Disease Dementia Research Articles

Phytoactive drugs used in the treatment of Alzheimer's disease and dementia.

The prevalence of Alzheimer's disease and other forms of dementia is increasing worldwide, and finding effective treatments for these conditions is a major public health challenge. Natural bioactive drugs have been identified as a promising source of potential treatments, due to their ability to target multiple pathways and their low toxicity. This paper reviews the current state of research on natural bioactive drugs used in the treatment of Alzheimer's disease and other dementias. The paper summarizes the findings of studies on various natural compounds, including curcumin, resveratrol, caffeine, genistein, quercetin, GinkoBiloba, Withaniasomnifera, Ginseng Brahmi, Giloy, and huperzine, and their effects on cognitive function, neuroinflammation, and amyloid-beta accumulation. In this review, we discuss the mechanism of action involved in the treatment of Alzheimer's disease. The paper also discusses the challenges associated with developing natural bioactive drugs for dementia treatment, including issues related to bioavailability and standardization. Finally, the paper suggests directions for future research in this area, including the need for more rigorous clinical trials and the development of novel delivery systems to improve the efficacy of natural bioactive drugs. Overall, this review highlights the potential of natural bioactive drugs as a promising avenue for the development of safe and effective treatments for Alzheimer's disease and other dementias.

Neuroinflammatory Response and Redox-regulation Activity of Hyperoside in Manganese-induced Neurotoxicity Model of Wistar Rats.

Excessive manganese exposure can lead to neurotoxicity with detrimental effects on the brain. Neuroinflammatory responses and redox regulation play pivotal roles in this process. Exploring the impact of hyperoside in a Wistar rat model offers insights into potential neuroprotective strategies against manganese-induced neurotoxicity. The study investigated the neuroprotective efficacy of hyperoside isolated from the ethanol leaf extract of Gongronema latifolium (HELEGL), in the brain tissue of Wistar rats following 15 consecutive days of exposure to 30 mg/L of MnCl2. Control animals in Group 1 had access to regular drinking water, while animals in groups 2-4 were exposed to MnCl2 in their drinking water. Groups 3 and 4 also received additional HELEGL at doses of 100 mg/kg and 200 mg/kg of body weight, respectively. In Group 5, HELEGL at a dose of 100 mg/kg of body weight was administered alone. Treatment with HELEGL commenced on day 8 via oral administration. HELEGL effectively mitigated MnCl2-induced memory impairment, organ-body weight discrepancies, and fluid intake deficits. Exposure to MnCl2 increased the activities or levels of various markers such as acyl peptide hydrolase, tumour necrosis factor-α, dipeptidyl peptidase IV, nitric oxide, IL-1β, prolyl oligopeptidase, caspase-3, myeloperoxidase, H2O2, and malondialdehyde, while it decreased the activities or levels of others, including AChE, BChE, DOPA, serotonin, epinephrine, norepinephrine, GST, GPx, CAT, SOD, GSH, and T-SH (p < 0.05). In contrast, HELEGL effectively counteracted the adverse effects of MnCl2 by alleviating oxidative stress, inflammation, apoptosis, mitochondrial dysfunction, cognitive deficits, and bolstering the antioxidant status. Moreover, HELEGL restored the normal histoarchitecture of the brain, which had been distorted by MnCl2. In summary, HELEGL reversed the causative factors of neurodegenerative diseases induced by MnCl2 exposure, suggesting its potential for further exploration as a prospective therapeutic agent in the management of Alzheimer's disease and related forms of dementia.

Dignity in people with dementia: A concept analysis.

