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Frontiers in Aging Neuroscience 2023Despite a large preclinical literature demonstrating neuroprotective effects of estrogen, use of menopausal hormone therapy (HT) for Alzheimer's disease (AD) risk...
INTRODUCTION
Despite a large preclinical literature demonstrating neuroprotective effects of estrogen, use of menopausal hormone therapy (HT) for Alzheimer's disease (AD) risk reduction has been controversial. Herein, we conducted a systematic review and meta-analysis of HT effects on AD and dementia risk.
METHODS
Our systematic search yielded 6 RCT reports (21,065 treated and 20,997 placebo participants) and 45 observational reports (768,866 patient cases and 5.5 million controls). We used fixed and random effect meta-analysis to derive pooled relative risk (RR) and 95% confidence intervals (C.I.) from these studies.
RESULTS
Randomized controlled trials conducted in postmenopausal women ages 65 and older show an increased risk of dementia with HT use compared with placebo [RR = 1.38, 95% C.I. 1.16-1.64, < 0.001], driven by estrogen-plus-progestogen therapy (EPT) [RR = 1.64, 95% C.I. 1.20-2.25, = 0.002] and no significant effects of estrogen-only therapy (ET) [RR = 1.19, 95% C.I. 0.92-1.54, = 0.18]. Conversely, observational studies indicate a reduced risk of AD [RR = 0.78, 95% C.I. 0.64-0.95, = 0.013] and all-cause dementia [RR = .81, 95% C.I. 0.70-0.94, = 0.007] with HT use, with protective effects noted with ET [RR = 0.86, 95% C.I. 0.77-0.95, = 0.002] but not with EPT [RR = 0.910, 95% C.I. 0.775-1.069, = 0.251]. Stratified analysis of pooled estimates indicates a 32% reduced risk of dementia with midlife ET [RR = 0.685, 95% C.I. 0.513-0.915, = 0.010] and non-significant reductions with midlife EPT [RR = 0.775, 95% C.I. 0.474-1.266, = 0.309]. Late-life HT use was associated with increased risk, albeit not significant [EPT: RR = 1.323, 95% C.I. 0.979-1.789, = 0.069; ET: RR = 1.066, 95% C.I. 0.996-1.140, = 0.066].
DISCUSSION
These findings support renewed research interest in evaluating midlife estrogen therapy for AD risk reduction.
PubMed: 37937120
DOI: 10.3389/fnagi.2023.1260427 -
Artificial intelligence for diagnostic and prognostic neuroimaging in dementia: A systematic review.Alzheimer's & Dementia : the Journal of... Dec 2023Artificial intelligence (AI) and neuroimaging offer new opportunities for diagnosis and prognosis of dementia. (Review)
Review
INTRODUCTION
Artificial intelligence (AI) and neuroimaging offer new opportunities for diagnosis and prognosis of dementia.
METHODS
We systematically reviewed studies reporting AI for neuroimaging in diagnosis and/or prognosis of cognitive neurodegenerative diseases.
RESULTS
A total of 255 studies were identified. Most studies relied on the Alzheimer's Disease Neuroimaging Initiative dataset. Algorithmic classifiers were the most commonly used AI method (48%) and discriminative models performed best for differentiating Alzheimer's disease from controls. The accuracy of algorithms varied with the patient cohort, imaging modalities, and stratifiers used. Few studies performed validation in an independent cohort.
DISCUSSION
The literature has several methodological limitations including lack of sufficient algorithm development descriptions and standard definitions. We make recommendations to improve model validation including addressing key clinical questions, providing sufficient description of AI methods and validating findings in independent datasets. Collaborative approaches between experts in AI and medicine will help achieve the promising potential of AI tools in practice.
HIGHLIGHTS
There has been a rapid expansion in the use of machine learning for diagnosis and prognosis in neurodegenerative disease Most studies (71%) relied on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset with no other individual dataset used more than five times There has been a recent rise in the use of more complex discriminative models (e.g., neural networks) that performed better than other classifiers for classification of AD vs healthy controls We make recommendations to address methodological considerations, addressing key clinical questions, and validation We also make recommendations for the field more broadly to standardize outcome measures, address gaps in the literature, and monitor sources of bias.
