bluuebunny/crossref_metadata_2025_split huggingface dataset:
The longitudinal course and determinants of apathy in UK care home residents with dementia
Authors: Sommerlad Andrew , Park Hee Kyung , Marston Louise , Livingston Gill 
Published: June 2023

AbstractBackgroundApathy in dementia is a common and troubling symptom associated with worse disease outcomes but its longitudinal course is unclear We aimed to 1) describe the prevalence and persistence of clinically‐significant apathy in UK care home residents with dementia, 2) investigate the association of other neuropsychiatric symptoms in people with clinically‐significant apathy, and 3) identify sociodemographic and disease related factors associated with worse apathy trajectory.MethodProspective cohort study of residents with dementia recruited from 86 voluntary, state or private UK care homes. At baseline, and 4, 8, 12, and 16 months, care home staff rated apathy using the Neuropsychiatric Inventory (clinically‐significant apathy if score ≥4, sub‐clinical if 1‐3). Staff also rated dementia severity using the Clinical Dementia Rating scale, and provided other sociodemographic information about each participant. We examined the prevalence and persistence of apathy and, in mixed linear models, its association with time, age, sex, dementia severity, antipsychotic use, and baseline apathy and other neuropsychiatric symptoms.ResultsOf 1419 included participants (mean age 85 years (SD 8.5), 975 (68.7%) women), 30% had mild dementia, 33% moderate, and 37% severe. The point prevalence of clinically‐significant apathy was 21.4% (n = 304) and the period prevalence during 16 months follow‐up was 47.3% (n = 671). The point‐prevalence and 16‐month period prevalence of any apathy was 33.3% and 85.1% respectively. The longitudinal course is shown in the figure. Of participants who had follow‐up data, 45 (3.8%) were always clinically‐significantly apathetic, 3 (0.3%) were always sub‐clinically apathetic, and 420 (36.2%) were never apathetic until death or end of follow‐up. In adjusted models, apathy increased over time and was associated with having more severe dementia, worse baseline apathy and other neuropsychiatric symptoms.ConclusionMost people with dementia are not apathetic but it is common and frequently fluctuates in its course. It is important for clinicians to know that most people with dementia do not develop apathy and it is not an inevitable symptom and often remits. People with more severe dementia and other neuropsychiatric symptoms are more likely to have an adverse apathy course, so may be a priority group for current and future treatments.
Antioxidant and anti‐inflammatory effects of Rooibos on cognitive signs of Alzheimer’s Disease in the context of early life adversity
Authors: Minné Donné , Docrat Taskeen , Marnewick Jeanine , Engel‐Hills Penelope 
Published: June 2023

AbstractBackgroundMedicinal plants are important in traditional healthcare in Africa especially in low‐resourced communities living under conditions of adversity. In South Africa, the fynbos plant Aspalathus linearis, or Rooibos, has been used for centuries as a restorative herbal tea. Over the past few decades, the immuno‐modulating properties of Rooibos have been firmly established with studies demonstrating potent antioxidant, anti‐inflammatory and anti‐cancer properties. These indications suggest that Rooibos can aid in prevention of Alzheimer’s Disease (AD), which is strongly linked to immune dysregulation. However, the overall efficacy of Rooibos supplementation may depend on individual differences in neuro‐inflammatory priming, which occurs in early development, partly as a result of stress.MethodIn a double‐blind, placebo‐controlled intervention trial, we aimed to investigate the effects of 12 weeks' supplementation with green or fermented rooibos following a washout period on biophysical and behavioural risk profiles for AD. Using a mixed‐factorial design in a sample of 340 adults, we assessed early life stress history and evaluatedclinical signs of neurodegenerationusing a standardised neuropsychological battery, and cognitive effort based on a pupil dilation task. Biochemical profiles were assessed using patient plasma samples for indices of antioxidant and anti‐inflammatory activity using ELISAs.ResultResults are currently pending.ConclusionThis study contributes to our growing understanding of the medicinal properties of Rooibos and how early life stress influences neuro‐immune processes. Given that tea drinking is an economical and widely adopted social‐cultural practice across all age groups, tea is ideal to target in designing low‐cost dietary interventions for neurodegenerative diseases like Alzheimer’s.
Improving collaboration between palliative care and neurology: Focus on patient, family & healthcare provider experience
Authors: Salwierz Patrick , Sumra Vishaal , Gumus Melisa , Lewin Warren , Martinez Maria , Patel Archna , Salvo Cristina , Swinkin Emily , Tartaglia Carmela , Tang‐Wai David F. , Li Melissa 
Published: June 2023

