Type Of Dementia Research Articles

Association between ABO genotypes and risk of dementia and neuroimaging markers: roles of sex and APOE status.

Whether the relationships between ABO blood genotypes (AA, AO, BB, BO, AB, and OO) and dementia are modified by gender and APOE status has been unclear. We used data from the UK Biobank, a population-based cohort study of 487,425 individuals. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) between ABO genotypes and risk of dementia. Multivariable linear regression models were used to estimate the relationship between ABO genotypes and MRI-based brain indices. Overall, 487,425 participants were included at baseline. After 34 million person-years follow up, 7,548 patients developed all-cause dementia. Before stratifying by sex and APOE status, compared to OO genotype, BB genotype was associated with increased risk of all-cause dementia (1.36, 1.03-1.80) and other types dementia (1.65, 1.20-2.28). After stratifying by sex, only in males, BB genotype was associated with higher risk of all-cause dementia (1.44, 1.02-2.09) and other types of dementia (1.95, 1.30-2.93). AB genotype in males was also associated with increased AD (1.34, 1.04-1.72). After further stratifying by APOE e4 status, BB genotype with two APOE e4 alleles showed even stronger association with all-cause dementia 4.29 (1.57, 11.72) and other types dementia (5.49, 1.70-17.69) in males. Also in males, AA genotype with one APOE e4 was associated with increased risks of all-cause dementia (1.27, 1.04-1.55), AD (1.45, 1.09-1.94) and other types dementia (1.40, 1.08-1.81). Linear regression models showed that in both sexes with APOE e4, AA genotype was associated with reduced total grey matter volume. Sex and APOE e4 carrier status modified the association between ABO genotypes and risk of dementia. In males, BB genotype was consistently associated with increased risk of dementia, especially in those with two APOE e4 alleles. Also, in males with one APOE e4, AA genotype might be linked to higher risk of dementia.

Ginkgo biloba: A Leaf of Hope in the Fight against Alzheimer's Dementia: Clinical Trial Systematic Review.

Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords-GB in AD and dementia-yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show that Ginkgo biloba has promising potential for the treatment of these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

Association Between Hypnotics and Dementia: A Mini Narrative Review

Objective This narrative review aims to provide a comprehensive assessment of the existing literature on the relationship between hypnotics and dementia, considering both potential link and inconclusive or lack of association.Methods Data from studies that investigate the association between hypnotic medications and dementia were reviewed. Studies included both cohort studies and systematic reviews, participants with various type of dementia and hypnotics including benzodiazepines (BZDs) and Z-drugs (ZDs).Results The existing literatures presents conflicting evidence regarding the association between hypnotics, including BZDs and ZDs, and the risk of dementia. Some studies suggest a potential link between prolonged use of hypnotics and an increased risk of dementia. However, other studies indicate inconclusive or lacking evidence regarding this association. Factors such as study design, sample characteristics, and control of confounding variables contribute to the variability in findings.Conclusion The relationship between hypnotics and dementia remains complex and controversial. While some studies suggest a potential association, others find inconclusive or conflicting evidence. Future research should focus on addressing methodological limitations, considering classifying dementia subtypes, and try to adjust medication lag time.

#876 Albuminuria and the risk of dementia and different dementia subtypes: the Stockholm Creatinine Measurements (SCREAM) project

