pmol/l). Using the insensitive assay, there was no significant difference in the levels of total oestradiol. CONCLUSIONS: The sensitivity of the assay determines the reported value of the oestradiol levels. Studies using a sensitive assay do not report significantly lower levels of total oestradiol in women with AD. This weighs against the hypothesis that low levels of total oestradiol are a risk factor for AD.

Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-Analysis

2018 ◽  
Vol 15 (7) ◽  
pp. 610-617 ◽  
Author(s):  
Huifeng Zhang ◽  
Dan Liu ◽  
Huanhuan Huang ◽  
Yujia Zhao ◽  
Hui Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enzyme Activity ◽  
Protein Level ◽  
Senile Plaque ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Significant Difference

Background: β-amyloid (Aβ) accumulates abnormally to senile plaque which is the initiator of Alzheimer's disease (AD). As one of the Aβ-degrading enzymes, Insulin-degrading enzyme (IDE) remains controversial for its protein level and activity in Alzheimer's brain. Methods: The electronic databases PubMed, EMBASE, The Cochrane Library, OVID and Sinomed were systemically searched up to Sep. 20th, 2017. And the published case-control or cohort studies were retrieved to perform the meta-analysis. Results: Seven studies for IDE protein level (AD cases = 293; controls = 126), three for mRNA level (AD cases = 138; controls = 81), and three for enzyme activity (AD cases = 123; controls = 75) were pooling together. The IDE protein level was significantly lower in AD cases than in controls (SMD = - 0.47, 95% CI [-0.69, -0.24], p < 0.001), but IDE mRNA and enzyme activity had no significant difference (SMD = 0.02, 95% CI [-0.40, 0.43] and SMD = 0.06, 95% CI [-0.41, 0.53] respectively). Subgroup analyses found that IDE protein level was decreased in both cortex and hippocampus of AD cases (SMD = -0.43, 95% CI [-0.71, -0.16], p = 0.002 and SMD = -0.53, 95% CI [-0.91, -0.15], p = 0.006 respectively). However, IDE mRNA was higher in cortex of AD cases (SMD = 0.71, 95% CI [0.14, 1.29], p = 0.01), not in hippocampus (SMD = -0.26, 95% CI [-0.58, 0.06]). Conclusions: Our results indicate that AD patients may have lower IDE protease level. Further relevant studies are still needed to verify whether IDE is one of the factors affecting Aβ abnormal accumulation and throw new insights for AD detection or therapy.

Acupuncture plus Herbal Medicine for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 45 (07) ◽  
pp. 1327-1344 ◽  
Author(s):  
Simin Zhou ◽  
Lanlan Dong ◽  
Yuan He ◽  
Hong Xiao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Chinese Medicine ◽  
Herbal Medicine ◽  
Traditional Chinese Medicine ◽  
Chinese Herbal Medicine ◽  
Meta Analysis ◽  
World Population ◽  
Chinese Herbal ◽  
Significant Difference

Alzheimer’s disease (AD) is associated with the unprecedented aging tendency in our world population and has become a significant health issue. The use of Traditional Chinese Medicine to treat AD has been increasing in recent years. The objective of this meta-analysis is to evaluate the effectiveness of combining acupuncture with herbal medicine to treat AD. Randomized controlled trials (RCTs) of acupuncture plus herbals versus treatment with western drugs for AD were retrieved from 11 databases. The data were extracted by two authors; dichotomous data were expressed as odds ratio (ORs) and 95% confidence intervals (CIs), while continuous data were calculated by mean differences (MDs) with 95% CIs. Although the combined analysis of the score of Activity of Daily Life (ADL) scale MD was [Formula: see text]3.59 (95% CI [Formula: see text]7.18–0.01, [Formula: see text]), which indicates there was no statistically significant difference between the two treatments at reducing the ADL scale score, the pooled results of 12 trials indicated that acupuncture plus Chinese herbal medicine was better than western drugs at improving the effectiveness rate (OR 2.24, 95% CI 1.40–3.56), the combined evidence of 11 articles showed that acupuncture plus Chinese herbal medicine was more effective than western drugs at improving the scores for the Mini Mental State Examination (MMSE) scale (2.10, 95% CI 0.69–3.51, [Formula: see text]) and the traditional Chinese medicine symptom (MD 5.07, 95% CI 3.90–6.25, [Formula: see text]). From the current research results, acupuncture plus herbal medicine may have advantages over western drugs for treating AD. Nevertheless, well-designed RCTs with a larger sample size are required in the future.

