Progressive Cognitive Impairment Research Articles

Fast-spiking parvalbumin-positive interneurons: new perspectives of treatment and future challenges in dementia.

Central nervous system parvalbumin-positive interneurons (PV-INs) are crucial and highly vulnerable to various stressors. They also play a significant role in the pathological processes of many neuropsychiatric diseases, especially those associated with cognitive impairment, such as Alzheimer's disease (AD), vascular dementia (VD), Lewy body dementia, and schizophrenia. Although accumulating evidence suggests that the loss of PV-INs is associated with memory impairment in dementia, the precise molecular mechanisms remain elusive. In this review, we delve into the current evidence regarding the physiological properties of PV-INs and summarize the latest insights into how their loss contributes to cognitive decline in dementia, particularly focusing on AD and VD. Additionally, we discuss the influence of PV-INs on brain development, the variations in their characteristics across different types of dementia, and how their loss affects the etiology and progression of cognitive impairments. Ultimately, our goal is to provide a comprehensive overview of PV-INs and to consider their potential as novel therapeutic targets in dementia treatment.

The cerebellar glucose metabolism in moyamoya vasculopathy and its correlation with neurocognitive performance after cerebral revascularization surgery: a [18F]FDG PET study.

The vascular cognitive impairment (VCI) is quite common in moyamoya vasculopathy (MMV). However, the abnormality of cerebellar glucose metabolism in MMV and its relationship with patients' neurocognitive performance were few reported. In this study, we aimed to investigate the relationship between neurocognitive performance and cerebellar glucose metabolism. Furthermore, the cerebellar glucose metabolism changes after combined revascularization surgery were also researched. We retrospectively analyzed the 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography ([18F]FDG PET) images and their neuropsychological scales in 93 eligible MMV patients by comparing their cerebellar standardized uptake values ratio (SUVR) and metabolic covariant network (MCN) among different neurocognitive groups. Then, forty-two MMV patients with VCI who underwent combined revascularization surgery were prospectively observed. According to their neuropsychological performance at 6-month follow-up, these patients were assigned to cognitive improved group (n = 22) and non-improved group (n = 20). The cerebellar SUVR and MCN changes were also analyzed. SUVR of right Lobule VI/Crus II/VIII decreased when cognitive impairment progression (P < 0.05, Least-Significant Difference [LSD] post hoc analysis). The cerebellar glucose metabolic pattern can be divided into two parts, in which the cerebellar posterior lobe was positively related to patients' neurocognitive performance, while the vermis and anterior lobe showed negative relationship with the neurocognitions (P < 0.001). Further MCN analysis expound that the degree of right Lobule VI/Crus II/VIII displayed decreased tendency as cognitive impairment worsened (P < 0.05, LSD post hoc analysis). After revascularization surgery, the SUVR of right cerebellar posterior lobe significantly promoted in improved group (P < 0.001). Besides, we also witnessed the SUVR improvement in left cerebral hemisphere, thalamus, and red nucleus (P < 0.001). The MCN analysis revealed that the posterior connective strength improvement among right Lobule VI and several cerebral regions significantly correlated with memory and executive screening (MES) score (P < 0.001, false discovery rate corrected). We found that the hypometabolism of cerebellar posterior lobe, especially in the right Lobule VI, was associated with MMV patients' neuropsychological performance, while the anterior lobe and vermis showed opposites tendencies. Combined revascularization surgery improved the posterior cerebellar metabolism and was associated with favorable neurocognitive outcomes, which might be related to the activation of cortico-rubral-cerebellar pathway.

