bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing the distribution of neuropsychiatric symptoms among individuals with depression and mild cognitive impairment
Authors: Keng Alvin , Kapustin Daniel , Ma Clement , Bingham Kathleen , Fischer Corinne E. , Mah Linda , Gallagher Damien , Butters Meryl A. , Bowie Christopher R , Voineskos Aristotle N. , Graff‐Guerrero Ariel , Flint Alastair , Herrmann Nathan , Pollock Bruce G. , Mulsant Benoit H. , Rajji Tarek K. , Kumar Sanjeev 
Published: December 2023

AbstractBackgroundNeuropsychiatric symptoms (NPS) are common during the course of neurocognitive disorders. NPS have been previously reported in early and late stages of Alzheimer’s Disease. However, our understanding of NPS in high‐risk states for dementia such as mild cognitive impairment (MCI) and major depressive disorder (MDD) is poor. The purpose of this study was to compare the frequency and factor structure of neuropsychiatric symptoms among individuals with Mild Cognitive Impairment (MCI), Major Depressive Disorder (MDD) in remission, and comorbid MCI and MDD (in remission) (MCI‐D).MethodWe used baseline data from the Prevention of Alzheimer’s Dementia with Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression (PACt‐MD) study, a multicenter trial across five academic sites in Toronto, Canada (clinical trial No. NCT0238667). We used ANOVA or χ2‐test to compare frequency of NPS across groups. We used factor analysis of Neuropsychiatric Inventory Questionnaire (NPI‐Q) items in the three groups.ResultWe included 374 participants with a mean age of 72.0 years (SD = 6.3). In the overall sample, at least one NPS was present in 64.2% participants, and 36.1% had at least moderate severity NPS (36.1%). Depression (54%, χ2 < 0.001) and apathy (28.7%, χ2 = 0.002) were more prevalent in the MCI‐D group as compared to MCI and MDD groups. In factor analysis, NPS grouped differently in MCI, MDD, and MCI‐D groups. A “psychotic” subgroup emerged among MCI and MCI‐D, but not in MDD. Night‐time behaviors and disinhibition grouped differently across all three groups.ConclusionPrevalence of NPS seems higher in persons with MCI‐D as compared to those with only MCI or MDD. The factor structure of NPS differed between MCI, MDD, and MCI‐D groups. Future studies should investigate the association of NPS factors with cognition, function, and illness biomarkers.
Rural‐Urban differences in the prevalence of depression and anxiety among middle‐aged and older Indians
Authors: H Aishwarya B , Rai Pooja , Malo Palash Kumar , Hameed Shafeeq K Shahul , Stezin Albert , Arvind Prathima , Lingegodwa Abhishek Mensegere , Mallikarjun Divya N , Narayanasamy Rajitha , Menon Meenakshi , R Meghana , M Amitha C , Partha Ajith , Velavarajan Goutham , Singh Sadhana , Issac Thomas Gregor , Sundarakumar Jonas S. 
Published: December 2023

AbstractBackgroundDepression and anxiety have a considerably adverse impact on physical, mental and cognitive abilities. Since rural communities generally have more difficult living circumstances than urban communities, it is likely that prevalence of depression and anxiety could be higher in the rural population. Socio‐demographic factors, such as gender and age could also significantly influence the prevalence of these conditions. This study aims to examine the above potential differences.MethodThis was a cross‐sectional study which included participant’s ≥45 years, of both genders, who were recruited as part of two ongoing, prospective, aging cohort studies – Srinivaspura Aging, Neuro Senescence and COGnition (SANSCOG) in rural India and Tata Longitudinal Study of Aging (TLSA) in urban India. Baseline clinical data of SANSCOG (rural) and TLSA (urban) participants was utilized. Geriatric Depression Scale (GDS‐30) and Generalized Anxiety Disorder scale (GAD‐7) were used to estimate the prevalence of depression and anxiety, respectively. Statistical analysis was performed using Binomial test to determine differences in prevalence of depression and anxiety between the two populations as well as gender and age group‐wise differences.ResultOverall prevalence of depression was significantly higher among rural (16.13%) than urban population (8.2%, p<0.001). Similar trend was seen for prevalence of anxiety (rural = 5.27%, urban = 2.42%, p = 0.002). Also, prevalence of depression was significantly higher among females than males in both rural (20% vs. 12%, p = <0.001) and urban participants (11% vs. 5%, p = 0.0003). Prevalence of anxiety was also significantly higher among females than males in rural (6% vs. 4%, p = 0.01) but not significantly different in urban population (3% vs. 2%, p = 0.36). There was no significant difference between the two age groups in either of the populations for depression (rural: <65 = 15% vs. ≥65 = 18%, p = 0.92 and urban: <65 = 9% vs. ≥65 = 7%, p = 0.18) or anxiety (rural: <65 = 6% vs. ≥65 = 4%, p = 0.12 and urban: <65 = 2% vs. ≥65 = 3%, p = 0.81).ConclusionRural Indians had significantly higher prevalence of depression and anxiety than their urban counterparts. Women in both these populations had significantly higher burden than men. However, no age group‐wise differences were observed. Public health initiatives to address the high burden of depression in rural Indian women are urgently needed.
Unmet need and public financing of home care in England
Authors: Adrion Emily R 
Published: December 2023

