bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of blood cell parameters of peripheral inflammation with cognitive function
Authors: Fang Yuan , Lunetta Kathryn L. , Mez Jesse , Satizabal Claudia L. , Alosco Michael L. , Qiu Wendy , Doyle Margaret F. , Murabito Joanne M. 
Published: December 2021

AbstractBackgroundChronic peripheral inflammation is associated with cognitive decline and increased risk of dementia. Easily measured circulating blood cell parameters, including the neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW), and mean platelet volume (MPV), reflect peripheral inflammation. We sought to investigate the cross‐sectional association between these measures and neuropsychological (NP) test performance in the Framingham Heart Study (FHS) Offspring, Third‐generation, and Omni cohorts.MethodWe identified FHS participants who attended an exam that included a complete blood cell count sample and underwent NP testing within five years of blood draw. Linear mixed effect models were used to investigate the association between the blood cell parameters (NLR, RDW, MPV) and individual NP test scores adjusting for age, sex, education, cohort, time between blood draw and NP testing, prevalent cardiovascular disease, APOE‐ε4 genotype, and C‐reactive protein, and accounting for familial correlation using a random effect. We additionally tested for interactions between age (≥ 60 years vs. < 60 years) and blood cell parameters on NP scores and associations were reported separately by age group when significant (P for interaction ≤ 0.01).ResultAmong the 3531 participants (mean age 60.3 years, range 25 to 97 years, 47% male), 80% had at least some college and 22% were APOE‐ε4 carriers. We observed significant association between higher NLR and poorer NP performance on visual reproductions – delayed recall, Trails B ‐ Trails A, and Hooper visual organization test, that assess visual memory, executive function, and visuospatial abilities respectively (Table). There was also a significant association between higher RDW and poorer performance on digit symbol test assessing executive function. We observed different effects for the two age groups for the association between RDW and a metric of executive function (i.e., Trails B ‐ Trails A), where higher RDW correlated with decreased cognitive performance in participants aged ≥ 60 years (n=1865).ConclusionChronic peripheral inflammation as measured by NLR and RDW associates with lower cognitive function in FHS participants ≥ 60 years. In younger individuals, chronic peripheral inflammation may have a smaller effect on cognitive function.
Dementia caregivers identify challenges and facilitators to attending health care visits
Authors: Gately Megan E , Muccini Sarah , McLaren Jaye E , Moo Lauren R 
Published: December 2021

AbstractBackgroundThe 2020 National Research Summit on Care, Services, and Supports for Persons with Dementia and Their Caregivers identified the need for person‐centered dementia care throughout the care continuum. Challenges include adapting health care to meet the complex needs of persons with dementia and their caregivers across a variety of settings.MethodTo understand dementia caregivers’ experience of the health care system, we conducted qualitative interviews with twenty‐four middle‐to‐older age caregivers of community‐dwelling people with dementia. Data were analyzed using conventional content analysis whereby the coding team sought to identify barriers and facilitators to person‐centered dementia care.ResultWe identified three categories and associated sub‐categories related to caregiver experience: 1) Preparing for the Visit, with sub‐categories Physical Challenges and Emotional Preparation; 2) Visit‐Related Time and Travel, with sub‐categories General Travel Challenges, Physical Limitations, Cognitive Limitations, and Benefits; and, 3) In‐visit Experience, with sub‐categories Physical Challenges and Emotional Preparation. Preparing for visit statements revealed barriers, such as patient resistance to attending visits due to not understanding the need. Visit‐related time and travel statements reflected a balance of challenges and facilitators, including general challenges such as traffic and dementia‐specific challenges such as patient agitation around visit wait times. Facilitators reflected the benefit of visits as opportunities for social participation. In‐visit experience statements reflected a mix of challenges and facilitators. Challenges included person with dementia difficulty participating in the health care visit due to poor insight and inability to answer questions, while facilitators included caregivers’ positive engagement with the care team. Across categories, caregivers assumed high‐level responsibility to accommodate for person with dementia physical and cognitive challenges.ConclusionCategories underscore the complexity of health care management for a person with dementia both in and around actual clinic appointments, highlighting both challenges related to person with dementia cognitive deficits and perceived benefits related to visits as opportunities for social participation and accessing resources. This study offers relevant insights about tailoring health care to accommodate for person with dementia deficits while supporting their caregivers.
Building relationships to enhance person‐centered care through emotion‐focused care
Authors: Abbott Katherine M , Heid Allison R , Spector Abby , Heppner Alex , VanHaitsma Kimberly S 
Published: December 2021