Progression of cognitive impairment in hemodialysis patients

Objective: Cognitive impairment increases the risk of mortality in patients with chronic kidney disease. Progressive cognitive decline can be a serious issue for hemodialysis (HD) patients even if they are young with few comorbid conditions. The aim of this prospective study is to evaluate HD patients using Montreal Cognitive Assessment (MoCA) and search for the signs of cognitive decline using cognitive domain scores. Method: Twenty-nine chronic HD patients were selected. All patients were tested with MoCA at baseline and after the two-years follow-up. Patients with heart failure, dementia, depression, visual disturbance, malignancy, active infections and, those with single-pool Kt/V

Predicting conversion of Alzheimer’s disease based on multi-modal fusion of neuroimaging and genetic data

Identifying progressive mild cognitive impairment (pMCI) and stable mild cognitive impairment (sMCI) play a significant role in the early diagnosis of Alzheimer’s disease (AD) and can be helpful in early treatment to reduce the risk of conversion to AD. We proposed a classification method of sMCIs and pMCIs based on multi-modality data fusion of single-nucleotide polymorphisms (SNP), ratio of gray matter volume (RGV) obtained by morphometric measures, and sMRI images to predict the progression of AD. We validated the effectiveness of the proposed method by applying it to the task of identifying the disease status on the Alzheimer’s Disease Neuroimaging Initiative dataset. The results showed that the classification performances of our method was better than other state-of-the-art methods, and the accuracy rate for the classification of pMCI and sMCI reached 94.37%. The accuracy of our method was better than that of existing classification methods based on multi-modality images, and the accuracy rate for the classification of pMCI and sMCI reached 94.37%. Our study demonstrated that compared with unimodal and bimodal data, the method based on trimodal data fusion can better distinguish sMCI and pMCI, obtaining higher prediction accuracy for AD conversion. In addition, as a morphological feature, ratio of gray matter volume played a key role in distinguish of sMCI and pMCI, which can be used for the early diagnosis of AD.

Genetic Mutations in Cell Junction Proteins Associated with Brain Calcification

AbstractIntracerebral calcium deposition, classified into primary familial brain calcification (PFBC) and secondary brain calcification, occurs within the brain parenchyma and vasculature. PFBC manifests with progressive motor decline, dysarthria, and cognitive impairment, with limited treatment options available. Recent research has suggested a link between dysfunction of the blood–brain barrier (BBB) and PFBC, with certain genetic variants potentially affecting neurovascular unit (NVU) function, thereby contributing to BBB integrity disruption and brain calcification. Cell junctions play an indispensable role in maintaining the function of NVUs. The pathogenic mechanisms of PFBC‐causative genes, such as PDGFRB, PDGFB, MYORG, and JAM2, involve NVU disruption. Cell junctions, such as tight junctions, gap junctions, adherens junctions, desmosomes, hemidesmosomes, and focal adhesions, are vital for cell–cell and cell–extracellular matrix connections, maintaining barrier function, cell adhesion, and facilitating ion and metabolite exchange. Several recent studies have highlighted the role of mutations in genes encoding cell junction proteins in the onset and progression of brain calcification and its related phenotypes. This emerging body of research offers a unique perspective for investigating the underlying mechanisms driving brain calcification. In this review, we conducted an examination of the literature reporting on genetic variants in cell junction proteins associated with brain calcification to delineate potential molecular pathways and investigate genotype–phenotype correlations. This approach not only reinforces the rationale for molecular subtyping of brain calcification but also lays the groundwork for the discovery of novel causative genes involved in pathogenesis. © 2024 International Parkinson and Movement Disorder Society.

Diagnosing Alzheimer Disease

ABSTRACT OBJECTIVE This article reviews the current understanding of Alzheimer disease (AD), including the natural history, common risk factors, and expected progression of AD neuropathologic change so that neurologists can apply this knowledge to identify patients with symptoms, signs, and findings on common diagnostic tests consistent with AD. LATEST DEVELOPMENTS The advent of potential disease-modifying therapies emphasizes the need to develop and deploy a practical and efficient approach to diagnose patients with cognitive impairment due to AD. ESSENTIAL POINTS The accumulation and spread of cerebral amyloid plaques and tau tangles in patients with AD leads to synaptic dysfunction, neuronal loss, and the eventual emergence and progression of cognitive impairment. A pragmatic and organized approach is needed to recognize patients with symptomatic AD in clinical practice, stage the level of impairment, confirm the clinical diagnosis, and apply this information to advance therapeutic decision making.

