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1.
Dietary soybean isoflavones in Alzheimer's disease prevention.
Lu, Y, An, Y, Lv, C, Ma, W, Xi, Y, Xiao, R
Asia Pacific journal of clinical nutrition. 2018;(5):946-954
Abstract
Soybean isoflavone (SIF) is a type of polyphenol present extensively in legumes. Because of its unique chemical construction and the physiological activity of the phenolic hydroxyl group, SIF exhibits strong antioxidant activity in antioxidant and nonantioxidant enzyme systems. Genistein is the major isoflavone in soy foods, accounting for more than 50% of the isoflavone content. The health effects of soybean dietary isoflavones on humans have gained increased attention. Recent studies have suggested that SIF may alleviate neurodegenerative diseases such as Alzheimer's disease (AD). Despite the comprehensive research on AD, effective treatments for AD are yet to be established. The early diagnosis and prevention of mild cognitive impairment (MCI) have become crucial for delaying AD development. Several dietary polyphenols have exerted cognitive effects on AD, and the appropriate intake of dietary SIF helps reduce the risk of AD. This study reviews the possible mechanisms of AD pathogenesis and their relationships with SIF intake; the results provide useful insights for AD prevention in the future.
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2.
Cerebrospinal Fluid Biomarkers in Alzheimer's Disease: An Invaluable Tool for Clinical Diagnosis and Trial Enrichment.
Parnetti, L, Eusebi, P
Journal of Alzheimer's disease : JAD. 2018;(s1):S281-S287
Abstract
Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting around 35 million people worldwide. Cerebrospinal fluid (CSF) biomarkers entered the diagnostic criteria as support for early diagnosis. The classical biochemical signature of AD includes total tau (T-tau), phosphorylated tau (P-tau), and the 42 amino acid peptide (Aβ42) of amyloid-β. Recent observations suggest that the use of CSF Aβ42:Aβ40 ratio rather than CSF Aβ42 alone could contribute to reduce inter-laboratory variation in Aβ values and increasing diagnostic performance of the CSF AD biomarkers in routine practice. However, research efforts aimed at enriching the CSF biomarker panel are ongoing. The CSF AD signature is also crucial for the design of clinical trials for AD, since it best guarantees AD pathology as the cause of cognitive impairment. Accordingly, CSF biomarkers have been now reported in the inclusion criteria of Phase I, Phase II, and Phase III clinical trials as enrichment strategy. So far, one of the most important reasons for the failure of AD clinical trials was the inclusion of participants with unlikely AD pathology. In order to implement the use of CSF biomarkers in AD routine diagnostic work-up and as accepted strategy for enriching trial populations, inter-laboratory variability should be minimized. Increasing efforts should also be devoted to promote data sharing practices, encouraging individual participant data meta-analyses.
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Present and Future of Ultra-High Field MRI in Neurodegenerative Disorders.
Donatelli, G, Ceravolo, R, Frosini, D, Tosetti, M, Bonuccelli, U, Cosottini, M
Current neurology and neuroscience reports. 2018;(6):31
Abstract
PURPOSE OF REVIEW With a high signal-to-noise ratio, unparalleled spatial resolution, and improved contrasts, ultra-high field MR (≥ 7 T) has great potential in depicting the normal radiological anatomy of smaller structures in the brain and can also provide more information about morphological, quantitative, and metabolic changes associated with a wide range of brain disorders. By focusing attention on specific brain regions believed to be associated with early pathological change, or by more closely inspecting recognized foci of brain pathology, ultra-high field MR can improve the accuracy and sensitivity of neuroimaging. This article reviews recent studies at ultra-high field about Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). RECENT FINDINGS The research on AD has mainly focused on detecting the thinning of hippocampal layers and the susceptibility effect supposed to be related to beta-amyloid deposition. In patients with PD, atypical parkinsonisms and subjects at risk of developing motor symptoms of Parkinson's disease, the main aim was to detect changes in the substantia nigra, probably related to increased iron deposition. In patients with ALS, both brain and spinal cord were investigated, with the aim of finding changes in the primary motor cortex and corticospinal tract which reflect neurodegeneration and neuroinflammation. Ultra-high field MR was shown to be useful for detecting subtle brain changes in patients with AD, and possible new diagnostic biomarkers in patients with PD and ALS were discovered. The ability of 7 T MR to provide prognostic biomarkers in subjects at risk for developing synucleinopathies is currently under evaluation.
