Disease Dementia Research Articles

Impact of the South African Child Support Grant on memory decline and dementia probability in rural and low-income mothers, 2014–2021

IntroductionAging populations across sub-Saharan Africa are rapidly expanding, leading to an increase in the burden of Alzheimer's disease and related dementias (ADRD). Cash transfer interventions are one plausible mechanism to combat ADRD at a population-level in low-income settings. We exploited exogenous variation in eligibility for South Africa's Child Support Grant (CSG) to estimate the longitudinal association between potential CSG benefit and cognitive trajectories in rural mothers with <10 children (n = 1090). MethodsSouth Africa's CSG delivers monthly cash payments to primary caregivers, predominantly mothers, to offset the costs associated with child rearing. This study implemented a quasi-experimental design using data (2014–2022) from a rural, low-income cohort in the Agincourt research area, South Africa. We fit linear mixed effects models and generalized linear models to estimate the association of potential CSG benefit per eligible child with memory decline and dementia probability, respectively. We stratified all models by the mother's total number of children (1–4 and 5–9) and examined effect modification by household wealth and the mother's education level. ResultsHaving above median CSG per eligible child was associated with higher baseline memory scores (β = 0.12 SD units, 95% CI = 0.02, 0.22) but steeper memory decline (β = −0.02 SD units, 95% CI = −0.04, -0.00) compared to below median CSG. Within stratified analyses, this effect was primarily observed among mothers with 5–9 children. No associations were observed between potential CSG per eligible child and dementia probability. ConclusionsOur findings support the use of large-scale cash transfers as a promising intervention to promote healthy cognitive aging in mid-life women within rural, low-income settings. However, we found evidence that the CSG in its current structure may not be sufficient support for women to sustain measurable cognitive benefits over the long-term.

Microstructural changes in the inferior tuberal hypothalamus correlate with daytime sleepiness in Lewy body disease.

Excessive daytime sleepiness (EDS) is a disabling symptom of Lewy body disorders (LBD). The hypothalamus is a key sleep-wake regulator, but its contribution to EDS in LBD remains unclear. Use diffusion MRI to evaluate the relationship of hypothalamic microstructure to EDS symptoms in LBD. We studied 102 patients with clinically-defined LBD (Parkinson's disease, n=93; Parkinson's disease dementia, n=4; and dementia with Lewy bodies, n=5) and Epworth Sleepiness Scale (ESS) within 2 years of MRI. Mean diffusivity (MD) was compared between EDS+ (ESS≥10, n=37) and EDS- (ESS<10, n=65) groups in the whole hypothalamus and three subregions, covarying for age and sex. Secondary analyses tested correlations between subregion MD and continuous ESS, global cognition, and motor scores; and between subregion volume and continuous ESS. MD was increased in EDS+ compared to EDS-only in the inferior tuberal subregion (Cohen's d=0.43, p=0.043, β=0.117±0.057), with trend level differences in the whole hypothalamus (Cohen's d=0.39, p=0.064, β=0.070±0.037) and superior tuberal subregion (Cohen's d=0.38, p=0.073, β=0.063±0.035). No difference was seen in the posterior subregion (Cohen's d=0.1, p=0.628, β=0.019±0.038). Significant correlations with continuous ESS were seen in MD of whole hypothalamus (r 2 =0.074, p=0.0057), superior tuberal (r 2 =0.081, p=0.0038), and inferior tuberal (r 2 =0.073, p=0.0059) subregions. There was no correlation of hypothalamic MD with global cognition or motor scores, and no correlation of whole/subregional hypothalamic volumes with ESS. Daytime sleepiness associates with increased MD in the inferior tuberal hypothalamus in an LBD cohort. This suggests degeneration within this region could contribute to EDS symptoms.

The genetic and environmental etiology of novel frequency-driven regional parcellations of abnormal white matter.