AbstractBackgroundThe prevalence of neurodegenerative diseases is increasing as the population ages. As these diseases are often incurable, progressive, and associated with significant loss of ability to communicate over time, it is paramount that advanced care planning (ACP) take place early in the disease trajectory to facilitate goal‐concordant care. There is increasing recognition of the barriers for neurologists to facilitate ACP and end‐of‐life care. Palliative care is a medical speciality that focuses on improving quality of life for patients living with serious illness, including helping with healthcare planning and decision‐making that align with the individual’s values and goals. However, there is a paucity of literature on how to best integrate palliative care or which elements of an integrated neuro‐palliative approach are the most beneficial to patients, caregivers, and clinicians.Our study aims to assess the experience of an embedded pilot clinic between Neurology and Palliative Care at the University Health Network (UHN) Memory Clinic on patients/caregivers and health care practitioners.MethodsWe aim to recruit 60 participants, including patients and family members, seen at the UHN Supportive Care Memory Clinic, and who screen positive for three of seven triggers for palliative care involvement for neurological patients as proposed by the National End of Life Care Programme of National Health Service in England. ACP conversations will follow an evidence‐based semi‐structured conversation guide. The impact of the clinic will be evaluated using patient, caregiver, and both Neurology and Palliative Care team member experience surveys. Secondary measures will include the percentage change in ACP and Power of Attorney documentation pre and post initiation of the clinic.ResultsFrom clinic inception in June 2020, 19 patients were seen (all‐virtual). Due to the COVID‐19 pandemic, the clinic was paused for the majority of 2021. Our study received UHN Quality Improvement approval in March 2021, and we began enrolling patients into our study in November 2021; enrolment is ongoing.ConclusionsThe results of this study will serve as a guide for quality improvement of our existing clinic and can inform future implementation of scalable integrated models of care between palliative care and neurology, and for other subspecialties and centres.
The paradox of Urban AD/ADRD caregiving during COVID‐19 pandemic
Authors: Harrington Candace C , Witt Cheryl D 
Published: June 2023

AbstractBackgroundThe SARS‐CoV‐2 RNA COVID‐19‐related societal safety measures triggered unintended consequences with unknown ramifications for the under‐reported, under‐studied, and under‐represented older female family caregivers of those with Alzheimer’s disease/Alzheimer’s disease related dementias(AD/ADRD). The purpose of this qualitative study was to investigate older female caregivers' lived experiences in the context of caring for family members with AD/ADRD during COVID‐19.MethodResearchers used the Dutch (Utrecht) method of phenomenology with interpretative description and thematic analysis, which is valuable to investigate the meaning and context of phenomena when scant research exists.ResultRegardless of community setting, caregivers' physical limitations and hastened disease progression contributed to caregiving fatigue and consideration of placement. Urban caregivers of those with AD/ADRD reported less support (personal and community agency support) in spite of greater access to services in this sample (N = 20). All respondents saw hastened progression of their family member’s dementia they attributed to social isolation. AD/ADRD caregivers who provided full‐time caregiving for their family member depended heavily on their care recipients' financial resources (social security, retirement, savings, and pensions) for basic living expenses. The caregivers reported fear of financial insecurity should their family member be placed in long‐term care.ConclusionThe findings from this study suggest the financial, emotional, and mental toll of caregiving during the COVID‐19 pandemic were greater in the urban sample than in the rural caregiving sample. These findings have practice, research, and policy implications for AD/ADRD caregivers and their care recipients.
Neuroprotective activity of Acanthus maderaspatensis L. against colchicine induced Alzheimer’s disease rat model
Authors: Anawal Lingaraj , Shalavadi Mallappa , V M Chandrashekhar 
Published: June 2023

