bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrical field strength from anodal prefrontal tDCS determines degree of white matter integrity changes in amnestic MCI patients
Authors: Kang Dong Woo 
Published: December 2023

AbstractBackgroundAn electrical field (EF) strength induced by tDCS affects a therapeutic effect. Additionally, sequential tDCS has improved white matter integrity in cognitively impaired patients. However, researchers have not evaluated the impact of EF strength on white matter integrity in the prodromal stage of dementia. This study aimed to elucidate the effect of EF strength from prefrontal anodal tDCS on white matter integrity change and the modulating role of relevant genetic and pathologic factors in this effect in amnestic mild cognitive impairment (MCI) patients.MethodIn 55 amnestic MCI patients, we delivered anodal‐tDCS (2 mA/day, five times/week, for two weeks) over the left dorsolateral prefrontal cortex (DLPFC), calculated the EF strength for the left inferior frontal gyrus and DLPFC through the stimulation navigation program analysis. Additionally, we assessed the white matter integrity by diffusion tensor imaging before and after two weeks of stimulation; finally, we evaluated the modulating factors: amyloid‐beta (Aβ) deposition, APOE ε4‐allele status, and BDNF polymorphism.ResultAs the EF intensity in the left inferior frontal gyrus increased, the range of changes in white matter integrity significantly increased in left anterior thalamic radiation, corticospinal tract, inferior fronto‐occipital fasciculus, and inferior longitudinal fasciculus. Additionally, we found that greater change in white matter integrity was observed with higher regional EF strength in the APOE ε4 non‐carriers and BDNF MET non‐carrier, which could be attributed to an interaction between these modulating factors and EF intensity in the left anterior thalamic radiation and right uncinate fasciculus.ConclusionThese findings provide evidence for the precision‐medicine‐based application of tDCS in the prodromal stage of dementia, inducing the optimized therapeutic effect.
Managing Alzheimer’s patients in rural areas of developing country
Authors: Pal S , Guha B , Roy T 
Published: December 2023

AbstractBackgroundNational‐health‐registry based data demonstrates Psychosocial support & treatment‐availability are major issues for Alzheimer’s ‐sufferers in resource‐poor‐nations. Hence our Non‐Government‐Organisation analysed & made this public health‐policy paper recommendation’s.NGO’s are close to rural/tribal‐communities. Cost of running NGO is economical than medical‐institution. Medical treatment cost is prohibitive and inaccessible for majority patients in Asia. Government‐Health‐Departments need to workout strategy to increase access to care.In resource‐poor‐setting unaffordable cost leads to poor‐therapeutic‐compliance & therefore high mortality. We developed training program to evolve sound /sustainable Alzheimer’s‐care for rural communitiesMethodsNo national‐program for financial help to Alzheimer’s patients exists in india. Treatment programs designed towards rural/tribal population needed. Since four years we offer guidance for drug‐therapy‐funding. This project is unique, as we are training NGO health workers to assist patients community in improving access to care. Depending on support given by donors, we provide financial‐assistance for treatment. We improved access to governmental hospitals. Initially we started with two towns & intend to offer our services to 23 villages by 2025.ResultsWe did face hiccups in mobilising volunteers/resources. Our strategy has minimum maintenance‐cost & high‐acceptability. Forums like AAIC‐2023 conference must support NGO‐activists to form workgroups with AAIC conference‐participants to further develop this concept on larger scale.ConclusionEconomical‐factors/access to therapy changes out‐come of treatment. With little training, few resources our community NGO in rural/tribal India formed well knit volunteers‐group who are giving free part‐time dedicated service. psychosocial‐support improves QOL reducing difficulties faces by resource‐poor‐southern countries. We urge participants to share views/expertise on this burning‐issue at AAIC‐2023‐venue to come out with sustainable policy paper for Asian nations.
“His reality certainly isn’t the reality that we know”: Care partner responses to differing realities among assisted living residents with dementia
Authors: Kemp Candace Lynn , Morgan Jennifer Craft , Perkins Molly , Burgess Elisabeth O , Hill Andrea M , Pullon Emerald , Bender Alexis Anne 
Published: December 2023

