bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stress system dysfunction and changes in brain volume and functional connectivity in older adults with subclinical depressive symptoms
Authors: Touron Edelweiss , de Flores Robin , Coulbaut Laurent , Palix Cassandre , Chocat Anne , Kuhn Elizabeth , Landeau Brigitte , Mézenge Florence , Roquet Daniel , Chauveau Léa , Haudry Sacha , Vivien Denis , la Sayette Vincent De , Marchant Natalie L , Chetelat Gael , Poisnel Géraldine ,   the Medit‐Ageing Research Group
Published: December 2023

AbstractBackgroundSubclinical depressive symptoms are associated with increased risk of Alzheimer’s disease (AD). This link could be related to stress system dysfunction, known to occur in both depression and AD, and to depend notably on the hippocampus which is particularly sensitive to AD. We aimed at investigating the links between levels of blood stress markers and changes in brain regions involved in the stress response in older adults with subclinical depressive symptoms.MethodCognitively unimpaired older adults with (DepS; n = 73) or without (NoDepS; n = 58) subclinical depressive symptoms (defined using the 15‐item version of the Geriatric Depression Scale), from the baseline data of the Age‐Well trial (NCT02977819) were included. For each participant, levels of cortisol, epinephrine and norepinephrine were obtained from blood sampling. Moreover, the functional connectivity (FC) between, and the gray matter (GM) volume of, the hypothalamus, hippocampus and hippocampal subfields were extracted from resting‐state functional, and structural T1‐weighted, MRI. Levels of blood stress markers and neuroimaging measures were compared between groups. Regression analyses were then conducted between levels of blood markers and brain measures. Analyses were corrected for age, sex, education and anxiety symptoms with statistical significance set to p<0.05.ResultHigher blood epinephrine level (p<0.024), and FC between the hypothalamus and the CA1 hippocampal subfield (p<0.040), was found in DepS compared to NoDepS (Fig.1). This higher epinephrine level was associated with greater FC between the hypothalamus and the CA1 (p<0.007) and Subiculum (p<0.013) subfields (Fig.2). Lower GM volume in the CA1 (p<0.008) and DG/CA2‐3‐4 (p<0.013) subfields was also found in the DepS group (Fig.3), but was not associated with epinephrine level. No significant between‐group difference in blood cortisol and norepinephrine levels was observed.ConclusionSubclinical depressive symptoms in aging are associated with higher blood epinephrine level related to greater FC between the hypothalamus and hippocampal subfields (CA1 and Subiculum) – suggesting an increased sympathetic nervous system activity. They are also associated with GM atrophy in specific hippocampal subfields, including the CA1 that is sensitive to AD. These two distinct mechanisms at this preclinical stage of depression may at least partly explain that depression is a risk factor for AD.
Ripple effects of small group care for patients with dementia in hospital on ward nurses
Authors: Degai Yuko , Otsuka Mariko , Nakagomi Saori , Narisawa Ken , Tokunaga Shiho 
Published: December 2023

AbstractBackgroundThe average length of stay in general beds is about 16 days in Japan . Providing quality care to inpatients with dementia has been a challenge in acute hospitals. In Japan, “in‐hospital daycare”, in which patients gather in specific places in the hospital for recreation and rehabilitation, is increasing. Therefore, we aimed to clarify the current situation of “in‐hospital daycare” at hospitals in Japan and the ripple effect on dementia care in wards.MethodA web‐based survey was conducted on 1,101 nurses working in hospitals who are certified as experts of dementia or geriatric care.ResultData were obtained from 272 nurses (response rate: 24.7%). 38 nurses (14%) have provided “in‐hospital daycare”, and 51 nurses (18.8%) provided it before the COVID‐19 pandemic. We analyzed data of these 89 nurses.91.0% of them recognized that “in‐hospital daycare” was effective for the patients who participated. In addition, they reported the ripple effect on ward nurses. Ripple effects are 〈ward nurses are more supportive of patient activity/diversional activity 〉〈Ward nurses are more aware of patient strengths〉〈Ward nurses noticed new aspects of patients and backgrounds, and deepened their understanding of patients〉〈Increased conversations between ward nurses and patients〉and so on.ConclusionAlthough only about 30% of facilities provide “in‐hospital day care”, it has not only an effect on participating patients, but also has a ripple effect on ward nurses. Results suggest that it contributes to improving the quality of dementia care in the ward.
DNA methylation profiling of individual neurons isolated from post‐mortem brain tissue using laser capture microdissection and adapted limiting dilution bisulfite pyrosequencing
Authors: Riemens Renzo J.M. , Kenis Gunter , Nolz Jennifer , Chaves Sonia C. Susano , Duroux Diane , Pishva Ehsan , Mastroeni Diego , Van Steen Kristel , Haaf Thomas , Hove Daniel L. A. 
Published: December 2023