AbstractBackgroundThe way we respond emotionally to others can impact how we provide care. Research has shown that employees with high emotional intelligence (EI) know what they are feeling, stop to think before they act, and have strategies for appropriately managing negative feelings and promoting positive feelings. These characteristics are vital to care team members whose entire day involves interacting with other people. Working with people is a double‐edged sword: it can be incredibly rewarding, but people also can bring out negative emotions – frustration, disappointment, anger, shame, and resentment. The ability to identify and manage emotions is particularly important for care team members who work with people living with dementia. While people living with moderate to severe dementia have lost much of their cognitive capacity, feelings remain intact far into the disease process. Care team members recognize that their job is not just to take care of residents’ physical needs; rather, it is to take care of the whole person – body, mind, and soul. Improving quality of life means being concerned about the whole person, and emotional well‐being in particular. We have developed an interactive, on‐line, self‐paced course for all people providing care to others with the specific goal of increasing awareness of emotions and helping to identify emotions in others. The training is supported by research indicating that individuals who can better manage their own emotions are better positioned to manage behaviors and emotions in others. The central concept of the training is to build individuals’ capacity for recognizing and managing their emotions and the emotions of others to enhance person‐centered care. While the course is relevant to any person who is a caregiver, it focuses on the context of providing care to an individual with dementia. The training is available to individuals at no cost due to generous grant funding. The goal of this presentation is to introduce the concept of EI, particularly as it applies to caregivers and then review how to access and navigate the course.
High frequency of functional cognitive decline among patients with low education
Authors: Borelli Wyllians Vendramini , de Senna Priscylla Nunes , Chaves Marcia L Fagundes , Castilhos Raphael Machado 
Published: December 2021

AbstractBackgroundFunctional cognitive decline (FCD) has been increasingly described as a blind spot of dementia care. Psychological distress, affective symptoms and disturbed self‐perception comprehend the most common causes of FCD. Herein, we aim to identify the frequency of FCD in a tertiary memory clinic from a very low education setting.MethodA retrospective analysis was conducted to identify new referrals to our tertiary memory clinic (Porto Alegre, southern Brazil) over a 6‐year period (2014 ‐ 2020). All individuals referred from the primary care setting of the public health system in this time period were included in this analysis. Patients underwent a diagnostic protocol including neurologic evaluation, cognitive screening, neuroimaging (CT or MRI) and laboratory testing. FCD was defined as patients with cognitive complaints/objective cognitive decline associated with psychological distress and affective symptoms, without evidence of underlying neurodegenerative disease. Data is shown in median [interquartile range].ResultA total of 474 patients (287 females, median age 72 [65‐78]) with a median of 5 [0‐10] years of education were referred to our memory clinic within the period from 2014 to 2020. FCD was the second more frequent final diagnosis (95, 19.8%), only behind of dementia due to Alzheimer's disease (106, 22.4%); other diagnosis were less frequent: Mild Cognitive Impairment (49, 10.3%), Subjective Cognitive Decline (35, 7.4%), Vascular dementia (34, 7.2%), Mixed‐type dementia (24, 5.1%), behavioral variant Frontotemporal Dementia (5, 1.1%), and other types (36, 7.6%). Patients with FCD were younger (69 [63‐75] vs. 74 [67‐78], p<0.001), and showed higher Geriatric Depression Scale (GDS‐15) than non‐FCD individuals (9 [5‐12] vs. 5 [2‐8], p<0.001). The education level did not differ (p>0.05).ConclusionFunctional Cognitive Decline was the second most frequent diagnosis among patients with very low education in a tertiary memory clinic. FCD individuals were younger, showed increased depressive symptoms than non‐FCD patients. Taken altogether with Subjective Cognitive Decline, functional disorders account for the majority of consultations referred to this tertiary setting. Public health strategies including the primary care setting may greatly improve early diagnosis and treatment to these patients.
Changed behaviours associated with cognitive decline: Views of people living with dementia, families and healthcare professionals
Authors: Burley Claire V , Chenoweth Lynnette , Casey Anne‐Nicole S , Brodaty Henry 
Published: December 2021