Abstract Background and Aims Studies investigating the association of chronic kidney disease and dementia predominantly focused on estimated glomerular filtration rate (eGFR) rather than albuminuria. The few studies focusing on albuminuria reported conflicting results, probably due to a lack of power, not taking into account the different dementia subtypes, not adjusting for eGFR, and the use of different albuminuria measurement techniques. This study therefore investigated the eGFR-independent risk of all-cause and type-specific dementia associated with albuminuria, quantified as urine albumin-creatinine ratio (ACR) and by dipstick, in a large population. Method We included subjects from the Stockholm Creatinine Measurements (SCREAM) project without a history of dementia and with age ≥65 years. The main analyses involved 138 688 subjects with at least one ACR test, and for sensitivity analyses, we involved 170 572 subjects with at least one dipstick proteinuria test. Albuminuria was quantified as KDIGO albuminuria A1-A3 stages. The primary outcome was incidence of all-cause dementia, and the key secondary outcomes were incidence of type-specific dementia. Dementia incidence was ascertained by record linkage with the national dementia registry (SveDem). ICD-10 coding was also used to classify subtypes only when there were no available dementia records in SveDem. Multivariable Cox regression models were used to calculate hazard ratios (HRs, 95% CIs) crude, and adjusted for confounders including baseline eGFR. Results During a median follow-up of 3.9 (IQR, 1.8-7.2) years, 9 970 subjects developed de novo dementia. After multivariable adjustment including baseline eGFR, subjects with an ACR of 30-299 mg/g or ≥300 mg/g had a 26% (HR, 1.26; 95% CI, 1.20-1.32) and 36% (HR, 1.36; 95% CI, 1.24-1.50) higher risk of developing all-cause dementia, respectively, when compared to subjects with an ACR <30 mg/g. Subjects with an ACR of 30-299 mg/g also presented a higher risk of developing several type-specific dementia, including Alzheimer's dementia (HR, 1.09, 95% CI, 1.01-1.17), vascular dementia (HR, 1.35, 95% CI, 1.22-1.48), and unspecified dementia (HR, 1.54, 95% CI, 1.41-1.69). No significant associations between albuminuria and the incidence of Lewy body dementia and Parkinson's Disease with dementia, frontotemporal dementia, as well as other types of dementia were observed. These results were generally robust in several sensitivity analyses, including replicating our main analyses in subjects with a dipstick proteinuria test instead of an ACR. Conclusion Increased albuminuria is associated with a higher risk of all-cause, Alzheimer's, and vascular dementia, independent of baseline eGFR and different albuminuria measurement techniques.

Cognitive trajectories preluding the onset of different dementia entities: a descriptive longitudinal study using the NACC database

ObjectiveTo describe the 10-year preclinical cognitive trajectories of older, non-demented individuals towards the onset of the four most prevalent types of dementia, i.e., Alzheimer’s disease(AD), Lewy body(LBD), vascular(VD) and frontotemporal dementia(FTD).MethodsOur analysis focused on data from older (≥ 60years) NACC (National Alzheimer’s Coordinating Center) participants. Four distinct presymptomatic dementia groups (AD-LBD-VD-FTD) and a comparison group of cognitively unimpaired(CU) participants were formed. Comprehensive cognitive assessments involving verbal episodic memory, semantic verbal fluency, confrontation naming, mental processing speed – attention and executive function – cognitive flexibility were conducted at baseline and on an approximately yearly basis. Descriptive analyses (adjusted general linear models) were performed to determine and compare the yearly cognitive scores of each group throughout the follow-up. Exploratory analyses were conducted to estimate the rates of cognitive decline.ResultsThere were 3343 participants who developed AD, 247 LBD, 108 FTD, 155 VD and 3398 composed the CU group. Participants with AD performed worse on episodic memory than those with VD and LBD for about 3 to 4 years prior to dementia onset (the FTD group documented an intermediate course). Presymptomatic verbal fluency and confrontation naming trajectories differentiated quite well between the FTD group and the remaining dementia entities. Participants with incident LBD and VD performed worse than those with AD on executive functions and mental processing speed-attention since about 5 years prior to the onset of dementia, and worse than those with FTD more proximally to the diagnosis of the disorder.ConclusionsHeterogeneous cognitive trajectories characterize the presymptomatic courses of the most prevalent dementia entities.

Peripheral vascular dysfunction and the aging brain.