Graph Convolutional Network for AD and MCI Diagnosis Utilizing Peripheral DNA Methylation: Réseau de neurones en graphes pour le diagnostic de la MA et du TCL à l'aide de la méthylation de l'ADN périphérique.

Blood DNA methylation (DNAm) alterations have been widely reported in the onset and progression of mild cognitive impairment (MCI) and Alzheimer's disease (AD); however, DNAm is underutilized as a diagnostic biomarker for these diseases. We aimed to evaluate the diagnostic performance of DNAm for MCI and AD, both individually and in combination with well-established AD biosignatures. A total of 1,891 blood samples from Alzheimer's Disease Neuroimaging Initiative (ADNI) studies were used to identify potential candidate DNAm biomarkers. Multimodal clinical data from 635 samples (normal control (NC), n = 193; MCI, n = 352; AD, n = 90) in the TADPOLE dataset were utilized to construct eight different classification models using a graph convolutional network, a machine learning framework. After feature selection, 17 DNAm sites were selected for subsequent analysis. Remarkable differences in DNAm levels were observed at the screened DNAm loci in all three cohorts. Adopting DNAm features into multimodal models significantly improved the classification performance for three dichotomous subtasks (NC vs. non-NC, MCI vs. non-MCI, and AD vs. non-AD), especially when combined with cerebrospinal fluid (CSF) features for NC (area under the curve (AUC): 0.8534) and MCI classification (AUC: 0.7675). A weak correlation between DNAm and both magnetic resonance imaging and CSF features in the NC and MCI cohorts suggests good complementarity between modalities (correlation coefficient ≤0.2). Our study offers new insights into peripheral DNAm in MCI and AD and suggests promising diagnostic performance of models integrating epigenomics, imaging, or CSF biomarkers.

Aberrant intra-network resting-state functional connectivity in chronic insomnia with or without cognitive impairment

Chronic insomnia (CI) is a common sleep disorder in middle-aged and elderly individuals. Long-term sleep deprivation can lead to physical, mental, and cognitive damage. Resting-state networks (RSNs) in the brain are closely linked to cognition and behavior. Therefore, we investigated changes in RSNs to explore behavioral and cognitive abnormalities in middle-aged and elderly CI patients. Resting state functional magnetic resonance imaging (rs-fMRI) and independent component analysis were used to study the intrinsic functional connectivity (FC) of the RSNs in 36 CI patients (20 CI with cognitive impairment (CI-I) patients and 16 CI without cognitive impairment (CI-N) patients) and 20 healthy controls (HC). Two-sample t-tests were used to compare RSNs differences between CI and HC groups and the RSNs differences between CI-I and CI-N groups. Partial correlation analysis was used to explore the relationship between the significant abnormal brain regions in RSN and clinical scales. Compared with HCs, CI patients showed significant differences in multiple RSNs, and FC values in two brain regions within RSNs were correlated with clinical scales. Furthermore, compared with CI-N group, CI-I group also showed significantly altered FC in multiple RSNs. Moreover, FC values in the right middle frontal gyrus within right frontal parietal network of CI-I patients were negatively correlated with the Mini-Mental State Examination scores. These results may explain hyperarousal, decreased attention and motor function impairments in CI patients. Furthermore, the aberrant alterations of RSNs in CI-I patients may play a crucial role in the onset and progression of cognitive impairment in CI patients.

Whole-genome sequencing to identify rare variants in East Asian patients with dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common form of age-related dementia, following Alzheimer’s disease (AD). DLB is associated with a worse prognosis than AD and is characterized by a more rapid progression of cognitive impairment and a poorer quality of life. In addition, the pathogenesis of DLB is less understood than that of AD, and only three genes—SNCA (α‐synuclein), APOE (apolipoprotein E), and GBA1 (glucosylceramidase beta 1)—have been convincingly demonstrated to be associated with DLB. In this study, we utilized whole-genome sequencing data from 1744 Japanese individuals, comprising 45 DLB patients and 1699 cognitively normal older adults, aiming to identify new genes associated with DLB. Our genome-wide association studies of genes with potentially deleterious mutations identified the CDH23 gene as being associated with DLB, reaching a Bonferroni-corrected significance (P = 7.43 × 10−4). The gene contained three ethnicity-specific heterozygous missense variants (rs181275139, rs563688802, and rs137937502). CDH23 has been linked to deafness syndromes, and DLB patients carrying these mutations displayed symptoms of subjective hearing loss, suggesting a potential association between DLB onset and auditory impairment. Additionally, we explored human leukocyte antigen (HLA) genotypes associated with DLB but found no significant associations. This result suggests that the pathology of DLB differs from that of Parkinson’s disease, which has been reported to have an association with HLA. Although a limitation of this study is the lack of replication of our findings, which require further validation in independent cohorts, our study enhances the understanding of the etiology of DLB in the Japanese population and provides new insights into the underlying mechanisms of its pathogenesis.

