Alzheimer's dementia (AD) is a major contributor to global disability, and effective therapies to modify disease progression are currently lacking. The neuro-inflammatory theory is a potential etiology underlying this neurodegenerative disease. Previous randomized, controlled trials (RCTs) have provided inconclusive results regarding efficacy of omega-3 polyunsaturated fatty acids (PUFAs) regimens, which might provide anti-inflammatory benefits in the management of AD, in improving cognitive function among participants with AD. The objective of this frequentist-model based network meta-analysis (NMA) was to evaluate the potential advantages of omega-3 PUFAs and currently FDA-approved medications for AD on overall cognitive function in AD individuals. The primary outcomes were: (1) changes in cognitive function, and (2) acceptability, which refers to all-cause discontinuation. Additionally, secondary outcomes included quality of life, behavioral disturbances and safety/tolerability, which was assessed through the frequency of any reported adverse event. This NMA included 52 RCTs (6 with omega-3 PUFAs and 46 with FDA-approved medications) involving 21,111 participants. The results showed that long-term high-dose (1500 - 2000 mg/day) of eicosapentaenoic acid (EPA)-dominant omega-3 PUFAs augmented with anti-oxidants had the highest potential for cognitive improvement among all investigated treatments [standardized mean difference=3.00, 95% confidence intervals (95%CIs)=1.84-4.16]. Compared to placebo, omega-3 PUFAs had similar acceptability [odds ratio (OR)=0.46, 95%CIs=0.04 to 5.87] and safety profiles (OR=1.24, 95%CIs=0.66 to 2.33)o. These findings support the potential neurotherapeutic effects of high dosage EPA-dominant omega-3 PUFAs for the amelioration of cognitive decline in patients with AD. Future large-scale, long-term RCTs should focus on different dosages of EPA-dominant omega-3 PUFAs regimens on improving cognitive dysfunction in patients with AD at different levels of inflammatory status and psychopathology.
BACKGROUND: Major depressive disorder (MDD) is highly debilitating, difficult to treat, has a high rate of recurrence, and negatively impacts the individual and society as a whole. One potential treatment for MDD is n-3 polyunsaturated fatty acids (n-3PUFAs), also known as omega-3 oils, naturally found in fatty fish, some other seafood, and some nuts and seeds. Various lines of evidence suggest a role for n-3PUFAs in MDD, but the evidence is far from conclusive. Reviews and meta-analyses clearly demonstrate heterogeneity between studies. Investigations of heterogeneity suggest different effects of n-3PUFAs, depending on the severity of depressive symptoms, where no effects of n-3PUFAs are found in studies of individuals with mild depressive symptomology, but possible benefit may be suggested in studies of individuals with more severe depressive symptomology. Hence it is important to establish their effectiveness in treating MDD. This review updates and incorporates an earlier review with the same research objective (Appleton 2015).
OBJECTIVES: To assess the effects of n-3 polyunsaturated fatty acids (also known as omega-3 fatty acids) versus a comparator (e.g. placebo, antidepressant treatment, standard care, no treatment, wait-list control) for major depressive disorder (MDD) in adults.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled trials (CENTRAL), Ovid MEDLINE, Embase and PsycINFO together with trial registries and grey literature sources (to 9 January 2021). We checked reference lists and contacted authors of included studies for additional information when necessary.
SELECTION CRITERIA: We included studies in the review if they: used a randomised controlled trial design; provided n-3PUFAs as an intervention; used a comparator; measured depressive symptomology as an outcome; and were conducted in adults with MDD. Primary outcomes were depressive symptomology (continuous data collected using a validated rating scale) and adverse events. Secondary outcomes were depressive symptomology (dichotomous data on remission and response), quality of life, and non-completion of studies.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. We assessed the certainty of the evidence using GRADE criteria.