The prevalence of white matter disease increases with age and is associated with cerebrovascular disease, cognitive decline, and risk for dementia. MRI measures of abnormal signal in the white matter (AWM) provide estimates of damage, however, regional patterns of AWM may be differentially influenced by genetic or environmental factors. With our data-driven regional parcellation approach, we created a probability distribution atlas using Vietnam Era Twin Study of Aging (VETSA) data (n = 475, mean age 67.6 years) and applied a watershed algorithm to define separate regional parcellations. We report biometrical twin modeling for five anatomically distinct regions: (1) Posterior, (2) Superior frontal and parietal, (3) Anterior and inferior frontal with deep areas, (4) Occipital, and (5) Anterior periventricular. We tested competing multivariate hypotheses to identify unique influences and to explain sources of covariance among the parcellations. Family aggregation could be entirely explained by additive genetic influences, with additive genetic variance (heritability) ranging from 0.69 to 0.79. Most genetic correlations between parcellations ranged from moderate to high (rg = 0.57-0.85), although two were small (rg = 0.35-0.39), consistent with varying degrees of unique genetic influences. This proof-of-principle investigation demonstrated the value of our novel, data-driven parcellations, with identifiable genetic and environmental differences, for future exploration.

Single-nucleus multiome analysis of human cerebellum in Alzheimer's disease-related dementia.

Although human cerebellum is known to be neuropathologically impaired in Alzheimer's disease (AD) and AD-related dementias (ADRD), the cell type-specific transcriptional and epigenomic changes that contribute to this pathology are not well understood. Here, we report single-nucleus multiome (snRNA-seq and snATAC-seq) analysis of 103,861 nuclei isolated from cerebellum from 9 human cases of AD/ADRD and 8 controls, and with frontal cortex of 6 AD donors for additional comparison. Using peak-to-gene linkage analysis, we identified 431,834 significant linkages between gene expression and cell subtype-specific chromatin accessibility regions enriched for candidate cis-regulatory elements (cCREs). These cCREs were associated with AD/ADRD-specific transcriptomic changes and disease-related gene regulatory networks, especially for RAR Related Orphan Receptor A (RORA) and E74 Like ETS Transcription Factor 1 (ELF1) in cerebellar Purkinje cells and granule cells, respectively. Trajectory analysis of granule cell populations further identified disease-relevant transcription factors, such as RORA, and their regulatory targets. Finally, we prioritized two likely causal genes, including Seizure Related 6 Homolog Like 2 (SEZ6L2) in Purkinje cells and KAT8 Regulatory NSL Complex Subunit 1 (KANSL1) in granule cells, through integrative analysis of cCREs derived from snATAC-seq, genome-wide AD/ADRD loci, and Hi-C looping data. This first cell subtype-specific regulatory landscape in the human cerebellum identified here offer novel genomic and epigenomic insights into the neuropathology and pathobiology of AD/ADRD and other neurological disorders if broadly applied.

A "glympse" into neurodegeneration: Diffusion MRI and cerebrospinal fluid aquaporin-4 for the assessment of glymphatic system in Alzheimer's disease and other dementias.