AbstractBackgroundTraditionally, the plants were used for various diseases and disorders, including neuronal disorders. The present study was designed to evaluate the neuroprotective effect of Acanthus maderaspatensis L. against colchicine induced neurobehavioral and biochemical changes in Alzheimer’s disease rat model.MethodNeuroprotective activity was carried out by colchicine induced Alzheimer’s disease on Sprague‐Dawley rats. Test group animals administrated with ethanol extract Acanthus maderaspatensis L. at dose of 200, 400 and 600mg/kg for 28 days. The behavioral parameters were assessed using the Morris water maze test, Digital actophotometer and Plus maze were performed at Days 0, 7, 14 and 28 on intracerebroventricular administration of colchicine for assessing the cognitive and gross behavioral activities in all groups. Biochemical parameter such as lipid peroxidation, glutathione, superoxide dismutase, catalase, total thiols and acetylcholinesterase were assessed and histopathology of brain tissue were assessed on the final day of the experiment.ResultEthanol extract of Acanthus maderaspatensis L. shows a dose dependent neuroprotective activity by significant decrease in time latency of Morris water maze (p<0.001) plus maze (p<0.001) increase in the locomotor activity (p<0.001) in EAM treated group compared to colchicine induced control group. Biochemical parameters showed significant decreases in lipid peroxidation (p<0.001) and increased in superoxide dismutase (p<0.001) catalase (p<0.001) glutathione (p<0.001) total thiols (p<0.001) and acetylcholinesterase level (p<0.001) in the EAM treated groups as compared with colchicine induced control group.ConclusionIn conclusion, the present study suggests that administration of ethanol extract of Acanthus maderaspatensis L. (EAM) possesses neuroprotective activity against colchicine induced cognitive impairment and associated oxidative stress in rats.
A systematic review of therapeutic strategies against amyloid‐β peptides in Alzheimer’s disease: Past, present, and future
Authors: Jeremic Danko , Jimenez‐Diaz Lydia , Navarro‐López Juan D. 
Published: June 2023

AbstractBackgroundLargely recognized too late, Alzheimer’s disease (AD) affects around 46 million people worldwide. The etiology of AD is still puzzling the scientific community, and its drug development and clinical trials have had high failure rate. In the recent decade, numerous studies targeting amyloid‐β peptides (Aβ) and their metabolism have been tested in patients, raising additional questions regarding AD.MethodIn order to integrate recent (from 2014) findings and analyze their clinical potential, we conducted a systematic review of investigational studies, follow‐up studies and review articles, that focus on anti‐Aβ therapies. The records were required to investigate the safety, tolerability, pharmacokinetics, efficacy, or immunogenicity of anti‐amyloid treatments in human population, excluding short and interrupted studies (<10 days), and clinical trials concerning other pathologies or comorbidities.ResultThus far, experimental therapies directed against Aβ have not been able to significantly reduce the progress of AD and memory impairment. The majority of therapeutic strategies were focused on amyloid precursor protein processing, and active or passive immunotherapy. Fewer studies evaluated drugs affecting Aβ misfolding, aggregation or clearance. Targeting β‐ and γ‐secretase have had unwanted results, but the activators of α‐secretase and immunotherapy against Aβ oligomers are giving some promise. Recent FDA approval and EU refusal of aducanumab sparked hopes and controversies, since the latest trial data confirmed amyloid plaque removal, without clear cognitive benefits.ConclusionTargeting only Aβ was not able to significantly improve the cognition of patients or modify the AD progression. The research is slowly moving toward multifunctional drugs targeting factors that precede the Aβ aggregation process, i.e., pathologic positive feedback loop linking Aβ production and other factors, such as neuronal hyperexcitability, neuroinflammation, or oxidative stress. Further development of early detection biomarkers, antibodies and additional agents that would act on both amyloid and non‐amyloid targets, could be the key to slowing down this global epidemic.FundingThis work was supported by grants BFU2017‐82494‐P and PID2020‐115823GB‐I00 funded by MCIN/AEI/ 10.13039/501100011033 and by ERDF “A way of making Europe” by the European Union; both to LJ‐D and JDN‐L. DJ held a predoctoral scholarship from Plan Propio de Investigación–ESF Programme of University of Castilla‐La Mancha.
Sex‐adjusted blood biomarkers differentiate AD from LATE
Authors: Wu Xinxing , Peng Chong , Cheng Qiang 
Published: June 2023

