-
Pharmaceuticals (Basel, Switzerland) Jun 2024The COVID-19 pandemic, caused by infection with the SARS-CoV-2 virus, is associated with cognitive impairment and Alzheimer's disease (AD) progression. Once it enters... (Review)
Review
The COVID-19 pandemic, caused by infection with the SARS-CoV-2 virus, is associated with cognitive impairment and Alzheimer's disease (AD) progression. Once it enters the brain, the SARS-CoV-2 virus stimulates accumulation of amyloids in the brain that are highly toxic to neural cells. These amyloids may trigger neurological symptoms in COVID-19. The meningeal lymphatic vessels (MLVs) play an important role in removal of toxins and mediate viral drainage from the brain. MLVs are considered a promising target to prevent COVID-19-exacerbated dementia. However, there are limited methods for augmentation of MLV function. This review highlights new discoveries in the field of COVID-19-mediated amyloid accumulation in the brain associated with the neurological symptoms and the development of promising strategies to stimulate clearance of amyloids from the brain through lymphatic and other pathways. These strategies are based on innovative methods of treating brain dysfunction induced by COVID-19 infection, including the use of photobiomodulation, plasmalogens, and medicinal herbs, which offer hope for addressing the challenges posed by the SARS-CoV-2 virus.
PubMed: 38931455
DOI: 10.3390/ph17060788 -
Molecules (Basel, Switzerland) Jun 2024The abnormal deposition of protein in the brain is the central factor in neurodegenerative disorders (NDs). These detrimental aggregates, stemming from the misfolding...
The abnormal deposition of protein in the brain is the central factor in neurodegenerative disorders (NDs). These detrimental aggregates, stemming from the misfolding and subsequent irregular aggregation of α-synuclein protein, are primarily accountable for conditions such as Parkinson's disease, Alzheimer's disease, and dementia. Two-photon-excited (TPE) probes are a promising tool for the early-stage diagnosis of these pathologies as they provide accurate spatial resolution, minimal intrusion, and the ability for prolonged observation. To identify compounds with the potential to function as diagnostic probes using two-photon techniques, we explore three distinct categories of compounds: Hydroxyl azobenzene (AZO-OH); Dicyano-vinyl bithiophene (DCVBT); and Tetra-amino phthalocyanine (PcZnNH). The molecules were structurally and optically characterized using a multi-technique approach via UV-vis absorption, Raman spectroscopy, three-dimensional fluorescence mapping (PLE), time-resolved photoluminescence (TRPL), and pump and probe measurements. Furthermore, quantum chemical and molecular docking calculations were performed to provide insights into the photophysical properties of the compounds as well as to assess their affinity with the α-synuclein protein. This innovative approach seeks to enhance the accuracy of in vivo probing, contributing to early Parkinson's disease (PD) detection and ultimately allowing for targeted intervention strategies.
Topics: alpha-Synuclein; Humans; Photons; Molecular Docking Simulation; Protein Aggregates; Azo Compounds; Fluorescent Dyes; Spectrum Analysis, Raman; Parkinson Disease; Thiophenes; Indoles; Molecular Structure
PubMed: 38930882
DOI: 10.3390/molecules29122817 -
Journal of Clinical Medicine Jun 2024SARS-CoV-2 continually mutates, with five identified variants. Many neurological manifestations were observed during the COVID-19 pandemic, with differences between...