The glymphatic system (GS) is a whole-brain perivascular network, consisting of three compartments: the periarterial and perivenous spaces and the interposed brain parenchyma. GS dysfunction has been implicated in neurodegenerative diseases, particularly Alzheimer's disease (AD). So far, comprehensive research on GS in humans has been limited by the absence of easily accessible biomarkers. Recently, promising non-invasive methods based on magnetic resonance imaging (MRI) along with aquaporin-4 (AQP4) quantification in the cerebrospinal fluid (CSF) were introduced for an indirect assessment of each of the three GS compartments. We recruited 111 consecutive subjects presenting with symptoms suggestive of degenerative cognitive decline, who underwent 3 T MRI scanning including multi-shell diffusion-weighted images. Forty nine out of 111 also underwent CSF examination with quantification of CSF-AQP4. CSF-AQP4 levels and MRI measures-including perivascular spaces (PVS) counts and volume fraction (PVSVF), white matter free water fraction (FW-WM) and mean kurtosis (MK-WM), diffusion tensor imaging analysis along the perivascular spaces (DTI-ALPS) (mean, left and right)-were compared among patients with AD (n = 47) and other neurodegenerative diseases (nAD = 24), patients with stable mild cognitive impairment (MCI = 17) and cognitively unimpaired (CU = 23) elderly people. Two runs of analysis were conducted, the first including all patients; the second after dividing both nAD and AD patients into two subgroups based on gray matter atrophy as a proxy of disease stage. Age, sex, years of education, and scanning time were included as confounding factors in the analyses. Considering the whole cohort, patients with AD showed significantly higher levels of CSF-AQP4 (exp(b) = 2.05, p = .005) and FW-WM FW-WM (exp(b) = 1.06, p = .043) than CU. AQP4 levels were also significantly higher in nAD in respect to CU (exp(b) = 2.98, p < .001). CSF-AQP4 and FW-WM were significantly higher in both less atrophic AD (exp(b) = 2.20, p = .006; exp(b) = 1.08, p = .019, respectively) and nAD patients (exp(b) = 2.66, p = .002; exp(b) = 1.10, p = .019, respectively) compared to CU subjects. Higher total (exp(b) = 1.59, p = .013) and centrum semiovale PVS counts (exp(b) = 1.89, p = .016), total (exp(b) = 1.50, p = .036) and WM PVSVF (exp(b) = 1.89, p = .005) together with lower MK-WM (exp(b) = 0.94, p = .006), mean and left ALPS (exp(b) = 0.91, p = .043; exp(b) = 0.88, p = .010 respectively) were observed in more atrophic AD patients in respect to CU. In addition, more atrophic nAD patients exhibited higher levels of AQP4 (exp(b) = 3.39, p = .002) than CU. Our results indicate significant changes in putative MRI biomarkers of GS and CSF-AQP4 levels in AD and in other neurodegenerative dementias, suggesting a close interaction between glymphatic dysfunction and neurodegeneration, particularly in the case of AD. However, the usefulness of some of these biomarkers as indirect and standalone indices of glymphatic activity may be hindered by their dependence on disease stage and structural brain damage.

Increasing research study engagement in minoritized populations: An example from the Black Women Inflammation and Tau Study.

Black women are sorely underrepresented in studies of Alzheimer's disease and related dementias (ADRD) despite higher rates of ADRD diagnoses than in non-Hispanic White women. There are many reasons for underrepresentation, including medical mistrust, limited access to clinical studies, and restrictive study inclusion criteria. These pervasive barriers to research participation are often not considered during study development and, if eventually thought of tend to be after the fact. Community-engaged research (CER) approaches are an effective method for reducing participation barriers. This article describes how CER approaches were used to develop the Black Women Inflammation and Tau Study (BWITS), a prospective study to identify biopsychosocial risk factors for ADRD in Black women. Guidelines discussed here for future ADRD research in diverse populations are informed by Community-Based Participatory Research (CBPR), the National Institute on Minority Health and Health Disparities (NIMHD), and the Patient-Centered Outcomes Research Institute (PCORI). HIGHLIGHTS: Understand the historical tragedies related to medical practices and research designs that may contribute to the underrepresentation of Black Americans in research studies today. Highlight community-engaged research approaches that effectively reduce participation barriers in minoritized groups. Review Community-Based Participatory Research, National Institute of Minority Health and Health Disparities, and the Patient-Centered Outcomes Research Institute guidelines for conducting research with minoritized communities. Describe using the three frameworks to inform the study development protocol for the Black Women Inflammation and Tau Study. Conclude by offering study design considerations that we hope can be a helpful starting point for others conducting research with minoritized communities.