scholarly journals Daily Versus Weekly Levothyroxine Tablet Replacement in Adults With Hypothyroidism: A Meta-Analysis

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A827-A827
Author(s):  
Harold Henrison Chang Chiu ◽  
Ramon Bagaporo Larrazabal ◽  
Angelique Bea Cariaga Uy ◽  
Cecilia A Jimeno
Keyword(s):  
Adverse Events ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Hormone Replacement ◽  
Hormone Deficiency ◽  
Significant Heterogeneity ◽  
Suitable Alternative ◽  
Significant Difference ◽  
The Difference ◽  
Tsh Levels

Abstract Background and Objectives: Hypothyroidism is a common hormone deficiency with a prevalence ranging from 4-5% worldwide. It is a very treatable condition with treatment in the form of thyroid hormone replacement, with an overall excellent prognosis if patients are compliant to regular treatment. Daily levothyroxine (LT4) is the treatment of choice and standard of care, sufficient to restore the thyroid stimulating hormone (TSH) to the normal range. For many patients, daily and lifelong therapy is required, and compliance/adherence then becomes a major issue. In such cases, weekly replacement may be a suitable alternative in terms of improving patient compliance. In this study, we aimed to determine the efficacy and safety of weekly versus daily levothyroxine replacement in patients with hypothyroidism. Methods: Electronic databases were searched, supplemented with manual searches. Two reviewers independently screened the abstracts, reviewed full-text papers, independently critically appraised the quality of included studies and abstracted the data. A meta-analysis was performed using the random-effects model on randomized controlled trials (RCTs) that reported standard doses of daily versus weekly levothyroxine administration in the treatment of hypothyroidism. The primary outcome is the difference in serum TSH levels between daily versus weekly levothyroxine administration, while secondary outcomes included clinical symptoms and adverse events using the hypothyroidism symptom scale. Results: The study included two randomized trials (N = 109) in the primary analysis. The difference in TSH levels was 1.78 mIU/mL higher (95% CI: 1.28, 2.28; P &lt; 0.00001) at 6 weeks and 1.22 mIU/mL higher (95% CI: 0.76,1.67; P &lt; 0.00001) at 12 weeks for the weekly replacement regimen, respectively. There was no significant heterogeneity noted between the two groups. There was no significant difference in terms hyperthyroid symptoms and adverse events measured by the hypothyroid symptom scales and echocardiographic parameters, respectively, before and after LT4 within each group. Conclusions: Our results showed that weekly LT4 administration has less suppression of TSH levels, while still remaining within the reference range of normal. It may be an alternative for patients especially in setting of noncompliance. However, more randomized trials with larger sample sizes and a longer duration of follow-up are needed to firmly establish the definite role of weekly LT4.

The Effectiveness and Safety of Chemical Drugs Combined with Acupuncture for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Shenghua Yu ◽  
Hongjie Liu ◽  
Li Xu ◽  
Yan Zhang ◽  
Yan Ma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Small Sample Size ◽  
Meta Analysis ◽  
Small Sample ◽  
Risk Of Bias ◽  
Disease Assessment ◽  
High Quality ◽  
Significant Difference

Introduction: Acupuncture has been applied with chemical drugs to treat Alzheimer’s disease (AD) in the clinic. Whether such combination is effective and safe should be studied although it is recommended by some researchers.Methods: To explore the effectiveness and safety of acupuncture combined with the chemical drugs for AD, databases like PubMed, Web of Science were searched to retrieve randomized controlled trials (RCTs) on AD treated with acupuncture and chemical drugs to perform meta-analysis. The risk of bias in each study was assessed using the Cochrane Risk of Bias scale. Meta-analysis was performed using RevMan 5.3.Results: Five studies were included in which only donepezil combined with acupuncture was evaluated. Acupuncture combined with donepezil showed a significant difference in effectiveness rate [RR=1.45, 95% CI (1.19, 1.77), P=0.0002] compared with donepezil. On the comparison of mini-mental state examination (MMSE) score and Alzheimer's disease assessment scale cognitive subscale (ADAS-Cog) score there was no difference. However, after one trial with severe AD patients was removed, acupuncture combined with donepezil showed better effect than donepezil alone. Conclusion: Acupuncture combined with donepezil could work on AD at the early stage or with mild AD, implying that acupuncture could be a complementary therapy for AD at early stage or with mild condition. Besides, scalp acupuncture seems to be more effective on improving cognitive function. However, this conclusion must be considered cautiously, given the small sample size and lack of trials of high quality. Therefore, more high-quality, multicenter, prospective, RCTs with large sample sizes are needed to further clarify the effect of acupuncture combined with chemical drugs for AD.