Topics: Humans; Alzheimer Disease; Prognosis; Artificial Intelligence; Neurodegenerative Diseases; Brain; Neuroimaging
PubMed: 37563912
DOI: 10.1002/alz.13412 -
Drugs & Aging Nov 2023The acetylcholinesterase inhibitors (AChEIs) donepezil, galantamine, and rivastigmine are commonly used in the management of various forms of dementia. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The acetylcholinesterase inhibitors (AChEIs) donepezil, galantamine, and rivastigmine are commonly used in the management of various forms of dementia.
OBJECTIVES
While these drugs are known to induce classic cholinergic adverse events such as diarrhea, their potential to cause psychiatric adverse events has yet to be thoroughly examined.
METHODS
We sought to determine the risk of psychiatric adverse events associated with the use of AChEIs through a systematic review and meta-analysis of double-blind randomized controlled trials involving patients with Alzheimer's dementia and Parkinson's dementia.
RESULTS
A total of 48 trials encompassing 22,845 patients were included in our analysis. Anorexia was the most commonly reported psychiatric adverse event, followed by agitation, insomnia, and depression. Individuals exposed to AChEIs had a greater risk of experiencing appetite disorders, insomnia, or depression compared with those who received placebo (anorexia: odds ratio [OR] 2.93, 95% confidence interval [CI] 2.29-3.75; p < 0.00001; decreased appetite: OR 1.93, 95% CI 1.33-2.82; p = 0.0006; insomnia: OR 1.55, 95% CI 1.25-1.93; p < 0.0001; and depression: OR 1.59, 95% CI 1.23-2.06, p = 0.0004). Appetite disorders were also more frequent with high-dose versus low-dose therapy. A subgroup analysis revealed that the risk of insomnia was higher for donepezil than for galantamine.
CONCLUSIONS
Our findings suggest that AChEI therapy may negatively impact psychological health, and careful monitoring of new psychiatric symptoms is warranted. Lowering the dose may resolve some psychiatric adverse events, as may switching to galantamine in the case of insomnia.
CLINICAL TRIAL REGISTRATION
The study was pre-registered on PROSPERO (CRD42021258376).
Topics: Humans; Acetylcholinesterase; Alzheimer Disease; Anorexia; Cholinesterase Inhibitors; Donepezil; Galantamine; Parkinson Disease; Phenylcarbamates; Randomized Controlled Trials as Topic; Rivastigmine; Sleep Initiation and Maintenance Disorders
PubMed: 37682445
DOI: 10.1007/s40266-023-01065-x -
Neurological Sciences : Official... Mar 2024In this systematic review and meta-analysis, we critically evaluate available evidence regarding the association between primary headaches and subsequent decline of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
In this systematic review and meta-analysis, we critically evaluate available evidence regarding the association between primary headaches and subsequent decline of cognitive function and dementia.
BACKGROUND
Recent studies suggested that headache disorders may increase the risk for dementia. However, available studies are conflicting.
METHODS
To identify qualifying studies, we searched scientific databases, including Pubmed, Scopus, Web of Science, Science Direct and BMC, screening for relevant papers. In order to reduce the heterogeneity between different studies, the analyses were further subdivided according to the clinical diagnoses and the study methodologies.
RESULTS
We identified 23 studies investigating the association between primary headaches and the risk of dementia. Of these, 18 met our inclusion criteria for meta-analysis (covering 924.140 individuals). Overall effect-size shows that primary headaches were associated with a small increase in dementia risk (OR = 1,15; CI 95%: 1,03-1,28; p = 0,02). Analyzing subgroups, we found that migraine was associated with both a moderate increased risk of all-cause dementia (OR = 1,26; p = 0,00; 95% CI: 1,13-1,40) as well as a moderate increased risk of Alzheimer's disease (OR = 2,00; p = 0,00; 95% CI: 1,46-2,75). This association was significant in both case-control and retrospective cohort studies but not in prospective studies.
CONCLUSIONS
Our study supports the presence of a link between primary headaches and dementia. However, in the subgroup analysis, only patients with migraine showed a moderate increase risk for all-cause dementia and for Alzheimer's disease. Additional rigorous studies are needed to elucidate the possible role of primary headaches on the risk of developing cognitive impairment and dementia.