Telephone-based mindfulness intervention positively impacts family communication and stress within rural, African American dementia caregiving teams

Objectives The objective of this paper is to explore how telephone-delivered mindfulness training impacts family conflict and communication within the informal dementia caregiving team, including primary caregivers, their care partner, and the care recipient. Method Primary caregivers and their care partners participated in an eight-week telephone-delivered mindfulness-based intervention (MBI). This study used mixed methods and a pre-post design to evaluate the intervention’s effect on family satisfaction, perceived support, and family conflict. Results Both family satisfaction and perceived informational support increased significantly, and qualitative analysis revealed four key themes illustrating how the mindfulness intervention served to positively impact family conflict and communication among participating caregivers. Conclusion This study provides preliminary evidence for the beneficial effects of an MBI on family functioning among rural African American caregivers of people with Alzheimer’s disease and related dementias.

A preliminary investigation of worry, cortical amyloid burden, and stressor-evoked brain and cardiovascular reactivity in older adults

Worry is a transdiagnostic symptom common to many neurocognitive disorders of aging, including early stages of Alzheimer's disease and related dementias (ADRD). Severe worry is associated with amyloid burden in cognitively intact older adults, yet the mechanisms underlying this association are not well understood. We hypothesize that this relationship involves altered brain and cardiovascular reactivity to acute stressors, a brain-body phenotype that also increases risk for cardiovascular disease. Twenty cognitively normal older adults (age 60 to 80) with varying levels of worry severity underwent positron emission tomography using Pittsburgh Compound-B and functional magnetic resonance imaging. We examined associations of worry severity and amyloid burden with cardiovascular reactivity, brain activation, and brain connectivity using a cognitive stressor task. Worry severity was not associated with global amyloid burden, but was associated with greater resting levels of cardiovascular physiology and lower systolic blood pressure reactivity. Worry severity also was associated with altered stressor-evoked activation and effective connectivity in brain circuits implicated in stress processing, emotion perception, and physiological regulation. These associations showed small to medium effect sizes. These preliminary findings introduce key components of a model that may link severe worry to ADRD risk via stressor-evoked brain-body interactions.

Contributions of the ADNI Biostatistics Core.

The goal of the Biostatistics Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI) has been to ensure that sound study designs and statistical methods are used to meet the overall goals of ADNI. We have supported the creation of a well-validated and well-curated longitudinal database of clinical and biomarker information on ADNI participants and helped to make this accessible and usable for researchers. We have developed a statistical methodology for characterizing the trajectories of clinical and biomarker change for ADNI participants across the spectrum from cognitively normal to dementia, including multivariate patterns and evidence for heterogeneity in cognitive aging. We have applied these methods and adapted them to improve clinical trial design. ADNI-4 will offer us a chance to help extend these efforts to a more diverse cohort with an even richer panel of biomarker data to support better knowledge of and treatment for Alzheimer's disease and related dementias. HIGHLIGHTS: The Alzheimer's Disease Neuroimaging Initiative (ADNI) Biostatistics Core provides study design and analytic support to ADNI investigators. Core members develop and apply novel statistical methodology to work with ADNI data and support clinical trial design. The Core contributes to the standardization, validation, and harmonization of biomarker data. The Core serves as a resource to the wider research community to address questions related to the data and study as a whole.

Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline

Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe. We identified 260 out of 942 immunologically relevant proteins in plasma that were differentially expressed in individuals with an infection history. Of the infection-related proteins, 35 predicted volumetric changes in brain regions vulnerable to infection-specific atrophy. Several of these proteins, including PIK3CG, PACSIN2, and PRKCB, were related to cognitive decline and plasma biomarkers of dementia (Aβ42/40, GFAP, NfL, pTau-181). Genetic variants that influenced expression of immunologically relevant infection-related proteins, including ITGB6 and TLR5, predicted brain volume loss. Our findings support the role of infections in dementia risk and identify molecular mediators by which infections may contribute to neurodegeneration.

Early Alzheimer's Disease Detection: A Review of Machine Learning Techniques for Forecasting Transition from Mild Cognitive Impairment.