AbstractBackgroundA challenge frequently encountered in neuroepigenomic research, especially in the context of neurodegenerative diseases such as Alzheimer’s disease, is the difficulty of measuring epigenetic patterns in heterogenous bulk tissue samples, as these are known to cause noise during profiling. A viable strategy to overcome this challenge is to analyze epigenetic marks in single neurons that have been isolated using laser capture microdissection (LCM).MethodIn this study, we developed a new approach for targeted DNA methylation profiling of individual genes that combines the use of LCM and limiting dilution bisulfite pyrosequencing (LDBSP). By utilizing this method, we were able to determine the cytosine‐phosphate‐guanine (CpG) methylation rates of single alleles obtained from 50 neurons, which were isolated from unfixed post‐mortem brain tissue.ResultWe demonstrate how the methylation status of multiple genes such as RHBDF2, OXT, TNXB, DNAJB13, PGLYRP1, C3, and LMX1B, can be quantified simultaneously using the method described above. In addition, we provide an adapted data analysis pipeline for LDBSP, which accounts for and corrects methylation rates obtained from multi‐allele reactions. Furthermore, we show that the efficiency of LDBSP on DNA derived from LCM‐isolated neurons is comparable to the efficiency in previous studies using other cell types.ConclusionThis method allows for a more precise determination of the DNA methylation status of each targeted gene in the neuronal cell samples under investigation, thereby increasing the validity of the technique.
Association of cognitive reserve with cognitive function and quality of life in the years following a diagnosis of dementia: initial findings from the IDEAL study
Authors: Gamble Laura D , Clare Linda , Martyr Anthony , Matthews Fiona E 
Published: December 2023

AbstractBackgroundEffects of brain pathology or ageing on cognitive function are moderated by an individual’s ability to optimise or maximise the use of the brain’s resources to perform tasks, and is a concept known as cognitive reserve. In dementia, cognitive reserve may reflect the capacity to provide a buffer against effects of dementia‐related brain pathology, resulting in a delay in signs and symptoms of dementia. Studies have found that a higher level of education may not only lead to a delay in the onset of dementia, but impact on the rate of cognitive decline following a diagnosis. Here we investigate whether a latent measure of cognitive reserve at diagnosis impacts on cognitive function or quality of life in the years following a diagnosis.MethodWe used longitudinal data from 1545 individuals with mild‐to‐moderate dementia participating in the IDEAL study. Assessments took place on entry, and at 12 and 24 months. A latent measure of cognitive reserve was created based on education, social class and engagement in social and cognitive activities. Latent growth curve models were used to look for associations of cognitive reserve at diagnosis with cognitive function and quality of life in the years following diagnosis.ResultA higher cognitive reserve was associated with higher cognitive function at the time of diagnosis, but following diagnosis individuals with a higher cognitive reserve had a faster rate of decline in cognitive function. Whilst higher cognitive reserve was associated with a higher quality of life at the time of diagnosis, there was no association between cognitive reserve and change in quality of life in the years following diagnosis.ConclusionThose with a higher cognitive reserve at baseline are more likely to decline in cognitive function at a greater rate following diagnosis suggesting that it may be possible to identify individuals who may decline more quickly based on their education, social class and social and cognitive activities later in life.
Distinctive modulation patterns of functional brain connectivity of the default mode network by negative social emotions are associated with Alzheimer’s disease biomarkers in community‐dwelling older adults – cross‐sectional findings from the Age‐Well trial
Authors: Klimecki Olga M , Lugo Sebastian Baez , Demnitz‐King Harriet , Gonneaud Julie , Poisnel Géraldine , Marchant Natalie L , Vuilleumier Patrik , Chetelat Gael 
Published: December 2023

