-
BMC Psychiatry Sep 2019Dementia represents a mental and economic burden for both patients and their caregivers. Therefore, the aim of this study is to explore the effectiveness of animal...
BACKGROUND
Dementia represents a mental and economic burden for both patients and their caregivers. Therefore, the aim of this study is to explore the effectiveness of animal assisted therapy (AAT) with special focus on canis therapy among people with dementia, specifically Alzheimer's disease.
METHODS
The key method of this review study is a systematic review of the research studies detected in the Web of Science, Scopus and PubMed. The search was conducted for the studies dating from 2016 till 31 August 2018 because several review studies were published before. Eventually, only six studies were involved into the final analysis.
RESULTS
The findings of this review, based on significant effect sizes, reveal that AAT may work as a beneficial and effective complementary treatment, especially in the area of behavioral and psychological symptoms, for patients with different degree of dementia severity if AAT is targeted at their specific needs and interests.
CONCLUSIONS
More research in the area of methodology for the implementation of AAT is necessary, and more research should be conducted with respect to the use of AAT for the improvement of cognitive functions in people with dementia.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Animal Assisted Therapy; Animals; Caregivers; Dementia; Dogs; Female; Humans; Male; Middle Aged; Treatment Outcome
PubMed: 31492131
DOI: 10.1186/s12888-019-2245-x -
Ageing Research Reviews Feb 2024The comparative clinical utility of the disease-modifying treatments for mild cognitive impairment and Alzheimer's disease that are approved or under review by the Food... (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy, tolerability and acceptability of donanemab, lecanemab, aducanumab and lithium on cognitive function in mild cognitive impairment and Alzheimer's disease: A systematic review and network meta-analysis.
BACKGROUND
The comparative clinical utility of the disease-modifying treatments for mild cognitive impairment and Alzheimer's disease that are approved or under review by the Food and Drug Administration (i.e., donanemab, lecanemab and aducanumab), and lithium, which is a potential disease-modifying agent for this condition, remains elusive.
OBJECTIVE
We aimed to compare the efficacy on cognitive decline, tolerability and acceptability of these drugs in this condition.
METHODS
We systematically searched in MEDLINE, CENTRAL, CINHAL and ClinicalTrials,gov for randomized controlled trials from their inception to 7 November 2023, and then performed a random-effect network meta-analysis.
RESULTS
The analysis included 8 randomized placebo-controlled trials with 6547 participants. On the Mini-Mental State Examination, lithium significantly outperformed donanemab, aducanumab and placebo. On the Alzheimer's Disease Assessment Scale-cognitive subscale, the efficacy of all active drugs was significantly higher than placebo. In addition, in the Clinical Dementia Rating sum of boxes, the efficacy of donanemab and lecanemab was significantly higher than placebo. Compared to placebo, donanemab and lecanemab were significantly less acceptable and tolerable. Aducanumab was also less well tolerated compared to placebo. There were no significant differences in the other comparisons.
CONCLUSION
Although it is yet to be determined which is more effective between lithium or lecanemab or donanemab, lithium may be more effective than aducanumab. Aducanumab, lecanemab and donanemab do not appear to differ in their effectiveness on cognitive function. Low-dose lithium may be safer than aducanumab, lecanemab and donanemab.
Topics: Humans; Alzheimer Disease; Lithium; Network Meta-Analysis; Cognitive Dysfunction; Cognition; Antibodies, Monoclonal, Humanized
PubMed: 38253184
DOI: 10.1016/j.arr.2024.102203 -
The Journal of Prevention of... 2022A systematic review of randomized controlled trials was conducted to determine the effect of physical exercise on physical-functional capacity, cognitive performance,...
OBJECTIVE
A systematic review of randomized controlled trials was conducted to determine the effect of physical exercise on physical-functional capacity, cognitive performance, neuropsychiatric symptoms, and quality of life in a population of older people with Alzheimer´s disease.
DATA SOURCES
Pubmed, Scopus, PEDro, Web of Science, CINAHL, Cochrane Library, grey literature and a reverse search from inception to April 2021 were searched to identify documents.