Aging is the greatest non-modifiable risk factor for most diseases, including cardiovascular diseases (CVD), which remain the leading cause of mortality worldwide. Robust evidence indicates that CVD are a strong determinant for reduced brain health and all-cause dementia with advancing age. CVD are also closely linked with peripheral and cerebral vascular dysfunction, common contributors to the development and progression of all types of dementia, that are largely driven by excessive levels of oxidative stress (e.g., reactive oxygen species [ROS]). Emerging evidence suggests that several fundamental aging mechanisms (e.g., "hallmarks" of aging), including chronic low-grade inflammation, mitochondrial dysfunction, cellular senescence and deregulated nutrient sensing contribute to excessive ROS production and are common to both peripheral and cerebral vascular dysfunction. Therefore, targeting these mechanisms to reduce ROS-related oxidative stress and improve peripheral and/or cerebral vascular function may be a promising strategy to reduce dementia risk with aging. Investigating how certain lifestyle strategies (e.g., aerobic exercise and diet modulation) and/or select pharmacological agents (natural and synthetic) intersect with aging "hallmarks" to promote peripheral and/or cerebral vascular health represent a viable option for reducing dementia risk with aging. Therefore, the primary purpose of this review is to explore mechanistic links among peripheral vascular dysfunction, cerebral vascular dysfunction, and reduced brain health with aging. Such insight and assessments of non-invasive measures of peripheral and cerebral vascular health with aging might provide a new approach for assessing dementia risk in older adults.

Influence of Behavioral and Psychological Symptoms on Caregiver Burden for Different Types of Dementia: Clinical Experience in Lima, Peru

Introduction: People caring for patients with dementia are prone to suffering from burden. Behavioral and psychological symptoms of dementia (BPSD) may have an impact on caregiver burden. In Latin American countries, there is a lack of research on caregiver burden. We aimed to determine which BPSD have the greatest impact on caregiver burden among Peruvian patients with dementia and to compare the effects of BPSD on caregiver burden across different types of dementia. Methods: A cross-sectional study was conducted on 231 patients living with Alzheimer’s dementia (AD), behavioral variant frontotemporal dementia (bvFTD), dementia with Lewy bodies (DLB), and vascular dementia (VD) and their caregivers who attended a Peruvian memory clinic. BPSD were assessed with the Neuropsychiatric Inventory (NPI). Caregiver burden was assessed with the Zarit Burden Inventory. We used analysis of variance to compare the AD, bvFTD, DLB, and VD groups. Correlations between Zarit Burden Inventory and NPI subscale scores were assessed with Spearman’s correlation. Results: DLB caregivers had significantly higher levels of burden than the other patient groups (p < 0.05) and higher total NPI scores than caregivers for other patient groups (p < 0.05). bvFTD caregivers had significantly higher total NPI scores than AD and VD caregivers (p < 0.05). Hallucinations, aberrant motor behavior, and apathy were the symptoms most significantly correlated with caregiver burden in those caring for DLB, bvFTD, and AD patients, respectively. Conclusion: Neuropsychiatric symptoms are higher in DLB caregivers. Hallucinations, aberrant motor behavior, and apathy are the main symptoms correlated with burden.

The low and high doses administration of lutein improves memory and synaptic plasticity impairment through different mechanisms in a rat model of vascular dementia.

Vascular dementia (VD) is a common type of dementia. This study aimed to evaluate the effects of low and high doses of lutein administration in bilateral-carotid vessel occlusion (2VO) rats. The rats were divided into the following groups: the control, sham-, vehicle (2VO+V) groups, and two groups after 2VO were treated with lutein 0.5 (2VO+LUT-o.5) and 5mg/kg (2VO+LUT-5). The passive-avoidance and Morris water maze were performed to examine fear and spatial memory. The field-potential recording was used to investigate the properties of basal synaptic transmission (BST), paired-pulse ratio (PPR), as an index for measurement of neurotransmitter release, and long-term potentiation (LTP). The hippocampus was removed to evaluate hippocampal cells, volume, and MDA level. Treatment with low and high doses improves spatial memory and LTP impairment in VD rats, but only the high dose restores the fear memory, hippocampal cell loss, and volume and MDA level. Interestingly, low-dose, but not high-dose, increased PPR. However, BST recovered only in the high-dose treated group. Treatment with a low dose might affect neurotransmitter release probability, but a high dose affects postsynaptic processes. It seems likely that low and high doses improve memory and LTP through different mechanisms.