AbstractBackgroundIn the United States and elsewhere, assisted living (AL) has become a primary provider of residential long‐term care for persons living with dementia. Residents typically are supported by care convoys, or networks, comprised of their family and friends, AL staff, as well as external care providers, all of whom exert influence on residents’ daily lives. As with other persons living with dementia, AL residents sometimes experience confusion over time, place, and scenario. Care partner responses to these differing realities are consequential to residents’ care experiences, quality of life, and ability to engage with others and in activities they find meaningful. Here, we examine, in‐depth, care partner responses to residents' confusion, the complex factors influencing their reactions, and the resulting outcomes.MethodWe present analysis of qualitative data gathered from the study, “Meaningful Engagement and Quality of Life among Assisted Living Residents with Dementia,” involving six diverse AL communities, each studied for a one‐year period. Researchers conducted 2,109 hours of participant observation captured in detailed fieldnotes. We also followed 59 residents with dementia and 167 of their care partners, conducting interviews to learn how best to promote meaningful engagement. Specifically, we analyzed all data relevant to residents’ “differing realities” and “care partner responses.”ResultCare partners varied in their responses to residents’ differing realities. Some, including many AL staff, routinely attempted to redirect residents by changing the subject and/or physically redirecting (e.g., if a widowed resident was searching for her husband). Certain care partners joined residents by attempting to understand their realities and “going along with them.” A small minority of care partners, mostly family members, ignored or attempted to correct or truth tell. Factors affecting care partner responses included: the nature of resident confusion and associated expressions and a care partner’s role, dementia knowledge and care resources, beliefs, and experiences. Truth‐telling or correcting frequently, though not always, led to frustration, anxiety, and socially withdrawing whereas responses that acknowledged the person’s reality frequently had better resident outcomes.ConclusionFindings have implications for training, practices, and policies aimed at enhancing care interactions and quality of life among persons living with dementia.
Spot, treat and stop delirium: Acceptability and feasibility of a novel ‘Delirium Wheel App’ to identify and manage delirium in a care home setting in the United Kingdom
Authors: Negi Rashi 
Published: December 2023

AbstractBackgroundDelirium is common in elderly, frail residents in care home settings, who may already be suffering from dementia. The prevalence of delirium in nursing homes can be up to 60%. Care home staff are potentially in a unique position to identify the subtle changes that can precede a full‐blown episode of delirium. Towards this aim, as a part of frailty initiative West Midlands, a delirium app, called ‘Delirium Wheel’ (https://rb.gy/ns80hw) was developed.MethodIn order to explore the feasibility of the Delirium Wheel (DW) app to support care home staff to care for patients experiencing delirium, a feasibility study was carried out between October 2022 to May 2023 in 6 care homes in Staffordshire. The care homes were given delirium app training and a survey was carried out to assess their baseline knowledge and skills in the identification and management of delirium. A further survey was carried out 12 weeks following the implementation of the app, with qualitative interviews carried out with a sample of the care home staff.ResultThe study is currently at Stage 1 of the data collection phase and the initial surveys have been collected evaluating baseline knowledge and practice within the care homes. Staff members have now been interviewed as part of Stage 2 of the study process, with the qualitative data currently being transcribed. The full results are expected to be reported by the end of April 2023.ConclusionThis study is the first research which formally tests this unique app as a digital tool to support healthcare professionals in the identification and management of a very common condition such as delirium. This empowers care home staff to have confidence in their own skills and have an app to support if there is any clinical uncertainty. As a result of this intervention, the probability of patient’s being able to be managed within the care home setting increases, leading to better patient related outcomes.
Transcriptional risk score in Alzheimer’s disease: from pathology to cognition
Authors: Pyun Jung‐Min , Park Young Ho , Wang Jiebiao , Bennett David A. A , Bice Paula , Kim Jun Pyo , Kim SangYun , Han Moon‐Ku , Saykin Andrew J. , Nho Kwangsik 
Published: December 2023