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White paper by the Society for CSF Analysis and Clinical Neurochemistry: Overcoming barriers in biomarker development and clinical translation.
Teunissen, CE, Otto, M, Engelborghs, S, Herukka, SK, Lehmann, S, Lewczuk, P, Lleó, A, Perret-Liaudet, A, Tumani, H, Turner, MR, et al
Alzheimer's research & therapy. 2018;(1):30
Abstract
Body fluid biomarkers have great potential for different clinical purposes, including diagnosis, prognosis, patient stratification and treatment effect monitoring. This is exemplified by current use of several excellent biomarkers, such as the Alzheimer's disease cerebrospinal fluid (CSF) biomarkers, anti-neuromyelitis optica antibodies and blood neurofilament light. We still, however, have a strong need for additional biomarkers and several gaps in their development and implementation should be filled. Examples of such gaps are i) limited knowledge of the causes of neurological diseases, and thus hypotheses about the best biomarkers to detect subclinical stages of these diseases; ii) the limited success translating discoveries obtained by e.g. initial mass spectrometry proteomic low-throughput studies into immunoassays for widespread clinical implementation; iii) lack of interaction among all stakeholders to optimise and adapt study designs throughout the biomarker development process to medical needs, which may change during the long period needed for biomarker development.The Society for CSF Analysis and Clinical Neurochemistry (established in 2015) has been founded as a concerted follow-up of large standardisation projects, including BIOMARKAPD and SOPHIA, and the BioMS-consortium.The main aims of the CSF society are to exchange high level international scientific experience, to facilitate the incorporation of CSF diagnostics into clinical practice and to give advice on inclusion of CSF analysis into clinical guidelines. The society has a broad scope, as its vision is that the gaps in development and implementation of biomarkers are shared among almost all neurological diseases and thus they can benefit from the activities of the society.
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123I-ioflupane SPET and 123I-MIBG in the diagnosis of Parkinson's disease and parkinsonian disorders and in the differential diagnosis between Alzheimer's and Lewy's bodies dementias.
Nuvoli, S, Palumbo, B, Malaspina, S, Madeddu, G, Spanu, A
Hellenic journal of nuclear medicine. 2018;(1):60-68
Abstract
Nuclear medicine procedures are widely used as "in vivo" biomarkers in a large number of brain diseases, especially in the diagnosis of Parkinson's disease (PD) and of parkinsonian disorders (pD). Furthermore, nuclear medicine is used in the differential diagnosis of dementias especially Alzheimer's disease (AD) and dementia with Lewy's bodies (LBD) which share many clinical symptoms and often LBD is misdiagnosed as AD. The differential diagnosis between these clinical entities is crucial for treatment since LBD also shares some clinical symptoms with parkinsonian disorders. We reviewed the most relevant papers that study the usefulness of both iodine-123-ioflupane studied by single photon emission tomography (123I-ioflupane SPET) and of 123I-metaiodobenzylguanidine (123I-MIBG) cardiac scintigraphy in the diagnosis of PD and pD and in the differential diagnosis between AD and LBD in order to contribute to the clinical practice of the diseases.
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The Association between Social Engagement, Loneliness, and Risk of Dementia: A Systematic Review and Meta-Analysis.
Penninkilampi, R, Casey, AN, Singh, MF, Brodaty, H
Journal of Alzheimer's disease : JAD. 2018;(4):1619-1633
Abstract
It has been reported that social engagement may be associated with dementia risk. We searched PubMed, EMBASE, PsycINFO, CINAHL, LILACS, Biomed Central, Scopus, and Web of Science from January 2012 - May 2017, supplemented by extraction from previous reviews. We included cohort and case-control studies examining the association between social engagement or loneliness and dementia risk, pooling data using a random-effects model. Registered: PROSPERO (CRD42017067074). We included 31 cohort and 2 case-control studies comprising 2,370,452 participants. Poor social engagement indices were associated with increased dementia risk, including having a poor social network (RR = 1.59, 95% CI 1.31-1.96; I2 = 0.00%) and poor social support (RR = 1.28, 95% CI 1.01-1.62; I2 = 55.51%). In long-term studies (≥10 years), good social engagement was modestly protective (RR = 0.88, 95% CI 0.80-0.96; I2 = 0.00%). Loneliness was non-significantly associated with increased risk (RR = 1.38, 95% CI 0.98-1.94; I2 = 45.32). Our findings encourage interventions targeting social isolation and disengagement for dementia prevention.
