Search Results (50)

Alzheimer’s disease (AD) and related dementias (ADRD) are neurodegenerative conditions that cause gradual deterioration of cognition, memory and language in the elderly. AD has been declared as a health priority by the World Health Organization (WHO) considering its severity and unavailability of a permanent cure. Although the global AD/ADRD population is made up of many ethno-racial groups, the majority of AD studies have focused on the Caucasian population. The few AD studies conducted on minority populations in the US have found that significant AD health disparities exist, demonstrating that African Americans and Hispanics have a significantly higher prevalence of AD and related dementias, with their risk often approaching twice that of White individuals. For the past few years, epigenomic research has played an important role in understanding health disparities among diverse racial and ethnic groups. Unlike genetic studies, which focus on the DNA sequence that one is born with, epigenomics investigates how changes in gene expression due to extrinsic environmental exposures may impact disease pathophysiology. Recent epigenomic studies appear to be promising in not only understanding disease pathology but also in developing diagnostic and therapeutic tools for AD with population specificity. However, there is only a handful of studies and review articles available addressing the epigenomic applications in irradicating racial disparities in AD/ADRD. Therefore, the aim of this review is to discuss the recent findings of epigenomic studies in AD and related dementias, their contribution in irradicating racioethnic disparities and insights into the future direction of their application in precision medicine. Full article

Emerging evidence suggests that viral infections may contribute to the onset and progression of Alzheimer’s disease (AD) and other forms of dementia. Understanding the mechanism of viral involvement in the pathogenesis of AD and related dementia (ADRD) could contribute to reducing the burden caused by these conditions, which affect a large portion of the aging population. Some studies indicate the link between AD and viral infections, notably coronaviruses and herpesviruses. In AD, excessive production of reactive oxygen species (ROS) results in the modifications of lipids, proteins, and nucleic acids, contributing to synaptic dysfunction and cognitive impairments. Experimental evidence suggests that viral infections linked to ADRD induce the cellular production of ROS, possibly contributing to the pathogenesis of these conditions. Despite significant advances in defining the roles of ROS in neurological disorders and viral infections, the specific roles of ROS in virus-associated ADRD have not been thoroughly investigated. The main objective of this review article is to comprehensively provide information on the experimental evidence for the production of ROS by viruses to help the readers investigate the role of ROS in the relationship between viral infections with ADRD. Full article

Background/Objectives: Falls are a leading cause of hospitalization, injury, and healthcare spending among older adults. Surveillance data on local falls, especially for those associated with Alzheimer’s disease and related dementias (ADRD), are limited. We conducted a surveillance analysis to describe fall-related hospitalizations and their associations with ADRD in Los Angeles County (LAC). Methods: We analyzed countywide hospital discharge data for LAC residents aged 50+ from 2016–2022 (n = 3,520,927) to assess differences in fall-related hospitalizations by ADRD status and demographic characteristics. We used multivariable logistic regression to identify predictors of fall status and multinomial regression to examine associations between ADRD status and discharge disposition. Results: Of all hospitalizations, 6.8% were fall-related. Individuals hospitalized for falls had longer stays, higher charges, and were more frequently female, older, and White. Fall frequency peaks consistently occurred during winter months, with higher seasonal variation among those without ADRD. After adjustment, ADRD diagnosis was associated with increased odds of fall-related hospitalization (AOR = 1.14) and non-routine discharge, including transfer to a short-term hospital (AOR = 1.35), skilled nursing or other care facilities (AOR = 1.88), and home health care (AOR = 1.23). Conclusions: This study provides one of the most comprehensive local assessments of fall-related hospitalization among older adults in the United States. The findings highlight the increased risk and care complexity among patients with ADRD. As results are descriptive and reflect cross-sectional surveillance, temporality and causality cannot be inferred. Nevertheless, the findings underscore the need for better surveillance and integrated fall prevention, discharge planning, and post-hospital support strategies tailored to individuals with ADRD. Full article