AbstractBackgroundTranscriptional risk scores (TRS), a summation of polarized expression levels of functional genes, have been proposed for disease risk assessment using transcriptome profiles. Our previously developed blood‐based TRS showed associations with diagnosis and neuroimaging biomarkers for Alzheimer’s disease (AD). Here, we developed brain‐based TRS models and calculated TRS using brain tissue‐based transcriptome profiles.MethodWe integrated AD genome‐wide association study summary and expression quantitative trait locus data to prioritize target genes using Mendelian randomization and then calculated individual TRS by summing the polarized z‐scores over the target genes. We used brain transcriptome data from the Religious Orders Study and Rush Memory and Aging Project cohort (ROSMAP; N = 634) as a discovery set and the Mount Sinai Brain Bank cohort (MSBB; N = 244) as a replication set. We performed association analysis of TRS with AD diagnosis, amyloidopathy, tauopathy, and cross‐sectional and longitudinal cognitive function. We compared AD classification performance of TRS with polygenic risk scores (PRS) using a machine learning approach (Fig. 1).ResultHigher TRS values were significantly associated with AD compared to cognitively normal controls (Table 1). Higher TRS values were also related with amyloidopathy, tauopathy, poor cognitive performance, and faster cognitive decline. The AD classification performance of PRS was increased with the inclusion of TRS up to 12% with the area under the curve value of 0.842 (Fig. 2). These findings were replicated in the replication dataset.ConclusionOur results showed that brain‐based TRS is associated with AD pathology and clinical course. Furthermore, TRS improves the AD classification performance of PRS. Along with static PRS, dynamic TRS based on transcriptional expression levels at a given time could be a potential disease‐stage specific AD biomarker.
Changes of brain metabolites in early Alzheimer’s disease: A high‐field magnetic resonance spectroscopy study on medication treatment effect
Authors: Zhang Ningnannan , Zhang Zhang , Song Xiaowei 
Published: December 2023

AbstractBackgroundAD involves deficits in essential brain chemicals. A functional neurocompensatory response in brain regions critical for executive control has been reported for early AD. It is unclear whether such an effect can be detected in brain metabolites and affected by medication treatments. In this study, we used single‐voxel proton magnetic resonance spectroscopy (SV‐1H‐MRS, short as MRS here) to quantify neurochemical changes non‐invasively. Our objectives are to 1) examine differences in key neurometabolites between brain regions either compromised or preserved in early AD and 2) test the potential effect of medication treatment on metabolite levels in the brain regions.MethodSixteen participants with early AD (76.8±8.0 yrs, 56.2% female) and 20 normal controls (73.6 ± 6.3 yrs, 60% female) had two MRS sessions six months apart. AD patients took cholinesterase inhibitors as part of standard care following the baseline scan. MRS acquisition used 4T MRI with LASER sequence from two voxels (5.12cm3), respectively placed in the posterior cingulate gyri (PCG) and the left dorsolateral prefrontal cortex (DLPFC). Spectra data were fitted using fitMAN and analyzed using ANOVA for main effect and interactions (voxel placement, subject group, scan time).ResultThe level of many metabolites was greater in the DLPFC than in the PCG voxels (Fs>4.01, ps<0.050), regardless of the subject group. Participants with early AD had lower levels of NAA and Gln (absolute value and ratio to Cr) and higher Cr/NAA than controls across the brain regions (Fs>4.09, ps<0.047). Post‐treatment, a change in Ala/Cr, Gly/Cr, Gly/NAA, and Lac/NAA (Fs>4.04, ps<0.048). There was an increase in Syl only in the DLPFC voxel (Fs>6.71, ps<0.029), whereas there was a decrease in Gly/NAA in the PCG voxel (F = 11.47, p = 0.005). In contrast, in controls, NAAG in the PCG voxel decreased between baseline and follow‐up (Fs>5.08, ps<0.027).ConclusionThe data showed a lower level of several metabolites essential for maintaining neuronal function and connectivity in early AD than normal aging, especially in brain regions that are compromised early in the disease process. The study suggested a positive impact of clinical management of early AD on enabling neurocompensation for at least six months.
Ante‐mortem cognitive trajectories of older adults with cerebrovascular disease across Aβ and tau biomarker profiles determined at autopsy in the National Alzheimer’s Coordinating Center database
Authors: Rosenich Emily , Lim Yen Ying 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is characterised biologically by beta‐amyloid (Aβ) plaques and tau tangles, but autopsy studies reveal that most older adults also present with cerebrovascular disease (CVD) markers. Effects of biological AD on cognition in the context of concurrent CVD remain unclear. In older adults with CVD pathology, this study sought to determine ante‐mortem cognitive trajectories associated with Aβ/tau positivity or negativity (+/−) at autopsy.MethodParticipants aged 65‐95 classified as cognitively unimpaired at baseline from the National Alzheimer’s Coordinating Center database, with ≥1 follow‐up between 2005‐2015, and available autopsy/APOE data were included (N = 924). Autopsy indicated that all participants had at least one of six CVD pathology markers. Participants were classified into four groups (A−T−, A+T−, A−T+, A+T+) based on semiquantitative Consortium to Establish a Registry for Alzheimer’s Disease neuritic plaque staging and Braak staging. Linear mixed models including group × time interactions assessed rate of change in Preclinical Alzheimer’s Cognitive Composite scores, episodic memory, and executive function. Interactions between age, sex, APOE ε4 × time and the interval between death/the final study visit were included as covariates.ResultA+T+ adults demonstrated significantly faster cognitive decline on all outcomes in the ∼10 years preceding death compared to A−T−, A+T−, and A−T+ adults (Table 1, Figure 1, d = 0.15 – 0.39). At final visit prior to death, a greater proportion of A+T+ adults (36%) received a dementia diagnosis compared to A−T+ (14%) or A+T− (15%) (p <.001). When analyses were restricted to exclude dementia diagnoses, significantly faster decline on all outcomes (p’s <.001, d = 0.06 – 0.36) was similarly observed in A+T+ adults compared to A−T−, A+T− and A−T+ adults (Figure 2). Cognitive trajectories were equivalent between A−T− and A+T− for all outcomes (p’s >.55).Conclusionln older adults with CVD pathology, A+T+ at autopsy was associated with greater cognitive decline over 10 years preceding death compared to A+T−, A−T+, and A−T− older adults. Faster cognitive decline in this group in the context of low final visit dementia diagnoses may suggest that post‐mortem A+T+ is associated with a steep trajectory of cognitive decline ante‐mortem, but that dementia progression is not inevitable.
Poor self‐rated health is associated with faster cognitive decline and greater small vessel disease in older adults with type 2 diabetes
Authors: Ramsingh Nadia , Lin Hung‐Mo , Ouyang Yuxia , Ravona‐Springer Ramit , Livny Abigail , Soleimani Laili , Bendlin Barbara B , Ben‐Meir Mery , Heymann Anthony , Sano Mary , Azuri Joseph , Beeri Michal S 
Published: December 2023