Brain function assessment of acupuncture for chronic insomnia disorder with mild cognitive dysfunction based on fNIRS: protocol for a randomized controlled trial.

Chronic Insomnia Disorder (CID) is highly prevalent among older adults and impairs cognitive function. Insomnia accelerates the progression of mild cognitive impairment (MCI) and increases the risk of developing dementia. Acupuncture has been demonstrated in improving sleep quality and cognitive function. This study aims to explore the functional brain characteristics of CID with MCI patients and to assess the effects of acupuncture therapy using functional near-infrared spectroscopy (fNIRS). This study is a single-center randomized controlled trial. Participants will be randomly assigned to the manual acupuncture group or the placebo acupuncture group for an 8-week intervention period. fNIRS data will be collected during resting test and working memory test at baseline and at end of the intervention. The primary outcome is the change of the Montreal Cognitive Assessment (MoCA) score, secondary outcomes include the change of Mini-Mental State Examination (MMSE), Insomnia Severity Index (ISI), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and Apathy Evaluation Scale-Informant (AES-I). The results of the study will provide insights into the effects of acupuncture on sleep quality and cognitive performance in CID with MCI patients. By utilizing fNIRS technology, we will elucidate the neural functional characteristic underlying the therapeutic benefits of acupuncture. https://ClinicalTrials.gov, identifier ChiCTR2300076182.

EFFICACY OF CANNABIDIOL (CBD) IN THE TREATMENT OF ALZHEIMER'S DISEASE: A CRITICAL REVIEW OF EVIDENCE AND CLINICAL IMPLICATIONS

Introduction: This study investigates the therapeutic potential of cannabidiol (CBD) in treating Alzheimer's disease (AD), which is characterized by progressive cognitive decline, memory impairment, and behavioral changes. As traditional treatment options are limited, the exploration of alternative therapies, including CBD, has gained prominence in recent years. Objective: The aim of this research is to evaluate the efficacy of CBD in modulating neuroinflammation and oxidative stress, as well as its potential impact on slowing the progression of Alzheimer's disease. Method: A literature review was conducted using ten articles published between 2019 and 2024. Databases such as the Virtual Health Library, LILACS Plus, and Medline were utilized, applying descriptors related to CBD and Alzheimer's disease. The articles were filtered based on specific inclusion criteria, focusing on studies published in Portuguese, Spanish, and English that are freely accessible online. Results: The reviewed literature indicates that CBD may inhibit the formation of beta-amyloid plaques, a hallmark of Alzheimer's pathology, suggesting its potential for both symptom relief and slowing disease progression. Additionally, the interaction between CBD and the endocannabinoid system (ECS) highlights its role in managing cognitive decline and memory issues associated with AD. Conclusion: While the findings are promising, there is a pressing need for more rigorous clinical studies to validate the efficacy and safety of CBD in Alzheimer's treatment. This research underscores the potential of cannabinoids as a therapeutic option in managing neurodegenerative diseases.