MAIN RESULTS: The review includes 35 relevant studies: 34 studies involving a total of 1924 participants investigated the impact of n-3PUFA supplementation compared to placebo, and one study involving 40 participants investigated the impact of n-3PUFA supplementation compared to antidepressant treatment. For the placebo comparison, n-3PUFA supplementation resulted in a small to modest benefit for depressive symptomology, compared to placebo: standardised mean difference (SMD) (random-effects model) -0.40 (95% confidence interval (CI) -0.64 to -0.16; 33 studies, 1848 participants; very low-certainty evidence), but this effect is unlikely to be clinically meaningful. An SMD of 0.40 represents a difference between groups in scores on the HDRS (17-item) of approximately 2.5 points (95% CI 1.0 to 4.0), where the minimal clinically important change score on this scale is 3.0 points. The confidence intervals include both a possible clinically important effect and a possible negligible effect, and there is considerable heterogeneity between studies. Sensitivity analyses, funnel plot inspection and comparison of our results with those of large well-conducted trials also suggest that this effect estimate may be biased towards a positive finding for n-3PUFAs. Although the numbers of individuals experiencing adverse events were similar in intervention and placebo groups (odds ratio (OR) 1.27, 95% CI 0.99 to 1.64; 24 studies, 1503 participants; very low-certainty evidence), the confidence intervals include a small decrease to a modest increase in adverse events with n-3PUFAs. There was no evidence for a difference between n-3PUFA and placebo groups in remission rates (OR 1.13, 95% CI 0.74 to 1.72; 8 studies, 609 participants, low-certainty evidence), response rates (OR 1.20, 95% CI 0.80 to 1.79; 17 studies, 794 participants; low-certainty evidence), quality of life (SMD -0.38 (95% CI -0.82 to 0.06), 12 studies, 476 participants, very low-certainty evidence), or trial non-completion (OR 0.92, 95% CI 0.70 to 1.22; 29 studies, 1777 participants, very low-certainty evidence). The evidence on which these results are based was also very limited, highly heterogeneous, and potentially biased. Only one study, involving 40 participants, was available for the antidepressant comparison. This study found no differences between treatment with n-3PUFAs and treatment with antidepressants in depressive symptomology (mean difference (MD) -0.70, 95% CI -5.88 to 4.48), rates of response to treatment (OR 1.23, 95% CI 0.35 to 4.31), or trial non-completion (OR 1.00, 95% CI 0.21 to 4.71). Confidence intervals are however very wide in all analyses, and do not rule out important beneficial or detrimental effects of n-3PUFAs compared to antidepressants. Adverse events were not reported in a manner suitable for analysis, and rates of depression remission and quality of life were not reported.
AUTHORS' CONCLUSIONS: At present, we do not have sufficient high-certainty evidence to determine the effects of n-3PUFAs as a treatment for MDD. Our primary analyses may suggest a small-to-modest, non-clinically beneficial effect of n-3PUFAs on depressive symptomology compared to placebo; however the estimate is imprecise, and we judged the certainty of the evidence on which this result is based to be low to very low. Our data may also suggest similar rates of adverse events and trial non-completion in n-3PUFA and placebo groups, but again our estimates are very imprecise. Effects of n-3PUFAs compared to antidepressants are very imprecise and uncertain. More complete evidence is required for both the potential positive and negative effects of n-3PUFAs for MDD.
BACKGROUND: Effects of drug treatment of clinical Alzheimer-type dementia (CATD) are uncertain.
PURPOSE: To summarize evidence on the effects of prescription drugs and supplements for CATD treatment.
DATA SOURCES: Electronic bibliographic databases (inception to November 2019), ClinicalTrials.gov (to November 2019), and systematic review bibliographies.
STUDY SELECTION: English-language trials of prescription drug and supplement treatment in older adults with CATD that report cognition, function, global measures, behavioral and psychological symptoms of dementia (BPSD), or harms. Minimum treatment was 24 weeks (≥2 weeks for selected BPSD).
DATA EXTRACTION: Studies with low or medium risk of bias (ROB) were analyzed. Two reviewers rated ROB. One reviewer extracted data; another verified extraction accuracy.