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Features and outcomes of drugs for combination therapy as multi-targets strategy to combat Alzheimer's disease.
Sahoo, AK, Dandapat, J, Dash, UC, Kanhar, S
Journal of ethnopharmacology. 2018;:42-73
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Alzheimer's disease (AD), a deleterious neurodegenerative disorder that impairs memory, cognitive functions and may lead to dementia in late stage of life. The pathogenic cause of AD remains incompletely understood and FDA approved drugs are partial inhibitors rather than curative. Most of drugs are synthetic or natural products as galanthamine is an alkaloid obtained from Galanthus spp. Huperzine A, an alkaloid found in Huperzia spp., gingkolides a diterpenoids from Gingko biloba and many ethnobotanicals like Withania somnifera (L.) Dunal., Physostigma venenosum Balf., Bacopa monnieri (L.) Wettst., Centella asiatica (L.) Urb. have been used by traditional Indian, Chinese, and European system of medicines in AD. Clinical significance opioid alkaloid in Papaver somniferum has shown another dimension to this study. Over exploitation of medicinal plants with limited bioactive principles has provided templates to design synthetic drugs in AD e.g. rivastigmine, phenserine, eptastigmine based on chemical structure of physostigmine of Physostigma venenosum Balf. Even ZT-1 a prodrug of Hup A and memogain a prodrug of galantamine has achieved new direction in drug development in AD. All these first-line cholinesterase-inhibitors are used as symptomatic treatments in AD. Single modality of "One-molecule-one-target" strategy for treating AD has failed and so future therapies on "Combination-drugs-multi-targets" strategy (CDMT) will need to address multiple aspects to block the progression of pathogenesis of AD. Besides, cholinergic and amyloid drugs, in this article we summarize proteinopathy-based drugs as AD therapeutics from a variety of biological sources. In this review, an attempt has been made to elucidate the molecular mode of action of various plant products, and synthetic drugs investigated in various preclinical and clinical tests in AD. It also discusses current attempts to formulate a comprehensive CDMT strategy to counter complex pathogenesis in AD. MATERIALS AND METHODS Information were collected from classical books on medicinal plants, pharmacopoeias and scientific databases like PubMed, Scopus, GoogleScholar, Web of Science and electronic searches were performed using Cochrane Library, Medline and EMBASE. Also published scientific literatures from Elsevier, Taylor and Francis, Springer, ACS, Wiley publishers and reports by government bodies and documentations were assessed. RESULTS 60 no. of natural and synthetic drugs have been studied with their significant bioactivities. A decision matrix designed for evaluation of drugs for considering to the hypothetic "CDMT" strategy in AD. We have introduced the scoring pattern of individual drugs and based on scoring pattern, drugs that fall within the scoring range of 18-25 are considered in the proposed CDMT. It also highlights the importance of available natural products and in future those drugs may be considered in CDMT along with the qualified synthetic drugs. CONCLUSION A successful validation of the CDMT strategy may open up a debate on health care reform to explore other possibilities of combination therapy. In doing so, it should focus on clinical and molecular relationships between AD and CDMT. A better understanding of these relationships could inform and impact future development of AD-directed treatment strategies. This strategy also involves in reducing costs in treatment phases which will be affordable to a common man suffering from AD.
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Physical Activity Interventions in Preventing Cognitive Decline and Alzheimer-Type Dementia: A Systematic Review.