Research progress on treatments for Alzheimer's disease

Abstract. Alzheimers disease (AD) is an irreversible neurological degenerative disease characterized by progressive cognitive impairment, and its pathogenesis remains unclear. Its main pathological features include neurofibrillary tangles formed by hyperphosphorylated tau protein and amyloid beta (A) plaque deposition. As the disease progresses, the patients self-care ability will become worse and worse. In the later stages, the patient will have to rely on others for daily life, which places a great burden on the patient, family, and society. Currently, there are a limited number of AD treatment drugs and their efficacy is limited, and they cannot effectively improve the condition of AD. This article reviews different methods for treating AD and provides a reference for the treatment of AD. At present, the treatment of senile dementia is mainly divided into two categories. The current treatment methods include Lencamab, bee therapy related drugs, NSCs transplantation therapy, Panax notoginseng saponins, and hyperbaric oxygen therapy. It is necessary to explore new treatment methods and drugs to improve treatment effectiveness and widely apply dementia in the elderly.

Endothelial progenitor cell-derived conditioned medium mitigates chronic cerebral ischemic injury through macrophage migration inhibitory factor-activated AKT pathway

BackgroundChronic cerebral ischemia (CCI) is a significant health issue characterized by hypoperfusion due to damage or occlusion of the cerebral or carotid arteries. CCI may lead to progressive cognitive impairment that is considered as a prelude to neurodegenerative diseases, including dementia and Alzheimer's disease (AD). Endothelial progenitor cells (EPCs) have been implicated in vascular repair in ischemic cerebrovascular diseases, primarily by differentiating into endothelial cells (ECs) or through paracrine effects. However, the clinical transplantation of stem cell therapies remains limited. In this study, we investigated the effects of EPC-derived conditioned medium (EPC-CM) on the impaired vasculature and neurological function in a rodent model of CCI and the mechanism involved.MethodsEPC-CM was analyzed by cytokine array to identify key factors involved in angiogenesis and cellular senescence. The effects and mechanism of the candidate factors in the EPC-CM were validated in vitro using oxygen–glucose deprivation (OGD)-injured ECs and EPCs. The therapeutic effects of EPC-CM and the identified key factor were further examined in a rat model of CCI, which was induced by bilateral internal carotid artery ligation (BICAL). EPC-CM was administered via intracisternal injection one week post BICAL. The cerebral microvasculature and neurobehavior of the rats were examined three weeks after BICAL.ResultsMacrophage migration inhibitory factor (MIF) was identified as a key factor in the EPC-CM. Recombinant MIF protein promoted angiogenesis and prevented senescence in the injured EPCs and ECs. The effect was similar to that of the EPC-CM. These therapeutic effects were diminished when the EPC-CM was co-treated with MIF-specific antibody (Ab). Additionally, the vascular, motor, and cognitive improvements observed in the BICAL rats treated with EPC-CM were abolished by co-treated with MIF Ab. Furthermore, we found MIF promoted angiogenesis and anti-senescence via activating the AKT pathway. Inhibition of the AKT pathway diminished the protective effects of MIF in the in vitro study.ConclusionsWe demonstrated that EPC-CM protected the brain from chronic ischemic injury and promoted functional recovery through MIF-mediated AKT pathway. These findings suggest EPC-CM holds potential as a novel cell-free therapeutic approach for treating CCI through the actions of MIF.

Application and effectiveness of adaptive AI in elderly healthcare.

In addressing elderly healthcare issues, cognitive impairment can cause significant disruptions in daily life and may potentially develop into dementia. Thus, finding ways to delay the progression of cognitive impairment is a critical issue. This study aims to develop an adaptive artificial intelligence (AI) mechanism that creates enjoyable and beneficial content to help delay cognitive impairment in the elderly. Utilising virtual reality (VR) and a fishing game, the design enhances reaction time and attention through interactive fishing activities. The AI personalises content based on individual performance to improve cognitive function. Experimental results showed that adaptive AI increased participant satisfaction from 86.84 to 91.05 points and future willingness from 75.26 to 85.68 points. The number of fish caught rose from 98 to 120, with the average per participant increasing from 2.64 to 2.85. This is undoubtedly the trend of the future. VR allows the elderly to have a more impactful and memorable first experience, while AI dynamically adjusts the game's difficulty based on the elderly's performance, addressing the issue of reduced willingness to continue due to inappropriate game difficulty. The VR game developed in this study is designed to be relaxing and incorporates mechanisms to promote the elderly's health. It is not restricted by location or time and, more importantly, meets the health promotion needs of the elderly.