AbstractBackgroundRecent evidence in Alzheimer’s diseases suggests that early dysfunction of emotional processing may precede the onset of cognitive decline and dementia. Altered functional brain connectivity patterns also occur along with other brain changes many years before clinical AD symptoms.MethodWe combined baseline multimodal neuroimaging data from cognitively healthy older adults (N = 125) enrolled in the Age‐Well trial of the Medit‐Ageing study. The aim was to elucidate the relationship of five AD risk factors (amyloid‐beta depositions and hypoperfusion with AV45‐PET, hippocampal atrophy, cognition with PACC‐5, cardiovascular risk with CAIDE) with carry‐over effects of social emotions and related brain functions. Using k‐means clustering analysis with the AD risk factors, we first defined participants with higher or lower preclinical risk for AD. We then used functional Magnetic Resonance Imaging to probe functional brain connectivity in resting periods following negative socio‐emotional videos in the SoVT‐Rest paradigm.ResultParticipants with a higher preclinical AD risk showed reduced positivity bias in affect ratings and reduced connectivity patterns between control‐related frontal brain regions and emotion‐related limbic regions (amygdala). In particular, this fronto‐limbic connectivity was associated with higher cardiovascular risk on the CAIDE composite score.ConclusionWe find evidence for changes in post‐emotion functional recovery patterns in fronto‐limbic brain networks in at‐risk individuals for AD. These changes might reflect impaired emotion regulation processes.
Inter‐ and intra‐individual variation in brain structural‐cognition relationships in aging
Authors: Patel Raihaan , Mackay Clare , Jansen Michelle G , Devenyi Gabriel A. , O'Donoghue M Clare , Kivimaki Mika , Singh‐Manoux Archana , Zsoldos Enikő , Ebmeier Klaus P , Chakravarty Mallar , Suri Sana 
Published: December 2023

AbstractBackgroundThe sources of inter‐ and intra‐individual variability in age‐related cognitive decline remain poorly understood. We examined the association between 20‐year trajectories of cognitive decline and multimodal brain structure and morphology in older age.MethodWe used the Whitehall II Study, an extensively characterised cohort with 3T brain magnetic resonance images acquired at older age (mean age = 69.52 ± 4.9) and 5 repeated cognitive performance assessments between mid‐life (mean age = 53.2 ±4.9 years) and late‐life (mean age = 67.7 ± 4.9). Using non‐negative matrix factorisation, we identified 10 brain components integrating cortical thickness, surface area, fractional anisotropy, and mean and radial diffusivities (Figure 1).ResultWe observed two latent variables describing distinct brain‐cognition associations. The first describes variations in 5 structural components associated with low mid‐life performance across multiple cognitive domains, decline in reasoning, but maintenance of fluency abilities. The second describes variations in 6 structural components associated with low mid‐life performance in fluency and memory, but retention of multiple abilities (Figure 2). Expression of latent variables predicts future cognition 3.2 years later (mean age = 70.87 ± 4.9) (Figure 3).ConclusionLongitudinal cognitive decline and maintenance across diverse cognitive functions are both positively and negatively associated with distinct markers of cortical structure. Latent brain‐behaviour relationships predict future cognitive performance.
Evaluation of performance of genoSCORETM for predicting onset of Alzheimer’s disease in a Japanese population
Authors: Gao Qian , Daunt Paula , Kikuchi Masataka , Miyashita Akinori , Ozaki Kouichi , Niida Shumpei , Iwatsubo Takeshi , Ikeuchi Takeshi , Gibson Alex , Pither Richard 
Published: December 2023