Alterations in both oral and gut microbiomes have been associated with Alzheimer’s disease and related dementia (ADRD). While extensive research has focused on the role of gut dysbiosis in ADRD, the contribution of the oral microbiome remains relatively understudied. This study aims to evaluate distinct patterns and potential synergistic effects of oral and gut microbiomes in a cohort of predominantly Hispanic individuals with cognitive impairment (CI) and without cognitive impairment (NC). We conducted 16S rRNA gene sequencing on stool and saliva samples from 32 participants (17 CI, 15 NC; 62.5% female, mean age = 70.4 ± 6.2 years) recruited in San Antonio, Texas, USA. Differential abundance analysis evaluated taxa with significant differences between both groups. While diversity metrics showed no significant differences between CI and NC groups, differential abundance analysis revealed an increased presence of oral genera such as Dialister, Fretibacterium, and Mycoplasma in CI participants. Conversely, CI individuals exhibited a decreased abundance of gut genera, including Shuttleworthia, Holdemania, and Subdoligranulum, which are known for their anti-inflammatory properties. No evidence was found for synergistic contributions between oral and gut microbiomes in the context of CI. Our findings suggest that like the gut microbiome, the oral microbiome of CI participants undergoes significant modifications. Notably, the identified oral microbes have been previously associated with periodontal diseases and gingivitis. These results underscore the necessity for further investigations with larger sample sizes to validate our findings and elucidate the complex interplay between oral and gut microbiomes in ADRD pathogenesis. Full article

(1) Background: Alzheimer’s disease and related dementias (ADRD) are a major cause of mortality among older adults globally. The cognitive decline associated with ADRD often reduces individuals’ ability to live independently over time, increasing reliance on caregivers. Assistive and socially assistive robots offer a promising means of supporting independent living. This narrative review examined how older adults with ADRD, their caregivers, and healthcare providers perceive and experience interactions with robots. (2) Methods: Guided by the Population, Phenomenon of Interest, and Context (PICo) framework, five databases were searched. Sixteen studies met the inclusion criteria. Extracted data were summarized, and a convergent synthesis integrated qualitative and quantitative findings. (3) Results: Drawing on content analysis, the qualitative findings were organized into three domains: user perceptions and experiences, barriers to adoption, and suggestions for improvement. Quantitative results emphasized usability, usefulness, acceptance, satisfaction, feature preferences, and barriers. While most stakeholders viewed robots as beneficial, acceptance was shaped by factors such as design features, timing of introduction, familiarity with technology, and perceived need. (4) Conclusions: This review highlights priorities for future research and development, including personalization, ethical safeguards, and caregiver integration, to improve the acceptance and effectiveness of robot-assisted support for individuals with cognitive impairment. Full article

Background: There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer’s Disease and related dementias (ADRD). Methods: In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on cognitive function through β-amyloid (Aβ) deposition and multi-omics profiling. We evaluated six male Mn-exposed workers (median age 63, exposure duration 31 years) and five historical controls (median age: 60 years), all of whom had undergone brain PET scans. Exposed individuals showed significantly higher Aβ deposition in exposed individuals (p < 0.05). The average annual cumulative respirable Mn was 329.23 ± 516.39 µg/m³ (geometric mean 118.59), and plasma Mn levels were significantly elevated in the exposed group (0.704 ± 0.2 ng/mL) compared to controls (0.397 ± 0.18 in controls). Results: LC-MS/MS-based pathway analyses revealed disruptions in olfactory signaling, mitochondrial fatty acid β-oxidation, biogenic amine synthesis, transmembrane transport, and choline metabolism. Simoa analysis showed notable alterations in ADRD-related plasma biomarkers. Protein microarray revealed significant differences (p < 0.05) in antibodies targeting neuronal and autoimmune proteins, including Aβ (25–35), GFAP, serotonin, NOVA1, and Siglec-1/CD169. Conclusion: These findings suggest Mn exposure is associated with neurodegenerative biomarker alterations and disrupted biological pathways relevant to cognitive decline. Full article

