Association of Platelet Activation with Vascular Cognitive Impairment: Implications in Dementia Development?

Stellos, Konstantinos; Katsiki, Niki; Tatsidou, P.; Bigalke, Boris; Laske, Christoph

doi:10.2174/157016111201140327164641

Cited by 28 publications

(15 citation statements)

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“…Several studies have confirmed that coronary artery disease is associated with cognitive impairment , reduced hippocampal volume and dementia . Recently, Graban and colleagues showed that coronary artery disease was more common in patients diagnosed with vascular dementia compared with controls .…”

Section: Coronary Artery Disease and Myocardial Infarctionmentioning

confidence: 95%

Heart failure and Alzheimer′s disease

et al. 2014

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It has recently been proposed that heart failure is a risk factor for Alzheimer′s disease. Decreased cerebral blood flow and neurohormonal activation due to heart failure may contribute to the dysfunction of the neurovascular unit and cause an energy crisis in neurons. This leads to the impaired clearance of amyloid beta and hyperphosphorylation of tau protein, resulting in the formation of amyloid beta plaques and neurofibrillary tangles. In this article, we will summarize the current understanding of the relationship between heart failure and Alzheimer′s disease based on epidemiological studies, brain imaging research, pathological findings and the use of animal models. The importance of atherosclerosis, myocardial infarction, atrial fibrillation, blood pressure and valve disease as well as the effect of relevant medications will be discussed.

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Section: Coronary Artery Disease and Myocardial Infarctionmentioning

confidence: 95%

Heart failure and Alzheimer′s disease

et al. 2014

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“…Atherosclerosis plays a major role in the development of both coronary artery disease and dementia. In the Cardiovascular Health Study cohort, the incidence of dementia was higher in those with prevalent coronary artery disease,28 and several studies have confirmed that coronary artery disease is associated with cognitive impairment,29–31 reduced hippocampal volume,32 dementia due to platelet hyperactivity,33 and increased senile plaque formation in cortical areas of the brain 34. A recent study by Graban and colleagues showed that coronary artery disease was observed more frequently in VaD patients 35.…”

Section: Heart Disease As a Risk Factor For Dementiamentioning

confidence: 95%

Heart disease as a risk factor for dementia

Ng¹,

Turek²,

Hakim³

2013

CLEP

117

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As life expectancy lengthens, dementia is becoming a significant human condition in terms of its prevalence and cost to society worldwide. It is important in that context to understand the preventable and treatable causes of dementia. This article exposes the link between dementia and heart disease in all its forms, including coronary artery disease, myocardial infarction, atrial fibrillation, valvular disease, and heart failure. This article also explores the cardiovascular risk factors and emphasizes that several of them are preventable and treatable. In addition to medical therapies, the lifestyle changes that may be useful in retarding the onset of dementia are also summarized.

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“…Approximatively, half of the patients diagnosed with dementia, have additional pathologies associated to the hallmarks of Aβ and tau, including vascular dementia, and dementia with Lewy bodies [ 12 , 13 ]. It is also increasingly recognized that AD and dementia are multifactorial diseases, with contributions to onset and progression including early synaptic failure [ 14 ], inflammation [ 15 ], oxidative stress [ 16 ], mitochondrial dysfunction [ 17 ], cerebrovascular impairment [ 18 , 19 ], depletion of neurotrophins [ 20 , 21 ], and excitotoxicity [ 22 ]. It is argued that effective treatment should target two or more factors in disease pathogenesis [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Re-engineering a neuroprotective, clinical drug as a procognitive agent with high in vivo potency and with GABAA potentiating activity for use in dementia

et al. 2015

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BackgroundSynaptic dysfunction is a key event in pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD) where synapse loss pathologically correlates with cognitive decline and dementia. Although evidence suggests that aberrant protein production and aggregation are the causative factors in familial subsets of such diseases, drugs singularly targeting these hallmark proteins, such as amyloid-β, have failed in late stage clinical trials. Therefore, to provide a successful disease-modifying compound and address synaptic dysfunction and memory loss in AD and mixed pathology dementia, we repurposed a clinically proven drug, CMZ, with neuroprotective and anti-inflammatory properties via addition of nitric oxide (NO) and cGMP signaling property.ResultsThe novel compound, NMZ, was shown to retain the GABAA potentiating actions of CMZ in vitro and sedative activity in vivo. Importantly, NMZ restored LTP in hippocampal slices from AD transgenic mice, whereas CMZ was without effect. NMZ reversed amnestic blockade of acetylcholine receptors by scopolamine as well as NMDA receptor blockade by a benzodiazepine and a NO synthase inhibitor in the step-through passive avoidance (STPA) test of learning and working memory. A PK/PD relationship was developed based on STPA analysis coupled with pharmacokinetic measures of drug levels in the brain: at 1 nM concentration in brain and plasma, NMZ was able to restore memory consolidation in mice.ConclusionOur findings show that NMZ embodies a promising pharmacological approach targeting synaptic dysfunction and opens new avenues for neuroprotective intervention strategies in mixed pathology AD, neurodegeneration, and dementia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-015-0208-9) contains supplementary material, which is available to authorized users.

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Association of Platelet Activation with Vascular Cognitive Impairment: Implications in Dementia Development?

Cited by 28 publications

References 0 publications

Heart failure and Alzheimer′s disease

Heart failure and Alzheimer′s disease

Heart disease as a risk factor for dementia

Re-engineering a neuroprotective, clinical drug as a procognitive agent with high in vivo potency and with GABAA potentiating activity for use in dementia

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