AbstractBackgroundChanged behaviours associated with cognitive decline (also known as neuropsychiatric symptoms (NPS), behavioural and psychological symptoms of dementia (BPSD), and responsive behaviours) occur in up to 90‐percent of people living with dementia (PLWD). They strongly correlate with functional and cognitive impairment and contribute to approximately 30‐percent of overall dementia costs. Decisions regarding care and strategies for changed behaviours are often determined by families and healthcare professionals and are not inclusive of PLWD. This is the first study that investigates terminology used to describe changed behaviours associated with cognitive decline from the perspective of PLWD, families/care partners and healthcare professionals. PLWD, families/care partners and healthcare professionals participated in semi‐structured interviews. A thematic iterative approach was used to code the data and identify common themes until theoretical saturation was reached (∼25 participants per group). Themes were compared between groups. Data were analysed deductively in relation to pre‐existing terminology regarding changed behaviours in cognitive decline, and inductively to discover new ideas on use of such terminology as perceived by PLWD and others. Thirty‐four volunteers have been interviewed so far: 16 PLWD, mean age 70yrs, mean Mini‐Mental State Examination score 26, and 18 family members/care partners. Preliminary analysis indicates that terms used by PLWD and families differ to terms used in existing professional frameworks (e.g., ‘disinhibition’ described as ‘loss of filter’ and ‘agitation/ aggression’ as ‘frustration’ or ‘lower tolerance’. Full results from PLWD, families/care partners and healthcare professionals will be presented (∼75 participants). This is the first report from PLWD themselves on their preferences for the terminology describing changed behaviours previously described as BPSD or NPS, suggesting a reconceptualization of changed behaviours may assist, e.g., from ‘agitated/ hard to handle’ to being frustrated with cognitive decline, discriminatory behaviour and insufficient support systems, and ‘having delusions/ false beliefs’ to thinking about and re‐experiencing previous traumatic events. In better understanding changed behaviours, families and professionals will be able to respond in a way that is helpful for PLWD. An integrated understanding of all views and factors involved will assist in better understanding changed behaviours, improve language use and the quality of care and support.
Anti‐inflammation as one of the mechanisms in the improvement of cognitive function by probiotic Bifidobacterium breve strain
Authors: Ohno Kazuya , Bernier Francois , Katsumata Noriko , Shimizu Takashi , Xiao Jin‐Zhong 
Published: December 2021