Chronic periodontitis, driven by the keystone pathogen Porphyromonas gingivalis, has been increasingly associated with Alzheimer’s disease (AD) and AD-related dementias (ADRDs). However, the mechanisms through which P. gingivalis-lipopolysaccharide (LPS)-induced release of neuroinflammatory proteins contribute to the pathogenesis of AD and ADRD remain inadequately understood. Caspase-4, a critical mediator of neuroinflammation, plays a pivotal role in these processes following exposure to P. gingivalis-LPS. In this study, we investigated the mechanistic role of caspase-4 in P. gingivalis-LPS-induced IL-1β production, neuroinflammation, oxidative stress, and mitochondrial alterations in human neuronal and microglial cell lines. Silencing of caspase-4 significantly attenuated IL-1β secretion by inhibiting the activation of the caspase-4-NLRP3-caspase-1-gasdermin D inflammasome pathway, confirming its role in neuroinflammation. Moreover, caspase-4 silencing reduced the activation of amyloid precursor protein and presenilin-1, as well as the secretion of amyloid-β peptides, suggesting a role for caspase-4 in amyloidogenesis. Caspase-4 inhibition also restored the expression of key neuroinflammatory markers, such as total tau, VEGF, TGF, and IL-6, highlighting its central role in regulating neuroinflammatory processes. Furthermore, caspase-4 modulated oxidative stress by regulating reactive oxygen species production and reducing oxidative stress markers like inducible nitric oxide synthase and 4-hydroxynonenal. Additionally, caspase-4 influenced mitochondrial membrane potential, mitochondrial biogenesis, fission, fusion, mitochondrial respiration, and ATP production, all of which were impaired by P. gingivalis-LPS but restored with caspase-4 inhibition. These findings provide novel insights into the role of caspase-4 in P. gingivalis-LPS-induced neuroinflammation, oxidative stress, and mitochondrial dysfunction, demonstrating caspase-4 as a potential therapeutic target for neurodegenerative conditions associated with AD and related dementias. Full article

Background: Cardiovascular disease (CVD) significantly impacts Alzheimer’s Disease and Related Dementia (AD/ADRD) mortality. South Carolina has a high incidence of CVD and dementia mortality. The aim of this study, therefore, was to examine the neurological causes of death and the leading causes of death in the South Carolina Alzheimer’s Disease Registry (SCADR). Method: Data from 2005–2018 were extracted from the SCADR using ICD-9 and ICD-10 codes. The top 10 leading causes of death (LCOD) were identified using death certificates. Some neurological causes of death were operationalized by combining related ICD codes, such as CVD_C (I219, I251, I500, I64) and chronic obstructive pulmonary disease (COP_C), (J449, C349), and ${\chi }^2$ was used to compare socio-demographic characteristics and mortality. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were estimated using extended Cox Proportional Hazard modeling, adjusting for socio-demographic factors. Results: A total of 207,093 registry cases were included in the analysis. About 70% of cases had Alzheimer’s Disease (AD) diagnosis, and 40% of all cases were 85 years and older. The LCOD was CVD_C (13.4%). The risk of death among cases with vascular dementia (VaD) was 1.17 times the risk of death among those with AD (aHR: 1.172, 95% CI: 1.148–1.196). Among all deaths, cases with COP_C had a significantly higher likelihood of death compared to those with CVD_C (aHR: 1.06, 95% CI: 1.025–1.090). Conclusions: The study highlights CVD_C as the LCOD in frequency, with survival analysis indicating COP_C risk of death as significantly higher compared to CVD_C deaths. There is a need to prioritize CVD and lung-related comorbidity prevention, assessment, and management programs for individuals living with ADRD. Full article

