Disease-modifying treatment strategies for Alzheimer disease (AD) are still under extensive research. Nowadays, only symptomatic treatments exist for this disease, all trying to counterbalance the ...neurotransmitter disturbance: 3 cholinesterase inhibitors and memantine. To block the progression of the disease, therapeutic agents are supposed to interfere with the pathogenic steps responsible for the clinical symptoms, classically including the deposition of extracellular amyloid β plaques and intracellular neurofibrillary tangle formation. Other underlying mechanisms are targeted by neuroprotective, anti-inflammatory, growth factor promotive, metabolic efficacious agents and stem cell therapies. Recent therapies have integrated multiple new features such as novel biomarkers, new neuropsychological outcomes, enrollment of earlier populations in the course of the disease, and innovative trial designs. In the near future different specific agents for every patient might be used in a “precision medicine” context, where aberrant biomarkers accompanied with a particular pattern of neuropsychological and neuroimaging findings could determine a specific treatment regimen within a customized therapeutic framework. In this review, we discuss potential disease-modifying therapies that are currently being studied and potential individualized therapeutic frameworks that can be proved beneficial for patients with AD.
Current and future treatments for Alzheimer’s disease Yiannopoulou, Konstantina G.; Papageorgiou, Sokratis G.
Therapeutic Advances in Neurological Disorders,
01/2013, Letnik:
6, Številka:
1
Book Review, Journal Article
Recenzirano
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Alzheimer’s dementia (AD) is increasingly being recognized as one of the most important medical and social problems in older people in industrialized and non-industrialized nations. To date, only ...symptomatic treatments exist for this disease, all trying to counterbalance the neurotransmitter disturbance. Three cholinesterase inhibitors (CIs) are currently available and have been approved for the treatment of mild to moderate AD. A further therapeutic option available for moderate to severe AD is memantine, an N-methyl-D-aspartate receptor noncompetitive antagonist. Treatments capable of stopping or at least effectively modifying the course of AD, referred to as ‘disease-modifying’ drugs, are still under extensive research. To block the progression of the disease they have to interfere with the pathogenic steps responsible for the clinical symptoms, including the deposition of extracellular amyloid β plaques and intracellular neurofibrillary tangle formation, inflammation, oxidative damage, iron deregulation and cholesterol metabolism. In this review we discuss current symptomatic treatments and new potential disease-modifying therapies for AD that are currently being studied in phase I–III trials.
The novel coronavirus disease (COVID-19) was first detected in Mainland China in December 2019, and soon it spread throughout the world, with multiple physical and psychological consequences across ...the affected populations.
The aim of the current study was to analyze the impact of COVID-19 pandemic on older adults with mild cognitive impairment (MCI)/dementia and their caregivers as well.
Two hundred and four caregivers took part in the study, completing a self-reported questionnaire about the person with MCI/dementia and their own, since the lockdown period which started in February and ended in May of 2020 in Greece.
Results indicated a significant overall decline of the people with MCI/dementia. Further, the domains in which people with MCI/dementia were mostly affected were: communication, mood, movement and compliance with the new measures. Caregivers also reported a great increase in their psychological and physical burden during this period, where the available support sources were limited.
The pandemic threatens to disrupt the basic routines that promote mental and physical health of both people with MCI/dementia and t heir caregivers.
Further measures to protect and provide support to people who suffer and their families are needed.
Neurodegeneration in Alzheimer's disease (AD) is closely associated with the accumulation of pathologic tau aggregates in the form of neurofibrillary tangles. We found that a p.Asp395Gly mutation in
...(valosin-containing protein) was associated with dementia characterized neuropathologically by neuronal vacuoles and neurofibrillary tangles. Moreover, VCP appeared to exhibit tau disaggregase activity in vitro, which was impaired by the p.Asp395Gly mutation. Additionally, intracerebral microinjection of pathologic tau led to increased tau aggregates in mice in which p.Asp395Gly
mice was knocked in, as compared with injected wild-type mice. These findings suggest that p.Asp395Gly
is an autosomal-dominant genetic mutation associated with neurofibrillary degeneration in part owing to reduced tau disaggregation, raising the possibility that VCP may represent a therapeutic target for the treatment of AD.
Alzheimer’s disease (AD) is the most common neurodegenerative disorder with obscure pathogenesis and no disease-modifying therapy to date. AD is multifactorial disease that develops from the complex ...interplay of genetic factors and environmental exposures. The E4 allele of the gene encoding apolipoprotein E (APOE) is the most common genetic risk factor for AD, whereas the E2 allele acts in a protective manner. A growing amount of epidemiological evidence suggests that several lifestyle habits and environmental factors may interact with APOE alleles to synergistically affect the risk of AD development. Among them, physical exercise, dietary habits including fat intake and ketogenic diet, higher education, traumatic brain injury, cigarette smoking, coffee consumption, alcohol intake, and exposure to pesticides and sunlight have gained increasing attention. Although the current evidence is inconsistent, it seems that younger APOE4 carriers in preclinical stages may benefit mostly from preventive lifestyle interventions, whereas older APOE4 noncarriers with dementia may show the most pronounced effects. The large discrepancies between the epidemiological studies may be attributed to differences in the sample sizes, the demographic characteristics of the participants, including age and sex, the methodological design, and potential related exposures and comorbidities as possible cofounding factors. In this Review, we aim to discuss available evidence of the prominent APOE genotype–environment interactions in regard to cognitive decline with a focus on AD, providing an overview of the current landscape in this field and suggesting future directions.