AbstractBackgroundThe development of diagnostic tools to identify disease risk is critical to enable selection of suitable individuals for inclusion in clinical trials, cohort studies and ultimately to identify patients most likely to benefit from newly approved therapies. Cytox has developed and validated a polygenic risk scoring (PRS) algorithm, genoSCORETM, for predicting the Late Onset Alzheimer’s disease (AD) based on the work pioneered by Escott‐Price, Williams et al 1. However, both training and testing has been performed in study populations containing primarily individuals with Caucasian ethnicity. To ensure that genoSCORE can equally be applicable to all ethnic groups, we have conducted an initial evaluation to understand predictive accuracy for the onset of AD in a Japanese population.MethodsThe PRS approach used in this study is built from a sum of weighted contributions of over 100,000s SNPs associated with disease2. Due to the limited SNP coverage of existing genetic data, we only used 63,499 SNPs and utilized the core genoSCORE algorithm to calculate PRS in a cohort of 2,081 AD and 2,327 CN Japanese subjects from J‐ADNI3 and Niigata University.ResultsThe preliminary result shows an AUC of 0.659 (0.643‐0.675, 95% CI) between AD and CN subjects while PRS presents a bimodal distribution, but the main distribution trend is comparable to a normal distribution of PRS of the ADNI (US) subjects. Although this is significantly less than that seen for Caucasian individuals in the ADNI study, it compares well with the results generated when the reduced number of SNPs are used only in the ADNI cohort subjects (AUC = 0.691).ConclusionsThe preliminary results show the potential use of genoSCORE in the Japanese population. However, the results are likely affected by the limited SNP coverage from the available genetic data for the Japanese population. To determine the true performance of the genoSCORE algorithm in a Japanese population, genotyping samples from this study using our proprietary variaTECTTM II array providing full SNP coverage is in progress. We will then determine the performance and make adjustments to the algorithm if required in a Japanese population of suitably characterized Alzheimer’s disease patients and age‐matched healthy controls.
Regional cortical hypoperfusion observed in elderly adults prior to development of mild cognitive impairment
Authors: Zhang Linda , Frank Darya , Alfayate Eva , del Ser Teodoro , Medina Miguel , Strange Bryan A 
Published: December 2023

AbstractBackgroundCardiovascular disease is associated with increased risk of developing mild cognitive impairment (MCI) and Alzheimer’s disease (AD), although the underlying mechanisms are not well understood. While it has been theorised that cerebral hypoperfusion caused by heart failure may directly lead to the formation of amyloid plaques and neurofibrillary tangles characteristic of AD, it has also been suggested that decreased perfusion occurs later in disease progression. We used arterial spin labelling (ASL) MRI to compare cerebral blood flow (CBF) between cognitively unimpaired elderly individuals who would remain cognitively stable and those who would later develop MCI to determine if hypoperfusion is detectable at a preclinical stage.Methods647 cognitively normal elderly participants with ASL and structural T1‐weighted MRI were selected from the Vallecas Project cohort, a single‐centre longitudinal study currently in its 12th year of annual follow‐up. 586 participants remained cognitively stable (CS) while 61 participants developed MCI over the course of the study. Cortical CBF maps derived from ASL images at the visit before MCI diagnosis were analysed in a voxelwise comparison with CS individuals, with age, sex, and total intracranial volume as covariates.ResultsCBF was significantly lower in the right insular cortex in future MCI converters than CS individuals (p<0.05, family‐wise error (FWE) corrected). Hypoperfusion was also significant in the anterior corpus callosum in future converters.ConclusionCerebral hypoperfusion, as measured by ASL, can already be observed in individuals before the onset of clinical symptoms.
A Scoping Review of Outdoor Activities for People Living with Dementia
Authors: Tavilsup Pattara , Abolarin Margaret , Tran Lan , Lui Allysan , Seitz Dallas 
Published: December 2023