Background: Emerging evidence suggests a potential link between heavy metals and Alzheimer’s disease and related dementias (AD/ADRD). This study compiled epidemiological evidence from research published over the past 11 years on the impact of metals on AD/ADRD in women. Women have unique risk factors for late onset of AD/ADRD, in addition to genetic factors, apolipoprotein E allele (APOE4), and longer life expectancy. Furthermore, women are twice likely as men to experience depression, which increases their risk of developing AD/ADRD. Our narrative review underscored the necessity of a sex-specific approach to address women’s vulnerability to AD/ADRD. Methods: Electronic databases, including PubMed, Google Scholar, NIOSH Toxline, and Scopus, were thoroughly searched to identify primary epidemiological studies on older women exposed to metals and published between 2014 to 2024. Results: We identified 34 epidemiological studies that met the inclusion criteria. The findings revealed a complex interplay between environmental metals such as lead (Pb), cadmium (Cd), arsenic (As), manganese (Mn), selenium (Se), iron (Fe), zinc (Zn), copper (Cu), magnesium (Mg), and calcium (Ca) and the risk of AD/ADRD in women. Significant adverse effects were reported for Cu, Cd, As, Pb, and Mn while significant protective effects were found between Se, Fe, and Zn in blood and AD/ADRD among older women. However, some studies also reported no correlations. Conclusions: Overall, our review identified contrasting results regarding the effects of metals on AD/ADRD in women. Future studies should collect additional evidence to understanding the effects of heavy metals on AD/ADRD in women for developing preventive measures. Full article

This review synthesizes the emerging understanding of the roles of glial cells and non-coding RNAs (ncRNAs) in the pathogenesis and progression of Alzheimer’s disease and related dementias (ADRDs). ADRDs encompass a spectrum of neurodegenerative disorders characterized by cognitive decline, memory impairment, and functional deterioration. The interplay between the most common types of glial cells—astrocytes, microglia, and oligodendrocytes—and ncRNAs is emerging as a critical factor in the development of ADRDs. Glial cells are essential for maintaining homeostasis within the central nervous system (CNS); however, their dysregulation can lead to neuroinflammation and neuronal dysfunction, exacerbating neurodegeneration. Reactive astrocytes and activated microglia can create neurotoxic environments that further impair neuronal health. Concurrently, ncRNAs, particularly long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have emerged as significant regulators of glial gene expression, influencing inflammatory responses and glial cell function. Understanding the complex interactions between glial cells and ncRNAs is crucial for developing targeted therapeutic strategies. By elucidating the mechanisms underlying their interactions, this review aims to highlight the critical importance of glial cells and ncRNAs in the context of neurodegenerative diseases, paving the way for innovative approaches to prevent and treat ADRDs. Ultimately, enhancing our understanding of these processes may lead to novel therapies and improved outcomes for individuals affected by these debilitating conditions. Full article

Background/Objectives: As the world’s population ages, the growing number of individuals affected by Alzheimer’s disease and related dementias (ADRDs) will undoubtedly continue to impose social and economic challenges. Informal caregivers play a crucial role in providing essential support for individuals with ADRD. However, there is limited research that investigates the psychosocial functioning of caregivers (partners) from minoritized groups. Methods: This study aimed to explore the experiences of lesbian, gay, bisexual, transgender and queer (LGBTQ+) caregivers of individuals with ADRDs. Semi-structured in-depth interviews were conducted with seven caregivers of partners diagnosed with ADRDs. Three themes were identified based on reflexive thematic analysis: (i) experiencing familial alienation; (ii) fear about the future; and (iii) finding strength in the face of adversity. Results: The research highlighted difficulties reported by LGBTQ+ caregivers, while also showing how such caregivers cope. The findings provide a basis for developing targeted interventions for caregivers from minoritized groups. Conclusions: These findings have important implications for policy and intervention development concerning LGBTQ+ caregivers’ mental and physical health outcomes. Full article

Older adults may experience worse wildfire fine particulate matter (PM_2.5) smoke-related health effects due to conditions such as Alzheimer’s disease and related dementias (ADRDs). We evaluated whether wildfire PM_2.5 was associated with acute hospitalizations among older adults with ADRD, linking modeled daily wildfire PM_2.5 concentrations and circulatory, respiratory, anxiety, and depression hospitalizations from 2006 to 2016. We employed a case-crossover design and conditional logistic regression to estimate associations between lagged daily wildfire PM_2.5 and hospitalizations. Also, we stratified cause-specific models by age, sex, emergency hospitalization status, and zip code-level urbanicity and poverty. The 1,546,753 hospitalizations among Medicare enrollees with ADRD were most coded for circulatory (71.7%), followed by respiratory (43.6%), depression (2.9%), and anxiety (0.7%) endpoints. We observed null associations between wildfire PM_2.5 and circulatory, respiratory, and anxiety hospitalizations over the six days following exposure. Same-day wildfire PM_2.5 was associated with decreased depression hospitalizations (rate ratio = 0.94, 95% CI: 0.90, 0.99). We saw some effect measure modifications by emergency hospitalization status and urbanicity. There were some stratum-specific effects for age, but the results remained mostly null. Future studies should use improved methods to identify ADRD and examine recent years with higher wildfire concentrations. Full article