AbstractBackgroundPersons living with dementia often wish to remain in their own homes for as long as possible. Given the unpredictable nature and progression of dementia, this means that many adults will require some degree of home‐based support in the initial stages of the disease, as well as requiring continuous, intensive support in the later stages. Public financing can play a central role in ensuring equitable access to home care, however, public financing is limited in many nations due to the high cost of these services. Without consistent government financing, many vulnerable adults may forgo needed care, risking adverse outcomes. In this study, we seek to examine unmet need and the role of public financing of home care among English adults over 50.MethodDrawing on waves 6‐9 (2013‐2019) of the English Longitudinal Study of Ageing, we use longitudinal fixed effects and pooled cross‐sectional models to understand patterns and predictors of unmet need for home care support services. We focus particularly on the type of home care received, differentiating between publicly financed and/or provided care, privately paid formal care, and informal home care services. We also differentiate between unmet need, where no help is received, and ‘under‐met’ need, where help is received but it does not fully meet the needs of the care recipient.ResultWorsening cognition and greater limitations in activities of daily living (ADL) and instrumental activities of daily living (IADL) are associated with fewer entirely unmet needs. Receipt of publicly financed and/or provided care is also associated with fewer unmet needs as compared to receiving informal and/or formal privately paid care. However, shifting from publicly financed/provided home care to exclusively informal and/or formal privately paid care is associated with lower odds of under‐met need, where the help provided does not fully meet the home care support needs of the recipient.ConclusionGreater ADL and IADL limitations and worsening cognition may trigger access to home care support services. Public financing/provision of home care may guard against needs going entirely unmet, however, the care that is received may not fully meet the support needs of those with dementia.
Hub brain regions for the remote spatial association between tau and Amyloid‐β proteins
Authors: Hojjati Seyed Hani , Feiz Farnia , Nayak Siddharth , Shteingart Jacob , Ozoria Sindy , Picha Saman Gholipour , Fernández Antonio , Devanand Davangere P. , Luchsinger Jose A , Stern Yaakov , Razlighi Qolamreza R 
Published: December 2023