DATA SYNTHESIS: Fifty-five studies reporting non-BPSD outcomes (most ≤26 weeks) and 12 reporting BPSD (most ≤12 weeks) were analyzed. Across CATD severity, mostly low-strength evidence suggested that, compared with placebo, cholinesterase inhibitors produced small average improvements in cognition (median standardized mean difference [SMD], 0.30 [range, 0.24 to 0.52]), no difference to small improvement in function (median SMD, 0.19 [range, -0.10 to 0.22]), no difference in the likelihood of at least moderate improvement in global clinical impression (median absolute risk difference, 4% [range, 2% to 4%]), and increased withdrawals due to adverse events. In adults with moderate to severe CATD receiving cholinesterase inhibitors, low- to insufficient-strength evidence suggested that, compared with placebo, add-on memantine inconsistently improved cognition and improved global clinical impression but not function. Evidence was mostly insufficient about prescription drugs for BPSD and about supplements for all outcomes.
LIMITATION: Most drugs had few trials without high ROB, especially for supplements, active drug comparisons, BPSD, and longer trials.
CONCLUSION: Cholinesterase inhibitors and memantine slightly reduced short-term cognitive decline, and cholinesterase inhibitors slightly reduced reported functional decline, but differences versus placebo were of uncertain clinical importance. Evidence was mostly insufficient on drug treatment of BPSD and on supplements for all outcomes.
PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897).
OBJECTIVE: We conducted this systematic review to support the U.S. Preventive Services Task Force in updating its 2014 recommendation on screening for cognitive impairment in older adults. Our review addressed the direct evidence on the benefits and harms of screening for cognitive impairment versus no screening, the test accuracy of screening instruments to detect mild cognitive impairment (MCI) and dementia, and the benefits and harms of treatment for MCI and mild to moderate dementia among community-dwelling older adults age 65 years and older.
DATA SOURCES: We performed an updated search of MEDLINE, PubMed Publisher-Supplied, PsycINFO, and the Cochrane Central Register of Controlled Trials for studies published through January 2019. We supplemented searches by examining reference lists from related articles and expert recommendations and searched federal and international trial registries for ongoing trials.
STUDY SELECTION: Two researchers reviewed 11,644 titles and abstracts and 966 full-text articles against prespecified inclusion criteria. We included test accuracy studies that included screening instruments that could be delivered in primary care in 10 minutes or less by a clinician or self-administered in 20 minutes or less compared with a reference standard. We included trials of major pharmacologic and nonpharmacologic interventions in persons with MCI or mild to moderate dementia and large, observational studies examining adverse effects of these interventions. We conducted dual, independent critical appraisal of all provisionally included studies and abstracted all important study details and results from all studies rated fair or good quality. Data were abstracted by one reviewer and confirmed by another.
DATA ANALYSIS: We synthesized data separately for each key question and within subcategories of screening instruments and treatments. For diagnostic accuracy studies, we focused on sensitivity and specificity of instruments that were evaluated in more than one study. We conducted a qualitative synthesis of results using summary tables and figures to capture key study characteristics, sources of clinical heterogeneity, and overall results of each study. Quantitative synthesis was limited to test performance of the Mini Mental State Examination (MMSE) (due to insufficient number of homogeneous studies for other instruments) and U.S. Food and Drug Administration (FDA)–approved medications to treat Alzheimer’s Disease on global cognitive outcomes, global function, and harms; nonpharmacologic interventions aimed at the patient on global cognitive outcomes; and caregiver and caregiver-patient dyad interventions on caregiver burden and depression outcomes. We ran random-effects meta-analyses using the DerSimonian and Laird method and sensitivity analyses using a Restricted Likelihood Estimation Model with the Knapp-Hartung correction to calculate the pooled differences in mean changes (for continuous data) and pooled risk ratio (for binary data). We used meta-regression to explore potential effect modification by various study, population, and intervention characteristics in cases where 10 or more studies were pooled. We generated funnel plots and conducted tests for small-study effects for all pooled analyses. Using established methods, we assessed the strength of evidence for each question.