Alzheimer's disease is a weakening neurodegenerative condition with profound cognitive implications, making early and accurate detection crucial for effective treatment. In recent years, machine learning, particularly deep learning, has shown significant promise in detecting mild cognitive impairment to Alzheimer's disease conversion. This review synthesizes research on machine learning approaches for predicting conversion from mild cognitive impairment to Alzheimer's disease dementia using magnetic resonance imaging, positron emission tomography, and other biomarkers. Various techniques used in literature such as machine learning, deep learning, and transfer learning were examined in this study. Additionally, data modalities and feature extraction methods analyzed by different researchers are discussed. This review provides a comprehensive overview of the current state of research in Alzheimer's disease detection and highlights future research directions.

The Alzheimer's Disease Neuroimaging Initiative Clinical Core.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) Clinical Core is responsible for coordination of all clinical activities at the ADNI sites, including project management, regulatory oversight, and site management and monitoring, as well as the collection of all clinical data and management of all study data. The Clinical Core is also charged with determining the clinical classifications and criteria for enrollment in evolving AD trials and enabling the ongoing characterization of the cross-sectional features and longitudinal trajectories of the ADNI cohorts with application of these findings to optimal clinical trial designs. More than 2400 individuals have been enrolled in the cohorts since the inception of ADNI, facilitating refinement of our understanding of the AD trajectory and allowing academic and industry investigators to model therapeutic trials across the disease spectrum from the presymptomatic stage through dementia. HIGHLIGHTS: Since 2004, the Alzheimer's Disease Neuroimaging Initiative (ADNI) Clinical Core has overseen the enrollment of > 2400 participants with mild cognitive impairment, mild Alzheimer's disease (AD) dementia, and normal cognition. The longitudinal dataset has elucidated the full cognitive and clinical trajectory of AD from its presymptomatic stage through the onset of dementia. The ADNI data have supported the design of most major trials in the field.

Implications of using administrative healthcare data to identify risk of motor vehicle crash-related injury: the importance of distinguishing crash from crash-related injury

BackgroundAdministrative healthcare databases, such as Medicare, are increasingly used to identify groups at risk of a crash. However, they only contain information on crash-related injuries, not all crashes. If the driver characteristics associated with crash and crash-related injury differ, conflating the two may result in ineffective or imprecise policy interventions.MethodsWe linked 10 years (2008–2017) of Medicare claims to New Jersey police crash reports to compare the demographics, clinical diagnoses, and prescription drug dispensings for crash-involved drivers ≥ 68 years with a police-reported crash to those with a claim for a crash-related injury. We calculated standardized mean differences to compare characteristics between groups.ResultsCrash-involved drivers with a Medicare claim for an injury were more likely than those with a police-reported crash to be female (62.4% vs. 51.8%, standardized mean difference [SMD] = 0.30), had more clinical diagnoses including Alzheimer’s disease and related dementias (13.0% vs. 9.2%, SMD = 0.20) and rheumatoid arthritis/osteoarthritis (69.5% vs 61.4%, SMD = 0.20), and a higher rate of dispensing for opioids (33.8% vs 27.6%, SMD = 0.18) and antiepileptics (12.9% vs 9.6%, SMD = 0.14) prior to the crash. Despite documented inconsistencies in coding practices, findings were robust when restricted to claims indicating the injured party was the driver or was left unspecified.ConclusionsTo identify effective mechanisms for reducing morbidity and mortality from crashes, researchers should consider augmenting administrative datasets with information from police crash reports, and vice versa. When those data are not available, we caution researchers and policymakers against the tendency to conflate crash and crash-related injury when interpreting their findings.

Effects of Community Assets on Major Health Conditions in England: A Data Analytic Approach.