Background: Dignity, an abstract and complex concept, is an essential part of humanity and an underlying guiding principle in healthcare. Previous literature indicates dignity is compromised in people with dementia (PwD), but those PwD maintain the capacity to live with dignity with appropriate external support. Alzheimer's disease and related dementias (ADRDs) lead to progressive functional decline and increased vulnerability and dependence, leading to heightened risks of PwD receiving inappropriate or insufficient care that diminishes dignity. Considering the increased disease prevalence and the continuously escalating costs of dementia care, establishing a productive value-based guideline may prevent suffering, maximize dignity, and thus promote quality of life (QoL).Aim: The goal of this project is to identify actionable targets for integrating dignity harmoniously and practically into care planning and management for PwD.Research Design: We conducted a concept analysis using Walker and Avant's eight-step process. A comprehensive literature search was conducted (PubMed and CINAHL) with the keywords "dignity," "dementia," "Alzheimer's disease," and "dementia care."Results: A total of 42 out of 4910 publications were included. The concept of dignity in PwD is operationalized as the promotion of worthiness and the accordance of respect that allows the presence and expression of a person's sense of self, regardless of physical, mental, or cognitive health. The concept has two subdimensions: absolute dignity which encompasses the inherent self and relative dignity characterized by its dynamic reflective nature. Worthiness and respect are the two main attributes, while autonomy is an underlying component of dignity. Specific antecedents of dignity in PwD are empowerment, non-maleficence, and adaptive environmental scaffolding. As a consequence of facilitating dignity in PwD, QoL may be enhanced.Conclusion: As a foundational and necessary humanistic value, incorporating dignity into dementia care can lead to efficient and effective care that optimizes QoL in PwD throughout their disease progression.

Effect of heatwaves on mortality of Alzheimer's disease and other dementias among elderly aged 60 years and above in China, 2013–2020: a population-based study

BackgroundChina has the largest number of dementia patients in the world, posing a significant health and economic burden. Alzheimer's disease (AD) and other dementia patients face a higher risk of mortality during heatwaves, but relevant studies on this topic have been limited so far. MethodsThe study extracted data from the China Cause of Death Reporting System (CDRS) on deaths of AD and other dementia patients aged 60 years and above between 2013-2020. Using an individual-level, time-stratified, and case-crossover study design, the effects of heatwaves across nine scenarios on dementia mortality were quantified by conditional logistic regression combined with distributed lag non-linear model (DLNM). Additionally, the attributable fractions (AFs) of deaths due to heatwaves were calculated. FindingsA total of 399,036 death cases were reported caused by AD and other dementias during the study period. It was found that heatwaves significantly increased the risk of death among people with AD and other dementias. As the intensities and durations of the heatwaves increased, the lag0-7 cumulative odds ratios (CORs) of mortality increased progressively from 1·140 (95% CI: 1·118, 1·163) under the mildest heatwave to 1·459 (95% CI: 1·403, 1·518) under the most severe one, across nine heatwave scenarios examined. Additionally, under specific heatwave scenarios, sex and regions modified the mortality risk, but no significant age differences were observed. The AFs of AD and other dementia mortality due to milder heatwaves were lower compared to more severe heatwaves, ranging from 12·281% (95% CI: 10·555%, 14·015%) to 31·460% (95% CI: 28·724%, 34·124%). InterpretationThe study provided critical insights into the substantial increase in heatwave-related mortality among AD and other dementia patients during and after heatwave events. The results from our quantitative analyses will provide needed scientific evidence for policymakers and practitioners to develop relevant policies and guidelines to protect the health and well-beings of vulnerable populations in future in the context of both seasonal changes and long-term climate change. FundingThis work was supported by the Project of Prevention and Intervention on Major Diseases for Elderly in China, NCNCD [00240201307], the National Key Research and Development Program of China [2022YFC2602301, 2023YFC2308703] and the Science and Technology Fundamental Resources Investigation Program of China [2017FY101201].