RESULTS: Screening (Key Questions 1–3): Only one trial was identified that examined the direct effect of screening for cognitive impairment on important patient outcomes, including potential harms. In that trial, at 12 months, there was no difference in health-related quality of life between those who were screened vs. not screened. Symptoms of depression and anxiety were also similar between groups at 1, 6, and 12 months as was health care utilization and advance care planning. We identified 59 studies that addressed the diagnostic accuracy of 49 screening instruments to detect cognitive impairment. Most instruments were only studied in a handful of well-designed diagnostic accuracy studies in primary care–relevant populations. The MMSE, a brief test taking 7 to 10 minutes to complete, remains the most thoroughly studied instrument. The pooled estimate across 15 studies (n=12,796) resulted in 89 percent sensitivity (95% CI, 0.85 to 0.92) and 89 percent specificity (95% CI, 0.85 to 0.93) to detect dementia at a cutoff of 23 or less or 24 or less. Other screening instruments evaluated in more than one study included the very brief instruments (≤5 minutes) of the CDT, MIS, MSQ, Mini-Cog, Lawton IADL, VF, AD8, and FAQ and the brief instruments (6 to 10 minutes) of the 7MS, AMT, MoCA, SLUMS, and TICS with sensitivity to detect dementia usually at 0.75 or higher and specificity at 0.80 or higher for all instruments. For self-administered, longer tests (>10 minutes), only the IQCODE was assessed in more than one study, with sensitivity to detect dementia ranging from 0.80 to 0.88 and specificity ranging from 0.51 to 0.91. Across all instruments, test performance was generally higher in the detection of dementia vs. mild cognitive impairment, although confidence intervals overlapped. No studies directly addressed the adverse psychological effects of screening or adverse effects from false-positive or false-negative testing. Treatment (Key Questions 4 and 5): We identified 224 trials and 3 observational studies representing more than 240,000 patients and/or caregivers that addressed the treatment or management of MCI or mild to moderate dementia. None of the treatment trials were linked with a screening program; in all cases, trial participants were persons with known MCI or dementia. Pharmacologic Interventions: Based on 45 trials (n=22,431) and three observational studies (n=190,076) that evaluated acetylcholinesterase inhibitors (AChEIs) (i.e., donepezil, galantamine, rivastigmine) and memantine, these medications may improve measures of global cognitive function in the short term, but the magnitude of change is small. In meta-analyses, the differences in changes between those on AChEIs or memantine compared with those on placebo ranged from approximately 1 to 2.5 points on the ADAS-Cog-11 and 0.5 to 1 point on the MMSE over 3 months to 3 years of followup. AChEIs and memantine appeared to increase the likelihood of improving or maintaining patients’ global function by 15 percent (for memantine) to 50 percent (for rivastigmine) in the short term (pooled 95% confidence interval range, 0.49 to 2.69). Other outcome measures were inconsistently reported. Total adverse events and discontinuation due to adverse events were more common with AChEIs, but not memantine, compared with placebo. Rates of serious adverse events overall were not higher among those taking medications vs. placebo, but individual studies noted increased rates of serious adverse events. Trials evaluating other medications or dietary supplements (k=29; n=6,489), including discontinuing antihypertensives, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (atorvastatin and simvastatin), nonsteroidal anti-inflammatory drugs (ibuprofen, naproxen, indomethacin, and celecoxib), gonadal steroids (estrogen [plus or minus progesterone] and testosterone), and dietary supplements and vitamins (multivitamins, B vitamins, vitamin E, and omega-3 fatty acids) showed no benefit on global cognitive or physical function in persons with mild to moderate dementia or MCI. Nonpharmacologic Interventions: We identified 61 trials (n=7,847) that evaluated nonpharmacologic patient-level interventions, including cognitive-focused, exercise, and multicomponent and other interventions. Among all interventions, there was no clear benefit on global or domain-specific measures of cognitive function compared with control conditions at 3 months to 2 years followup. Effect estimates generally favored the intervention groups over control groups, but the magnitude of effect was inconsistent across trials and represented very wide confidence intervals (ranging from no effect to a large effect). Physical function outcomes, including change in activities of daily living and independent activities of daily living, as well as quality of life and mental and neuropsychiatric symptoms, were inconsistently reported. There was, however, a pattern of effect for exercise interventions, with small improvements seen in measures of physical function and symptoms for intervention groups, whereas control groups reported worsening function. Caregiver and caregiver-patient dyad interventions including psychoeducation for the caregiver and care and case management interventions, reported in 88 trials (n=14,880), resulted in a consistent benefit on caregiver burden and depression outcomes. Effect sizes were mostly small, however, and were of unclear clinical significance. Little harm was evident in the few nonpharmacologic intervention trials that reported harms.