AbstractBackgroundThe pathology of Alzheimer’s disease (AD) is characterized by two types of proteins: intracellular neurofibrillary tau tangles and extracellular β‐amyloid (Aβ) plaques. In the present observational studies, spatial discrepancies between these two proteins across the brain regions are well‐documented. However, the association between these two proteins remains elusive in different stages of depositions.MethodsWe aimed to investigate the remote association between tau and Aβ uptakes by using 572 elderlies 67.11 ± 6.08 (476 healthy control (HC) and 96 mild cognitive impairments (MCI)) Aβ and tau positron emission tomography (PET) scans. We leveraged 47 tau‐PET and 97 Aβ‐PET scans of healthy young individuals (aged 20‐40) to find the regional cut‐points for 68 cortical regions in the brain. Then by using these cut‐points and tau PET scans of all elderly individuals, we identified four groups of individuals (no tau phase, pre‐acceleration phase, acceleration phase, and post‐acceleration phase) (Table 1). Finally, a regional multiple linear regression model is performed for each group to detect the hubs region based on the remote association between each target region of tau and all other regions Aβ in the different phases of tau accumulations (controlling for gender, age, intracranial volume, and each target region Aβ).ResultsFirst, we show that the left and right entorhinal cortex, and right parahippocampal tau are the hubs of remote association with Aβ in several cortical regions (especially temporal regions) in the early stage of aggregation (Figure 1). Second, we identify tau in the same regions, continuing to demonstrate the highest remote associations with cortical Aβ (Figure 2) in the acceleration phase.ConclusionThe remote association appears in medial temporal lobe (MTL) tau during the early stage, as well as the later stage of tau accumulation (pre‐acceleration and acceleration phases). While the cellular mechanism of remote association is still elusive, in vivo studies have demonstrated that the Aβ triggers tau deposition indirectly in distal regions. Understanding the association between tau and Aβ at the preclinical stage of AD is critically important for a better consideration of tau spreading, especially in disease‐related brain regions.
The Effect of Telomere Length on Gray Matter Volume Change and Cortical Thickness
Authors: Yetim Ezgi , Topcuoglu Mehmet Akif , Kutlay Nuket Yurur , Tukun Ajlan , Oguz Kader Karli , Arsava Ethem Murat 
Published: December 2023

AbstractBackgroundTelomeres are specific nucleotide repeats that play an important role in preventing DNA damage during cell division. Telomere length holds promise as a predictor for age‐related diseases. However, the relationship between leukocyte telomere length and structural changes in the brain is not well understood. The aim of this study is to evaluate the cross‐sectional and longitudinal relationship between telomere length, structural features of the brain, and to examine the interindividual differences in age‐related brain atrophy within the framework of biological age.MethodsA total of 202 individuals ≥50 years of age without any neurological complaints were included in the study. Telomere length measurements from the peripheral blood leukocytes and brain magnetic resonance imaging (MRI) were performed in all participants. Forty‐six of the individuals without any major health events during the follow‐up period were evaluated with a second structural brain MRI after an average of 4.7 years. The relationship between global gray matter volume change and telomere length was investigated with multivariate models. In addition, longitudinal surface‐based analysis was used to determine the relationship between telomere length and cortical thinning regionally.ResultsThe mean (standard deviation) age of the population was 65.9 (8.6) years; female gender constituted 60.9% of the cohort. The mean telomere length was 7.5 (2.0) kB. Telomere length was not significantly associated with brain volumes and cortical thickness. However, in the longitudinal phase of the study, we found a negative correlation between basal telomere length and the rate of total gray matter volume decrease over time (r = ‐0.370; p = 0.012). This significant relationship persisted after adjusting for age, gender, follow‐up time, and baseline total gray matter volume (Standardized β = ‐0.286, p = 0.05). Longitudinal surface‐based image analysis also revealed a negative association between telomere length and left superior parietal cortex thickness, which remained significant after cluster correction.ConclusionTelomere length might be a predictor of age‐dependent structural changes in the brain. The left superior parietal cortex, in particular, tended to possess a vulnerability in this interplay.
The role of psychosocial factors on cognitive test outcomes among cognitively unimpaired African American women
Authors: Gracia Fernando I , Aguilar Alejandra , Large Stephanie E , Hall James 
Published: December 2023