AbstractBackgroundOutdoor or nature‐based activities can potentially offer benefits to improve the quality of life for people living with dementia (PLWD). The aim of this scoping review is to gain a clear understanding of current studies on outdoor activities for PLWD and their caregivers, as well as to identify gaps in the literature that may require further research.MethodWe systematically searched the following electronic databases: MEDLINE (Ovid); EMBASE (Ovid); APA PsycINFO (Ovid); CINAHL; Cochrane followed the guidelines recommended by the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses Extension for scoping reviews (PRISMA‐ScR) (Tricco et al., 2018). We included primary studies that met the following criteria:1) the study population includes either PLWD or people self‐identified as caring for people with dementia; 2) study outcomes are related to outdoor activities and/or nature; 3) the study report effects of how the outdoor activities change the diagnosis of dementia either qualitatively and/or quantitatively; 4) primary studies and literature reviews, dissertations, conference presentations or discussion papers, peer reviews and non‐peer reviewed; 6) all geographical areas but published in English and year 1980 to presentResultOur initial search resulted in 7678 potentially relevant titles and abstracts. This number was decreased to 299 articles for the full‐text review. The extracted data have been charted by the following categories: authors, year of publication, study location, aims/purpose, characteristics of included studies, methods, outcomes, and key findings. The findings were summarized using frequency counts of concepts and characteristics. Thematic analysis was undertaken which identified four themes. More specifically, we identified 1) Benefits of outdoor or nature‐based activities; 2) Interventions to improve quality of life; 3) Barriers and challenges to accessing outdoors and nature; 4) Recommendations for outdoors or nature‐based activities.ConclusionThere is growing evidence for the benefit of outdoor activities, recommendations to improve outdoor activities and which interventions are most beneficial among people with dementia. There is limited information about factors which may act as barriers for people with dementia which will be important to ensure wider access to these activities.
The relation of loneliness and social resources with neuropathology, and cognitive resilience to neuropathology
Authors: Wagner Maude , Wilson Robert S. , Boyle Patricia A , Leurgans Sue E. , Schneider Julie A , Bennett David A. A , Grodstein Francine , Capuano Ana W. 
Published: December 2023

AbstractBackgroundAlthough numerous studies report an association between loneliness and social resources with cognitive decline and dementia risk, the underlying pathways remain to be explored. Thus, we investigated two possible pathways: an association of loneliness and social resources with (i) neuropathology and (ii) with cognitive resilience to neuropathology.MethodWe examined 792 decedents from the Rush Memory and Aging Project, free of dementia at their initial report of the psychosocial risk factors of interest (loneliness, social activity, social support, social network size); all eligible participants completed ≥2 cognitive evaluations and had a postmortem neuropathology evaluation. First, we examined the associations between each psychosocial factor and nine neurodegenerative and vascular neuropathologies, using linear or logistic regression models. Second, we assessed the associations between each psychosocial factor and two cognitive resilience (CR) measures. The measures quantify how late‐life cognitive levels (CR) and cognitive decline (CRSlope) differ from what is expected, given the profile of neuropathology. All models controlled for sex, education, age at death, and medical comorbidities.ResultWe found few associations between each psychosocial factor and all nine individual neuropathologies; for example, greater loneliness was not associated with higher global AD pathology (estimated mean difference [MD] for each one‐unit increment in loneliness score = 0.002, 95%CI = ‐0.07,0.07, P = .9), while more social engagement was associated with less global AD pathology (social activity: MD = ‐0.03, 95%CI = ‐0.11,0.05, P = .5; social support: MD = 0.05, 95%CI = ‐0.02,0.11, P = .2). However, we found strong associations between higher degree of loneliness with worse CR (MD = ‐0.25, 95%CI = ‐0.37,‐0.14, P<.0001) and CRSlope (MD = ‐0.23, 95%CI = ‐0.34,‐0.11, P = .0002). In addition, greater participation in social activities was associated with better CR (MD = 0.24, 95%CI = 0.12,0.36, P = .0001) and CRSlope (MD = 0.13, 95%CI = 0.01,0.25, P = .04). There was no relationship between social support or social network and CR.ConclusionThese findings suggest that loneliness and social activity in late life are not directly associated with the accumulation of neuropathologies but may be associated with resilience to neuropathologies.