LIMITATIONS: There is a lack of evidence around how screening for and treating MCI and early-stage dementia affects decision making outcomes. Furthermore, there has been little reproducibility in testing specific screening instruments in primary care populations. The treatment literature is limited by a lack of consistency in the specific outcomes reported and short followup duration. It is difficult to interpret the clinical importance of the small average effects seen among treatment trials, and many measures likely have limited responsiveness for patients with less pronounced cognitive impairment. Consistent and standardized reporting of results according to meaningful thresholds of clinical significance would be helpful in interpreting the small average effects on continuous outcome measures. Other important measures such as quality of life, physical function, and institutionalization, were inconsistently reported.
CONCLUSIONS: Several brief screening instruments can adequately detect cognitive impairment, especially in populations with a higher prevalence of underlying dementia. There is no empiric evidence, however, that screening for cognitive impairment or early diagnosis of cognitive impairment improves patient, caregiver, family, or clinician decision making or other important outcomes nor causes harm. In general, there is support that AChEIs and memantine and interventions that support caregivers, including those that help coordinate care for patients and caregivers, can result in small improvements in the short term. Unfortunately, the average effects of these benefits are quite small and likely not of clinical significance. Any benefits are further limited by the commonly experienced side effects of medications and the limited availability of complex caregiver interventions. Cognitive stimulation and training, exercise interventions, and other medications and supplements showed some favorable effects on patients’ cognitive and physical function, but trial evidence lacked consistency and the estimates of benefit were imprecise. There is less evidence related to screening for and treating MCI. The test performance of the few instruments evaluated to detect MCI was lower than the sensitivity and specificity to detect dementia and there is little evidence for any pharmacologic or nonpharmacologic interventions to preserve or improve patient functioning in persons with MCI.
BACKGROUND AND AIMS: Balanced nutrition which can help in maintaining immunity is essential for prevention and management of viral infections. While data regarding nutrition in coronavirus infection (COVID-19) are not available, in this review, we aimed to evaluate evidence from previous clinical trials that studied nutrition-based interventions for viral diseases (with special emphasis on respiratory infections), and summarise our observations.
METHODS: A systematic search strategy was employed using keywords to search the literature in 3 key medical databases: PubMed®, Web of Science® and SciVerse Scopus®. Studies were considered eligible if they were controlled trials in humans, measuring immunological parameters, on viral and respiratory infections. Clinical trials on vitamins, minerals, nutraceuticals and probiotics were included.
RESULTS: A total of 640 records were identified initially and 22 studies were included from other sources. After excluding duplicates and articles that did not meet the inclusion criteria, 43 studies were obtained (vitamins: 13; minerals: 8; nutraceuticals: 18 and probiotics: 4). Among vitamins, A and D showed a potential benefit, especially in deficient populations. Among trace elements, selenium and zinc have also shown favourable immune-modulatory effects in viral respiratory infections. Several nutraceuticals and probiotics may also have some role in enhancing immune functions. Micronutrients may be beneficial in nutritionally depleted elderly population.
CONCLUSIONS: We summaries possible benefits of some vitamins, trace elements, nutraceuticals and probiotics in viral infections. Nutrition principles based on these data could be useful in possible prevention and management of COVID-19.
IMPORTANCE: Early identification of cognitive impairment may improve patient and caregiver health outcomes.
OBJECTIVE: To systematically review the test accuracy of cognitive screening instruments and benefits and harms of interventions to treat cognitive impairment in older adults (≥65 years) to inform the US Preventive Services Task Force.
DATA SOURCES: MEDLINE, PubMed, PsycINFO, and Cochrane Central Register of Controlled Trials through January 2019, with literature surveillance through November 22, 2019.