Peripheral GFAP and NfL as early biomarkers for dementia: longitudinal insights from the UK Biobank

BackgroundPeripheral glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are sensitive markers of neuroinflammation and neuronal damage. Previous studies with highly selected participants have shown that peripheral GFAP and NfL levels are elevated in the pre-clinical phase of Alzheimer’s disease (AD) and dementia. However, the predictive value of GFAP and NfL for dementia requires more evidence from population-based cohorts.MethodsThis was a prospective cohort study to evaluate UK Biobank participants enrolled from 2006 to 2010 using plasma GFAP and NfL measurements measured by Olink Target Platform and prospectively followed up for dementia diagnosis. Primary outcome was the risk of clinical diagnosed dementia. Secondary outcomes were cognition. Linear regression was used to assess the associations between peripheral GFAP and NfL with cognition. Cox proportional hazard models with cross-validations were used to estimate associations between elevated GFAP and NfL with risk of dementia. All models were adjusted for covariates.ResultsA subsample of 48,542 participants in the UK Biobank with peripheral GFAP and NfL measurements were evaluated. With an average follow-up of 13.18 ± 2.42 years, 1312 new all-cause dementia cases were identified. Peripheral GFAP and NfL increased up to 15 years before dementia diagnosis was made. After strictly adjusting for confounders, increment in NfL was found to be associated with decreased numeric memory and prolonged reaction time. A greater annualized rate of change in GFAP was significantly associated with faster global cognitive decline. Elevation of GFAP (hazard ratio (HR) ranges from 2.25 to 3.15) and NfL (HR ranges from 1.98 to 4.23) increased the risk for several types of dementia. GFAP and NfL significantly improved the predictive values for dementia using previous models (area under the curve (AUC) ranges from 0.80 to 0.89, C-index ranges from 0.86 to 0.91). The AD genetic risk score and number of APOE*E4 alleles strongly correlated with GFAP and NfL levels.ConclusionsThese results suggest that peripheral GFAP and NfL are potential biomarkers for the early diagnosis of dementia. In addition, anti-inflammatory therapies in the initial stages of dementia may have potential benefits.

Advances in Therapeutics to Alleviate Cognitive Decline and Neuropsychiatric Symptoms of Alzheimer's Disease.

Dementia exists as a 'progressive clinical syndrome of deteriorating mental function significant enough to interfere with activities of daily living', with the most prevalent type of dementia being Alzheimer's disease (AD), accounting for about 80% of diagnosed cases. AD is associated with an increased risk of comorbidity with other clinical conditions such as hypertension, diabetes, and neuropsychiatric symptoms (NPS) including, agitation, anxiety, and depression as well as increased mortality in late life. For example, up to 70% of patients diagnosed with AD are affected by anxiety. As aging is the major risk factor for AD, this represents a huge global burden in ageing populations. Over the last 10 years, significant efforts have been made to recognize the complexity of AD and understand the aetiology and pathophysiology of the disease as well as biomarkers for early detection. Yet, earlier treatment options, including acetylcholinesterase inhibitors and glutamate receptor regulators, have been limited as they work by targeting the symptoms, with only the more recent FDA-approved drugs being designed to target amyloid-β protein with the aim of slowing down the progression of the disease. However, these drugs may only help temporarily, cannot stop or reverse the disease, and do not act by reducing NPS associated with AD. The first-line treatment options for the management of NPS are selective serotonin reuptake inhibitors/selective noradrenaline reuptake inhibitors (SSRIs/SNRIs) targeting the monoaminergic system; however, they are not rational drug choices for the management of anxiety disorders since the GABAergic system has a prominent role in their development. Considering the overall treatment failures and side effects of currently available medication, there is an unmet clinical need for rationally designed therapies for anxiety disorders associated with AD. In this review, we summarize the current status of the therapy of AD and aim to highlight novel angles for future drug therapy in our ongoing efforts to alleviate the cognitive deficits and NPS associated with this devastating disease.

Meta-analysis on the interrelationship between sarcopenia and mild cognitive impairment, Alzheimer's disease and other forms of dementia.