Use of CSF α-synuclein in the differential diagnosis between Alzheimer's disease and other neurodegenerative disorders

2015 ◽  
Vol 27 (9) ◽  
pp. 1429-1438 ◽  
Author(s):  
Zheng-Yu Wang ◽  
Zhen-Min Han ◽  
Qi-Fei Liu ◽  
Wei Tang ◽  
Kui Ye ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Differential Diagnosis ◽  
Neurodegenerative Disorders ◽  
Meta Analysis ◽  
Lewy Bodies ◽  
Cochrane Library ◽  
Random Effects Models ◽  
Significant Difference ◽  
Meta Analyses

ABSTRACTBackground:The etiology and pathogenesis of neurodegenerative disorders has yet to be elucidated, so their differential diagnosis is a challenge. This is especially true in differentiating Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson disease (PD), and multiple system atrophy (MSA).Methods:A total of 11 eligible articles were identified by search of electronic databases including PubMed, Springer Link, Elsevier, and the Cochrane Library, up to June 2014. In meta-analyses, standardized mean differences (SMD), with 95% confidence intervals (CI), comparing cerebrospinal fluid (CSF) measures of α-synuclein between the above conditions were calculated using random-effects models.Results:CSF α-synuclein concentrations were significantly higher in AD compared to DLB [SMD: 0.32, 95% CI: (0.02, 0.62), z = 2.07, P = 0.038]; PD [SMD: 0.87, 95% CI: (0.15, 1.58), z = 2.38, P = 0.017]; or MSA [SMD: 1.14, 95% CI: (0.15, 2.14), z = 2.25, P = 0.025]. However, no significant difference was found between patients with AD and neurological cognitively normal controls [SMD: 0.02, 95% CI: (−0.21, 0.24), z = 0.13, P = 0.894].Conclusions:Results of these meta-analysis suggest that quantification of CSF α-synuclein could help distinguish AD from other neurodegenerative disorders such as DLB, PD, or MSA.

scholarly journals Differences in Multimodal EEG and Clinical Correlations Between Alzheimer’s Disease and Frontotemporal Dementia

2021 ◽  
Author(s):  
Nan Lin ◽  
Jing Gao ◽  
Chenhui Mao ◽  
Heyang Sun ◽  
Qiang Lu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Spectral Analysis ◽  
Frontotemporal Dementia ◽  
Clinical Data ◽  
Early Onset ◽  
Late Onset ◽  
Clinical Severity ◽  
Significant Difference ◽  
The Difference

Abstract Background. Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are the two main types of dementia. We aim to investigate the difference between AD and FTD by use of multimodal EEG analyses. Additionally, the difference in correlations between EEG and clinical data was also investigated.Methods. Thirty-one patients diagnosed with AD and 15 patients with FTD were recruited (2008.1-2020.2), along with 24 healthy controls. Clinical data were reviewed. EEG microstate analysis, spectral analyses, and connectivity analysis were performed. Results. Microstate duration was increased in AD for microstate B and increased in FTD for microstate A compared to controls. Correspondingly, microstate C occurrence was decreased in both dementia groups, compared to control group. After divided into early onset and late onset AD, increased mean duration and reduced mean occurrence were observed in early onset AD, compared to late onset AD, with no significant difference in visual EEG score. CSF Aβ42 was correlated to microstate B coverage in AD (r = -0.833, P = 0.010), and microstate D occurrence in FTD (r = 0.786, P = 0.021). ADL and MMSE were also related to visual EEG score and microstate, but for different variables in the two dementia groups. Spectral analysis revealed decreased power in 8-30 Hz and increased power in delta band in both dementia. AD had higher spectral power in the temporal region, compared to FTD. Reduced alpha and beta coherences were demonstrated in AD in bilateral frontal, fronto-temporal, and fronto-occipital connections, and in FTD in the right frontal and fronto-temporal connections. Conclusions. Multimodal EEG analyses show different results between AD and FTD. Reduced coherence is across more brain areas in AD, including intra-anterior and anterior-posterior regions, compared to FTD, which only had frontal-temporal connectivity involved. Spectral analysis revealed a general EEG slowing. Increased microstate duration and decreased occurrence may be attributed to EEG slowing, for different classes in different types of dementia. Microstate may be more sensitive than visual EEG inspection. The correlations with clinical severity and biomarkers indicate that EEG is a potential biomarker for diagnosis and disease assessment.