AbstractBackgroundSelf‐rated health (SRH) is a predictor for poor health outcomes and cognition. Older adults with type 2 diabetes (T2D) have multi‐morbidity and greater cognitive impairment. In this study we investigated the association of SRH with cognitive decline and brain pathology in older adults with T2D.MethodParticipants (n = 1,149) were from the Israel Diabetes and Cognitive Decline study, SRH was an age referential question categorized to low (n = 210), moderate (n = 410) or high (n = 529). Cognition was measured by four cognitive domains: episodic memory, executive functions, language, and attention/working memory. Global cognition was the average of the cognitive domains. Statistical models adjusted for sociodemographic, cardiovascular, and clinical variables. In a randomly selected subsample (n = 230) that had MRI, we examined relationships between baseline SRH and brain characteristics (white matter hyperintensities (WMHs), hippocampal, and total gray matter volumes).ResultThe association of low SRH with decline in executive functions accelerated over time, when compared to high SRH (est = ‐0.0036; p = <0.001). This pattern was also observed for the association of low versus high SRH with global cognition (est = ‐0.0023; p = 0.010). Low SRH at baseline was associated with higher volumes of WMHs (est = 9.8420; p<0.0008). SRH was not associated with other cognitive domains, or with hippocampal and total gray matterConclusionLow SRH is associated with cognitive decline in T2D older adults and may serve for risk assessment and enrichment. WMHs may represent an underlying mechanism.
Circadian rhythms in older adults are associated with sleep quality, cognitive function, and ß‐amyloid burden: an accelerometry analysis of the Lifestyle Enriching Activities for Research in Neuroscience Intervention Trial ‐ LEARNit
Authors: Eckhardt Joanna L , Isenberg A. Lisette , Stradford Joy , Aslanyan Vahan , Fenton Laura E. , Monreal Teresa , Pa Judy 
Published: December 2023