Sarcopenia has been associated with adverse health outcomes, including cognitive dysfunction. However, its specific interrelationship with neurocognitive disorders such as mild cognitive impairment (MCI), Alzheimer's disease (AD) or other types of dementia has not been thoroughly explored. This meta-analysis aims to summarize the existing evidence on this interrelationship. This systematic review was pre-registered on PROSPERO (CRD42022366309) and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Databases, including PubMed, Embase, CINAHL, Scopus, Web of Science, PEDro, SPORTDiscus and the Cochrane Central Register of Controlled Trials, and the data registry ClinicalTrials.gov were searched from inception to 8 June 2023. Observational studies (cross-sectional and cohort) and interventional studies reporting on the association and prevalence of sarcopenia in MCI, AD or other types of dementia in adults ≥50years were included. For the meta-analysis, pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated for the association of sarcopenia with the neurocognitive disorders using random-effects/fixed-effects models. Subgroup analyses were performed to identify potential sources of heterogeneity. A total of 77 studies consisting of 92058 subjects were finally included in the qualitative analysis (71 cross-sectional, 4 cohort and 2 interventional studies). Studies were heterogeneous, using different diagnostic criteria to define both sarcopenia and cognitive status. The majority of studies (n=38) included Asian community-dwelling older adults. Most studies investigated the association of sarcopenia with AD (33/77) and MCI (32/77). For studies focusing on other forms of dementia, two studies included Lewy body dementia and one study included Parkinson's dementia, whereas the remaining studies did not specify dementia aetiology (n=21). Three cohort studies explored the association between sarcopenia and incident MCI, whereas only one cohort study explored the association between dementia and incident sarcopenia. Two interventional studies investigated whether an exercise programme could prevent the progression of sarcopenia in older adults with dementia or AD. The information for the meta-analysis was extracted from 26 studies. Sarcopenia was significantly associated with MCI (pooled OR=1.58, 95% CI 1.42-1.76) (n=14), AD (pooled OR=2.97, 95% CI 2.15-4.08) (n=3) and non-AD dementia (pooled OR=1.68, 95% CI 1.09-2.58) (n=9). The significance and magnitude of the associations differed in subgroup analyses by study design, population, definition of sarcopenia or used tool to measure cognitive status. This meta-analysis showed that sarcopenia is significantly associated with MCI, AD and other types of dementia. These findings suggest the importance of early screening and prevention of sarcopenia in older people with cognitive dysfunction, although further longitudinal research is needed to clarify the causal relationship.

Risk of Dementia in Korean Vietnam War Veterans

BackgroundThe number of cases of all types of dementia is increasing, and a significant increase in prevalence has been noted among veterans. Evidence of an association between dementia and exposure to chemicals such as Agent Orange from the Vietnam War is still limited, and there is a reported lack of awareness.ObjectiveThis study aimed to investigate the risk of dementia among Vietnam War veterans in Korea.DesignThis retrospective longitudinal study compared the incidence of dementia between Vietnam War veterans and the general population.SettingThis study used data from the nationally representative Korean Vietnam War Veterans’ Health Study Cohort, a combined dataset sourced from the Ministry of Patriots and Veterans Affairs in Korea and the National Health Insurance Sharing Service database.ParticipantsThere were 191,272 Vietnam War veterans and 1,000,320 people of different ages, sexes, and residences. matched control in 2002. The total number of person-years were 18,543,181.MeasurementsThe dementia group included participants who had visited a medical facility with any of the following ICD-10 codes in the follow-up periods: “F00 Dementia in Alzheimer’s disease,” “F01 Vascular dementia,” “F02 Dementia in other diseases classified elsewhere,” or “F03 Unspecified dementia.”ResultsThe incidence rate ratio for all types of dementia was 1.16, with higher ratios observed for vascular and unspecified dementia, particularly in the younger age groups. There was a significant increase in the risk of dementia, Alzheimer’s disease, vascular dementia, and unspecified dementia.ConclusionVietnam War veterans showed an increased risk for all types of dementia. These findings are hypothesized to be due to the effects of the chemicals used during the Vietnam War, which can cause a variety of neurodegenerative diseases. Further studies are warranted to investigate the potential health determinants related to the Vietnam War, focusing on the neurodegenerative effects.