Exploring mitochondrial blood-based and genetic markers in older adults with mild cognitive impairment and remitted major depressive disorder

Mild cognitive impairment (MCI) is a prodromal stage in aging to possible progression to Alzheimer’s disease and related dementia (ADRD), where co-occurrence of major depressive disorder (MDD) accelerates the progression. Metabolic and mitochondrial abnormalities in ADRD and other neurodegenerative disorders have been widely suggested, while possible mitochondrial dysfunction has been associated with etiopathology of both MCI and MDD. Hence, investigation of mitochondrial markers in MCI, MDD, and presence of both conditions is warranted. In total, 332 older adult participants were included: 168 with MCI, 108 with MCI plus remitted MDD (rMDD), and 56 with rMDD but without MCI. We measured plasma circulating mitochondrial DNA (ccf-mtDNA), lactate, and extracted nuclear mitochondrial encoded (NMt) single-nucleotide variants (SNVs) (n = 312). Non-parametric statistical tests on ccf-mtDNA and lactate levels were performed on the diagnosis, clinical and cardiometabolic variables. Binary sequence kernel association test (SKAT-O) and burden test were performed on NMt-SNV, adjusted for age, race, gender, type II diabetes, and APOE genotype. Lower level of lactate was observed in MCI (KW χ2 = 14.8, P = 0.0024), more specifically, significant differences of lower plasma lactate between MCI only and rMDD, but not between MCI+rMDD and MCI were found, suggesting potential roles in MCI driving lactate lower levels. While higher levels of ccf-mtDNA were observed in APOE-ε4 carrier (χ2 = 5.04, P = 0.05). This relationship was present only in MCI (P = 0.043) and MCI+rMDD groups (P = 0.023). No significant nuclear-encoded mitochondrial gene associations were observed with MCI or MDD. The results suggest decreased level of plasma lactate in individuals with MCI and MCI+rMDD, with inverse correlation with ccf-mtDNA, in addition to effect of APOE-ε4 in further increasing ccf-mtDNA specifically in participants with cognitive impairment. These findings contribute to a deeper understanding of the mitochondrial markers in MCI and MDD, warranting further research to explore the precise roles of mitochondrial abnormalities in the development and progression of MCI.

Representing the Needs of Rural Caregivers of People Living with Alzheimer’s Disease and Related Dementias through User Personas

Abstract Background and Objectives Rural caregivers of people living with Alzheimer’s disease and related dementias (ADRD) face unique caregiving challenges. Current interventions do not address many of the systemic barriers experienced by rural ADRD caregivers, including barriers related to geography, healthcare services access, and financial insecurity. The objective of this study was to gain a deeper understanding of rural ADRD caregivers’ needs, strengths, and strategies in obtaining caregiving support, and to represent these attributes in the form of personas that can be used to design interventions for rural ADRD caregivers. Research Design and Methods In this qualitative user-centered design study, we conducted semi-structured interviews with self-identified caregivers of people living with ADRD in rural areas. Interview data was copied to a virtual whiteboard, and affinity diagramming was used to confirm a priori attributes and yield inductive attributes relevant to rural ADRD caregivers. Attributes were assigned to personas, which were then validated through team-based discussion, consultation with a study advisory board, and review by rural caregivers and community partners. Results Analyses of N=19 interviews yielded seven inductive attributes relevant to rural ADRD caregivers of persons living with ADRD and five distinct personas: Capable Christine, Connected Connie, Isolated Irene, Learning Larry, and Discerning Dan. Personas differed on inductive attributes including financial security, subjective rurality, attitudes, connectedness, and information behavior, including preferences for traditional versus technology-based information seeking. Discussion and Implications The personas identified in the present study can be used as tools to represent and efficiently communicate the intersection and interaction of attributes relevant to designing interventions and technologies to meet the support needs of rural ADRD caregivers.

Population health status and green urban areas: impact on health outcomes in two Italian regions

