Vitamin and mineral supplementation for preventing dementia or delaying cognitive decline in people with mild cognitive impairment

McCleery, Jenny; Abraham, Rajesh P; Denton, David A; Rutjes, Anne W S; Chong, Lee Yee; Al-Assaf, Aalya S; Griffith, Daniel J; Rafeeq, Shireen; Yaman, Hakan; Malik, Muzaffar; Nisio, Marcello Di; Martínez, Gabriel García; Vernooij, Robin W.M.; Tabet, Naji

doi:10.1002/14651858.cd011905.pub2

Cited by 105 publications

(93 citation statements)

References 173 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, a notable finding of the current work is that we were unable to detect evidence for an oAβ-induced microglial inflammatory response, in contrast to previous in vitro studies [24,47,51]. This does not appear to be due to deficiency in the BV2 cells themselves, as stimulation with bacterial lipopolysaccharide was still able to trigger a potent inflammatory response.…”

Section: Discussioncontrasting

confidence: 99%

“…Nevertheless, oAβ was clearly able to induce ROS production at levels capable of damaging bystander cells, which if replicated in vivo may be a driving factor in ongoing neuronal damage and secondary neuroinflammation seen in AD. Production of ROS is far from the sole damaging effect of oAβ in the brain, as is borne out by the, at best, equivocal results from clinical trials of antioxidants in AD [50,51]. Nevertheless, targeting a receptor with the potential to suppress ROS production, restore microglial metabolic homeostasis and promote resolution, as is the case for Fpr2/3, has significant potential for therapeutic development.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Reversal of β-amyloid induced microglial toxicityin vitroby activation of Fpr2/3

Wickstead

Karim

Manuel

et al. 2020

Preprint

View full text Add to dashboard Cite

19Background and Purpose 20 Microglial inflammatory activity is thought to be a major contributor to the pathology of 21 neurodegenerative conditions such as Alzheimer's disease (AD), and strategies to restrain 22 their behaviour are under active investigation. Classically, anti-inflammatory approaches aim 23 to suppress pro-inflammatory mediator production, but exploitation of inflammatory resolution, 24 the endogenous process whereby an inflammatory reaction is terminated, has not been fully 25 investigated as a therapeutic approach in AD. In this study, we sought to provide proof-of-26 principal that the major pro-resolving actor, formyl peptide receptor 2, Fpr2, could be targeted 27 to reverse microglial activation induced by the AD-associated pro-inflammatory stimulus, 28 oligomeric β-amyloid (oAβ). 30Experimental Approach 31The immortalised murine microglial cell line BV2 was employed as a model system to 32 investigate the pro-resolving effects of the Fpr2 ligand QC1 upon oAβ-induced inflammatory, 33 oxidative and metabolic behaviour. Cytotoxic behaviour of BV2 cells was assessed through 34 use of co-cultures with retinoic acid-differentiated human SH-SY5Y cells. 36 Key Results 37Stimulation of BV2 cells with oAβ at 100nM did not induce classical inflammatory marker 38 production but did stimulate production of reactive oxygen species (ROS), an effect that could 39 be reversed by subsequent treatment with the Fpr2 ligand QC1. Further investigation revealed 40 that oAβ-induced ROS production was associated with NADPH oxidase activation and a shift 41 in BV2 cell metabolic phenotype, activating the pentose phosphate pathway and NADPH 42 production, changes that were again reversed by QC1 treatment. Microglial oAβ-stimulated 43 ROS production was sufficient to induce apoptosis of bystander SH-SY5Y cells, an effect that 44 could be prevented by QC1 treatment. 46 Conclusion and Implications 47In this study, we provide proof-of-concept data that indicate exploitation of the pro-resolving 48 receptor Fpr2 can reverse damaging oAβ-induced microglial activation. Future strategies 49 aiming to restrain neuroinflammation in conditions such as AD should examine pro-resolving 50 actors as a mechanism to harness the brain's endogenous healing pathways and limit 51 neuroinflammatory damage. 52 53 Keywords: Fpr2/3, Microglia, Oxidative stress, Alzheimer's disease 54 Background 55 56 AD is the single greatest cause of dementia, affecting approximately 4% of individuals aged 57 over 65 years and with a global disease burden of around 37 million individuals [1]. This figure 58 is set to increase as the population ages, and is expected to reach around 78 million people 59 by 2050 [2]. There are currently no effective treatments for the condition.60 61 Whilst the two core pathological lesions of AD, extracellular β-amyloid (Aβ) plaques and 62 intraneuronal tau tangles, have long been studied, the contribution to pathology provided by 63 neuroinflammation, and the role of the microglia in AD pathogenesis, has only recently been...

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reversal of β-amyloid induced microglial toxicityin vitroby activation of Fpr2/3

Wickstead

Karim

Manuel

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…However, the effects of vitamins on cognitive function of non-demented elderly have been inconsistent even in meta-analyses on randomized or quasi-randomized, placebo-controlled trials [6][7][8][9][10][11][12][13][14]. These conflicting results may be attributable to several limitations of previous meta-analyses.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Vitamins on Cognitive Function of Non-Demented People: A Systematic Review and Meta-Analysis