STUDY SELECTION
Publications investigating the effect of any type of physical exercise-based intervention in any of its multiple modalities on physical-functional capacity, cognitive performance, neuropsychiatric symptoms, and quality of life were searched.
DATA EXTRACTION
The data were extracted into predesigned data extraction tables. Risk of bias was evaluated through the PEDro scale and its internal validity scale.
DATA SYNTHESIS
A total of 8 different randomized controlled trials with a total sample of 562 non-overlap Alzheimer disease patients between 50-90 years and a mean age of 75.2 ± 3.9 years were eligible for analyses. Physical-functional capacity was evaluated in 6 of 8 studies and cognitive performance was evaluated in 5 of 8 studies, all of them showed improvements in these variables when compared with the controls, except for two studies in physical-functional capacity and one study for cognitive performance. In the physical-functional capacity and cognitive performance variables, aerobic physical exercise was used in isolation, or in a multimodal way, combining aerobic, strength and balance exercise, from 2 to 7 weekly sessions with doses between 30 and 90 minutes, and a duration of the program comprised of 9 weeks to 6 months. Neuropsychiatric symptoms and quality of life were evaluated in 2 of 8 studies, which the intervention groups experienced significant improvements when compared with the control groups, except for one study that found similar differences in quality of life between both groups. In the neuropsychiatric symptoms and quality of life variables, only aerobic physical exercise was used, in a more homogeneous way, from 2 to 3 weekly sessions with doses of 30 to 60 minutes, and a total program duration of 9 to 16 weeks.
CONCLUSIONS
Despite the scarcity of studies, especially those based on multimodal proposals, and the heterogeneity in the protocols, this systematic review found moderate to limited evidence that aerobic physical exercise on its own or combined in a multimodal program that also includes strength and balance exercise can be a useful tool in the management of patients with Alzheimer's disease with the aim of maintaining and/or improving physical-functional capacity and cognitive performance. In addition, this review found moderate evidence of the positive impact that aerobic physical exercise could have in reducing neuropsychiatric symptoms and improving quality of life in patients with Alzheimer´s disease. PROSPERO registration number: CRD42021229891.
Topics: Aged; Aged, 80 and over; Humans; Middle Aged; Alzheimer Disease; Exercise; Exercise Therapy; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36281664
DOI: 10.14283/jpad.2022.57 -
European Journal of Medical Research Nov 2023Alzheimer's disease (AD) is a worldwide public health problem and is difficult to cure. Drugs aimed at slowing the progression of the disease have been developed, with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alzheimer's disease (AD) is a worldwide public health problem and is difficult to cure. Drugs aimed at slowing the progression of the disease have been developed, with the Food and Drug Administration (FDA) granting accelerated approval for aducanumab on June 21, 2021 and a new accelerated approval for lecanemab on January 22, 2023. We performed this systematic review and meta-analysis to assess the efficacy and safety of FDA-approved anti-amyloid-β (anti-Aβ) monoclonal antibodies (mabs) for the treatment of AD.
METHOD
PubMed, Embase, and Cochrane Library were systematically searched to identify relevant studies published before May 2023. Efficacy outcomes included Aβ, neuroimaging, and biomarker outcomes. Safety outcomes included amyloid-related imaging abnormalities with edema or effusions (ARIA-E) and ARIA with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (ARIA-H). Review Manager 5.4 software was used to assess the data. The standard mean differences (SMDs) or odds ratio (OR) with 95% confidence interval (95% CI) were analyzed and calculated with a random effect model or a fixed effect model.