SARS-CoV-2 continually mutates, with five identified variants. Many neurological manifestations were observed during the COVID-19 pandemic, with differences between virus variants. The aim of this study is to assess the frequency and characteristics of neurological manifestations during COVID-19 in hospitalized patients over three waves in Poland with comparison and analysis correlation with the course of infection. This retrospective single-center study included 600 consecutive adults with confirmed COVID-19, hospitalized during 3 waves (pre-Delta, Delta and Omicron) in Poland. Demographic and clinical information and neurological manifestations were collected and compared across three periods. The median age of the study group was 68, lower during the Delta wave. In the Omicron period, the disease severity at admission and inflammatory markers concentration were the lowest. Neurological manifestations were observed in 49%. The most common were altered mentation, headache, myalgia, mood disorder, ischemic stroke and encephalopathy. Smell and taste disturbances (STDs) were less frequent in the Omicron period. Neurological complications were predominant in the pre-Delta and Omicron periods. Ischemic stroke was observed more often in pre-Delta period. Altered mentation was related to higher severity at admission, worse lab test results, higher admission to ICU and mortality, while headache reduced mortality. Pre-existing dementia was related to higher mortality. Neurological manifestations of COVID-19 are frequent, with a lower rate of STDs in the Omicron period and more often cerebrovascular diseases in the pre-Delta period. Headache improves the course of COVID-19, while altered mentation, stroke and neurological comorbidities increase severity and mortality.
PubMed: 38930003
DOI: 10.3390/jcm13123477 -
Journal of Clinical Medicine Jun 2024Dementia remains an underdiagnosed syndrome, and there is a need to improve the early detection of cognitive decline. This narrative review examines the role of... (Review)
Review
Dementia remains an underdiagnosed syndrome, and there is a need to improve the early detection of cognitive decline. This narrative review examines the role of neuropsychological assessment in the characterization of cognitive changes associated with dementia syndrome at different states. The first section describes the early indicators of cognitive decline and the major barriers to their identification. Further, the optimal cognitive screening conditions and the most widely accepted tests are described. The second section analyzes the main differences in cognitive performance between Alzheimer's disease and other subtypes of dementia. Finally, the current challenges of neuropsychological assessment in aging/dementia and future approaches are discussed. Essentially, we find that current research is beginning to uncover early cognitive changes that precede dementia, while continuing to improve and refine the differential diagnosis of neurodegenerative disorders that cause dementia. However, neuropsychology faces several barriers, including the cultural diversity of the populations, a limited implementation in public health systems, and the adaptation to technological advances. Nowadays, neuropsychological assessment plays a fundamental role in characterizing cognitive decline in the different stages of dementia, but more efforts are needed to develop harmonized procedures that facilitate its use in different clinical contexts and research protocols.
PubMed: 38929971
DOI: 10.3390/jcm13123442 -
Journal of Clinical Medicine Jun 2024Carotid-femoral pulse wave velocity (cfPWV), acknowledged as a reliable proxy of arterial stiffness, is an independent predictor of cardiovascular (CV) events....
Carotid-femoral pulse wave velocity (cfPWV), acknowledged as a reliable proxy of arterial stiffness, is an independent predictor of cardiovascular (CV) events. Carotid-femoral PWV is considered the gold standard for the estimation of arterial stiffness. cfPWV is a demanding, time consuming and expensive method, and an estimated PWV (ePWV) has been suggested as an alternative method when cfPWV is not available. Our aim was to analyze the predictive role of ePWV for CV and all-cause mortality in the general population. In a stratified random sample of 1086 subjects from the general Croatian adult population (EH-UH study) (men 42.4%, average age 53 ± 16), subjects were followed for 17 years. ePWV was calculated using the following formula: ePWV = 9.587 - 0.402 × age + 4.560 × 10 × age2 - 2.621 × 10 × age2 × MBP + 3.176 × 10 × age × MBP - 1.832 × 10 × MBP. MBP= (DBP) + 0.4(SBP - DBP). At the end of the follow-up period, there were 228 deaths (CV, stroke, cancer, dementia and degenerative diseases, COLD, and others 43.4%, 10.5%, 28.5%, 5.2%, 3.1%, 9.3%, respectively). In the third ePWV tercile, we observed more deaths due to CV disease than to cancer (20.5% vs. 51.04%). In a Cox regression analysis, for each increase in ePWV of 1 m/s, there was a 14% increase risk for CV death. In the subgroup of subjects with higher CV risk, we found ePWV to be a significant predictor of CV deaths (ePWV (m/s) CI 1.108; < 0.029; HR 3.03, 95% CI 1.118-8.211). In subjects with high CV risk, ePWV was a significant and independent predictor of CV mortality.