Abstract Background Living in urban areas has been linked to a rise in noncommunicable diseases. Nevertheless, there is scarcity of evidence emphasizing the combined impacts of certain urban attributes (e.g. pollution, excessive soil sealing, urban temperatures) and the existence of green spaces on health outcomes. Further studies are imperative to evaluate the association between chronic illnesses such as dementia and ischemic heart disease, and the presence of urban green areas. Methods We conducted an ecological study in two Italian regions. Prevalence of chronic diseases in Tuscany and Latium were obtained at the municipality level from public health databases available online and Normalized Difference Vegetation Index (NDVI) was calculated for 2023. Descriptive analyses and Poisson regression models were run to assess the association between green space and chronic diseases prevalence, adjusting for age, sex, education, employment, foreign residents, income, urbanicity and spatial correlation. Results Preliminary analyses were conducted on 273 municipalities in Tuscany. Mean prevalence per 1000 inhabitants of dementia and ischemic heart disease were 15.75 (SD = 5.3) and 48.25 (SD = 11.06), respectively. Mean NDVI across municipalities was 0.37 (SD = 0.04). Higher green exposure is associated with lower prevalence of ischemic heart disease (β= -0.21; p &amp;lt; 0.05) and dementia (β=-0.3, p &amp;lt; 0.05). Analyses will be executed for the Latium region and complete results will be available by mid-June. Conclusions The presence of urban greenery appears to be associated with a reduction in chronic illnesses. While further studies are warranted, it is crucial to adopt urban policies focused on green spaces and citizens’ health outcomes. Generating evidence for decision-makers is essential for shaping urban environments in ways that promote both health and overall human wellbeing. Key messages • Living in green urban areas appears to positively impact human health, reducing chronic disease prevalence. • Greenery serve as a tool for mitigating and adapting to the climate crisis, promoting health.

Genetic and lifestyle risks for coronary artery disease and risk of incident dementia

Abstract Background Lifestyle risk factors for coronary artery disease (CAD) have been associated with neurodegeneration and dementia. Whether an underlying genetic risk for the development of CAD further increases this risk, however, remains unclear. Purpose To examine whether an increased genetic risk for CAD is associated with an increased risk of dementia, and to investigate whether lifestyle factors modify these associations. Methods A prospective cohort study of 457,353 participants of European ancestry without dementia at baseline (mean [SD], age 57 [8] years; 55% were female) was conducted within the UK Biobank study. Exposures were a genome-wide polygenic risk score (PRS) for CAD and a modified version of the American Heart Association’s Life’s Essential 8 (LE8) cardiovascular health score comprising four biological (BMI, BP, lipids, glucose) and four lifestyle (smoking status, diet, physical activity, and sleep duration) risk factors previously linked to both CAD and dementia. Dementia diagnoses were obtained from death register and inpatient records. Results 9,337 cases of all-cause dementia were observed over a median 13.9-year follow-up. There were no significant interactions between genetic risk for CAD and lifestyle factors for all-cause dementia, or any other dementia subtype. After adjusting for potential demographic confounders, a higher genetic risk for CAD was associated with elevated risk of developing all-cause dementia (hazard ratio (HR) per 1-SD increase in PRS = 1.08 [95% CI, 1.05-1.10]), Alzheimer’s disease (HR 1.08 [1.03-1.12]), and vascular dementia (HR 1.13 [1.06-1.19]). An unfavourable LE8 cardiovascular health score was also associated with an increased risk of developing all-cause dementia (HR 1.05 [1.02-1.08]), predominantly through its association with vascular dementia (HR 1.14 [1.06-1.22]), as we found no evidence for any associations between LE8 and Alzheimer’s disease (HR 1.00 [0.97-1.02]). Conclusion These findings indicate that a high genetic risk for CAD is associated with an increased risk of developing major dementia subtypes. Regardless of this underlying genetic risk, however, our results suggest that lifestyle interventions designed to reduce the risk of CAD may also reduce one’s risk of developing dementia, particularly in those with underlying vascular pathology.

Predicting the onset of Alzheimer’s disease and related dementia using electronic health records: findings from the cache county study on memory in aging (1995–2008)