STUDY SELECTION: Fair- to good-quality English-language studies of cognitive impairment screening instruments, and pharmacologic and nonpharmacologic treatments aimed at persons with mild cognitive impairment (MCI), mild to moderate dementia, or their caregivers.
DATA EXTRACTION AND SYNTHESIS: Independent critical appraisal and data abstraction; random-effects meta-analyses and qualitative synthesis.
MAIN OUTCOMES AND MEASURES: Sensitivity, specificity; patient, caregiver, and clinician decision-making; patient function, quality of life, and neuropsychiatric symptoms; caregiver burden and well-being.
RESULTS: The review included 287 studies with more than 280 000 older adults. One randomized clinical trial (RCT) (n = 4005) examined the direct effect of screening for cognitive impairment on patient outcomes, including potential harms, finding no significant differences in health-related quality of life at 12 months (effect size, 0.009 [95% CI, -0.063 to 0.080]). Fifty-nine studies (n = 38 531) addressed the accuracy of 49 screening instruments to detect cognitive impairment. The Mini-Mental State Examination was the most-studied instrument, with a pooled sensitivity of 0.89 (95% CI, 0.85 to 0.92) and specificity of 0.89 (95% CI, 0.85 to 0.93) to detect dementia using a cutoff of 23 or less or 24 or less (15 studies, n = 12 796). Two hundred twenty-four RCTs and 3 observational studies including more than 240 000 patients or caregivers addressed the treatment of MCI or mild to moderate dementia. None of the treatment trials were linked with a screening program; in all cases, participants were persons with known cognitive impairment. Medications approved to treat Alzheimer disease (donepezil, galantamine, rivastigmine, and memantine) improved scores on the ADAS-Cog 11 by 1 to 2.5 points over 3 months to 3 years. Psychoeducation interventions for caregivers resulted in a small benefit for caregiver burden (standardized mean difference, -0.24 [95% CI, -0.36 to -0.13) over 3 to 12 months. Intervention benefits were small and of uncertain clinical importance.
CONCLUSIONS AND RELEVANCE: Screening instruments can adequately detect cognitive impairment. There is no empirical evidence, however, that screening for cognitive impairment improves patient or caregiver outcomes or causes harm. It remains unclear whether interventions for patients or caregivers provide clinically important benefits for older adults with earlier detected cognitive impairment or their caregivers.
OBJECTIVE: To summarize evidence on: (1) the accuracy of brief cognitive tests for identifying clinical Alzheimer’s-type dementia (CATD) in individuals with suspected cognitive impairment; (2) the accuracy of biomarkers for identifying Alzheimer’s disease (AD) in individuals with dementia; and (3) the benefits and harms of prescription drugs and supplements for cognition, function, and behavioral and psychological symptoms of dementia (BPSD) in patients with CATD.
DATA SOURCES: Electronic bibliographic databases to March 2019, ClinicalTrials.gov, systematic review bibliographies.
REVIEW METHODS: Cognitive test accuracy studies must have used explicit CATD diagnostic criteria and a non-CATD control group. Biomarker accuracy studies must have used neuropathologic criteria to define AD cases and non-AD controls. All treatment trials must have enrolled participants with CATD; those evaluating BPSD enrolled individuals with CATD and BPSD. Minimum trial duration was 2 weeks for agitation, aggression, psychosis, and disinhibited sexual behavior, and 24 weeks for other outcomes. Two reviewers rated risk of bias (ROB) and strength of evidence. One reviewer extracted data; a second checked accuracy. We analyzed English-language studies with low or medium ROB.