Characteristics of T Cells in Single-Cell Datasets of Peripheral Blood and Cerebrospinal Fluid in Alzheimer's Disease Patients.

Alzheimer's disease (AD) is the most common type of dementia, causing a huge socioeconomic burden. In parallel with the widespread uptake of single-cell RNA sequencing (scRNA-seq) technology, there has been a rapid accumulation of data produced by researching AD at single-cell resolution, which is more conductive to explore the neuroimmune-related mechanism of AD. To explore the potential features of T cells in the peripheral blood and cerebrospinal fluid of AD patients. Two datasets, GSE181279 and GSE134578, were integrated from GEO database. Seurat, Monocle, CellChat, scRepertoire, and singleR packages were mainly employed for data analysis. Our analysis demonstrated that in peripheral blood, T cells were significantly expanded, and these expanded T cells were possessed effector function, such as CD8+TEMRA, CD4+TEMRA, and CD8+TEM. Interestingly, CD8+TEMRA and CD4+TEMRA cells positioned adjacently after dimensions reduction and clustering. Notably, we identified that the expanded T cells were developed from Naïve T cells and TCM cells, and TEM cells was in the intermediate state of this developing process. Additionally, in cerebrospinal fluid of AD patients, the amplified T cells were mainly CD8+TEMRA cells, and the number and strength of communication between CD4+TEM, CD8+TEM, and CD8+TEMRA were decreased in AD patients. Our comprehensive analyses identified the cells in cerebrospinal fluid from AD patients are expanded TEMRA or TEM cells and the TEMRA cells communicating with other immune cells is weakened, which may be an important immune feature that leads to AD.

Quantitative Metabolomic Analysis of the Rat Hippocampus: Effects of Age and of the Development of Alzheimer's Disease-Like Pathology.

Alzheimer's disease (AD) is the most common type of dementia in the elderly. Incomplete knowledge about the pathogenesis of this disease determines the absence of medications for the treatment of AD today. Animal models can provide the necessary knowledge to understand the mechanisms of biochemical processes occurring in the body in health and disease. To identify the most promising metabolomic predictors and biomarkers reflecting metabolic disorders in the development of AD signs. High resolution 1H NMR spectroscopy was used for quantitative metabolomic profiling of the hippocampus of OXYS rats, an animal model of sporadic AD, which demonstrates key characteristics of this disease. Animals were examined during several key periods: 20 days group corresponds to the "preclinical" period preceding the development of AD signs, during their manifestation (3 months), and active progression (18 months). Wistar rats of the same age were used as control. Ranges of variation and mean concentrations were established for 59 brain metabolites. The main metabolic patterns during aging, which are involved in energy metabolism pathways and metabolic shifts of neurotransmitters, have been established. Of particular note is the significant increase of scyllo-inositol and decrease of hypotaurine in the hippocampus of OXYS rats as compared to Wistars for all studied age groups. We suggest that the accumulation of scyllo-inositol and the reduction of hypotaurine in the brain, even at an early age, can be considered as predictors and potential biomarkers of the development of AD signs in OXYS rats and, probably, in humans.

Mitochondria-Related Candidate Genes and Diagnostic Model to Predict Late-Onset Alzheimer's Disease and Mild Cognitive Impairment.