et al. 2020

View full text Add to dashboard Cite

Previous evidence has suggested that vitamins might be beneficial for cognition. This systematic review aimed to investigate the efficacy of B vitamins, antioxidant vitamins, and vitamin D on the cognitive function of non-demented middle-aged or older people. Randomized or quasi-randomized controlled trials of individuals aged 40 years or older were included. PubMed/MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Library databases, and other grey literature sources were searched up to November 2019. Their methodological quality was evaluated using the Cochrane Risk of Bias tool. Twenty-three studies on B vitamins (n = 22–1053; comprising folate, B6, and B12), nine on antioxidant vitamins (n = 185–20,469), and six on vitamin D (n = 55–4122) were included. Taking B vitamins for over 3 months was beneficial for global cognition (standardized mean difference (SMD) −0.18, 95% CI −0.30 to −0.06) and episodic memory (SMD −0.09, 95% CI −0.15 to −0.04). However, antioxidant vitamins (SMD −0.02, 95% CI −0.08 to 0.03) and vitamin D (SMD −0.06, 95% CI −0.36 to 0.23) were not. Antioxidant vitamins were beneficial for global cognition in sensitivity analyses using final measurement data as mean difference estimates (SMD, −0.04, 95% CI −0.08 to −0.01). Taking B vitamins and possibly antioxidant vitamins may be beneficial for the cognitive function of non-demented people.

show abstract

“…The question that we tried to answer was whether the signals produced based on epidemiological parameters in the database have any relevance to the reported incremental success of >250 clinical trials addressing neurodegeneration in the period 01-2007 to 10-2017, extracted in PubMed (referred to as "training set", see Methods, File C in S1 Data). The relevance of the enquiry is driven by a known disconnect between the promising epidemiological data and incremental results in the clinical trials of individual agents [15][16]. Table 1 shows relationship between database-born metric Regression Score (REG) derived in the individual mechanisms and BAL/TOT = ((RCT+)-(RCT-))/TOT for clinical trials (Pearson correlation R = 0.35), where BAL is the balance of positive RCT+ and negative RCTtrial outcomes, TOT is the total number of trials for the mechanism of interest.…”

Section: Screening Of Individual Pharmacological Mechanisms For Corrementioning

confidence: 99%

“…Presented analysis attempts to avoid single theoretical assumption bias by data-driven exploration of an evidence of incremental success observed in multiple clinical trials. Since the effects of standalone agents are likely small, each of them is not likely to show any translational value when tested in controlled clinical trials individually [15,16]. On the other hand, when applied simultaneously, these agents may engage multiple molecular mechanisms, or differentially impact partially overlapping cohorts of susceptible patients, thus, providing larger overall effect in a general population of patients.…”

mentioning

confidence: 99%

Pharmacological signatures of the reduced incidence and the progression of cognitive decline in ageing populations suggest the protective role of beneficial polypharmacy

Mayburd

Koivogui²,

Baranova

2019

PLoS ONE

View full text Add to dashboard Cite

Preventive treatments for dementia are warranted. Here we show that utilization of certain combinations of prescription medications and supplements correlates with reduced rates of cognitive decline. More than 1,900 FDA-approved agents and supplements were collapsed into 53 mechanism-based groups and traced in electronic medical records (EMRs) for >50,000 patients. These mechanistic groups were aligned with the data presented in more than 300 clinical trials, then regression model was built to fit the signals from EMRs to clinical trial performance. While EMR signals of each single agents correlated with clinical performance relatively weakly, the signals produced by combinations of active compounds were highly correlated with the clinical trial performance (R = 0.93, p = 3.8 x10^-8). Higher ranking pharmacological modalities were traced in patient profiles as their combinations, producing protective complexity estimates reflecting degrees of exposure to beneficial polypharmacy. For each age strata, the higher was the protective complexity score, the lower was the prevalence of dementia, with maximized life-long effects for the highest regression score /diversity compositions. The connection was less strong in individuals already diagnosed with cognitive impairment. Confounder analysis confirmed an independent effect of protective complexity in multivariate context. A sub-cohort with lifelong odds of dementia decreased > 5-folds was identified; this sub-cohort should be studied in further details, including controlled clinical trials. In short, our study systematically explored combinatorial preventive treatment regimens for age-associated multi-morbidity, with an emphasis on neurodegeneration, and provided extensive evidence for their feasibility.Funding: AM is the Founder of Neurocombinatorix LLC, and MK is affiliated with the organization. Neurocombinatorix LLC does not conduct commercial activity and did not provide any funds for research. The authors volunteered to the effort without any salaries, no other parties have a role in the study design, data collection and analysis, Recent decreases in the rate of dementia and a shift to later ages of onset are encouraging [4]. However, in a first quartile of life expectancy, dementia still accounts for 1 in every 6 deaths, and is a major source of disability [1]. While multiple clinical trials for single dementia combating agents are ongoing [5], earlier stages of neurodegeneration process largely remain unexplored in humans.On the other hand, recent studies in model animals are encouraging. Particular successful efforts in visible rejuvenation of already differentiated tissues are reviewed in [6]). NAD+ supplementation has been associated with an extension of murine lifespan by 10-15% [7,8] through the mechanism likely related to overall brain function. The maintenance of microvasculature [9,10], the clearance of misfolded proteins [11], the neuroprotection [12,13], and the regulation of cholinesterase [13] were shown to be comparably important for the prevention...

show abstract

Vitamin and mineral supplementation for preventing dementia or delaying cognitive decline in people with mild cognitive impairment

Abstract: Vitamin and mineral supplementation for preventing dementia or delaying cognitive decline in people with mild cognitive impairment.

Cited by 105 publications

References 173 publications

Reversal of β-amyloid induced microglial toxicityin vitroby activation of Fpr2/3

Reversal of β-amyloid induced microglial toxicityin vitroby activation of Fpr2/3

Efficacy of Vitamins on Cognitive Function of Non-Demented People: A Systematic Review and Meta-Analysis

Pharmacological signatures of the reduced incidence and the progression of cognitive decline in ageing populations suggest the protective role of beneficial polypharmacy

Contact Info

Product

Resources

About