Alzheimer's disease (AD) is a neurodegenerative disease whose various pathophysiological aspects are still being investigated. Recently, it has been hypothesized that AD may be associated with a ...dysbiosis of microbes in the intestine. In fact, the intestinal flora is able to influence the activity of the brain and cause its dysfunctions.Given the growing interest in this topic, the purpose of this review is to analyze the role of antibiotics in relation to the gut microbiota and AD. In the first part of the review, we briefly review the role of gut microbiota in the brain and the various theories supporting the hypothesis that dysbiosis can be associated with AD pathophysiology. In the second part, we analyze the possible role of antibiotics in these events. Antibiotics are normally used to remove or prevent bacterial colonization in the human body, without targeting specific types of bacteria. As a result, broad-spectrum antibiotics can greatly affect the composition of the gut microbiota, reduce its biodiversity, and delay colonization for a long period after administration. Thus, the action of antibiotics in AD could be wide and even opposite, depending on the type of antibiotic and on the specific role of the microbiome in AD pathogenesis.Alteration of the gut microbiota can induce changes in brain activity, which raise the possibility of therapeutic manipulation of the microbiome in AD and other neurological disorders. This field of research is currently undergoing great development, but therapeutic applications are still far away. Whether a therapeutic manipulation of gut microbiota in AD could be achieved using antibiotics is still not known. The future of antibiotics in AD depends on the research progresses in the role of gut bacteria. We must first understand how and when gut bacteria act to promote AD. Once the role of gut microbiota in AD is well established, one can think to induce modifications of the gut microbiota with the use of pre-, pro-, or antibiotics to produce therapeutic effects.
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MicroRNAs (miRNAs) are small non-coding nucleic acids able to post-transcriptionally regulate gene expression by binding to complementary sequences of target messenger RNA (mRNA). It has been ...estimated that at least 1% of the human genome encodes miRNA and every miRNA can regulate up to 200 mRNAs. These findings suggest that dysregulation of miRNA expression could be associated with several human pathological conditions including central neurological disorders. Alzheimer's disease (AD) is a neurodegenerative disorder and the most common cause of dementia in the elderly. The characteristic symptoms are a progressive loss of memory and other cognitive functions due to the impairment of particular types of neurons and synapses, leading to neuronal death. At present, the available symptomatic treatments can only slow down disease progression without stopping it. miRNAs are widely found within the nervous system where they are key regulators of functions such as neurite outgrowth, dendritic spine morphology, neuronal differentiation, and synaptic plasticity. This has been the clue for considering miRNAs crucial molecules to be studied in AD, and nowadays, dysfunction of miRNAs in AD is increasingly recognized. In this review, we summarized existing evidence about miRNAs as biomarkers or therapeutic agents. The field of miRNAs as biomarkers is more advanced in terms of human data, and it is likely that miRNAs will be used successfully in the near future. Given the huge number of miRNAs potentially involved in diagnostics, miRNA panels will be used for specific tasks such as the stage of the disease, the risk prediction, and disease progression. The field of miRNAs as therapeutics is rapidly developing, and it offers a huge variety of solutions. These include positive effects related to beta-amyloid or tau reduction, increased number of neurons, inhibition of apoptosis, protection of synapses, transformation of other cellular elements into missing/deficient neurons in AD, and so on. It is predictable that both areas of research will be carried forward. However, given the absence of an AD therapy able to stop or reverse the disease, it is desirable to accelerate research on miRNAs as therapeutic agents.
Effect of a Vegan Diet on Alzheimer's Disease Katonova, Alzbeta; Sheardova, Katerina; Amlerova, Jana ...
International journal of molecular sciences,
11/2022, Volume:
23, Issue:
23
Journal Article
Peer reviewed
Open access
There is evidence indicating that a vegan diet could be beneficial in the prevention of neurodegenerative disorders, including Alzheimer's disease (AD). The purpose of this review is to summarize the ...current knowledge on the positive and negative aspects of a vegan diet regarding the risk of AD. Regarding AD prevention, a vegan diet includes low levels of saturated fats and cholesterol, contributing to a healthy blood lipid profile. Furthermore, it is rich in phytonutrients, such as vitamins, antioxidants, and dietary fiber, that may help prevent cognitive decline. Moreover, a vegan diet contributes to the assumption of quercetin, a natural inhibitor of monoamine oxidase (MAO), which can contribute to maintaining mental health and reducing AD risk. Nonetheless, the data available do not allow an assessment of whether strict veganism is beneficial for AD prevention compared with vegetarianism or other diets. A vegan diet lacks specific vitamins and micronutrients and may result in nutritional deficiencies. Vegans not supplementing micronutrients are more prone to vitamin B12, vitamin D, and DHA deficiencies, which have been linked to AD. Thus, an evaluation of the net effect of a vegan diet on AD prevention and/or progression should be ascertained by taking into account all the positive and negative effects described here.