Topics: Humans; Alzheimer Disease; Retrospective Studies; Prospective Studies; Headache; Cognitive Dysfunction; Risk Factors; Migraine Disorders
PubMed: 37721571
DOI: 10.1007/s10072-023-07069-0 -
European Journal of Medical Research Sep 2023To conduct a meta-analysis of the effectiveness of creative story therapy versus routine nursing alone for the treatment of dementia. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a meta-analysis of the effectiveness of creative story therapy versus routine nursing alone for the treatment of dementia.
METHODS
We manually searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), China VIP Database (VIP), China Biomedical Literature Database (CBM), and Wanfang Data up to May 2023. Randomized controlled trials (RCTs) of creative story therapy combined with routine nursing versus routine nursing for the treatment of dementia were included.
RESULTS
A total of 597 participants were enrolled in the 9 RCTs. Among them, 296 were in the creative story therapy group, and 301 were in the routine nursing group. We found statistically significant effects of creative story therapy combined with routine nursing on cognitive function [standardized mean difference (SMD) = 0.99, 95% CI 0.57, 1.41, P < 0.00001], CSDD score [mean difference (MD) = - 1.71, 95% CI - 3.27, - 0.14, P < 0.00001], quality of life [SMD = 0.97, 95% CI 0.04, 1.90, P = 0.04], and social communication [MD = 0.46, 95% CI 0.17, 0.74, P < 0.00001] between the creative story therapy group and routine nursing groups; no significant difference in change in basic needs communication [MD = 0.09, 95% CI - 0.58, 0.76, P < 0.00001].
CONCLUSION
This meta-analysis shows that creative story therapy combined with routine nursing has significant effectiveness in improving cognitive function and depression in people with dementia. More high-quality RCTs are required to validate these results.
Topics: Humans; China; Cognition; Knowledge; PubMed; Dementia
PubMed: 37705077
DOI: 10.1186/s40001-023-01337-7 -
European Geriatric Medicine Feb 2024Dementia and Alzheimer's disease (AD) pose significant challenges to public health globally with no effective treatment strategies available. Therefore, the research... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Dementia and Alzheimer's disease (AD) pose significant challenges to public health globally with no effective treatment strategies available. Therefore, the research focuses on developing effective prophylaxis to prevent the onset of these diseases. Recent studies have suggested that low-dose aspirin may help reduce the risk of dementia. Nonetheless, evidence regarding the correlation between aspirin consumption and the onset of dementia and AD is limited. This review aims to provide an up-to-date summary of the existing evidence and evaluate the association between aspirin and the onset of dementia and Alzheimer's disease.
METHODS
A systematic search of PubMed, Embase, Web of Science, PsycINFO, and CINAHL databases was conducted to find eligible studies published until April 2023. A random-effects meta-analysis of the eligible studies was then performed to assess the link between aspirin use and the onset of dementia and Alzheimer's disease. Additionally, we conducted subgroup analyses to evaluate the overall effect of low-dose (75-100 mg) aspirin consumption on the onset of dementia and AD.
RESULTS
A total of 875 studies were identified, with only 22 meeting the inclusion criteria. There was no statistically significant impact of aspirin consumption on the onset of dementia (HR 1.13, 11 studies) or Alzheimer's disease (HR 0.91, 3 studies). Additionally, subgroup analysis showed that taking low doses of aspirin (75-100 mg) did not significantly affect the onset of either dementia (HR 0.96, 13 studies) or Alzheimer's disease (HR 0.85, 2 studies).
CONCLUSIONS
Aspirin use does not decrease the risk of dementia or AD, even when taken in low doses. However, the quality of the studies analyzed was inadequate, with only three randomized controlled trials included in the review. Future high-quality studies are needed to assess the effect of aspirin consumption on these diseases. These findings may assist clinicians in selecting appropriate prophylactic strategies for patients at risk of developing dementia and AD.
Topics: Humans; Alzheimer Disease; Aspirin
PubMed: 37870707
DOI: 10.1007/s41999-023-00877-9 -
Ageing Research Reviews Dec 2023To synthesize evidence and summarize research findings related to the effectiveness and feasibility of dance movement intervention (DMI) in older adults with mild... (Meta-Analysis)
Meta-Analysis
The effectiveness of dance movement interventions for older adults with mild cognitive impairment, Alzheimer's disease, and dementia: A systematic scoping review and meta-analysis.