RESULT
Overall, 4471 patients from 6 randomized controlled trials (RCTs), with 2190 patients in the treatment group and 2281 patients in the placebo group meeting the inclusion criteria. FDA-approved anti-Aβ mabs showed statistically significant improvements in clinical outcomes, including CDR-SB (P = 0.01), ADCS-ADL-MCI (P = 0.00003), ADCOMS (P < 0.00001), ADAS-Cog (P < 0.00001). Moreover, FDA-approved anti-Aβ mabs increased cerebrospinal fluid (CSF) Aβ1-42 (P = 0.002) and plasma Aβ42/40 ratios (P = 0.0008). They also decreased CSF P-Tau (P < 0.00001), CSF T-Tau (P < 0.00001), and plasma p-tau181 (P < 0.00001). FDA-approved anti-Aβ mabs perform neuroimaging changes in amyloid Positron Emission Tomography Standardized Uptake Value ratio (PET SUVr) (P < 0.00001). However, compared with placebo, FDA-approved anti-Aβ mabs had higher risk of ARIA-E (P < 0.00001) and ARIA-H (P < 0001).
CONCLUSION
FDA-approved anti-Aβ mabs have a role in slowing disease progression in patients with AD, at the cost of an increased probability of side effects.
Topics: United States; Humans; Alzheimer Disease; United States Food and Drug Administration; Randomized Controlled Trials as Topic; Amyloid beta-Peptides; Biomarkers
PubMed: 38017568
DOI: 10.1186/s40001-023-01512-w -
Alzheimer's & Dementia : the Journal of... Nov 2019Several microRNAs (miRNAs) have been implicated in Alzheimer's disease pathogenesis, but the evidence from individual case-control studies remains inconclusive. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several microRNAs (miRNAs) have been implicated in Alzheimer's disease pathogenesis, but the evidence from individual case-control studies remains inconclusive.
METHODS
A systematic literature review was performed, followed by standardized multistage data extraction, quality control, and meta-analyses on eligible data for brain, blood, and cerebrospinal fluid specimens. Results were compared with miRNAs reported in the abstracts of eligible studies or recent qualitative reviews to assess novelty.
RESULTS
Data from 147 independent data sets across 107 publications were quantitatively assessed in 461 meta-analyses. Twenty-five, five, and 32 miRNAs showed studywide significant differential expression (α < 1·08 × 10) in brain, cerebrospinal fluid, and blood-derived specimens, respectively, with 5 miRNAs showing differential expression in both brain and blood. Of these 57 miRNAs, 13 had not been reported in the abstracts of previous original or review articles.
DISCUSSION
Our systematic assessment of differential miRNA expression is the first of its kind in Alzheimer's disease and highlights several miRNAs of potential relevance.
Topics: Alzheimer Disease; Biomarkers; Brain; Case-Control Studies; Epigenomics; Humans; MicroRNAs
PubMed: 31495604
DOI: 10.1016/j.jalz.2019.06.4952 -
Nutritional Neuroscience Oct 2018Alzheimer's disease (AD) is a neurodegeneration disorder characterized by progressive impairments of memory, language, reasoning, and other cognitive functions. Evidence...
INTRODUCTION
Alzheimer's disease (AD) is a neurodegeneration disorder characterized by progressive impairments of memory, language, reasoning, and other cognitive functions. Evidence suggests that omega-3 fatty acids may act as a possible protection factor in AD.
OBJECTIVE
To evaluate the results available in the literature involving omega-3 fatty acids supplementation and its effect on cognitive function in AD patients.
METHODS
A systematic review of MEDLINE (from PubMed), Excerpta Medica Database, and Cochrane Library databases was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria consisted in original intervention studies, controlled by placebo, that assessed the impact of supplementation or dietary intake of omega-3 fatty acids on cognitive function, in humans with AD, without limitation for prime date of publication.
RESULTS
Initial search resulted in 361 articles. Seven studies fully met the inclusion criteria. Most studies did not find statistically significant results for the omega-3 fatty acids supplementation compared to placebo, and those who show some benefit do it only in a few cognitive assessment scales. However, the effects of omega-3 fatty acids appear to be most effectively demonstrated in patients with very mild AD.
CONCLUSION
The effects of omega-3 fatty acids supplementation in mild AD corroborate epidemiological observational studies showing that omega-3 fatty acids may be beneficial in disease onset, when there is slight impairment of brain function. Although some studies have shown changes in scales of cognitive function in more severe cases, they are not enough to support omega-3 fatty acids supplementation in the treatment of AD.