PubMed: 38929906
DOI: 10.3390/jcm13123377 -
Journal of Personalized Medicine Jun 2024This study examines the impact of reminiscence therapy on cognitive and emotional well-being in institutionalized older patients with dementia. Conducted at the...
This study examines the impact of reminiscence therapy on cognitive and emotional well-being in institutionalized older patients with dementia. Conducted at the Long-Term Care Health Facility for the Elderly, the research involved 34 participants who underwent therapy sessions that included personalized discussions of past experiences. Using physiological markers such as electroencephalography alpha and beta waves, along with psychological measures such as the Hasegawa Dementia Scale-Revised, the study aimed to quantify the effects of the therapy. Although the results indicated positive correlations between alpha and beta waves, suggesting enhanced relaxation and cognitive engagement, improvements in Hasegawa Dementia Scale-Revised scores were not statistically significant, pointing to variability in therapeutic effectiveness among patients. Despite these mixed outcomes, the findings support the potential of reminiscence therapy as a non-pharmacological intervention to improve the quality of life of dementia patients, though they also underscore the necessity for further research to refine therapy protocols and enhance applicability.
PubMed: 38929850
DOI: 10.3390/jpm14060629 -
Journal of Personalized Medicine Jun 2024Chronic kidney disease (CKD) is strongly associated with dementia. However, its independent association with Alzheimer's or Parkinson's disease remains unclear. This...
Chronic kidney disease (CKD) is strongly associated with dementia. However, its independent association with Alzheimer's or Parkinson's disease remains unclear. This study investigated the prospective association of patients with CKD aged ≥55 years with an increased risk of Alzheimer's or Parkinson's disease. We conducted a retrospective cohort analysis using a national cohort sample of approximately one million patients. Primary outcome indicators measured included incidence of all-cause dementia, Alzheimer's disease, and Parkinson's disease events using person-years at risk. The hazard ratio was adjusted using the Cox proportional hazards model. We included 952 patients without CKD and 476 with CKD over 55 years using propensity score matching. The CKD group exhibited higher incidences of all-cause dementia, Parkinson's disease, and Alzheimer's disease than the non-CKD group. Furthermore, the CKD group had an elevated risk of all-cause dementia and a significantly increased risk of Parkinson's disease, especially among older women. Notably, the risk of Parkinson's disease was higher within the first 3 years of CKD diagnosis. These findings emphasize the link between CKD in mid- and late-life individuals and a higher incidence of all-cause dementia and Parkinson's disease rather than Alzheimer's disease.
PubMed: 38929818
DOI: 10.3390/jpm14060597 -
Life (Basel, Switzerland) Jun 2024Parkinson's disease (PD) caused by gene triplication (3X) leads to early onset, rapid progression, and often dementia. Understanding the impact of 3X and its absence is...
Parkinson's disease (PD) caused by gene triplication (3X) leads to early onset, rapid progression, and often dementia. Understanding the impact of 3X and its absence is crucial. This study investigates the differentiation of human induced pluripotent stem cell (hiPSC)-derived floor-plate progenitors into dopaminergic neurons. Three different genotypes were evaluated in this study: patient-derived hiPSCs with 3X, a gene-edited isogenic line with a frame-shift mutation on all alleles ( 4KO), and a normal wild-type control. Our aim was to assess how the substantia nigra pars compacta (SNpc) microenvironment, damaged by 6-hydroxydopamine (6-OHDA), influences tyrosine hydroxylase-positive (Th+) neuron differentiation in these genetic variations. This study confirms successful in vitro differentiation into neuronal lineage in all cell lines. However, the 4KO line showed unusual LIM homeobox transcription factor 1 alpha (Lmx1a) extranuclear distribution. Crucially, both 3X and 4KO lines had reduced Th+ neuron expression, despite initial successful neuronal differentiation after two months post-transplantation. This indicates that while the SNpc environment supports early neuronal survival, gene alterations-either amplification or knock-out-negatively impact Th+ dopaminergic neuron maturation. These findings highlight 's critical role in PD and underscore the value of hiPSC models in studying neurodegenerative diseases.