OBJECTIVES
To synthesize evidence and summarize research findings related to the effectiveness and feasibility of dance movement intervention (DMI) in older adults with mild cognitive impairment (MCI), Alzheimer's disease (AD), and dementia; to systemically map existing research gaps and research directions for future practice.
METHODS
A systematic search was conducted using six electronic databases: Web of Science, PubMed, PsycINFO, MEDLINE, ScienceDirect, and Cochrane Central Register of Controlled Trials. The methodological quality of included studies was assessed using the Cochrane Risk of Bias Tool for Randomized Trials (RoB 2) and The Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I).
RESULTS
29 dance intervention studies (13 RCT studies) were included in the scoping review: 62% of MCI, 10% of AD, and 28% of dementia; a total of 1708 participants (Female=1247; Male=461) aged from 63.8 ( ± 5.24) to 85.8 ( ± 5.27) years old. Eight RCT studies were included in the meta-analysis; results indicated that dance interventions had a significant effect on global cognition, memory, balance, and significantly decreased depression. No significant effects were found for executive function.
CONCLUSIONS
Dance is a non-pharmacological, effective, affordable, and engaging intervention that can be used as a complementary treatment for older adults with MCI, AD, and dementia.
Topics: Aged; Female; Humans; Male; Alzheimer Disease; Cognition; Cognitive Dysfunction; Dancing; Executive Function
PubMed: 37944706
DOI: 10.1016/j.arr.2023.102120 -
Medicine Oct 2023Herpes Zoster, commonly known as shingles, is a viral infection that affects a significant portion of the adult population; however, its potential role in the onset or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Herpes Zoster, commonly known as shingles, is a viral infection that affects a significant portion of the adult population; however, its potential role in the onset or progression of neurodegenerative disorders like dementia remains unclear.
METHODS
We searched the following databases: PubMed, Scopus, Cochrane library, and Web of Science. We included any randomized control trials and controlled observational studies as Cross-sectional, prospective, or retrospective cohort and case-control studies that investigated the prevalence of dementia in Herpes Zoster Virus (HZV)-infected patients and HZV-free control group or if the study investigated the prevalence of HZV in demented patients. Also, if the studies measured the levels of dementia biomarkers in patients with HZV compared with a healthy control group.
RESULTS
After the complete screening, 9 studies were included in the meta-analysis. In the outcome of the incidence of HZV, the pooled analysis showed no statistically significant difference between the dementia group and the No dementia group (RR = 1.04% CI = 0.86-1.25, P = .70). In the outcome of incidences of dementia and Alzheimer's disease, the pooled analysis showed no statistically significant difference between the HZV group and the incidence of dementia (RR = 0.99, 95% CI = 0.92-1.08, P = .89), (RR = 3.74, 95% CI = 0.22-62.70, P = .36) respectively. In the outcome of incidences of Herpes Zoster ophthalmicus (HZO), the generic inverse variance showed a statistically significant association between patients who have HZO and increased incidence of dementia (RR = 6.26, 95% CI = 1.30-30.19, P = .02).
CONCLUSION
Our study showed no significant association between HZV and the incidence of dementia or Alzheimer's disease, but it shows a significant association between HZO and the incidence of dementia. More multicenter studies are needed to establish the actual association between the HZV and dementia.
Topics: Adult; Humans; Herpesvirus 3, Human; Retrospective Studies; Alzheimer Disease; Prospective Studies; Cross-Sectional Studies; Herpes Zoster; Chickenpox
PubMed: 37904465
DOI: 10.1097/MD.0000000000034503 -
Systematic Reviews Aug 2023Subjective cognitive impairment (SCI) substantially increases dementia risk and is often conceptualised as the preclinical asymptomatic phase of the cognitive decline...
BACKGROUND
Subjective cognitive impairment (SCI) substantially increases dementia risk and is often conceptualised as the preclinical asymptomatic phase of the cognitive decline continuum. Due to the lack of pharmacological interventions available to treat SCI and reduce dementia risk, and the popularity of herbal and nutritional medicines, the primary aim of this review was to investigate the efficacy on cognitive function and safety of herbal and nutritional medicines (relative to a control) for older adults with and without SCI. The secondary aims were to describe the study characteristics and assess the methodological quality of included studies.