The broader determinants of health including a wide range of community assets are extremely important in relation to public health outcomes. Multiple health conditions, multimorbidity, is a growing problem in many populations worldwide. This paper quantified the effect of community assets on major health conditions for the population of England over six years, at a fine spatial scale using a data analytic approach. Community assets, which included indices of the health system, green space, pollution, poverty, urban environment, safety, and sport and leisure facilities, were quantified in relation to major health conditions. The health conditions examined included high blood pressure, obesity, dementia, diabetes, mental health, cardiovascular conditions, musculoskeletal conditions, respiratory conditions, kidney and liver disease, and cancer. Cluster analysis and dendrograms were calculated for the community assets and major health conditions. For each health condition, a statistical model with all community assets was fitted, and model selection was performed. The number of significant community assets for each health condition was recorded. The unique variance, explained by each significant community asset per health condition, was quantified using hierarchical variance partitioning within an analysis of variance model. The resulting data indicate major health conditions are often clustered, as are community assets. The results suggest that diversity and richness of community assets are key to major health condition outcomes. Primary care service waiting times and distance to public parks were significant predictors of all health conditions examined. Primary care waiting times explained the vast majority of the variances across health conditions, with the exception of obesity, which was better explained by absolute poverty. The implications of the combined findings of the health condition clusters and explanatory power of community assets are discussed. The vast majority of determinants of health could be accounted for by healthcare system performance and distance to public green space, with important covariate socioeconomic factors. Emphases on community approaches, significant relationships, and asset strengths and deficits are needed alongside targeted interventions. Whilst the performance of the public health system remains of key importance, community assets and local infrastructure remain paramount to the broader determinants of health.

Whole exome sequencing analyses identified novel genes for Alzheimer's disease and related dementia.

The heritability of Alzheimer's disease (AD) is estimated to be 58%-79%. However, known genes can only partially explain the heritability. Here, we conducted gene-based exome-wide association study (ExWAS) of rare variants and single-variant ExWAS of common variants, utilizing data of 54,569 clinically diagnosed/proxy AD and related dementia (ADRD) and 295,421 controls from the UK Biobank. Gene-based ExWAS identified 11 genes predicting a higher ADRD risk, including five novel ones, namely FRMD8, DDX1, DNMT3L, MORC1, and TGM2, along with six previously reported ones, SORL1, GRN, PSEN1, ABCA7, GBA, and ADAM10. Single-variant ExWAS identified two ADRD-associated novel genes, SLCO1C1 and NDNF. The identified genes were predominantly enriched in amyloid-β process pathways, microglia, and brain regions like hippocampus. The druggability evidence suggests that DDX1, DNMT3L, TGM2, SLCO1C1, and NDNF could be effective drug targets. Our study contributes to the current body of evidence on the genetic etiology of ADRD. Gene-based analyses of rare variants identified five novel genes for Alzheimer's disease and related dementia (ADRD), including FRMD8, DDX1, DNMT3L, MORC1, and TGM2. Single-variant analyses of common variants identified two novel genes for ADRD, including SLCO1C1 and NDNF. The identified genes were predominantly enriched in amyloid-β process pathways, microglia, and brain regions like hippocampus. DDX1, DNMT3L, TGM2, SLCO1C1, and NDNF could be effective drug targets.

Triggering Tau Fibrillization by Electroreduction: A New Tool for Studying Amyloid Diseases

The pathological aggregation of the microtubule-associated protein tau is a hallmark of various neurodegenerative disorders, including Alzheimer’s disease (AD), Pick’s disease and frontotemporal dementia. Tau protein’s reversible assembly and binding to microtubules in brain neurons are regulated by charge-neutralizing phosphorylation. Hyperphosphorylation, on the other hand, leads to irreversible formation of cytotoxic filaments. Under physiological conditions, tau remains remarkably stable, exhibiting intrinsically disordered behavior and reversible assembly. Irreversible aggregation requires specific mutations, preformed seeds or nucleating polyanionic cofactors. However, heparin-induced fibrils differ structurally from brain-derived filaments, and the presence of such cofactors can impede therapeutic agent development. We have developed a quick and easy method to generate cofactor-free filaments using heterogeneous electroreduction as a surrogate for charge-neutralization by hyperphosphorylation. We combine electrochemistry with in situ UV absorbance, circular dichroism and dynamic light scattering spectroscopies to dynamically follow tau’s conformational changes and assembly. Electroreduction of positively charged residues of the protein leads to rapid formation of b-rich structures, even at times as short as 15 minutes. The extent of assembly can be controlled by fine-tuning electroreductive potentials and electrolyte conditions. Relevance of this new method was confirmed by examining the impact of an early-onset AD-causing tau mutant and known inhibitors on aggregation kinetics. Our results demonstrate comparable effects to heparin-induced fibrils, as assessed by thioflavin-T fluorescence, dynamic light scattering, circular dichroism and electron microscopy. Low-voltage electroreduction provides a platform to study the effects of tau mutations and effectors, as well as to develop rapid assays to test how additional effectors may inhibit, disassemble or direct the trajectory of tau assembly. The versatility of our approach also suggests its potential applicability to a broader spectrum of neurodegenerative amyloid diseases.