IntroductionClinical notes, biomarkers, and neuroimaging have proven valuable in dementia prediction models. Whether commonly available structured clinical data can predict dementia is an emerging area of research. We aimed to predict gold-standard, research-based diagnoses of dementia including Alzheimer’s disease (AD) and/or Alzheimer’s disease related dementias (ADRD), in addition to ICD-based AD and/or ADRD diagnoses, in a well-phenotyped, population-based cohort using a machine learning approach.MethodsAdministrative healthcare data (k = 163 diagnostic features), in addition to census/vital record sociodemographic data (k = 6 features), were linked to the Cache County Study (CCS, 1995–2008).ResultsAmong successfully linked UPDB-CCS participants (n = 4206), 522 (12.4%) had incident dementia (AD alone, AD comorbid with ADRD, or ADRD alone) as per the CCS “gold standard” assessments. Random Forest models, with a 1-year prediction window, achieved the best performance with an Area Under the Curve (AUC) of 0.67. Accuracy declined for dementia subtypes: AD/ADRD (AUC = 0.65); ADRD (AUC = 0.49). Accuracy improved when using ICD-based dementia diagnoses (AUC = 0.77).DiscussionCommonly available structured clinical data (without labs, notes, or prescription information) demonstrate modest ability to predict “gold-standard” research-based AD/ADRD diagnoses, corroborated by prior research. Using ICD diagnostic codes to identify dementia as done in the majority of machine learning dementia prediction models, as compared to “gold-standard” dementia diagnoses, can result in higher accuracy, but whether these models are predicting true dementia warrants further research.

Patients with dementia: prevalence and type of drug–drug interactions

BackgroundPatients with Alzheimer’s disease (AD) and other dementias are more frequently exposed to polymedication, mainly due to the presence of comorbidities, are particularly vulnerable to drug-related problems, and present greater risk of adverse effects due to drug–drug interactions (DDIs).PurposeTo assess the prevalence of clinically relevant interactions in dementia patients using a routine database, we describe the most frequent interactions and risk factors associated with them to facilitate specific interventions and programs to prevent and minimize them.MethodsAn observational, descriptive, and cross-sectional study that included patients with AD and other types of dementia (n = 100, 64% female) was conducted to identify potential DDI in their treatment using the Lexi-Interact/Lexicomp® database.ResultsA total of 769 drugs were prescribed, involving 190 different active ingredients; 83% of the treatments included five or more drugs. DDI occurred in 87% of the patients, of which 63.2% were female. A total of 689 DDIs were found, grouped in 448 drug pairs, with a mean of 6.9 ± 7.1 (range, 0–31) DDIs per patient, and 680 DDIs were considered clinically relevant. It was observed that 89.8% of the DDIs had a moderate level of severity, 23.5% had a good level of relevance, and pharmacodynamic-based DDIs accounted for 89.5%. The drugs most frequently involved in DDIs were quetiapine (24.5%) and acetylsalicylic acid (10%). A total of 97 DDIs were detected between the acetylcholinesterase inhibitors (AChEIs), and the remaining drugs were administered concomitantly. One of the most frequent DDIs was between AChEIs and beta-blocking agents (n = 29, 4.3%). The most important factors that showed the strongest association with the presence of drug interactions were the use of AChEIs (p = 0.01) and the total number of drugs (p = 0.014) taken by the patient.ConclusionPatients with dementia present increased risk of DDIs. Among the most common drugs are psychotropic drugs, which are involved in pharmacodynamic interactions caused by the concomitant use of CNS-targeted drugs. The results highlight the difficulty to evaluate DDIs in clinical practice due to polymedication and variety of comorbidities. Therefore, it is important to review their treatment and consider metabolism inhibition or induction, and potentially P450 substrate overlapping.

A Million Person Study Innovation: Evaluating Cognitive Impairment and other Morbidity Outcomes from Chronic Radiation Exposure Through Linkages with the Centers for Medicaid and Medicare Services Assessment and Claims Data.