Topics: Alzheimer Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cognition; Controlled Clinical Trials as Topic; Diet, Healthy; Dietary Supplements; Evidence-Based Medicine; Fatty Acids, Omega-3; Fish Oils; Fishes; Humans; Neuroprotective Agents; Nootropic Agents; Patient Compliance; Reproducibility of Results; Seafood; Severity of Illness Index
PubMed: 28466678
DOI: 10.1080/1028415X.2017.1321813 -
Alzheimer's Research & Therapy Feb 2019The objective of this systematic review was (1) to give an overview of the available short screening instruments for the early detection of Alzheimer's disease (AD) and...
OBJECTIVES
The objective of this systematic review was (1) to give an overview of the available short screening instruments for the early detection of Alzheimer's disease (AD) and (2) to review the psychometric properties of these instruments.
METHODS
First, a systematic search of titles and abstracts of PubMed and Web of Science was conducted between February and July 2015 and updated in April 2016 and May 2018. Only papers written in English or Dutch were considered. All full-text papers about cognitive screening instruments for the early detection of AD were included, resulting in the identification of 38 pencil and paper tests and 12 computer tests. In a second step, the psychometric quality of these instruments was evaluated. Therefore, the same databases were searched again to identify papers that described the psychometric properties of the instruments meanwhile applying diagnostic criteria for the diagnostic groups included.
RESULTS
Out of 1454 papers, 96 clearly discussed the psychometric properties of the instruments. Eighty-nine papers discussed pencil and paper tests of which 80 were validated in a memory clinic setting. Based on the number of studies (31 articles) and the sensitivity (84%) and specificity (74%) values, the Montreal Cognitive Assessment (MoCA) seems to be a promising (pencil and paper) screening test for memory clinic testing as well as for population screening. Regarding computer tests, validation studies were only available for 7 out of 12 tests.
CONCLUSIONS
A large number of screening tests for AD are available. However, most tests are only validated in a memory clinic setting and description of the psychometric properties of the instruments is limited. Especially, computer tests require further research. The MoCA is a promising instrument, but the specificity to detect early AD is rather low.
Topics: Alzheimer Disease; Brief Psychiatric Rating Scale; Cognition; Cognitive Dysfunction; Early Diagnosis; Humans; Mental Status and Dementia Tests
PubMed: 30819244
DOI: 10.1186/s13195-019-0474-3 -
Alzheimer's Research & Therapy Jan 2019Alzheimer's disease (AD) pathology begins several years before the clinical onset. The long preclinical phase is composed of three stages according to the 2011National... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alzheimer's disease (AD) pathology begins several years before the clinical onset. The long preclinical phase is composed of three stages according to the 2011National Institute on Aging and Alzheimer's Association (NIA-AA) criteria, followed by mild cognitive impairment (MCI), a featured clinical entity defined as "due to AD", or "prodromal AD", when pathophysiological biomarkers (i.e., cerebrospinal fluid or positron emission tomography with amyloid tracer) are positive. In the clinical setting, there is a clear need to detect the earliest symptoms not yet fulfilling MCI criteria, in order to proceed to biomarker assessment for diagnostic definition, thus offering treatment with disease-modifying drugs to patients as early as possible. According to the available evidence, we thus estimated the prevalence and risk of progression at each preclinical AD stage, with special interest in Stage 3.
METHODS
Cross-sectional and longitudinal studies published from April 2008 to May 2018 were obtained through MEDLINE-PubMed, screened, and systematically reviewed by four independent reviewers. Data from included studies were meta-analyzed using random-effects models. Heterogeneity was assessed by I statistics.
RESULTS
Estimated overall prevalence of preclinical AD was 22% (95% CI = 18-26%). Rate of biomarker positivity overlapped in cognitively normal individuals and people with subjective cognitive decline. The risk of progression increases across preclinical AD stages, with individuals classified as NIA-AA Stage 3 showing the highest risk (73%, 95% CI = 40-92%) compared to those in Stage 2 (38%, 95% CI = 21-59%) and Stage 1 (20%, 95% CI = 10-34%).