Amyloid Imaging Update: How the Amyloid Landscape Is Changing in Light of the Recent Food and Drug Administration Approval of Antiamyloid Therapeutics.

It has been some time since the Journal of Nuclear Medicine and Technology has published an article on best practices in amyloid imaging. In light of the recent Food and Drug Administration approval of new antiamyloid therapies (AATs) to decrease amyloid plaques in the brain and slow progression of mild cognitive impairment, and the potential increase in the number of amyloid PET scans being acquired to document amyloid plaques, the Journal of Nuclear Medicine and Technology felt it was a perfect time to publish a refresher on best practices. AATs are administered to help slow progression of mild cognitive impairment, allowing patients to live independently a little longer before having to give up their independence and move in with family or into an assisted living facility. Neurologists prescribing AATs must first document that the patient has amyloid plaques. To do this, amyloid PET can be performed, or a lumbar puncture can be used to look for amyloid plaques in the cerebrospinal fluid. Although the latter is more cost-effective and has no associated radiation exposure, it is highly invasive compared with amyloid PET. High-quality amyloid PET scans interpretated by a trained nuclear medicine physician are the first step and key to providing the dementia expert and patient with accurate information on amyloid status, allowing for the best decisions on patient management.

Anti-Ma-2 associated encephalitis presenting as slowly progressive dementia and cerebellar atrophy

Abstract Cognitive impairment can be a manifestation of a neurodegenerative disease or may have a reversible etiology. Among reversible causes, metabolic, nutritional and autoimmune conditions are commonly evaluated. We report 43-year-old lady who presented with history of personality changes first noted three years back. Subsequently, she developed slowness in speech and activities of her daily living, hypersomnolence, dream enactment, unexplained weight gain and memory impairment. Cognitive assessment revealed poor delayed recall, impaired copying, calculation deficits and bradyphrenia. Mild bradykinesia and rigidity of upper limbs were also noted. MRI brain showed minimal cerebral atrophy and gross cerebellar atrophy. Blood investigation revealed strongly positive anti Ma-2 antibodies. Whole body PET-CT was negative. Ma-2 encephalitis is characterised by diencephalic, brainstem and /or limbic involvement. Presence of Ma-2 antibodies has strong link with malignancies, commonest being the testicular cancer. Anti- neuronal antibodies in association with progressive cognitive impairment in the absence of encephalitis like picture is increasingly being recognized. Although autoimmune work up is generally advocated for rapidly progressive dementia, this case highlights the need to consider antineuronal antibody evaluation in a young individual with longer duration of symptoms.

Executive Functioning and Processing Speed as Predictors of Global Cognitive Decline in Alzheimer Disease.

There is a lack of cognitive tools to predict disease progression in mild cognitive impairment (MCI) and Alzheimer's disease (AD). We assessed patients with MCI, AD, and cognitively healthy controls (cHC) using NIH toolbox assessments for attention/concentration and executive functioning and overall cognitive decline by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog). Among 183 participants over a median follow-up of 540 days, both between- and within-subjects variance in NIH toolbox and ADAS-Cog assessments increased from cHC to MCI to AD patients. Among patients with AD, pattern comparison processing speed (PCPS) and dimensional change card sort tests (DCCS) declined at 3 and 6 months prior to global cognitive decline (p=0.008 & 0.0012). A 5-point decrease in either PCPS or DCCS increased risk of global cognitive decline (HR 1.32 (1.08-1.60) and 1.62 (1.16-2.26)). Testing for cognitive domains of attention/concentration and executive functioning may predict subsequent global cognitive, and functional decline.