The study of One Million U.S. Radiation Workers and Veterans, the Million Person Study (MPS), examines the health consequences, both cancer and non-cancer, of exposure to ionizing radiation received gradually over time. Recently the MPS has focused on mortality patterns from neurological and behavioral conditions, e.g., Parkinson's disease, Alzheimer's disease, dementia, and motor neuron disease such as amyotrophic lateral sclerosis. A fuller picture of radiation-related late effects comes from studying both mortality and the occurrence (incidence) of conditions not leading to death. Accordingly, the MPS is identifying neurocognitive diagnoses from fee-for-service insurance claims from the Centers for Medicare and Medicaid Services (CMS), among Medicare beneficiaries beginning in 1999 (the earliest date claims data are available). Linkages to date have identified ∼540,000 workers with available health information. Such linkages provide individual information on important co-factor and confounding variables such as smoking, alcohol consumption, blood pressure, obesity, diabetes and many other health and demographic characteristics. The total person-level set of time-dependent variables, outcomes, organ-specific dose measures, co-factors, and demographics will be massive and much too large to be evaluated with standard software. Thus, development of specialized open-source software designed for large datasets (Colossus) is nearly complete. The wealth of information available from CMS claims data, coupled with individual dose reconstructions, will thus greatly enhance the quality and precision of health evaluations for this new field of low-dose radiation and neurocognitive effects.

Social disconnectedness and the rate of medical conditions: a Danish population-based cohort study

Abstract Background Lack of social connections has a serious impact on health, increasing the risk of medical conditions such as depression, dementia, and coronary heart disease. However, evidence is limited by a disease-specific focus. We aimed to provide a comprehensive overview of differences in incidence rates of a broad range of medical conditions according to social disconnectedness (i.e., loneliness, social isolation, and low social support). Methods We conducted a cohort study using data on loneliness, social isolation, low social support, and a composite measure from the 2013 and 2017 Danish National Health Survey. Survey data was linked with register data on 11 categories of medical conditions through 2021. Poisson regression was applied to estimate incidence rate ratios (IRRs), incidence rate differences, and explore interaction with pre-existing mental disorders. Results Among 162,497 survey participants, 7.6%, 3.5%, and 14.8% were identified as lonely, socially isolated, and with low social support, respectively. Lonely individuals and individuals with low social support had a higher incidence rate of all 11 categories of medical conditions (interquartile range of IRRs, loneliness 1.22-1.49 and low social support 1.10-1.14), whereas this was the case for nine categories among socially isolated individuals (interquartile range of IRRs, 1.01-1.31). Applying the composite measure, the highest IRR was 2.61 (95% CI, 2.34-2.88) for a mental disorder and the lowest 1.03 (95% CI, 0.95-1.10) for cancer. We found neither major sex differences nor substantial interaction with pre-existing mental disorders. Conclusions Our study confirms and extends the available evidence on social disconnectedness and the risk of medical conditions. The attained knowledge may be of significance for mapping group-specific preventative needs and guiding interventions and health practitioners aiming to reduce the disease burden among socially disconnected individuals. Key messages • Based on survey and register data from 162,497 individuals, our study suggests that social disconnectedness, especially loneliness, is a determinant of a broad range of medical conditions. • The findings may be of importance for identifying and targeting the disease burden among socially disconnected individuals.

International and intercultural training on the use of Art Therapy for Dementia Care

Abstract In 2023 more than 55 million people had dementia worldwide, with nearly 10 million new cases every year. Currently art therapy has been widely adopted in the assistance of people with dementia because of the positive outcomes in terms of reducing depressive and behavioural symptoms and of improving the patients’ overall quality of life. In literature there was a knowledge gap on social and health professionals’ training for being able to effectively use art therapy in relation with different origins of people with dementia in a multi-ethnic world. This research aimed to assess the impact of promoting joint international and intercultural training session for social workers and health professionals’ students. The used methodology was a prospective research-intervention study with the conductions of two seasonal schools (Florence - Italy in July and Ankara - Tukey in October 2023) on the use of art therapy in the different stages of dementia disease within the Erasmus+ Project DementiaCare (2021-1-TR01-KA220-HED-000027648). Each seasonal school was attended by 25 students from Italy (5), Portugal (5), Slovenia (5), and Turkey (10) to ensure an international and intercultural approach. Pre- and post- test results showed the increased knowledge of students on the theoretical notions on dementia care and art therapy. Positive opinion on the projects developed by mixed group of students (with representants of the 5 involved universities) manifested the enforcement of their relational competences and skills mutually adapting their way of doing and communication register to the multi-ethnic and multi-cultural group’s needs. Evidence showed how mutual knowledge among social and health professionals with different cultures and their joint training allowed these professionals to be able to provide an integrated and effective assistance to every patient with dementia, personalizing assistance according with their different traditions and historical memories. Key messages • Art therapy has been adopted as non-pharmacological approach in dementia care to mitigate progression of symptoms’ severity, serving as alternative tool for self-expression for patients. • Conducting joint international and intercultural training sessions for social and health professionals in art therapy enabled them to develop a respectful, multi-ethical approach to dementia care.