RESULTS: We analyzed 56 unique studies on the accuracy of brief cognitive tests for CATD, 24 on accuracy of biomarkers for AD (15 brain imaging, nine cerebrospinal fluid [CSF] testing), and 67 trials of CATD treatment (54 reporting cognition or function, 13 reporting BPSD). Multiple brief cognitive tests were highly sensitive and specific (≥0.8) for distinguishing CATD from normal cognition, but less so for distinguishing mild CATD from normal cognition or CATD from mild cognitive impairment (MCI). Based on few studies, compared with clinical evaluation alone, amyloid positron emission tomography (PET), fluorodeoxyglucose (FDG)-PET, and combinations of CSF tests added to clinical evaluation may improve accuracy for distinguishing AD from non-AD dementia. Regardless of CATD severity, cholinesterase-inhibitors produced small improvements in cognition and function compared with placebo but may increase serious adverse events and withdrawals due to adverse events. For moderate to severe CATD, memantine plus a cholinesterase inhibitor slightly improved global change and inconsistently improved cognition, but not function, compared with a cholinesterase inhibitor alone. Evidence was mostly insufficient about the effects of prescription drugs and supplements on agitation, aggression, psychosis, or disinhibited sexual behavior.
CONCLUSIONS: Brief cognitive tests accurately distinguished CATD from normal cognition, but were less accurate distinguishing smaller clinical differences. Whether biomarkers improve diagnostic accuracy when added to clinical evaluation needs further verification, but potential benefits of testing are limited by lack of effective treatments for AD and non-AD dementias. Cholinesterase-inhibitors slightly outperformed placebo for cognition and function, but evidence of whether any drug treatments improved BPSD was largely insufficient.
Los pacientes con artritis suelen tomar suplementos de aceite de pescado para aliviar los síntomas, pero existen pruebas limitadas sobre su eficacia. El objetivo fue evaluar si los suplementos de aceite marino reducen el dolor y / o mejoran otros resultados clínicos en pacientes con artritis. Se registraron sistemáticamente seis bases de datos (24 de febrero de 2015). Se incluyeron ensayos aleatorios de suplementos orales de todos los aceites marinos en comparación con un control en pacientes con artritis. La validez interna se evaluó mediante la herramienta Cochrane de riesgo de sesgo y se exploró la heterogeneidad utilizando el análisis de metarregresión basado en el máximo de verosimilitud (REML) restringido. Clasificación de Recomendaciones Evaluación, Desarrollo y Evaluación (GRADE) se utilizó para calificar la calidad general de la evidencia. Cuarenta y dos ensayos se incluyeron; 30 ensayos informaron datos completos sobre el dolor. La diferencia de medias estandarizada (DME) sugirió un efecto favorable (-0,24, intervalo de confianza del 95%, IC, -0,42 a -0,07, heterogeneidad, I² = 63%, y un efecto significativo en los pacientes con artritis reumatoide (22 ensayos; 0,21; IC del 95%: -0,42 a -0,004) y otros diagnósticos mixtos (3 ensayos; -0,63; IC del 95%: -1,20 a -0,06), pero no en pacientes con osteoartritis (5 ensayos; -0,17; IC del 95% , -0.57-0.24) La evidencia para el uso de aceite marino para aliviar el dolor en pacientes con artritis fue en general de baja calidad, pero de calidad moderada en pacientes con artritis reumatoide.
Many clinical trials of omega-3 fatty acids, supplied as fish oil supplements, have been carried out in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), lupus nephritis, and osteoarthritis (OA) over the past 3 decades. This review attempts to summarize the highlights of these studies to evaluate the clinical efficacy for omega-3 fatty acids to be added alongside existing treatment regimens. A total of 20 clinical trials have been carried out in RA, of which 16 exhibited significant improvements in multiple disease clinical outcomes. Nine clinical trials have been completed in SLE and lupus nephritis, of which 6 exhibited significant improvements in 1 or more clinical outcomes. A total of 4 clinical trials have been conducted in OA, of which 3 exhibited significant improvements in at least 1 clinical parameter. Multiple mechanisms for the clinical effects of omega-3 fatty acids have been implicated, including the modulation of eicosanoid synthesis toward a more anti-inflammatory profile and suppressed production of proinflammatory cytokines. Overall, fish oil supplements appear to be a safe and effective agent that could be added to the current treatment regimens in RA. Longer-term trials with larger patient cohort sizes are warranted to establish any long-term benefits of fish oil supplements in SLE, lupus nephritis, and OA.