AbstractBackgroundRecently, the gut‐brain axis has received a lot of attention as some probiotics have been reported to have a beneficial effect on CNS diseases. Our previous studies show that the probiotic strain, Bifidobacterium breve MCC1274 (synonym B. breve A1), improves memory scores in Alzheimer’s disease model and human subjects with self‐reported memory complaints. Furthermore, in a trial with healthy adults with MCI (Mild Cognitive Impairment), we found that B. breve MCC1274 significantly improved the cognitive function [1]. In the present study, we investigated the association of blood parameters with the improvement of cognitive function by B. breve MCC1274.MethodIn a double blind, randomized placebo‐controlled trial, healthy adults aged 50‐79 years with MCI consumed probiotic capsules (2x1010 CFU/day) or placebo capsules for 16 weeks. Cognitive function was measured before and after the intervention using RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) and JMCIS (Japanese version of MCI Screen) as neuropsychological tests. Hematological and biological blood parameters were measured to assess the safety and elucidate the possible action mechanism.ResultOut of 80 participants, 79 subjects completed the study and after 16 weeks intervention, RBANS total score was significantly improved in the probiotic group in particular with significant improvement in domain scores of immediate memory, visuospatial/constructional, and delayed memory. Hematological and biological blood parameters showed no significant differences between the two groups. Interestingly, however, a significant correlation was found between the changes in blood HbA1c and RBANS total score in B. breve MCC1274 group (ρ=‐0.4218, p=0.0067). A stratified analysis based on baseline HbA1c with a median value (5.4%) showed a more remarkable benefit on the cognitive function by the probiotic consumption in the higher median subgroup (Fig 1). As many studies have reported an association between HbA1c and inflammation‐related dementia, this data suggests the mechanism of action of the probiotics may involve reducing inflammation.ConclusionThe present data shows that B. breve MCC1274 improves cognitive function by reducing inflammation in healthy adults with MCI and may be a potential strategy for preventing dementia. Reference: (1) Xiao et al. Journal of Alzheimer’s Disease, 2020.
Apolipoprotein E4‐driven effects on inflammatory and neurotrophic factors in peripheral extracellular vesicles from cognitively impaired not demented participants converted to Alzheimer’s disease
Authors: Kheder Mohamed Raâfet Ben , Haddad Mohamed , Laurin Danielle , Ramassamy Charles 
Published: December 2021

AbstractBackgroundIn brain, extracellular vesicles (EVs) play an essential role in neuron‐glia interface and ensure the crosstalk between the brain and the periphery. Only a few studies have demonstrated the apolipoprotein E4 variant (APOE ε4)‐driven dysfunction of EVs pathway and the risk to develop Alzheimer’s disease (AD). To better understand the role of APOE ε4 in pre‐clinical AD, we determined levels of pathogenic, neurotrophic and inflammatory proteins in peripheral EVs (pEVs) and in plasma from cognitively impaired‐not demented (CIND) participants stratified upon the absence (APOE ε4‐) or the presence (APOE ε4+) of the ε4 allele of APOE.MethodLevels of 15 neurodegenerative, neurotrophic and neuroinflammatory proteins were quantified in pEVs by the multiplex Luminex assay and compared to their plasma levels from cognitively normal and CIND participantsResultFor the first time, several neurotrophic and inflammatory markers including LCN‐2, S100B, ANGPTL‐4, NPTX‐2 and α‐synuclein were evidenced in pEVs. Some proteins such as α‐Syn, NPTX‐2 and S100B were enriched in pEVs as compared to plasma. APOE ε4+ was associated with differential regulation of 7 markers and compromised the release of pEVs formed by an endosomal route. The pentraxin‐2/α‐synuclein ratio measured in pEVs was able to predict AD 5 years before the onset among APOE ε4+ CIND individuals. Discussion: Our findings suggest an alteration of the endosomal pathway in APOE ε4+ carriers and that pEVs pentraxin‐2/α‐synuclein ratio could serve as a useful early biomarker for AD susceptibility.ConclusionThe findings reported herein provide a comprehensive insight and enhance our knowledge on the emerging role of ApoE4 in abnormal pEVs cargo proteins processing and the identification of blood‐based biomarkers.
E2511, a novel small compound TrkA allosteric modulator, induces a specific trophic signaling via direct binding to TrkA, and can reverse the loss of choline acetyltransferase (ChAT) positive neurons in transgenic models of AD
Authors: Tomioka Takeyasu , Moriyama Yoshiyuki , Hiramatsu Naoki , Kosasa Takashi , Kondo Keita , Wakita Hisashi 
Published: December 2021