Involvement of Complement in Alzheimer's Disease: From Genetics Through Pathology to Therapeutic Strategies.

Complement is a critical component of innate immunity, evolved to defend against pathogens and clear toxic debris rangingfrom dead and dying cells to immune complexes. These roles make complement a key player in homeostasis; however, complement has a dark side. When the rigid control mechanisms fail, complement becomes dysregulated, acting as a driver of inflammation and resultant pathology in numerous diseases. Roles of complement in Alzheimer's disease (AD) and other dementias have emerged in recent years, supported by genetic, biomarker and pathological evidence and animal model studies. Numerous questions remain regarding the precise roles of complement in the brain in health and disease, including where and when complement is expressed, how it contributes to immune defence and garbage disposal in the healthy brain, and exactly how complement contributes to pathology in dementias. In this brief review, we will summarise current knowledge on complement roles in brain, present the evidence implicating complement in AD and explore whether complement represents an attractive therapeutic target for AD.

In Case You Haven't Heard…

Keeping your brain sharp as you age has a lot to do with your heart — and the younger you start taking better care of it, the better — according to a new scientific statement published by the American Heart Association (AHA), CNN Health reported Oct. 10. “Dementia is commonly seen as an incurable and relentless disease that cannot be prevented,” said Fernando Testai, M.D., Ph.D., a professor of neurology and rehabilitation at the University of Illinois College of Medicine in Chicago, in a statement. “Evidence shows, however, that adopting a healthy lifestyle and identifying and treating vascular risk factors early may help preserve normal brain function and reduce the burden of Alzheimer's disease and other related dementias,” said Testai, who chaired the statement writing group. Nearly 130 million adults in the United States have some form of heart disease, according to the AHA. The disease also takes a toll on the brain. The narrowing of arteries that occurs with coronary heart disease and high blood pressure can reduce blood flow and cause damage to the small blood vessels in the brain, resulting in cognitive impairment, the AHA said. High blood pressure and Type 2 diabetes can also reduce blood flow to the brain and increase inflammation, leading to cognitive decline and dementia. Having coronary heart disease raises the risk of future dementia by 27% compared with people without heart disease, the AHA statement said.

Biomarker Assessment in Parkinson’s Disease Dementia and Dementia with Lewy Bodies by the Immunomagnetic Reduction Assay and Clinical Measures

Background: Plasma biomarker assays provide an opportunity to reassess whether Alzheimer’s disease, Parkinson’s disease dementia (PDD), and dementia with Lewy bodies (DLB) plasma biomarkers are diagnostically useful. Objective: We hypothesized that immunomagnetic reduction (IMR) of plasma biomarkers could differentiate between patients with PDD and DLB and healthy patients when combined with established clinical testing measures. Methods: Plasma samples from 61 participants (12 PDD, 12 DLB, 37 controls) were analyzed using IMR to quantify amyloid-β 42 (Aβ42), total tau (t-tau), phosphorylated tau at threonine 181 (p-tau181), and α-synuclein (α-syn). Receiver operating characteristic curve (ROC) analysis was used to obtain sensitivity, specificity, and area under the ROC curve. Biomarker results were combined with clinical measures from the Unified Parkinson’s Disease Rating Scale (UPDRS), Montreal Cognitive Assessment, and Hoehn-Yahr stage to optimize diagnostic test performance. Results: Participants with PDD had higher α-syn than those with DLB and healthy participants and were distinguishable by their biomarker products Aβ42×p-tau181 and Aβ42×α-syn. Patients with DLB had higher p-tau181 than those with PDD and healthy participants and were distinguishable by their concentrations of α-syn×p-tau181. Plasma α-syn plus UPDRS versus either test alone increased sensitivity, specificity, and AUC when healthy patients were compared with those with PDD and DLB. Combined clinical examination scores and plasma biomarker products demonstrated utility in differentiating PDD from DLB when p-tau181 was combined with UPDRS, α-syn was combined with UPDRS, and α-syn×p-tau181 was combined with UPDRS. Conclusions: In this pilot study, IMR plasma p-tau181 and α-syn may discriminate between PDD and DLB when used in conjunction with clinical testing.