CONCLUSION
Available data consistently show that risk of progression increases across the preclinical AD stages, where Stage 3 shows a risk of progression comparable to MCI due to AD. Accordingly, an effort should be made to also operationalize the diagnostic work-up in subjects with subtle cognitive deficits not yet fulfilling MCI criteria. The possibility to define, in the clinical routine, a patient as "pre-MCI due to AD" could offer these subjects the opportunity to use disease-modifying drugs at best.
Topics: Alzheimer Disease; Cross-Sectional Studies; Disease Progression; Humans; Longitudinal Studies; Prevalence; Prodromal Symptoms; Risk Factors
PubMed: 30646955
DOI: 10.1186/s13195-018-0459-7 -
Current Alzheimer Research 2019In recent years, several reviews have addressed the effectiveness of dance therapy in dementia, healthy older adults, or the elderly in general. However, reviews...
BACKGROUND
In recent years, several reviews have addressed the effectiveness of dance therapy in dementia, healthy older adults, or the elderly in general. However, reviews regarding the effect of this therapy exclusively on patients diagnosed with Alzheimer's disease have not been found.
OBJECTIVE
The purpose of this study is to review the available literature describing clinical trials which explore the effects of dancing on psychological and physical outcomes, functionality, cognitive function, and quality of life in patients diagnosed with Alzheimer's disease. In addition, this review aims to assess the quality of studies that perform dance therapy interventions in these patients.
METHODS
This study is a systematic review of randomized and non-randomized clinical trials regarding the effect of intervention including a dancing activity in people diagnosed with Alzheimer's disease.
RESULTS
In total, the evidence for this review rests on 12 studies with a total of 349 participants. The findings of this mini-review confirm the positive effect of dance therapy on physical and cognitive function, functionality, psychological outcomes, and quality of life in people with Alzheimer's disease.
CONCLUSION
Most of the studies implementing dance as part of the therapeutic treatment has shown to improve or slow the worsening in the quality of life of patients with Alzheimer's disease and their caregivers. Future research focused on these patients should use a more exhaustive methodology and make a more detailed description of these kind of interventions.
Topics: Alzheimer Disease; Caregivers; Dance Therapy; Humans; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 31345149
DOI: 10.2174/1567205016666190725151614 -
Molecular Neurobiology Sep 2019Currently there are 850,000 people with Alzheimer's disease in the UK, with an estimated rise to 1.1 million by 2025. Alzheimer's disease is characterised by the...
Currently there are 850,000 people with Alzheimer's disease in the UK, with an estimated rise to 1.1 million by 2025. Alzheimer's disease is characterised by the accumulation of amyloid-beta plaques and hyperphosphorylated tau in the brain causing a progressive decline in cognitive impairment. Small non-coding microRNA (miRNA) sequences have been found to be deregulated in the peripheral blood of Alzheimer patients. A systematic review was conducted to extract all miRNA found to be significantly deregulated in the peripheral blood. These deregulated miRNAs were cross-referenced against the miRNAs deregulated in the brain at Braak Stage III. This resulted in a panel of 10 miRNAs (hsa-mir-107, hsa-mir-26b, hsa-mir-30e, hsa-mir-34a, hsa-mir-485, hsa-mir200c, hsa-mir-210, hsa-mir-146a, hsa-mir-34c, and hsa-mir-125b) hypothesised to be deregulated early in Alzheimer's disease, nearly 20 years before the onset of clinical symptoms. After network analysis of the 10 miRNAs, they were found to be associated with the immune system, cell cycle, gene expression, cellular response to stress, neuron growth factor signalling, wnt signalling, cellular senescence, and Rho GTPases.
Topics: Alzheimer Disease; Animals; Biomarkers; Brain; Gene Regulatory Networks; Humans; MicroRNAs
PubMed: 30734227
DOI: 10.1007/s12035-019-1500-y