Examining the Relationships Between Indoor Environmental Quality Parameters Pertaining to Light, Noise, Temperature, and Humidity and the Behavioral and Psychological Symptoms of People Living With Dementia: Scoping Review.

A common challenge for individuals caring for people with Alzheimer disease and related dementias is managing the behavioral and psychological symptoms of dementia (BPSD). Effective management of BPSD will increase the quality of life of people living with dementia, lessen caregivers' burden, and lower health care cost. In this review, we seek to (1) examine how indoor environmental quality parameters pertaining to light, noise, temperature, and humidity are associated with BPSD and how controlling these parameters can help manage these symptoms and (2) identify the current state of knowledge in this area, current gaps in the research, and potential future directions. Searches were conducted in the CINAHL, Embase, MEDLINE, and PsycINFO databases for papers published from January 2007 to February 2024. We searched for studies examining the relationship between indoor environmental quality parameters pertaining to light, noise, temperature, and humidity and BPSD. A total of 3123 papers were identified in the original search in October 2020. After an additional 2 searches and screening, 38 (0.69%) of the 5476 papers were included. Among the included papers, light was the most studied environmental factor (34/38, 89%), while there were fewer studies (from 5/38, 13% to 11/38, 29%) examining the relationships between other environmental factors and BPSD. Of the 38 studies, 8 (21%) examined multiple indoor environmental quality parameters. Subjective data were the only source of environmental assessments in 6 (16%) of the 38 studies. The findings regarding the relationship between agitation and light therapy are conflicted, while the studies that examined the relationship between BPSD and temperature or humidity are all observational. The results suggest that when the environmental factors are deemed overstimulating or understimulating for an individual with dementia, the behavioral symptoms tend to be exacerbated. The findings of this scoping review may inform the design of long-term care units and older adult housing to support aging in place. More research is still needed to better understand the relationship between indoor environmental quality parameters and BPSD, and there is a need for more objective measurements of both the indoor environmental quality parameters and behavioral symptoms. One future direction is to incorporate objective sensing and advanced computational methods in real-time assessments to initiate just-in-time environmental interventions. Better management of BPSD will benefit patients, caregivers, and the health care system.

Infection burden, periodontal pathogens, and their interactive association with incident all-cause and Alzheimer's disease dementia in a large national survey.

Relationships and interplay of an infection burden (IB) and periodontal pathogens or periodontal disease (Pd) markers with Alzheimer's disease (AD) and all-cause dementia among US adults were examined. Less than or equal to 2997 participants from the National Health and Nutrition Survey III were linked to CMS-Medicare [≥45 years (1988-1994); ≤30 years follow-up]. Hepatitis C (hazard ratio=3.33, p=0.004) and herpes simplex virus 2 were strongly associated with greater all-cause dementia risk. Porphyromonas gingivalis and Streptococcus oralis were associated with greater AD risk at higher IB. The red-green periodontal pathogen cluster coupled with higher IB count increased the risk of all-cause dementia among minority racial groups. Pocket probing depth associated with dementia risk at lower IB in the overall sample. Select viruses and bacteria were associated with all-cause and AD dementia, while the IB interacted with Pd markers in relation to these outcomes. Interplay of infection burden (IB) and periodontal disease with dementia was tested. ≤2997 participants from NHANES III were linked to Medicare. Hepatitis C and herpes simplex virus 2 strongly associated with dementia risk. Tetanus sero-positivity increased Alzheimer's disease (AD) risk. Porphyromonas gingivalis and Streptococcus oralis associated with AD at higher IB. Red-green periodontal cluster at high IB, increased dementia in racial minorities. Pocket probing depth associated with dementia risk at lower IB.