ANTECEDENTES: n-3 ácidos grasos poliinsaturados derivados de Marina (AGPI) pueden tener un efecto beneficioso sobre la inflamación a través de la reducción de las concentraciones de eicosanoides proinflamatorios. El objetivo fue evaluar el efecto de los PUFA n-3 de origen marino de la prostaglandina E2 (PGE2), tromboxano B2 (TXB2) y el leucotrieno B4 (LTB4) mediante la revisión sistemática y meta-análisis de ensayos controlados aleatorios.
MÉTODO Y RESULTADOS: Una estrategia de búsqueda estructurada en PubMed, Web of Science y Cochrane hasta noviembre de 2015 representaba a cabo en este meta-análisis. Diferencia de medias estándar se utilizó para calcular el tamaño del efecto de origen marino n-3 PUFA en PGE2, TXB2 y LTB4 en un modelo de efectos aleatorios. Un total de 18 ECA con 826 sujetos fueron incluidos en esta revisión sistemática y meta-análisis. La suplementación de AGPI n-3 de origen marino se redujo significativamente las concentraciones de TXB2 en el suero / plasma en sujetos con alto riesgo de enfermedades cardiovasculares (DME: -1,26; IC del 95%: -1.65, -0.86) y LTB4 en los neutrófilos en sujetos saludables ( sujetos con enfermedades no autoinmunes crónicas o enfermedades autoinmunes) (DME: -0,59: IC del 95%: -1.02, -0.16). Los análisis de subgrupos mostró una reducción significativa de LTB4 en sujetos con artritis reumatoide (DME: -0,83; IC del 95%: -1.37, -0.29), pero no en pacientes no autoinmunes enfermedad crónica (DME: -0,33; IC del 95%: - 0,97, 0,31). Sin sesgo de publicación significativo se muestra en el meta-análisis.
Conclusiones de origen marino n-3 PUFA tuvo un efecto beneficioso en la reducción de la concentración de TXB2 en la sangre de los sujetos con alto riesgo de enfermedades cardiovasculares, así como LTB4 en los neutrófilos en sujetos saludables, y que los sujetos con AR mostró menor contenido de LTB4 con la suplementación de de origen marino n-3 PUFA.
Alzheimer's dementia (AD) is a major contributor to global disability, and effective therapies to modify disease progression are currently lacking. The neuro-inflammatory theory is a potential etiology underlying this neurodegenerative disease. Previous randomized, controlled trials (RCTs) have provided inconclusive results regarding efficacy of omega-3 polyunsaturated fatty acids (PUFAs) regimens, which might provide anti-inflammatory benefits in the management of AD, in improving cognitive function among participants with AD. The objective of this frequentist-model based network meta-analysis (NMA) was to evaluate the potential advantages of omega-3 PUFAs and currently FDA-approved medications for AD on overall cognitive function in AD individuals. The primary outcomes were: (1) changes in cognitive function, and (2) acceptability, which refers to all-cause discontinuation. Additionally, secondary outcomes included quality of life, behavioral disturbances and safety/tolerability, which was assessed through the frequency of any reported adverse event. This NMA included 52 RCTs (6 with omega-3 PUFAs and 46 with FDA-approved medications) involving 21,111 participants. The results showed that long-term high-dose (1500 - 2000 mg/day) of eicosapentaenoic acid (EPA)-dominant omega-3 PUFAs augmented with anti-oxidants had the highest potential for cognitive improvement among all investigated treatments [standardized mean difference=3.00, 95% confidence intervals (95%CIs)=1.84-4.16]. Compared to placebo, omega-3 PUFAs had similar acceptability [odds ratio (OR)=0.46, 95%CIs=0.04 to 5.87] and safety profiles (OR=1.24, 95%CIs=0.66 to 2.33)o. These findings support the potential neurotherapeutic effects of high dosage EPA-dominant omega-3 PUFAs for the amelioration of cognitive decline in patients with AD. Future large-scale, long-term RCTs should focus on different dosages of EPA-dominant omega-3 PUFAs regimens on improving cognitive dysfunction in patients with AD at different levels of inflammatory status and psychopathology.
Pregunta de la revisión sistemática»Revisión sistemática de intervenciones