AbstractBackgroundAlzheimer’s disease (AD) is a complex neurodegenerative disorder that affects cognition, memory, and behavior, while limbic‐predominant age‐related TDP‐43 encephalopathy (LATE) is a recently defined common neurodegenerative disease that mimics the clinical symptoms of AD (Table 1). At present, there are no effective diagnostic biomarkers for LATE which can mainly be confirmed by autopsy.MethodWe applied machine learning algorithms to identify informative blood biomarkers differentiating AD from LATE. To identify blood‐based biomarkers for discriminating AD from LATE based on imbalanced data, we proposed an innovative integrated feature selection‐based approach, Preprocessing, Environmental factor analysis, Feature selection, and Validation (PEFV).ResultWe focused on the association analysis of blood markers that differentiate LATE and/or AD, on ROSMAP (Figure 1), by considering the factors including medication and diet. We pre‐identified some sensitive medication and dietary factors, and then based on these factors, we performed sex‐stratified group analyses. We identified 3 small sets of blood biomarkers that distinguish AD from LATE adjusted for each case, including All, Male, and Female. In addition, we analyzed 3 scenarios for each case: pure LATE vs. LATE+AD, pure AD vs. AD+LATE, and pure AD vs. pure LATE (Tables 2‐4). While usually, a single biomarker cannot achieve high accuracy and reliability due to the complexity of both AD and LATE, the set of biomarkers we identified for each scenario was small. For example, in Male case, 8 biomarkers were needed to distinguish LATE+AD from LATE with an accuracy rate of 61%, an improvement of about 10% over using all blood test features; 3 biomarkers were needed to distinguish LATE+AD from AD with an accuracy rate of 77%, an improvement of about 23% over using all blood test features; 4 biomarkers were needed to distinguish AD from LATE with an accuracy rate of 75%, an improvement of about 22% over using all blood test features.ConclusionIn this study, based on blood tests, we explored blood‐based biomarkers that can differentiate AD from LATE with imbalanced data by our proposed approach PEFV and used it to discover informative blood biomarkers distinguishing AD from LATE.
Assessing neuroinflammatory differences in FTLD‐Tau vs FTLD‐TDP using free water diffusion
Authors: Sumra Vishaal , Chad Jordan A , Vasilevskaya Anna , Mora‐Fisher Daniela , Anor Cassandra Jessica , Misquitta Karen , Lang Anthony E , Slow Elizabeth , Pasternak Ofer , Trataglia Maria Carmela 
Published: June 2023