AbstractBackgroundPrevious research shows that chronic stress and depression have deleterious effects on cognition. African American (AA) women disproportionately experience higher rates of poor mental and physical health outcomes, and a growing body of research links chronic stressors to these inequities. In AA’s, Subjective Cognitive Concerns (SCC) have not been widely studied and may be an early indicator of cognitive decline. This study aims to investigate the effect of psychosocial factors such as chronic stress, depression, and SCC on cognitive test outcomes in cognitively unimpaired AA women.MethodData from 232 cognitively unimpaired AA women were collected from the Health and Aging Brain Study: Health Disparities, a community‐based epidemiological study of aging. To assess chronic stress, we used the Chronic Stress scale. Depression was accessed via Geriatric Depression Scale (GDS). SCC, which is an algorithm‐derived variable was used to classify participants as either having or not having SCC. Linear regressions were calculated with cognitive test scores as the outcome variable and chronic stress, GDS, age, education, and SCC as predicting variables. The cognitive tests included Weschler Memory Scale ‐III Logical Memory (LM) 1 & 2, Trail Making Test (TMT) Part ‐ A & B, and Digit Span (DS). For each significant linear regression, structure coefficients were calculated.ResultAll linear regression models were statistically significant, ranging from LM1, LM2, TMT A & B p < 0.001 to DS p = 0.005. In LM1, structure coefficients demonstrated that education was the only significant factor correlated with the effect in the model. For TMT A and B, education and age were significantly correlated. LM2 and DS establish a different pattern with GDS, and education significantly correlated with the effect. Stress was also significantly associated with the effect on DS.ConclusionThe results demonstrate in cognitively unimpaired AA women, the GDS scores were related to decreased performance across multiple memory measures (DS and LM2). Chronic stress may be related to reduced performance in working memory. In AA women, future research should examine the relationship between discrimination, chronic stress, affective symptoms, and allostatic load on cognition. Early interventions targeting psychosocial factors may improve care for diverse communities.
A prospective study investigating the relation between blood‐based biomarkers for Alzheimer’s disease and diagnosis/patient management in primary care: The CANTATE‐PC study
Authors: Claessen Thomas , Vigneswaran Sinthujah , Verberk Inge M.W. , den Braber Anouk , Smit Maartje , Wilson David , Nierman Melchior C. , Kooren Jurgen A. , van der Flier Wiesje M. , van Harten Argonde C. , Teunissen Charlotte E. 
Published: December 2023

AbstractBackgroundWith the advent of disease‐modifying therapies, the need for accurate and cost‐effective diagnosis of Alzheimer’s disease (AD) is high. As the first step in the patient journey, the general practitioner plays an essential role in the diagnostic process. Accurately diagnosing AD in primary care is challenging, because early signs of AD frequently go unrecognized and other forms of dementia may be misdiagnosed as AD. We aim to take a first step towards identifying the utility of a panel of 5 blood‐based biomarkers for AD in primary care, assessing the relation between AD plasma biomarkers, diagnosis and patient management.MethodClinical Implementation of Amyloid Neurodegeneration and Tau testing in primary care (CANTATE‐PC) is a prospective study conducted in the Netherlands. CANTATE‐PC aims to enroll 400 participants > 50 years old who present to primary care with cognitive complaints or behavioral changes. Patients with known alcohol or drug abuse are excluded (figure 1). Participants are recruited from 20 primary care practices. At baseline demographic data, medical data and questionnaires regarding global cognitive performance, the nature and severity of cognitive complaints, and iADL are collected from participants (table 1). After enrollment, The general practitioner answers 5 questions about their working diagnosis, patient management and the utility of plasma biomarkers for AD for this individual patient via an online questionnaire, both at baseline and after 6 months. Blood is collected via venipuncture, performed at home or at a local laboratory. Amyloid‐beta42/40 ratio, hyperphosphorylated tau, glial fibrillary acidic protein and neurofilament light are analyzed using Single Molecule Assays (SiMoA, Quanterix Corp.). Primarily, we assess the association between plasma AD biomarkers as predictors and working diagnosis and patient management as outcome measures. Our secondary outcomes are (a) to ascertain if diagnosis and patient management differ between patients with and without plasma evidence of underlying AD (b) to explore associations between plasma biomarkers and the severity of cognitive complaints, global cognitive performance and functioning in iADL and to (c) qualitatively identify scenarios where plasma biomarkers can improve current care.ResultNoneConclusionThis is the first step towards providing clinical relevance for AD plasma biomarkers in primary care.
Single‐nuclei RNA sequencing provides evidence for glial senescence in Alzheimer’s disease
Authors: Fancy Nurun N , Smith Amy , Tsartsalis Stergios , Muirhead Robert , Chau Vicky , Davey Karen , Mcgarry Aisling , Khozoie Combiz , Willumsen Nanet , Zhang Xiaowen , Jackson Johanna , Matthews Paul M , Jenkyns Marion 
Published: December 2023