METHOD
Five databases (Cochrane, MEDLINE, CINAHL, PsycInfo, and EMBASE) were searched from database inception with weekly alerts established until review finalisation on 18 September 2022. Articles were eligible if they included the following: study population of older adults with and without SCI, herbal and nutritional medicines as an intervention, evaluated cognitive outcomes and were randomised control trials.
RESULTS
Data were extracted from 21/7666 eligible full-text articles, and the risk of methodological bias was assessed (with SCI = 9/21; without SCI = 12/21). Most studies (20/21) employed parallel, randomised, placebo-controlled designs and were 12 weeks in length. Herbal supplements were widely used (17/21), namely a form of Ginkgo biloba (8/21) or Bacopa monnieri (6/21). Measures of cognition varied across studies, with 14/21 reporting improvements in at least one domain of cognitive functioning over time, in the intervention group (compared to control). A total of 14/21 studies were deemed as having an overall high methodological risk of bias, 6/21 had some concerns, and only one study (using an SCI population) was assessed as having a low risk of methodological bias.
CONCLUSIONS
Overall, this review found that there is a low quality of evidence regarding the efficacy of cognitive function and safety of herbal and nutritional medicines for older adults with and without SCI, due to a high risk of bias across studies. Additionally, further work needs to be done in classifying and understanding SCI and selecting appropriate trial primary outcomes before future studies can more accurately determine the efficacy of interventions for this population.
Topics: Humans; Aged; Cognition; Cognitive Dysfunction; Databases, Factual; MEDLINE; Dementia; Randomized Controlled Trials as Topic
PubMed: 37592293
DOI: 10.1186/s13643-023-02301-6 -
Phytomedicine : International Journal... Oct 2023Neurovascular glial unit (NVGU) dysfunction has been reported to be an early and critical event in the pathophysiology of Alzheimer's disease (AD) and vascular dementia...
BACKGROUND
Neurovascular glial unit (NVGU) dysfunction has been reported to be an early and critical event in the pathophysiology of Alzheimer's disease (AD) and vascular dementia (VD). Although herbal medicines, with their favorable safety profiles and low adverse effects, have been suggested to be useful for the treatment of cognitive impairment, the potential role of the NVGU as the target of the effects of herbal medicines is still unclear.
PURPOSE
This review aimed to retrieve evidence from experimental studies of phytopharmaceuticals targeting the NVGU for the treatment of cognitive impairment in AD and VD, and discussed the potential of phytopharmaceuticals to improve cognitive impairment from the perspective of the NVGU.
STUDY DESIGN AND METHODS
We systematically searched PubMed, Google Scholar, Web of Science, and CNKI. The keywords used for searching information on the NVGU in the treatment of cognitive impairments included "Alzheimer's disease," "Vascular dementia," "Herbal medicines," "Natural products," "Neurovascular," "Adverse reaction," and "Toxicity, etc." We selected studies on the basis of predefined eligibility criteria.
RESULTS
NVGU mainly consists of endothelial cells, pericytes, astrocytes, microglia, oligodendrocytes, and neurons, and damage to these cells can induce cognitive impairment by impairing the blood-brain barrier (BBB) and cerebral blood flow (CBF) as well as neuronal function. The active components of herbal medicines, including Ginkgo biloba L., Ginseng Radix et Rhizoma, Epimedium Folium, Chuanxiong Rhizoma, Carthami flos, and Acorus tatarinowii Schott, as well as traditional Chinese medicine prescriptions have shown the potential to improve BBB function and increase CBF to prevent cognitive impairment by inhibiting astrocyte and microglia activation, protecting oligodendrocyte myelin function, reducing neuronal apoptosis, and promoting angiogenesis.
CONCLUSIONS
Herbal medicines demonstrate great potential to prevent cognitive impairment. Multiple components from herbal medicines may function through different signaling pathways to target the NVGU. Future studies using novel drug-carrier or delivery systems targeting the NVGU will certainly facilitate the development of phytopharmaceuticals for AD and VD.
Topics: Alzheimer Disease; Cognitive Dysfunction; Dementia, Vascular; Drugs, Chinese Herbal; Endothelial Cells; Phytotherapy; Plant Extracts; Plants, Medicinal; Humans
PubMed: 37573807
DOI: 10.1016/j.phymed.2023.155009