PubMed: 38929711
DOI: 10.3390/life14060728 -
Medicina (Kaunas, Lithuania) Jun 2024The focus on mild cognitive dysfunction in adults is of great interest, given the risk of worsening and conversion to dementia. Cognitive dysfunctions are characterized... (Randomized Controlled Trial)
Randomized Controlled Trial
The focus on mild cognitive dysfunction in adults is of great interest, given the risk of worsening and conversion to dementia. Cognitive dysfunctions are characterized by a decrease in the weight and volume of the brain, due to cortical atrophy, with a widening of the grooves and flattening of the convolutions. Brain atrophy that mainly involves the hippocampus is related to the progression of cognitive impairment and the conversion from mild cognitive dysfunction to dementia. Currently, there is no treatment for MCI. Results from a trial on Alzheimer's disease (ASCOMALVA trial) suggest that a sustained cholinergic challenge can slow the progression of brain atrophy typical of Alzheimer's disease associated with vascular damage. This study intends to evaluate the efficacy of choline alphoscerate in patients with mild cognitive impairment (MCI) and associated vascular damage, in stabilizing and/or slowing brain atrophy typical of adult-onset cognitive dysfunction, and in improving and/or slowing the progression of cognitive and behavioral symptoms associated with MCI. : This randomized controlled trial will recruit 60 patients that will be evaluated and randomized in a 1:1 ratio to receive choline alphoscerate (1200 mg/day) or placebo, for 12 months. Analyses will be carried out using SPSS vesion No 26 the Statistician in charge of this study, with the statistical significance level chosen as 0.05. : This trial may provide evidence about the efficacy of treatment with the cholinergic precursor choline alphoscerate in patients with mild cognitive dysfunction. The results of this study will be published in peer-reviewed journals. EudraCT number: 2020-000576-38.
Topics: Humans; Cognitive Dysfunction; Glycerylphosphorylcholine; Male; Female; Aged; Middle Aged; Cholinergic Agents; Randomized Controlled Trials as Topic
PubMed: 38929542
DOI: 10.3390/medicina60060925 -
Medicina (Kaunas, Lithuania) May 2024: Dementia is increasing worldwide. This study aimed to examine the impact of comorbidity burden and frailty on dementia prognosis in patients with dementia. : This...
: Dementia is increasing worldwide. This study aimed to examine the impact of comorbidity burden and frailty on dementia prognosis in patients with dementia. : This retrospective cohort study was conducted with 47 patients with dementia who were followed for up to two years. The Modified Charlson Comorbidity Index (MCCI), Mini-Mental State Examination (MMSE-E), and Edmonton Fragility Scale were used besides laboratory and clinical findings. : The mean age of the 47 patients was 78.77 ± 12.44 years. During the follow-up period, MMSE-E scores were observed to improve in 50% of the patients. Initial MMSE-E scores were found to be lowest in men and patients with coronary artery disease or depression, while final MMSE-E scores were observed to be lowest in patients with depression and low vitamin B12 or vitamin D levels. The rates of decrease in MMSE-E scores in non-, moderately and severely frail patients were 21.4%, 55.6%, and 70.6%, respectively. There was a moderate negative correlation between MMSE-E scores and both comorbidity burden and frailty scores. The mediation analysis revealed that frailty was a complete mediator, and that comorbidity burden led to an increase in frailty and a decrease in MMSE-E scores. During the follow-up period, patients with moderate frailty, hypertension, diabetes mellitus, alcohol and tobacco use, low B12 levels, or hypothyroidism showed an increased risk of decrease in cognitive functions. : There was a significant association between dementia prognosis and both frailty and biological deficits. We recommend the adoption of a syndemic approach in the follow-up of dementia, as we believe that the prevention of frailty and associated biological deficits will contribute to slowing dementia's clinical course.
Topics: Humans; Male; Female; Retrospective Studies; Aged; Dementia; Prognosis; Aged, 80 and over; Frailty; Cohort Studies; Comorbidity; Frail Elderly; Middle Aged
PubMed: 38929527
DOI: 10.3390/medicina60060910