AbstractBackgroundAgeing is the greatest risk factor for Alzheimer’s disease (AD). While accumulation of senescent cells is one of the major hallmarks of ageing, the effect of the senescence burden is yet to be explored in AD. The aims of this study were to i) quantify senescent microglia, oligodendrocyte and astrocyte in human brain in AD, ii) determine the driver of cell senescence in AD, and iii) AD pathology associated senescence.MethodWe multiplexed Image Mass Cytometry (IMC) to co‐localise cell type markers (IBA1, OLIG2, GFAP), senescence markers (GLB1 and p16) and β‐amyloid (4G8) to detect senescence in tissues from Middle Temporal Gyrus (MTG) of 10 AD and 10 non‐disease control (NDC). We also generated snRNA‐seq from three different brain regions of the same subject namely Entorhinal (EC), MTG (Mid‐temporal Cortex) and Somatosensory Cortex (SSC) of 9 AD and 9 NDC. We performed geneset enrichment analysis using a set of curated senescence associated genesets in snRNA‐seq using AUcell and dream (variancePartition). We further performed trajectory analysis using Monocle3 to characterise β‐amyloid associated senescence signatures in the snRNAseq data.ResultMore than 25% microglia, oligodendrocyte and astrocyte were positive for GLB1 in AD brains while only around 5% glia showed GLB1 expression in NDC. Around 25% peri‐plaque microglia within 10 µm around β‐amyloid plaques in AD showed expression of GLB1 while only 3% of microglia >10 µm had associated senescence markers. Senescence genes were significantly upregulated in AD compared to NDC and were positively correlated with increase amyloid densities in all three glial cells (not in neurons). Trajectories of the glial nuclei described increased expression of pathways related to replicative senescence, cellular activation and stress response in microglia and oxidative stress in oligodendroglia, and astrocyte. Senescence gene signatures were positively associated with both β‐amyloid and pTau.ConclusionOur results highlight the high burden of senescent glia and provide evidence for distinct mechanisms of senescence in microglia (both replicative and stress‐induced) relative to oligodendroglia and astrocyte (stress‐induced) in AD. Both β‐amyloid and pTau associated increase in senescence gene signatures suggest that senescence is an important feature in the late stage of AD.
Functional connectivity changes in subjects at risk of developing Alzheimer’s disease
Authors: García‐Colomo Alejandra , Nebreda Alberto , Carrasco‐Gómez Martín , de Frutos Jaisalmer , Toraño Federico Ramirez , Bruña Fernández Ricardo , Maestú Fernando 
Published: December 2023

AbstractBackgroundAlzheimer’s disease is currently diagnosed after sufficient cognitive impairment and clinical dysfunction are manifest. The underlying neurological damage and dysfunction at that point are vast and extensive, and the processes behind it have been going on for decades. Consequently, recent research has been focused on the identification of early biomarkers.The initial damage induced by the increase in Aβ levels manifests as neuronal hyperexcitability that translates to network alterations and an early hypersynchrony.For this study, we used magnetoencephalography (MEG) to measure changes in neuronal activity of cognitively unimpaired adults (50‐80 y/o) at different levels of risk of developing AD. We also measured plasma levels of p‐tau231, a novel biomarker known to increase very early in the pathological continuum of the disease.The main objective was to evaluate longitudinal changes in the connectivity of three regions known to be affected in the progression of AD, and which, according to previous studies, exhibit hyperconnectivity in subjects at greater risk of AD.Method69 subjects with family history (FH+) of AD and 28 individuals with no history (FH‐) were included in the study. A CBPT was used to measure longitudinal connectivity changes, and significant clusters were correlated with p‐tau231 levels.ResultThe FH+ results show significant clusters of longitudinal change that closely resemble those obtained by Ramírez‐Toranõ et al. (2021). All three clusters present greater connectivity values in the second MEG recording. A significant positive correlation was found between the connectivity values at the second MEG recording and p‐tau231 in the left precuneus. The same positive trend was found for right precuneus and left anterior cingulate.ConclusionTo our knowledge, this is the first longitudinal study performed on cognitively unimpaired subjects, addressing connectivity changes and studying the relationship between those values and plasma biomarkers. The precuneus is one of the areas that accumulates early damage due to the pathology of AD. We believe that the hyperconnectivity found in both precuneus can be considered an early biomarker of AD risk, and the correlation with p‐tau231 levels support its pathological nature.