Late-onset Alzheimer's disease (LOAD) is the most common type of dementia, but its pathogenesis remains unclear, and there is a lack of simple and convenient early diagnostic markers to predict the occurrence. Our study aimed to identify diagnostic candidate genes to predict LOAD by machine learning methods. Three publicly available datasets from the Gene Expression Omnibus (GEO) database containing peripheral blood gene expression data for LOAD, mild cognitive impairment (MCI), and controls (CN) were downloaded. Differential expression analysis, the least absolute shrinkage and selection operator (LASSO), and support vector machine recursive feature elimination (SVM-RFE) were used to identify LOAD diagnostic candidate genes. These candidate genes were then validated in the validation group and clinical samples, and a LOAD prediction model was established. LASSO and SVM-RFE analyses identified 3 mitochondria-related genes (MRGs) as candidate genes, including NDUFA1, NDUFS5, and NDUFB3. In the verification of 3 MRGs, the AUC values showed that NDUFA1, NDUFS5 had better predictability. We also verified the candidate MRGs in MCI groups, the AUC values showed good performance. We then used NDUFA1, NDUFS5 and age to build a LOAD diagnostic model and AUC was 0.723. Results of qRT-PCR experiments with clinical blood samples showed that the three candidate genes were expressed significantly lower in the LOAD and MCI groups when compared to CN. Two mitochondrial-related candidate genes, NDUFA1 and NDUFS5, were identified as diagnostic markers for LOAD and MCI. Combining these two candidate genes with age, a LOAD diagnostic prediction model was successfully constructed.

Alzheimer's Disease: A Journey Through Causes, Symptoms, and Current Challenges

Alzheimer's Sickness (Promotion), an ever-evolving neurodegenerative confusion, remains as the most common type of dementia. It tirelessly disintegrates mental capability, taking recollections and disturbing the capacity to perform regular undertakings. Notwithstanding critical exploration endeavors, the specific reason for Promotion stays a conundrum. This article digs into the trademark side effects that arise as the infection grabs hold, divulging the significant weight it puts on people and medical services frameworks the same. While current treatment choices give some indicative help, they miss the mark concerning offering a fix or even successfully ending the tenacious movement of Promotion. Nonetheless, ongoing headways in understanding the sickness' pathophysiology have touched off an encouraging sign. Analysts are currently taking apart the complex instruments fundamental Promotion, making ready for the advancement of additional designated helpful techniques. This recently discovered information highlights the basic requirement for proceeded with research tries to battle this crippling condition. By unwinding the secrets encompassing Promotion, we can make progress toward a future where viable medicines oversee side effects as well as forestall or try and opposite the course of this staggering infection. Keywords: Neurodegenerative disorder, Dementia, Cognitive function, Symptomatic relief, Pathophysiology, Therapeutic strategies

Association between adding salt in food and dementia in European descent: A mendelian randomization study.

High salt intake has been proposed as a risk factor for dementia. However, causal relationship between salt intake and dementia remains uncertain. The aim of this study was to employ a mendelian randomization (MR) design to investigate the causal impact of salt intake on the risk of dementia. Genome-wide association study (GWAS) data of exposures and outcomes (any dementia, cognitive performance, different types of dementia, Alzheimer's disease [AD], and Parkinson's disease) were obtained from the IEU database. MR estimates were generated though inverse-variance weighted model. MR-Egger, weighted median, and MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) method also used in our study. Sensitivity analyses included Cochran's Q test, MR-Egger intercept, MR-PRESSO global test and outlier test, leave-one-out analysis, and funnel plot assessment. Our MR analysis provided evidence of a causal association between high salt added to food and dementia (odds ratio [OR]=1.73, 95% confidence interval [CI]: 1.21-2.49, and p=.003), dementia in AD (OR=2.10, 95% CI: 1.15-3.83, and p=.015), and undefined dementia (OR=2.61, 95% CI: 1.26-5.39, and p=.009). Higher salt added was also associated with increased risk of AD (OR=1.80, 95% CI: 1.12-2.87, and p=.014) and lower cognitive performance (β=-.133, 95% CI: -.229 to -.038, and p=.006). This study provides evidence suggesting that high salt intake is causally associated with an increased risk of developing dementia, including AD and undefined dementia, highlighting the potential importance of reducing salt consumption as a preventive measure.

Trends of use and characterisation of anti-dementia drugs users: a large multinational-network population-based study.