Does Certainty of Genuine Treatment Increase the Drug Response in Alzheimer’s Disease Patients: A Meta-Analysis and Critical Discussion

2021 ◽  
pp. 1-12
Author(s):  
Susan Tomczak Matthiesen ◽  
Sophie Rosenkjær ◽  
Moa Pontén ◽  
Karin B. Jensen ◽  
Hanne Gottrup ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Effects ◽  
Meta Analysis ◽  
Specific Treatment ◽  
Critical Discussion ◽  
Pharmacological Treatments ◽  
Open Label ◽  
Significant Difference ◽  
Pre Treatment

Background: Non-specific treatment effects, such as expectations, contribute to the effectiveness of pharmacological treatments across diseases. However, the contribution of expectancy, i.e., certainty of receiving treatment, in patients with Alzheimer’s disease (AD) is unknown. Objective: The aim is to investigate whether certainty of receiving a genuine treatment influences the response to active treatment in AD patients. Methods: The efficacy of active treatments in open-label trials, where patients are certain of receiving treatment (100%certainty), was compared to the same active treatments in randomized controlled trials (RCT), where patients are uncertain of receiving treatment or placebo (50%certainty). Results: In the seven open-label trials, there was no significant difference between post- and pre-treatment scores (difference in means = 0.14, 95%CI [–0.51; 0.81], p = 0.66). In the eight RCT trials, there was a significant difference between post- and pre-treatment (difference in means = –0.91, 95%CI [–1.43; –0.41], p <  0.001). There was a statistically significant difference between open-label and RCT trials (difference = 1.06, 95%CI [0.23; 1.90], p = 0.001). Conclusion: Patients with AD did not benefit from certainty of receiving genuine treatment. This could be due to the nature/progression of the disease, but it could also be related to an order effect in the practice of running AD trials, where RCTs are conducted prior to open label. These findings have implications for the understanding of non-specific treatment effects in AD patients as well as for the design of clinical trials that test pharmacological treatments in AD.

Effect of Apolipoprotein E ɛ4 Carrier Status on Cognitive Response to Acetylcholinesterase Inhibitors in Patients with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

2018 ◽  
Vol 45 (5-6) ◽  
pp. 335-352 ◽  
Author(s):  
Ying-Chih Cheng ◽  
Yu-Chen Huang ◽  
Hsing-Cheng Liu
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Meta Analysis ◽  
Acetylcholinesterase Inhibitors ◽  
Cognitive Outcomes ◽  
Carrier Status ◽  
Apoe Ε4 ◽  
Significant Difference

Background: The apolipoprotein E ɛ4 (APOE ɛ4) genotype is the major genetic risk factor for Alzheimer’s disease (AD). However, its effect on an individual’s response to treatment is less well understood. Many studies have reported that the presence or absence of APOE ɛ4 may have influence on the therapeutic response for acetylcholinesterase inhibitors (AChEIs), but the results were inconsistent. This study performed a systematic review and meta-analysis to evaluate the association between response of treatment with AChEIs and the APOE ɛ4 carrier status. Methods: Clinical studies with AD patients reporting APOE ɛ4 genotype were included in the analysis. Cognitive outcome was measured by the change in Mini-Mental State Examination (MMSE), cognition subscales of the Alzheimer’s Disease Assessment Scale (ADAS-cog), or Cognitive Abilities Screening Instrument (CASI). A random effects model was employed to calculate the standardized mean difference (SMD) and odds ratio (OR). Results: Of the 284 screened abstracts, 38 studies were identified, 30 of which were included for meta-analysis. Continuous data for assessing the association between APOE ε4 and cognitive outcomes of AChEIs were available from 18 studies. The cognitive outcomes showed no significant difference between APOE ε4 carriers and APOE ε4 non-carriers (SMD = 0.022, 95% CI: –0.089∼0.133, p = 0.702, I2 = 55.3%). Twelve studies with binary data were included, also revealing insignificant difference between the two groups (OR = 1.164, 95% CI: 0.928∼1.459, p = 0.189, I2 = 16.4%). Subgroup analysis indicated that AChEIs were significantly more effective than placebo in both groups. Conclusions: APOE ɛ4 carrier status had no significant influence on the treatment response to AChEIs in patients with AD. AChEIs had a positive therapeutic effect compared with placebo regardless of APOE ε4 carrier status.