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Epilepsy as a chronic neurological disorder is characterized by recurrent, unprovoked epileptic seizures. In about half of the people who suffer from epilepsy, the root cause of the disorder is ...unknown. In the other cases, different factors can cause the onset of epilepsy. In recent years, the role of gut microbiota has been recognized in many neurological disorders, including epilepsy. These data are based on studies of the gut microbiota–brain axis, a relationship starting by a dysbiosis followed by an alteration of brain functions. Interestingly, epileptic patients may show signs of dysbiosis, therefore the normalization of the gut microbiota may lead to improvement of epilepsy and to greater efficacy of anticonvulsant drugs. In this descriptive review, we analyze the evidences for the role of gut microbiota in epilepsy and hypothesize a mechanism of action of these microorganisms in the pathogenesis and treatment of the disease. Human studies revealed an increased prevalence of Firmicutes in patients with refractory epilepsy. Exposure to various compounds can change microbiota composition, decreasing or exacerbating epileptic seizures. These include antibiotics, epileptic drugs, probiotics and ketogenic diet. Finally, we hypothesize that physical activity may play a role in epilepsy through the modulation of the gut microbiota.
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Increased survival, differentiation, and apoptotic death are common mechanisms relevant for both cancer and neurodegenerative diseases. Although these disorders are characterized by different ...manifestations, it appears that a common mechanism may be present which directs the fate of a cell to either degeneration or proliferation. There are two classes of proteins that have been extensively investigated in these diseases but their possible interaction during signal transduction has not been studied. Prolyl isomerase Pin1 is an enzyme which translates Ser/Thr-Pro phosphorylation into conformational changes able to modify the activities of its substrates. Its role in cancer development has been linked to its capacity to induce conformational changes to the tumor suppressor gene p53. Neurotrophins belong to a family of proteins that induce opposite effects on neuronal cells such as increased survival, development, and function. According to their function, alteration of these proteins during neurodegenerative processes has been investigated and reported in a number of experimental paradigms involving animal models and humans. However, in recent years, it has been shown that Pin1 downregulation is present in neurodegenerative disorders, while increased expression of neurotrophins and their receptors is found in certain types of cancer and correlate with poor prognosis. Notably, at the level of signal transduction, Pin1 and neurotrophin activity regulate the outcome of similar pathways such as proline-directed kinase and, most importantly, p53 signaling. Thus the possible existence of a loop between Pin1 and neurotrophins was investigated to understand the pathogenesis of these diseases.
Smart mobile phone use is increasing worldwide, as is the ability of mobile devices to monitor daily routines, behaviors, and even cognitive changes. There is a growing opportunity for users to share ...the data collected with their medical providers which may serve as an accessible cognitive impairment screening tool. Data logged or tracked in an app and analyzed with machine learning (ML) could identify subtle cognitive changes and lead to more timely diagnoses on an individual and population level. This review comments on existing evidence of mobile device applications designed to passively and/or actively collect data on cognition relevant for early detection and diagnosis of Alzheimer's disease (AD). The PubMed database was searched to identify existing literature on apps related to dementia and cognitive health data collection. The initial search deadline was December 1, 2022. Additional literature published in 2023 was accounted for with a follow-up search prior to publication. Criteria for inclusion was limited to articles in English which referenced data collection via mobile app from adults 50+ concerned, at risk of, or diagnosed with AD dementia. We identified relevant literature (
= 25) which fit our criteria. Many publications were excluded because they focused on apps which fail to collect data and simply provide users with cognitive health information. We found that although data collecting cognition-related apps have existed for years, the use of these apps as screening tools remains underdeveloped; however, it may serve as proof of concept and feasibility as there is much supporting evidence on their predictive utility. Concerns about the validity of mobile apps for cognitive screening and privacy issues remain prevalent. Mobile applications and use of ML is widely considered a financially and socially viable method of compiling symptomatic data but currently this large potential dataset, screening tool, and research resource is still largely untapped.