An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data. Primary care data (country/database) from the UK/CPRD-GOLD (2007-20), Spain/SIDIAP (2010-20) and the Netherlands/IPCI (2008-20), standardised to a common data model. Cohort study. Participants: dementia patients ≥40years old with ≥1year of previous data. Follow-up: until the end of the study period, transfer out of the catchment area, death or incident prescription of rivastigmine, galantamine, donepezil or memantine. Other variables: age/sex, type of dementia, comorbidities. Statistics: overall and yearly age/sex IR, with 95% confidence interval, per 100,000 person-years (IR per 105 PY (95%CI)). We identified a total of (incident anti-dementia users/dementia patients) 41,024/110,642 in UK/CPRD-GOLD, 51,667/134,927 in Spain/SIDIAP and 2,088/17,559 in the Netherlands/IPCI.In the UK, IR (per 105 PY (95%CI)) of ADD decreased from 2007 (30,829 (28,891-32,862)) to 2010 (17,793 (17,083-18,524)), then increased up to 2019 (31,601 (30,483 to 32,749)) and decrease in 2020 (24,067 (23,021-25,148)). In Spain, IR (per 105 PY (95%CI)) of ADD decreased by 72% from 2010 (51,003 (49,199-52,855)) to 2020 (14,571 (14,109-15,043)). In the Netherlands, IR (per 105 PY (95%CI)) of ADD decreased by 77% from 2009 (21,151 (14,967-29,031)) to 2020 (4763 (4176-5409)). Subjects aged ≥65-79years and men (in the UK and the Netherlands) initiated more frequently an ADD. Treatment of dementia remains highly heterogeneous. Further consensus in the pharmacological management of patients living with dementia is urgently needed.

Frailty Predicts Dementia and Death in Older Adults Living in Long-Term Care

ObjectivesTo investigate how the accumulation of deficits traditionally related and not traditionally related to dementia predicts dementia and mortality. DesignA retrospective cohort study with up to 9 years of follow-up. Setting and ParticipantsLong-term care residents aged ≥65 with or without dementia. MethodsFrailty indices based on health deficit accumulation were constructed. The FI-t consisted of 27 deficits traditionally related to dementia; the FI-n consisted of 27 deficits not traditionally related to dementia; the FI-a consisted of all 54 deficits taken from the FI-t and the FI-n. ResultsIn this long-term care sample (n = 29,758; mean age = 84.6 ± 8.0; 63.8% female), 91% of the residents had at least 1 impairment in activities of daily living, 61% had a diagnosis of dementia, and the vast majority were frail (53% had FI-a > 0.2). Residents with dementia had a higher FI-t compared with those without dementia (0.278 ± 0.110 vs. 0.272 ± 0.108), whereas residents without dementia had a higher FI-n (0.143 ± 0.082 vs. 0.136 ± 0.079). Within 9 years, 97% of the sample had died; a 0.01 increase of the FI-a was associated with a 4% increase of the mortality risk, adjusting for age, sex, admission year, stay length, and dementia type. Residents who developed dementia after admission to long-term care had higher baseline FI-t and FI-a (P's < .003) than those who remained without dementia. Conclusions and ImplicationsFrailty is highly prevalent in older adults living in long-term care, irrespective of the presence or absence of dementia. Accumulation of deficits, either traditionally related or unrelated to dementia, is associated with risks of death and dementia, and more deficits increases the probability. Our findings have implications for improving the quality of care of older adults in long-term care, by monitoring the degree of frailty at admission, managing distinct needs in relation to dementia, and enhancing frailty level-informed care and services.

Is There a Role of Vitamin D in Alzheimer's Disease?

Alzheimer's disease (AD) represents the most prevalent type of neurodegenerative dementia and the sixth leading cause of death worldwide. The so-called "non-calcemic actions" of vitamin D have been increasingly described, and its insufficiency has already been linked to the onset and progression of the main neurological diseases, including AD. Immune-mediated Aβ plaque's phagocytosis and clearance, immune response, oxidative stress, and mitochondrial function are all influenced by vitamin D, and these functions are considered relevant in AD pathogenesis. However, it has been shown that the genomic vitamin D signaling pathway is already impaired in the AD brain, making things more complicated. In this paper, we aim to summarise the role of vitamin D in AD and review the results of the supplementation trials in AD patients.