Cognitive disorders and psychiatric pathologies, particularly Alzheimer’s disease (AD) and Major depressive disorder (MDD), represent a considerable health burden, impacting millions of people in the United States and worldwide. Notably, comorbidities of MDD and anxiety are prevalent in the early stages of mild cognitive impairment (MCI), which is the preceding phase of Alzheimer’s disease and related dementia (ADRD). The symptoms of MDD and anxiety affect up to 80% of individuals in the advanced stages of the neurodegenerative conditions. Despite overlapping clinical manifestations, the pathogenesis of AD/ADRD and MDD remains inadequately elucidated. Until now, dozens of drugs for treating AD/ADRD have failed in clinical trials because they have not proven beneficial in reversing or preventing the progression of these neuropsychiatric indications. This underscores the need to identify new drug targets that could reverse neuropsychiatric symptoms and delay the progress of AD/ADRD. In this context, phosphodiesterase 4 (PDE4) arises as a primary enzyme in the modulation of cognition and mood disorders, particularly through its enzymatic action on cyclic adenosine monophosphate (cAMP) and its downstream anti-inflammatory pathways. Despite the considerable cognitive and antidepressant potential of PDE4 inhibitors, their translation into clinical practice is hampered by profound side effects. Recent studies have focused on the effects of PDE4 and its subtype-selective isoform inhibitors, aiming to delineate their precise mechanistic contributions to neuropsychiatric symptoms with greater specificity. This review aims to analyze the current advances regarding PDE4 inhibition—specifically the selective targeting of its isoforms and elucidate the therapeutic implications of enhanced cAMP signaling and the consequent anti-inflammatory responses in ameliorating the symptomatology associated with AD and ADRD. Full article

Background/Objectives: Alzheimer’s disease (AD) and related dementias (ADRD) disproportionately impact racial and ethnic minorities. Contributing biological factors that explain this disparity have been elusive. Moreover, non-invasive biomarkers for early detection of AD are needed. Endothelin-1 (ET-1), a vasoconstrictive factor linked to cerebral vascular disease pathology and neuronal injury, could provide insights to better understand racial disparities in AD. As a potent vasoconstrictive peptide that regulates contractions in smooth muscle, endothelial cells, and pericytes, ET-1 may result in cerebral vascular constriction, leading to cerebral hypoperfusion; over time, this may result in neuronal injury, contributing to the pathology of AD. The role of the ET-1 system as a driver of ethnic disparities in AD requires further investigation. In the United States (U.S.), ET-1 dysregulation in Hispanic/Latinx (H/L) ethnic populations has largely been unexplored. Genetics linking ET-1 dysregulation and racial disparities in AD also require further investigation. In this study, we examined the role of the ET-1 protein in human plasma as a potential biomarker with predictive value for correlating with the development of AD by age, race, and sex. Methods: We examined ET-1 protein levels using quantitative mass spectrometry in AA and NHW patients with AD, along with controls. Results: A partial correlation between age at draw and ET-1, stratified by race and sex, while controlling for AD status, was significant for female AAs (r = 0.385, p = 0.016). When the data were not stratified but controlled for AD status, the partial correlation between age at draw and ET-1 was not significant (r = 0.108, p = 0.259). Conclusions: Based on the small number of plasma specimens and no plasma specimens from H/L individuals with AD, we conclude that ET-1 was clearly not a significant factor in predicting AD in this study and will require a larger scale study for validation. Full article