AbstractBackgroundSeveral studies demonstrate circadian rhythm disturbances in patients with Alzheimer’s disease. However, less is known about circadian rhythms in older adults with early mild cognitive impairment. Wrist‐worn accelerometers provide continuous, objective, high resolution quantification of 24‐hour rest activity rhythms. This study examines the relationship between circadian rhythms and sleep, cognition, and ß‐amyloid (Aß) burden.MethodThis study examines baseline data from the “Lifestyle Enriching Activities for Research in Neuroscience Intervention Trial” (LEARNit). Sixty‐six older adults ages 55‐80 experiencing early cognitive changes wore a GENEActiv accelerometer for approximately 30 consecutive days. Accelerometer data was analyzed using the R package GGIR (version 2.8‐1), and circadian rhythm measures were extracted using the GGIR secondary package ActCR (version 0.3.0). Circadian rhythm variables include intradaily variability (fragmentation), interdaily stability (rhythm synchronization to light‐dark cycle), acrotime (peak activity time), and Midline Estimated Statistics of Rhythm or MESOR (mean activity level). Up‐MESOR and Down‐MESOR represent the timing of activity increasing above or decreasing below MESOR, respectively—lower values of each indicate a phase advance (shift towards morning), whereas higher values indicate a phase delay (shift towards evening). Sleep was assessed as mean sleep efficiency and Wake After Sleep Onset, or WASO (accumulated wakefulness after sleep onset). Cognitive tests include the Montreal Cognitive Assessment (MoCA) for global cognition and attention/processing speed (Digit Symbol Task). Aß burden was measured by positron emission tomography standard uptake value ratio for fifty‐six participants. Age‐adjusted linear regression models were used to test associations between circadian rhythms and sleep, cognition, and Aß.ResultParticipant characteristics are summarized in Table 1 and results are summarized in Figure 1. Intradaily variability (b = ‐0.095, p = 0.03) and interdaily stability (b = 0.34, p = 0.01) were both associated with mean sleep efficiency. Intradaily variability (b = 1.41, p<0.001) and interdaily stability (b = ‐4.45, p<0.001) were associated with WASO. Up‐MESOR was associated with MoCA total score (b = ‐0.41, p = 0.03). Up‐MESOR (b = ‐2.12, p = 0.006), Down‐MESOR (b = ‐1.99, p = 0.02), and acrotime (b = ‐4.20, p<0.001) were associated with Digit Symbol score. Down‐MESOR was significantly associated with Aß (b = ‐0.029, p = 0.02).ConclusionCircadian rhythm robustness is positively associated with better sleep quality. Participants with dynamic circadian rhythm phases demonstrated poorer cognition and higher Aß burden.
Differential Heart Rate Variability Profiles During Sleep in Older Adults with Remitted Early‐onset versus Late‐onset Depression
Authors: Kong Shawn Dexiao , Espinosa Nicole , McKinnon Andrew C , Gordon Christopher J , Wassing Rick , Hoyos Camilla M , Mowszowski Loren , Hickie Ian B , Naismith Sharon L 
Published: December 2023

AbstractBackgroundSleep is a physiological state involving a dynamic autonomic profile that is ideal for detecting subtle changes in autonomic nervous system functioning. The current study sought to determine if heart rate variability (HRV) during different periods of sleep is impaired in older adults with early‐onset (EOD), late‐onset (LOD), and no history of lifetime depression (NOD).MethodA total of 188 older adults aged 50‐90 years were recruited from the Healthy Brain Ageing clinic at the Brain and Mind Centre, University of Sydney. This samples comprised 49 participants with EOD, 37 with LOD, and 102 with NOD. Each participant underwent medical, psychiatric and neuropsychological assessments, as well as overnight polysomnography.ResultFindings show that for HRV during wake‐after‐sleep‐onset (WASO), only older adults with remitted EOD have significantly lower SDNN and Shannon Entropy, two HRV indices of interest, in comparison to the NOD group, suggesting that those with EOD have diminished overall autonomic function and cardiac complexity respectively. By contrast, older adults with remitted LOD have significantly lower parasympathetic activities during deeper sleep stages (i.e. N2 and N3), as evidenced by a reduction in high‐frequency HRV relative to the EOD group. Overall, our findings suggest that the EOD and LOD phenotypes have differential heart rate profiles during sleep.ConclusionA history of depression, in particular whether this history is early‐ or late‐ onset, is associated with the integrity of autonomic functioning during both wakefulness and sleep in older adults. HRV may have potential as a biomarker of depression and could complement other biomarkers to enhance diagnostic accuracy and prognostic monitoring. As older adults with early‐life depression seem to experience more pronounced autonomic dysfunction, this further emphasizes the need for early and effective interventions, as well as proactive preventative strategies for those with remitted major depressive disorder.