2287 Residents with dementia had an increase in BMI after the introduction of an extra meal in nursing homes in Norway

Abstract Introduction The past decade, many nursing homes in Norway have introduced an extra meal daily, with a hot lunch, and pushing dinner to later in the day. This initiative aims to reduce the long-time interval between breakfast and supper. This study examines how an extra meal affects the residents’ body mass index (BMI) at nursing homes in Norway. Research questions include how an extra meal affects BMI among residents in the dementia unit. Method We used a cross-sectional design to analyse data from residents over 65 years old in dementia care units. Both parametric and non-parametric statistical tests were used to evaluate changes in BMI. Results The results of the study show that the dementia unit experienced an increase in BMI following the introduction of an extra meal. At most, we saw a weight gain of up to 7 kg over two years among residents. Our study reveals that the introduction of an extra meal resulted in a slight increase in BMI among the residents with dementia, which does not correspond with previous studies indicating malnutrition among these residents. The dementia disease reduces functional abilities, and challenges related to mealtime behaviour, restlessness, and depression can lead to weight loss. The fact that our results show a slight increase in BMI at the dementia units may be related to these residents often being troubled with restlessness and not finding the peace to consume a full meal. By introducing an extra meal, the total food intake increases since residents still eat a little at each meal, and focusing more on accommodating each resident might have influenced the increase in BMI values. Conclusion The study indicates that the introduction of an extra meal has a positive effect on the BMI value of residents with dementia in nursing homes.

Mechanisms of mitophagy and oxidative stress in cerebral ischemia-reperfusion, vascular dementia, and Alzheimer's disease.

Neurological diseases have consistently represented a significant challenge in both clinical treatment and scientific research. As research has progressed, the significance of mitochondria in the pathogenesis and progression of neurological diseases has become increasingly prominent. Mitochondria serve not only as a source of energy, but also as regulators of cellular growth and death. Both oxidative stress and mitophagy are intimately associated with mitochondria, and there is mounting evidence that mitophagy and oxidative stress exert a pivotal regulatory influence on the pathogenesis of neurological diseases. In recent years, there has been a notable rise in the prevalence of cerebral ischemia/reperfusion injury (CI/RI), vascular dementia (VaD), and Alzheimer's disease (AD), which collectively represent a significant public health concern. Reduced levels of mitophagy have been observed in CI/RI, VaD and AD. The improvement of associated pathology has been demonstrated through the increase of mitophagy levels. CI/RI results in cerebral tissue ischemia and hypoxia, which causes oxidative stress, disruption of the blood-brain barrier (BBB) and damage to the cerebral vasculature. The BBB disruption and cerebral vascular injury may induce or exacerbate VaD to some extent. In addition, inadequate cerebral perfusion due to vascular injury or altered function may exacerbate the accumulation of amyloid β (Aβ) thereby contributing to or exacerbating AD pathology. Intravenous tissue plasminogen activator (tPA; alteplase) and endovascular thrombectomy are effective treatments for stroke. However, there is a narrow window of opportunity for the administration of tPA and thrombectomy, which results in a markedly elevated incidence of disability among patients with CI/RI. It is regrettable that there are currently no there are still no specific drugs for VaD and AD. Despite the availability of the U.S. Food and Drug Administration (FDA)-approved clinical first-line drugs for AD, including memantine, donepezil hydrochloride, and galantamine, these agents do not fundamentally block the pathological process of AD. In this paper, we undertake a review of the mechanisms of mitophagy and oxidative stress in neurological disorders, a summary of the clinical trials conducted in recent years, and a proposal for a new strategy for targeted treatment of neurological disorders based on both mitophagy and oxidative stress.