scholarly journals The Effect of Hormone Replacement Therapy on Cognitive Function in Female Patients With Alzheimer's Disease: A Meta-Analysis

2020 ◽  
Vol 35 ◽  
pp. 153331752093858
Author(s):  
ChengCheng Zhou ◽  
Qingguang Wu ◽  
Zongwei Wang ◽  
Qi Wang ◽  
Youya Liang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hormone Replacement Therapy ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Replacement Therapy ◽  
Meta Analysis ◽  
Hormone Replacement ◽  
Disease Assessment ◽  
Female Patients

Previous studies have indicated that estrogen may delay disease progression and minimize the cognitive decline in patients with Alzheimer's disease (AD). However, the evidence for an estrogen deficiency in women with dementia and cognitive dysfunction is inconsistent. In the present review, a fixed effect meta-analysis revealed that the hormone replacement therapy (HRT) group exhibited significant improvements in Alzheimer Disease Assessment Scale-Cognitive subscale scores relative to those observed in the placebo group, suggesting that HRT is feasible for treating cognitive decline in patients with AD. However, no significant differences in Mini-Mental State Examination and Clinical Dementia Rating scale scores were observed between the 2 groups. The results of our systematic review indicate that HRT can improve cognitive function in female patients with AD. Due to limitations in sample size and the available literature, further multicenter trials with larger sample sizes are required to support these findings.

Efficacy and safety of idalopirdine for Alzheimer’s disease: a systematic review and meta-analysis

2018 ◽  
Vol 31 (11) ◽  
pp. 1627-1633 ◽  
Author(s):  
Shinji Matsunaga ◽  
Hiroshige Fujishiro ◽  
Hajime Takechi
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Effect Size ◽  
Meta Analysis ◽  
Disease Assessment ◽  
High Dose ◽  
Significant Heterogeneity ◽  
Elevated Liver Enzymes ◽  
Significant Difference

ABSTRACTObjective:The efficacy and tolerability of idalopirdine, a selective 5-hydroxytryptamine6 receptor antagonist, in patients with Alzheimer’s disease (AD) is uncertain. A systematic review and meta-analysis of randomized controlled trials (RCTs) testing idalopirdine for patients with AD was performed.Methods:We included RCTs of idalopirdine for patients with AD and used Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) scores as a primary measure.Results:Four RCTs with 2,803 patients with AD were included. There was no significant difference in ADAS-cog between the idalopirdine and placebo groups [mean difference (MD) = −0.41,P= 0.32,I2= 62%]. However, significant heterogeneity remained. Sensitivity analysis revealed that idalopirdine was more effective than placebo for ADAS-cog in the high dose and moderate AD subgroups (high dose subgroup: MD = −2.15,P= 0.005, moderate AD subgroup: MD = −2.15,P= 0.005). Moreover, meta-regression analysis showed that idalopirdine effect size for ADAS-cog was associated with mean dose (coefficient, −0.0289), ADAS-cog at baseline (coefficient, −0.9519), and proportion of male participants (coefficient, 0.2214). For safety outcomes, idalopirdine was associated with a higher incidence of at least one adverse event and increased γ-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and vomiting than placebo. There were no significant differences in other secondary outcomes between both treatments.Conclusions:Idalopirdine is not effective for AD patients and is associated with a risk of elevated liver enzymes and vomiting. Although idalopirdine might be more effective at high doses and in moderate AD subgroups, the effect size is small and may be limited.

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