AbstractBackgroundLoss of cholinergic neurons in Alzheimer’s disease (AD) is an early pathogenic event correlated with cognitive impairment. Nerve growth factor (NGF) plays a major role in the maintenance and function of cholinergic neurons. Decrease in NGF‐Tropomyosin receptor kinase A (TrkA) induced trophic signaling contributes to cholinergic neurodegeneration and cognitive decline during the course of AD. The activation of the trophic signaling could be a promising therapy for AD, reinnervating basal forebrain cholinergic neurons. We provide evidence that our novel small compound E2511 is TrkA allosteric modulator showing an increase in specific trophic signaling via direct binding to TrkA.MethodE2511 was characterized in several in vitro assays such as NMR assay for detecting binding to TrkA and biochemical studies for evaluating the phosphorylation level of TrkA in each site using rat primary septal neurons. The in vivo effects of the compound on TrkA signaling were investigated in human Tau P301S transgenic mice (Tau tg mice) by biochemical studies such as western blot analysis, while assessing whether the compound induces hyperalgesia in behaviour studies and pain‐related signaling in normal and pain model rats. Moreover, the trophic effect of the compound on cholinergic neurons was investigated in Tau tg mice.ResultE2511 enhanced phosphorylation level of TrkA in the presence of NGF via direct binding to TrkA in rat primary neurons, and phosphorylation level of each site of TrkA induced by the compound was different from that of NGF. In vivo experiments demonstrated that oral administration of E2511 elevated trophic signaling in the septum, while induction of hyperalgesia was not detected. Furthermore, chronic administration of E2511 reversed the loss of ChAT‐positive cells in Tau tg mice by therapeutic treatment.ConclusionE2511 enhances specific trophic signaling by altering TrkA signaling as specific allosteric modulator via direct binding to TrkA, and E2511 shows the reinnervative effect on cholinergic neurons through activation of TrkA signaling without induction of NGF‐like adverse effect.
Rationale and design of the NEwTON study: A prospective cohort study of patients at risk of chronic traumatic encephalopathy
Authors: van Amerongen Suzan , Vijverberg Everard G.B. , Pijnenburg Yolande A.L. , Scheltens Philip 
Published: December 2021

AbstractBackgroundTraumatic brain injury increases the risk of neurodegenerative diseases later in life. Repetitive head injury, more specific in contact sports, is associated with cognitive, neurobehavioral and motor impairments in the light of a unique neurodegenerative disorder: chronic traumatic encephalopathy (CTE). Yet, the clinical presentation, risk factors and diagnostic biomarkers of CTE have remained unclear. The general objective of the NEwTON study is to establish a prospective cohort of patients with high risk of CTE, to further study the link between repetitive head injury and neurodegeneration. We aim to phenotype the study population, identify potential biomarkers and measure clinical progression.MethodNEwTON is a prospective cohort study which aims to recruit approximately 80 patients at risk of CTE (features of the traumatic encephalopathy syndrome, Montenigro 2014) and healthy control subjects. Inclusion criteria are: history of repetitive head injury (contact sports, military service, other exposure), progressive cognitive and/or neurobehavioral symptoms, age 45‐75 years and symptom duration of ≥12 months. The control group will consist of age‐matched healthy participants without history of significant traumatic brain injury or participation in contact sports/professional military service. Subjects are invited to participate after diagnostic screening at our memory clinic or recruited by advertisement.ResultPatients will undergo comprehensive baseline screening, including neurological examination, neuropsychological tests, questionnaires and brain magnetic resonance imaging (MRI) for anatomical imaging, diffusion tensor imaging (DTI), resting state functional MRI (rsfMRI) and Quantitative Susceptibility Mapping (QSM). Questionnaires include topics on life‐time head injury, subjective cognitive change and neuropsychiatric symptoms. Blood and cerebrospinal fluid will be stored in the NEwTON biobank. Patients will be informed about our brain donation program in collaboration with the Netherlands Brain Brank. Testing for control subjects will be limited to baseline neuropsychological tests, blood draw and MRI. Patient follow‐up will take place annually and includes neuropsychological assessment, questionnaires and blood draw.ConclusionThe NEwTON study will contain the first cohort in the Netherlands with prospective observational data of patients with high risk of CTE. This study design will be an umbrella protocol and it is expected that other sub‐studies will use this cohort in the future.