Vascular cognitive impairment (VCI) is the second most common cause of cognitive deficit after Alzheimer's disease. Since VCI patients represent an important target population for prevention, an ...ongoing effort has been made to elucidate the pathogenesis of this disorder. In this review, we summarize the information from animal models on the molecular changes that occur in the brain during a cerebral vascular insult and ultimately lead to cognitive deficits in VCI. Animal models cannot effectively represent the complex clinical picture of VCI in humans. Nonetheless, they allow some understanding of the important molecular mechanisms leading to cognitive deficits. VCI may be caused by various mechanisms and metabolic pathways. The pathological mechanisms, in terms of cognitive deficits, may span from oxidative stress to vascular clearance of toxic waste products (such as amyloid beta) and from neuroinflammation to impaired function of microglia, astrocytes, pericytes, and endothelial cells. Impaired production of elements of the immune response, such as cytokines, and vascular factors, such as insulin-like growth factor 1 (IGF-1), may also affect cognitive functions. No single event could be seen as being the unique cause of cognitive deficits in VCI. These events are interconnected, and may produce cascade effects resulting in cognitive impairment.
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Mild behavioral impairment (MBI) is a syndrome describing late-onset persistent neuropsychiatric symptoms (NPS) in non-demented older adults. Few studies to date have investigated the associations of ...MBI with structural brain changes. Our aim was to explore structural correlates of NPS in a non-demented memory clinic sample using the Mild Behavioral Impairment Checklist (MBI-C) that has been developed to measure MBI.
One hundred sixteen non-demented older adults from the Czech Brain Aging Study with subjective cognitive concerns were classified as subjective cognitive decline (
= 37) or mild cognitive impairment (
= 79). Participants underwent neurological and neuropsychological examinations and brain magnetic resonance imaging (MRI) (1.5 T). The Czech version of the MBI-C was administered to participants' informants. Five
selected brain regions were measured, namely, thicknesses of the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and entorhinal cortex (ERC) and volume of the hippocampus (HV), and correlated with MBI-C total and domain scores.
Entorhinal cortex was associated with MBI-C total score (
= -0.368,
< 0.001) and with impulse dyscontrol score (
= -0.284,
= 0.002). HV was associated with decreased motivation (
= -0.248,
= 0.008) and impulse dyscontrol score (
= -0.240,
= 0.011).
Neuropsychiatric symptoms, particularly in the MBI impulse dyscontrol and motivation domains, are associated with medial temporal lobe atrophy in a clinical cohort of non-demented older adults. This study supports earlier involvement of temporal rather than frontal regions in NPS manifestation. Since these regions are typically affected early in the course of Alzheimer's disease (AD), the MBI-C may potentially help further identify individuals at-risk of developing AD dementia.
Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among these individuals, deterioration in spatial navigation, ...manifested by poor hippocampus-dependent allocentric navigation, may occur well before the clinical onset of dementia. Our aim was to determine whether allocentric spatial navigation impairment would be proportional to right hippocampal volume loss irrespective of general brain atrophy. We also contrasted the respective spatial navigation scores of the real-space human Morris water maze with its corresponding 2D computer version. We included 42 cognitively impaired patients with either amnestic mild cognitive impairment (n = 23) or mild and moderate AD (n = 19), and 14 cognitively intact older controls. All participants underwent 1.5T MRI brain scanning with subsequent automatic measurement of the total brain and hippocampal (right and left) volumes. Allocentric spatial navigation was tested in the real-space version of the human Morris water maze and in its corresponding computer version. Participants used two navigational cues to locate an invisible goal independent of the start position. We found that smaller right hippocampal volume was associated with poorer navigation performance in both the real-space (β = –0.62, P < 0.001) and virtual (β = –0.43, P = 0.026) versions, controlling for demographic variables, total brain and left hippocampal volumes. In subsequent analyses, the results were significant in cognitively impaired (P ≤ 0.05) but not in cognitively healthy (P > 0.59) subjects. The respective real-space and virtual scores strongly correlated with each other. Our findings indicate that the right hippocampus plays a critical role in allocentric navigation, particularly when cognitive impairment is present.
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