Brasure, M, Desai, P, Davila, H, Nelson, VA, Calvert, C, Jutkowitz, E, Butler, M, Fink, HA, Ratner, E, Hemmy, LS, et al
Annals of internal medicine. 2018;(1):30-38
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Abstract
BACKGROUND The prevalence of cognitive impairment and dementia is expected to increase dramatically as the population ages, creating burdens on families and health care systems. PURPOSE To assess the effectiveness of physical activity interventions in slowing cognitive decline and delaying the onset of cognitive impairment and dementia in adults without diagnosed cognitive impairments. DATA SOURCES Several electronic databases from January 2009 to July 2017 and bibliographies of systematic reviews. STUDY SELECTION Trials published in English that lasted 6 months or longer, enrolled adults without clinically diagnosed cognitive impairments, and compared cognitive and dementia outcomes between physical activity interventions and inactive controls. DATA EXTRACTION Extraction by 1 reviewer and confirmed by a second; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence. DATA SYNTHESIS Of 32 eligible trials, 16 with low to moderate risk of bias compared a physical activity intervention with an inactive control. Most trials had 6-month follow-up; a few had 1- or 2-year follow-up. Evidence was insufficient to draw conclusions about the effectiveness of aerobic training, resistance training, or tai chi for improving cognition. Low-strength evidence showed that multicomponent physical activity interventions had no effect on cognitive function. Low-strength evidence showed that a multidomain intervention comprising physical activity, diet, and cognitive training improved several cognitive outcomes. Evidence regarding effects on dementia prevention was insufficient for all physical activity interventions. LIMITATION Heterogeneous interventions and cognitive test measures, small and underpowered studies, and inability to assess the clinical significance of cognitive test outcomes. CONCLUSION Evidence that short-term, single-component physical activity interventions promote cognitive function and prevent cognitive decline or dementia in older adults is largely insufficient. A multidomain intervention showed a delay in cognitive decline (low-strength evidence). PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.
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Comparison of multiple interventions for older adults with Alzheimer disease or mild cognitive impairment: A PRISMA-compliant network meta-analysis.
Liang, JH, Xu, Y, Lin, L, Jia, RX, Zhang, HB, Hang, L
Medicine. 2018;(20):e10744
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Abstract
BACKGROUND The increasing prevalence of Alzheimer disease (AD) emphasizes the need for effective treatments. Both pharmacological therapies such as nutrition therapy (NT) and nonpharmacologic therapies including traditional treatment or personalized treatment (e.g., physical exercise, music therapy, computerized cognitive training) have been approved for the treatment of AD or mild cognitive impairment (MCI) in numerous areas. METHODS The aim of this study was to compare 4 types of interventions, physical exercise (PE), music therapy (MT), computerized cognitive training (CCT), and NT, in older adults with mild to moderate AD or MCI and identify the most effective intervention for their cognitive function. We used a system of search strategies to identify relevant studies and include randomized controlled trials (RCTs), placebo-controlled trials evaluating the efficacy and safety of 4 interventions in patients with AD or MCI. We updated the relevant studies which were published before March 2017 as a full-text article. Using Bayesian network meta-analysis (NMA), we ranked cognitive ability based objectively on Mini-Mental State Examination (MMSE), and assessed neuropsychiatric symptoms based on Neuropsychiatric Inventory (NPI). Pairwise and network meta-analyses were sequentially performed for efficacy and safety of intervention compared to control group through RCTs included. RESULTS We included 17 RCTs. Fifteen trials (n = 1747) were pooled for cognition and no obvious heterogeneity was found (I = 21.7%, P = .212) in NMA, the mean difference (MD) of PE (MD = 2.1, confidence interval [CI]: 0.44-3.8) revealed that PE was significantly efficacious in the treatment group in terms of MMSE. Five trials (n = 660) assessed neuropsychiatric symptoms with an obvious heterogeneity (I = 61.6%, P = .034), the MD of CCT (MD = -7.7, CI: -14 to -2.4), revealing that CCT was significantly efficacious in NPI. CONCLUSIONS As the first NMA comparing different interventions for AD and MCI, our study suggests that PE and CCT might have a significant improvement in cognition and neuropsychiatric symptoms respectively. Moreover, nonpharmacological therapies might be better than pharmacological therapies.
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Effects and mechanisms of actions of phytochemicals on Alzheimer's disease neuropathology.
Hartman, RE, Ross, DM
Frontiers in bioscience (Elite edition). 2018;(2):300-333
Abstract
Alzheimer's disease affects millions of people, yet, there are only a limited number approaches for it pharmacological treatment. Thus, identifying factors that decrease the risk of developing Alzheimer's disease is of paramount importance. A growing body of epidemiological and experimental evidence suggests that dietary fruits and vegetables have neuroprotective effects against the harmful effects of oxidative stress, neuroinflammation, and aging. These effects are mediated by various phytochemical compounds found in plants that exhibit antioxidant, anti-inflammatory, and other beneficial properties. This review addresses epidemiological and experimental evidence for the effects and potential mechanisms of several commonly consumed phytochemicals on neuropathology and outcomes of Alzheimer's disease. Based on available evidence, we suggest that regular consumption of bioactive phytochemicals from a variety of fruits and vegetables attenuates age- and insult-related neuropathology in Alzheimer's disease.