: Parkinson's disease (PD) is a clinically heterogeneous disorder with poorly understood pathological contributing factors. Depression presents one of the most frequent non-motor PD manifestations, ...and several genetic polymorphisms have been suggested that could affect the depression risk in PD. Therefore, in this review we have collected recent studies addressing the role of genetic factors in the development of depression in PD, aiming to gain insights into its molecular pathobiology and enable the future development of targeted and effective treatment strategies.
: we have searched PubMed and Scopus databases for peer-reviewed research articles published in English (pre-clinical and clinical studies as well as relevant reviews and meta-analyses) investigating the genetic architecture and pathophysiology of PD depression.
: in particular, polymorphisms in genes related to the serotoninergic pathway (sodium-dependent serotonin transporter gene,
, tryptophan hydrolase-2 gene,
), dopamine metabolism and neurotransmission (dopamine receptor D3 gene,
, aldehyde dehydrogenase 2 gene,
, neurotrophic factors (brain-derived neurotrophic factor gene,
), endocannabinoid system (cannabinoid receptor gene, CNR1), circadian rhythm (thyrotroph embryonic factor gene,
), the sodium-dependent neutral amino acid transporter B(0)AT2 gene,
), and
genetic locus were detected as altering susceptibility to depression among PD patients. However, polymorphisms in the dopamine transporter gene (
), monoamine oxidase A (
) and B (
) genes, catechol-O-methyltransferase gene (
),
, and
have not been related to PD depression.
: the specific mechanisms underlying the potential role of genetic diversity in PD depression are still under investigation, however, there is evidence that they may involve neurotransmitter imbalance, mitochondrial impairment, oxidative stress, and neuroinflammation, as well as the dysregulation of neurotrophic factors and their downstream signaling pathways.
The clinical features and pathophysiology of neuropsychiatric symptoms (NPSs) in dementia have been extensively studied. However, the genetic architecture and underlying neurobiological mechanisms of ...NPSs at preclinical stages of cognitive decline and Alzheimer's disease (AD) remain largely unknown. Mild behavioral impairment (MBI) represents an at-risk state for incident cognitive impairment and is defined by the emergence of persistent NPSs among non-demented individuals in later life. These NPSs include affective dysregulation, decreased motivation, impulse dyscontrol, abnormal perception and thought content, and social inappropriateness. Accumulating evidence has recently begun to shed more light on the genetic background of MBI, focusing on its potential association with genetic factors related to AD. The Apolipoprotein E (APOE) genotype and the MS4A locus have been associated with affective dysregulation, ZCWPW1 with social inappropriateness and psychosis, BIN1 and EPHA1 with psychosis, and NME8 with apathy. The association between MBI and polygenic risk scores (PRSs) in terms of AD dementia has been also explored. Potential implicated mechanisms include neuroinflammation, synaptic dysfunction, epigenetic modifications, oxidative stress responses, proteosomal impairment, and abnormal immune responses. In this review, we summarize and critically discuss the available evidence on the genetic background of MBI with an emphasis on AD, aiming to gain insights into the potential underlying neurobiological mechanisms, which till now remain largely unexplored. In addition, we propose future areas of research in this emerging field, with the aim to better understand the molecular pathophysiology of MBI and its genetic links with cognitive decline.
Parkinson's disease (PD) is the second most common neurodegenerative disorder with an unclear etiology and no disease-modifying treatment to date. PD is considered a multifactorial disease, since ...both genetic and environmental factors contribute to its pathogenesis, although the molecular mechanisms linking these two key disease modifiers remain obscure. In this context, epigenetic mechanisms that alter gene expression without affecting the DNA sequence through DNA methylation, histone post-transcriptional modifications, and non-coding RNAs may represent the key mediators of the genetic-environmental interactions underlying PD pathogenesis. Environmental exposures may cause chemical alterations in several cellular functions, including gene expression. Emerging evidence has highlighted that smoking, coffee consumption, pesticide exposure, and heavy metals (manganese, arsenic, lead, etc.) may potentially affect the risk of PD development at least partially via epigenetic modifications. Herein, we discuss recent accumulating pre-clinical and clinical evidence of the impact of lifestyle and environmental factors on the epigenetic mechanisms underlying PD development, aiming to shed more light on the pathogenesis and stimulate future research.
The purpose of this study was to evaluate the macular and retinal nerve fiber layer (RNFL) thickness, and the electrical activity of the macula in patients with Alzheimer's disease (AD).
30 patients ...with AD and 30 age and sex matched healthy controls were studied. The thickness and the electrical activity of the macula were evaluated by means of optical coherence tomography (OCT) and multifocal-electroretinogram (mf-ERG).
Visual acuity, as well as visual fields and colour vision testing of all patients were normal. However, the mean foveal thickness was 148.50 μm (vs. 171.50 μm in the control group, p=0.001) and the RNFL thickness was 104.5 μm in the superior area (vs 123 μm in the control group, p < 0.0001) and 116.5 μm in the inferior area (vs. 138 μm in the control group, p < 0.0001) around the optic nerve. The mean P1 response density amplitude of the foveal area was 146.50 nV/deg2 (vs. 293 nV/deg2 in the control group, p < 0.0001) and the perifoveal area was 56.60 nV/deg2 (vs. 81.50 nv/deg2 in the control group, p < 0.001).
Our study showed that in patients with AD, even without visual failure there was a decrease in macular and RNFL thickness, as well as a decrease of the electrical activity of the macula.
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