AbstractBackgroundFrontotemporal lobar degeneration (FTLD) is associated with two pathological substrates: Tau and TAR‐DNA‐binding protein 43 (TDP‐43). In‐vivo detection of the pathological substrate is still not possible in FTLD‐related syndromes but progressive supranuclear palsy (PSP) is consistently associated with FTLD‐Tau while semantic‐variant primary progressive aphasia (svPPA) and FTD‐MND (FTD‐ALS) are associated with FTLD‐TDP. In the absence of disease‐specific markers in FTLD, it is necessary to identify biomarkers that can help distinguish FTLD‐Tau and FTLD‐TDP. Recent research has implicated neuroinflammation as a common feature across FTLD subtypes (Bright et al., 2019), however further research is required to investigate neuroinflammatory differences between FTLD‐Tau and FTLD‐TDP, given that microglial burden and activation may differ in FTLD subtypes (Woollacott et al., 2020). The free water fraction (FW), a metric generated from diffusion MRI (dMRI) (Pasternak et al., 2009), is a non‐specific marker of neuroinflammation (Bergamino, Walsh and Stokes, 2021). We will investigate differences in FW diffusion between patients with presumed FTLD‐Tau versus FTLD‐TDP. We hypothesize that differences in neuroinflammation between FTLD‐Tau and FTLD‐TDP can be identified using the free water measure, which may infer neuroinflammatory differences.MethodFree‐water maps were generated from dMRI datasets obtained from 43 subjects: 19 with presumed FTLD‐Tau (PSP, mean age = 70), 6 with presumed FTLD‐TDP (mean age = 67, 4 svPPA, 2 FTD‐ALS), and 19 healthy controls (mean age 63). Grey matter (GM) was segmented from T1‐weighted MRIs using FSL’s ‘fast’, projected onto the diffusion MRI space, where free‐water maps were averaged across the GM. The average free water estimates from FTLD‐Tau, FTLD‐TDP and control datasets were tested for group differences using student’s t‐tests and analysis of covariance (ANCOVA), with age as a covariate.ResultsANCOVA revealed significant differences between the groups (F = 6.47, p < 0.01). Post‐hoc tests showed significantly higher free‐water in FTLD‐Tau (p<0.01) and FTLD‐TDP (p<0.01) compared to controls. There was also higher free water in FTLD‐TDP in comparison to FTLD‐Tau, approaching significance (p = 0.0503)ConclusionOur preliminary data shows significant differences between healthy controls and patients with FTLD‐Tau and FTLD‐TDP and a trend for increased free water in FTLD‐TDP patients vs FTLD‐Tau, which may be indicative of neuroinflammatory differences.
Preclinical Alzheimer’s Disease accurate prediction using plasma cell‐free RNA sequences
Authors: Cisterna‐García Alejandro , Chen Hsiang‐Han , Norton Joanne , Gentsch Jen , Bergmann Kristy , Wang Fengxian , Budde John P. , Cruchaga Carlos , Botía Juan A. , Ibanez Laura 
Published: June 2023

AbstractBackgroundCerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers are used to clinically diagnose AD with an accuracy of 70‐80%. However, they are invasive and expensive and need to be further studied on preclinical‐AD. Additionally, a blood‐based biomarker can be of great use. In order to obtain a blood‐based biomarker, we have sequenced plasma cell‐free RNA (cfRNA) from preclinical‐AD individuals to develop prediction models for AD using machine learning (Figure 1).MethodPlasma samples were obtained from the Knight‐Alzheimer‐Disease‐Research‐Center [preclinical‐AD (n = 67), clinical‐AD (n = 92), and controls (n = 48)] (Table 1) and sequenced in two batches. Sequences were processed following standard pipelines and normalized using DESeq2. Preclinical‐AD (n = 47) and controls (n = 26) from one sequencing batch were used to train the predictive model, then preclinical‐AD (n = 20) and controls (n = 22) from the other batch were used as testing population. We applied a Z‐score scaling to the normalized gene counts and used Kullback–Leibler (KL) divergence to select the genes that had similar expression distribution in both sequencing experiments (Figure 2). We used different KL thresholds to select genes as predictors and then Ridge regression to find the best predictive models. After we tested the models on preclinical‐AD, they were further tested on the clinical‐AD individuals. Finally, Parkinson’s disease (n = 96), dementia with Lewy bodies (n = 17), and frontotemporal dementia (n = 16) individuals were used to test for specificity analyses of the AD prediction models (Table 2).ResultBest predictors sizes include 40, 90, and 220 genes yielding models with 85.7%, 90.5%, and 95.2% testing accuracy respectively. Predicted AD risk consistently correlates with Aβ42 levels. The best model included genes such as MT‐ATP6, GAB2, or MAPK14, which have been associated with AD. We tested the specificity of these models for other neurodegenerative diseases, and we observed specificity for AD in comparison to PD, FTD, and DLB (Figure 3).ConclusionPlasma cfRNA is a promising tool to screen for preclinical AD. It has the potential to be used as a minimally invasive biomarker for AD since it has an accuracy higher or comparable to CSF biomarkers and it is AD‐specific.