Modern views on pathogenesis of cognitive impairment in patients with type 2 diabetes mellitus

Currently, the features of the pathogenesis of cognitive impairment in patients with diabetes mellitus are being actively studied. The study of the mutual influence of these pathologies is of particular relevant not only in connection with a decrease in cognitive functions in patients with diabetes mellitus, but also due to the fact that the management of diabetes mellitus requires a thorough approach to the implementation of doctor’s recommendations and self-control on the part of the patient himself. The degree of cognitive impairment has a direct impact on patient compliance and, consequently, on the management and control of the disease. A comprehensive strategy is necessary for the prevention and progression of cognitive impairments in patients with diabetes mellitus. This strategy should include minimizing modifiable risk factors, controlling comorbidities, maintaining a healthy lifestyle, following a diet, engaging in regular physical activity, and medication therapy. Also, one of the key aspects is the control of blood glucose levels. Regular monitoring and maintaining a stable level of sugar can significantly reduce the risk of developing cognitive impairments in diabetic patients. This review also analyzes the effects of oral hypoglycemic drugs, incretin-based therapy and insulin on the risk of developing cognitive impairments. This review examines important aspects of the role of pathogenetic links and clinical manifestations of type 2 diabetes mellitus in the development of cognitive impairment and the possibility of influencing their development and rate of progression. Understanding these relationships will help develop effective strategies for the prevention and treatment of cognitive impairments in patients with diabetes mellitus.

Review on Alzheimers Disease

Abstract: Loss of Abstract Thinking Someone with Alzheimer’s disease may lose the ability to draw conclusions and solve problems. It may become difficult to balance a checkbook, for example, because the patient has forgotten what to do with the numbers. About 29.8 million people worldwide had been diagnosed with Alzheimer’s disease (AD) in 2015, And the number is projected to triple by 2050. In 2018, AD was the fifth leading cause of death in Americans with 65 years of age or older, but the progress of AD drug research is very limited. It is Helpful to identify the key factors and research trends of AD for guiding further more effective Studies. Alzheimer’s disease is a degenerative disease of the brain, the most common cause of dementia in the geriatric population, and a major cause of death. Alzheimer’s disease is one of the fastest growing risk factors in middle age, which Increases the risk of Alzheimer’s disease in coronary weddings and higher levels of Homocysteine, which can lead to withdrawal due to lifestyle changes. Cigarettes prevent Alzheimer’s disease by recalling memories. Also, despite the fact that there is no Definitive cure for Alzheimer’s, the ability to increase acetylcholine levels and reduce Ameloid beta deposition and your medications such as Donepezil has proven to be very Effective when treating Alzheimer’s disease (AD) is a progressive neurodegenerative disease. It Is characterized by progressive cognitive deterioration together with Declining activities of daily living and behavioral changes. It is the Most common type of pre-senile and senile dementia. Alzheimer disease (AD) is a heterogeneous disease with a complex pathobiology. The presence Extracellular b-amyloid deposition as neuritic plaques and intracellular accumulation of hyperphos . Phorylated tau as neurofibrillary tangles remains the primary neuropathologic criteria for AD diagnosis. However, a number of recent fundamental discoveries highlight important pathological roles For other critical cellular and molecular processes. Despite this, no disease-modifying treatment Currently exists, and numerous phase 3 clinical trials have failed to demonstrate benefits. Here ,We review recent advances in our understanding of AD pathobiology and discuss current treatment Strategies, highlighting recent clinical trials and opportunities for developing future disease modifying therapies.

Mitochondrial Dysfunction in Parkinson's Disease: A Contribution to Cognitive Impairment?

Among the non-motor symptoms associated with Parkinson's disease (PD), cognitive impairment is one of the most common and disabling. It can occur either early or late during the disease, and it is heterogeneous in terms of its clinical manifestations, such as Subjective Cognitive Dysfunction (SCD), Mild Cognitive Impairment (MCI), and Parkinson's Disease Dementia (PDD). The aim of the present review is to delve deeper into the molecular mechanisms underlying cognitive decline in PD. This is extremely important to delineate the guidelines for the differential diagnosis and prognosis of the dysfunction, to identify the molecular and neuronal mechanisms involved, and to plan therapeutic strategies that can halt cognitive impairment progression. Specifically, the present review will discuss the pathogenetic mechanisms involved in the progression of cognitive impairment in PD, with attention to mitochondria and their contribution to synaptic dysfunction and neuronal deterioration in the brain regions responsible for non-motor manifestations of the disease.