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.

Reducing confusion surrounding expert conceptions of Alzheimer's and dementia: A practical analysis.

Biological, clinicobiological and clinical conceptions of Alzheimer's disease and related dementias are being promoted simultaneously to different practical ends. The co-existence of contemporary conceptions and the 'scary label' associated with older diagnostic criteria create the possibility of misunderstanding and harm. In this comment, we argue in favour of socio-ethical interventions targeted to health workers and the general public so as to lower the uncertainties introduced by contemporary diagnostic criteria and to articulate how they relate to established criteria.

Prevalence and influencing factors of cognitive frailty among Chinese older adults: A systematic review and meta-analysis.

Cognitive frailty refers to the coexistence of physical frailty and cognitive impairment in older adults, without a concurrent diagnosis of Alzheimer's disease or other dementias. This review aims to evaluate the prevalence of CF subtypes and identify influencing factors among Chinese older adults. The following databases were searched: PubMed/Medline, Embase, Cochrane Library, WOS, PsycINFO and CNKI et al (1 January 2001 to 20 October 2022). The risk of bias was assessed using the Agency for Healthcare Research and Quality Evidence-based Practice Center Methods Guide. Stata 17.0 software was used to pool the prevalence of cognitive frailty, and the pooled odds ratio and 95% CI of the influencing factors were calculated. The meta-analysis (56 studies and 80,320 participants) revealed the following prevalence rates: CF (18.9%), reversible CF (19.5%), potentially reversible CF (17.5%), CF in community-dwelling older adults (14.3%), CF in nursing homes (22.7%) and CF in older inpatients (25.2%). Influential factors identified included age, gender, education, nutrition, depression, exercise, sleep and comorbidity. The prevalence of CF among Chinese older adults is notably high, and it probably underestimates the prevalence of reversible cognitive frailty. It is crucial to encourage adherence to healthy behaviours, as it can effectively reduce and delay the onset of cognitive frailty.

The Alzheimer's Disease Neuroimaging Initiative-4 (ADNI-4) Engagement Core: A culturally informed, community-engaged research (CI-CER) model to advance brain health equity.

The Alzheimer's Disease Neuroimaging Initiative-4 (ADNI-4) Engagement Core was launched to advance Alzheimer's disease (AD) and AD-related dementia (ADRD) health equity research in underrepresented populations (URPs). We describe our evidence-based, scalable culturally informed, community-engaged research (CI-CER) model and demonstrate its preliminary success in increasing URP enrollment. URPs include ethnoculturally minoritized, lower education (≤ 12 years), and rural populations. The CI-CER model includes: (1) culturally informed methodology (e.g., less restrictive inclusion/exclusion criteria, sociocultural measures, financial compensation, results disclosure, Spanish Language Capacity Workgroup) and (2) inclusive engagement methods (e.g., the Engagement Core team; Hub Sites; Community-Science Partnership Board). As of April 2024, 60% of ADNI-4 new in-clinic enrollees were from ethnoculturally or educationally URPs. This exceeds ADNI-4's≥50% URP representation goal for new enrollees but may not represent final enrollment. Findings show a CI-CER model increases URP enrollment in AD/ADRD clinical research and has important implications for clinical trials to advance health equity. The Alzheimer's Disease Neuroimaging Initiative-4 (ADNI-4) uses a culturally informed, community-engaged research (CI-CER) approach. The CI-CER approach is scalable and sustainable for broad, multisite implementation. ADNI-4 is currently exceeding its inclusion goals for underrepresented populations.