Dementia: A problem for our age

Abbott, Alison

doi:10.1038/475s2a

Cited by 219 publications

(141 citation statements)

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“…Alzheimer's disease (AD), the most common dementia that accounts for an estimated of 60-80% of cases, is one of the leading causes of morbidity and death worldwide (1). Accumulating evidence has shown that excessive and dysregulated inflammation is implicated in the progression of AD, contributing to the cellular death and associated neurodegeneration (2,3).…”

Section: Introductionmentioning

confidence: 99%

Curcumin Inhibits the AKT/NF-κB Signaling via CpG Demethylation of the Promoter and Restoration of NEP in the N2a Cell Line

Deng

Wang

et al. 2014

AAPS J

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Abstract. Curcumin (CUR), a non-toxic polyphenol from Curcuma longa, has been investigated as a potential therapy with anti-inflammatory and anti-oxidative effects for Alzheimer's disease (AD), which depicts features of chronic inflammatory environment resulting in cellular death. However, it remains largely unknown whether the anti-inflammatory effect of CUR in AD is associated with its property of CpG demethylation, which is another function of CUR with the most research interest during recent years. Neprilysin (NEP, EP24.11), a zinc-dependent metallopeptidase expressed relatively low in the brain, is emerging as a potent inhibitor of AKT/Protein Kinase B. In addition, hypermethylated promoter of NEP has been reported to be associated with decreases in NEP expression. In the present study, using bisulfite-sequencing PCR (BSP) assay, we showed that the CpG sites in NEP gene were hypermethylated both in wild-type mouse neuroblastoma N2a cells (N2a/wt) and N2a cells stably expressing human Swedish mutant amyloid precursor protein (APP) (N2a/APPswe) associated with familial early onset AD. CUR treatment induced restoration of NEP gene via CpG demethylation. This CUR-mediated upregulation of NEP expression was also concomitant with the inhibition of AKT, subsequent suppression of nuclear transcription factor-κB (NF-κB) and its downstream pro-inflammatory targets including COX-2, iNOS in N2a/APPswe cells. This study represents the first evidence on a link between CpG demethylation effect on NEP and anti-inflammation ability of CUR that may provide a novel mechanistic insight into the anti-inflammatory actions of CUR as well as new basis for using CUR as a therapeutic intervention for AD.

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Section: Introductionmentioning

confidence: 99%

Curcumin Inhibits the AKT/NF-κB Signaling via CpG Demethylation of the Promoter and Restoration of NEP in the N2a Cell Line

Deng

Wang

et al. 2014

AAPS J

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“…Cognitive impairment continues to be common in the ageing US population 1 . Treating patients with cognitive impairment has been shown to be significantly more costly compared to equivalent care for those without deficits 2 .…”

Section: Introductionmentioning

confidence: 99%

Microembolization Is Associated With Transient Cognitive Decline in Patients Undergoing Carotid Interventions

Hitchner

Soman

Long

et al. 2016

Journal of Vascular Surgery

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OBJECTIVE-Carotid interventions are important in helping to reduce the risk of stroke for patients with high-grade carotid artery stenosis; however, incidence of subclinical cerebral microemboli can occur during these procedures. Previously, associations have been found between incidence of microemboli and postoperative decline in memory. We therefore sought to determine whether this decline persisted long-term and to assess changes in other cognitive domains. METHODS-Patientswere prospectively recruited under an IRB-approved protocol at a single academic center. Neuropsychological testing was administered preoperatively and at 1 month and 6 month intervals postoperatively. Cognitive domains that were evaluated included verbal memory, visual memory, psychomotor speed, dexterity, and executive function. Diffusion weighted MRI (DWI) sequencing was performed preoperatively and within 48 hours postoperatively to identify procedure-related microemboli. Univariate and multivariate regression models were used to identify relationships between microembolization, demographics, and cognition.RESULTS-80 patients were included; all were male and average age was 69 years. Forty patients underwent CAS and 40 CEA. 45% were diabetic, 50% had CAD, and 41% had prior neurologic symptoms. 45 (56%) of the patients had new postoperative microemboli. Microembolization was significantly more common in the CAS cohort (P<.005). Univariate analysis demonstrated that patients with procedure-related embolization showed decline 1 month postoperatively in verbal memory and Trail Making A measures. Multivariate analysis demonstrated that procedure-related embolization (OR: 2.8, P=.04) and pre-op symptomatic stenosis (OR: 3.2, P=.026) were independently predictors of decline for the RAVLT Short Delay measure at 1 month; however, at 6 months there was no significant relationship between emboli

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“…Furthermore, these studies excluded patients with any psychological problems such as dementia, limiting the generalizability of the findings from this systematic research review to a specific and potentially very small population. The prevalence of psychological problems such as dementia increase with old age (Abbott, 2011) therefore future research should consider including such patients in order to assess the effectiveness of pursuit eye movement interventions on a wider population which would consequently increase the generalizability of findings.…”

Section: Discussionmentioning

confidence: 99%

A Systematic Research Review Assessing the Effectiveness of Pursuit Interventions in Spatial Neglect Following Stroke

Hill

Coats

Halstead

et al. 2015

Transl. Stroke Res.

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BACKGOUND: Rehabilitation after stroke is imperative for patients with spatial neglect as it can help improve behavioural, social and cognitive outcomes in these patients, and therefore reduce the financial burden on public health services. The main aim of this review is to investigate the effectiveness of active pursuit eye movements for rehabilitation interventions in patients with spatial neglect following stroke. METHODS:Potential papers for inclusion were gathered by searching key terms in four main databases (AMED, Global Health, Pubmed/Medline and PsychInfo) in addition to screening relevant reference lists. Two reviewers independently selected papers for inclusion based on agreed inclusion criteria (n = 9 with 147 participants). Risk of bias was assessed using the QUADAS-2 tool. RESULTS:All papers reported a statistically significant result in patients who received an intervention which used pursuit eye movements, and this was reported both as a short term (immediate) effect and as a sustained effect up to eight weeks after treatment. These effects were also reported in comparison with interventions using saccadic eye movements. One study also reported increased neural activity in a number of brain regions following pursuit based intervention. CONCLUSIONS:Overall, there is good evidence in support of pursuit intervention used in the rehabilitation of stroke and spatial neglect over and above traditional interventions based on saccadic eye movements. Future research should aim to increase sample sizes, provide information on statistical power, record accurate eye movement responses, and use randomised designs to reduce selection bias.

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Dementia: A problem for our age

Cited by 219 publications

References 0 publications

Curcumin Inhibits the AKT/NF-κB Signaling via CpG Demethylation of the Promoter and Restoration of NEP in the N2a Cell Line

Curcumin Inhibits the AKT/NF-κB Signaling via CpG Demethylation of the Promoter and Restoration of NEP in the N2a Cell Line

Microembolization Is Associated With Transient Cognitive Decline in Patients Undergoing Carotid Interventions

A Systematic Research Review Assessing the Effectiveness of Pursuit Interventions in Spatial Neglect Following Stroke

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