bluuebunny/crossref_metadata_2025_split huggingface dataset:
Life satisfaction is associated with the relationship between mild cognitive impairment and the incidence of disability
Authors: Katayama Osamu , Lee Sangyoon , Bae Seongryu , Makino Keitaro , Chiba Ippei , Harada Kenji , Shinkai Yohei , Shimada Hiroyuki 
Published: December 2021

AbstractBackgroundLife satisfaction has been shown to be lower in older adults with a higher risk for dementia. For many years, dementia has been the highest factor in the incidence of disability among older Japanese adults. The relationship between the incidence of disability and cognitive status has already been clarified, but whether life satisfaction is related to this relationship has not yet been clarified. Therefore, the purpose of this study was to clarify whether life satisfaction is related to the relationship between incidence of disability and cognitive status.MethodParticipants comprised 2798 older adults (1579 women; mean age: 73.0 years, SD = 5.9, range 65–96 years) from the National Center for Geriatrics and Gerontology–Study of Geriatric Syndromes. Baseline measurements, including cognitive status (NC, normal cognition; MCI, mild cognitive impairment; GCI, global cognitive impairment), life satisfaction, and demographic characteristics. Life satisfaction was measured using the life satisfaction scale (LSS), ranging from 13 to 52. LSS was stratified into three levels based on the score: lowest, moderate, and highest. Associations between disability incidence and cognitive status were examined for each group according to life satisfaction; monthly assessment for disability was monitored through long‐term care insurance certification for at least 2 years.ResultDuring a mean follow‐up of 35.3 months (SD = 6.0), 193 participants developed a disability. The potential confounding factors adjusted hazard ratios (refer to NC) for incidence of disability in the group with the lowest life satisfaction were 1.83 (CI, 1.03 to 3.26; P = 0.040) and 1.73 (CI, 0.70 to 4.33; P = 0.238) for MCI and GCI, respectively. Similarly, in the group with moderate life satisfaction, MCI and GCI were 2.00 (CI, 1.01 to 3.94; P = 0.046) and 1.90 (CI, 0.57 to 6.28; P = 0.291), respectively. On the other hand, in the group with the highest life satisfaction, MCI and GCI were 1.41 (CI, 0.79 to 2.51; P = 0.245) and 0.96 (CI, 0.36 to 2.55; P = 0.937), respectively.ConclusionMCI was associated with disability incidence, and the effect was more pronounced among older adults who had lower life satisfaction.
Effect of physical environment on person‐centred dementia care in a long‐term care facility: Focus group interviews with staff
Authors: Lee Sook Young , Hung Lillian , Chaudhury Habib 
Published: December 2021

AbstractBackgroundAccording to the spread of the person‐centred care approaches, the physical environment has been acknowledged as an important component of a dementia care facility. This study demonstrated that staff experiences and opinions of the physical environment in supporting their care practices for residents living with dementia in long‐term care facilities in Canada and Sweden. Focus group interviews were used with 24 staff members. Semi‐open questions were asked about the role of physical environment on care practice, job satisfaction, and interaction with residents. Data were analyzed by thematic analysis. This study yield three environmental themes: i) design atmosphere, ii) space arrangements, and iii) sensory stimuli. The findings demonstrate that well‐designed environment factors such as homelikeness, an open space plan and stimulating outdoor, positively encourage the emotion of staff as well as residents, which leads to build trust and relationship and to increase job satisfaction. This study highlights the complexities of how care was influenced by the physical environment of the care setting.
Development of D‐enantiomeric peptides as tau aggregation inhibitors directed against the hexapeptide motif PHF6* of tau
Authors: Funke Susanne Aileen , Malhis Marwa , Kaniyappan Senthilvelrajan , Aillaud Isabelle , Chandupatla Ram Reddy , Horn Anselm H.C. , Mandelkow Eckhard , Sticht Heinrich 
Published: December 2021

AbstractBackgroundTwo hexapeptide motifs within Tau, designated PHF6* (275VQIINK280) and PHF6 (306VQIVYK311), are known to drive Tau aggregation, making them attractive targets for the development of Tau aggregation inhibitors for therapeutic options.MethodEmploying mirror‐image phage display with a large peptide library, we have identified PHF6* fibril binding peptides consisting of D‐enantiomeric amino acids. D‐enantiomeric peptides are extremely protease stable and considerably less immunogenic than L‐peptides, and the suitability of D‐peptides for therapeutic purposes has already been demonstrated. The most promising D‐peptide and its ability to inhibit Tau aggregation was investigated using various biochemical and biophysical methods, and compared to the performance of PHF6‐ or other PHF6*‐binding peptides selected earlier by our and other groups.ResultMMD3 and MMD3rev inhibited PHF6*, TauRDΔK280 and full‐length Tau fibrillization in vitro. Our data demonstrated that the peptides prevent the formation of Tau ß‐sheet‐rich fibrils by formation of large amorphous aggregates. The binding mode of MMD3 and MMD3rev to PHF6* fibrils was investigated by in silico modeling.ConclusionOur peptides were able to penetrate cells and might be interesting for therapeutic and diagnostic applications in AD research.
Multimorbidity and the risk of incident dementia in UK Biobank
Authors: Calvin Catherine M , Littlejohns Thomas J , Kuzma Elzbieta 
Published: December 2021

AbstractBackgroundThere is strong evidence that certain individual conditions, such as diabetes, hypertension and stroke, increase the risk of dementia. However, there is limited longitudinal research investigating the role of multimorbidity as a risk factor for developing dementia.MethodParticipants were selected from UK Biobank, a population‐based cohort of half a million women and men aged between 40‐73 years at recruitment. Between 2006‐2010, participants completed a range of assessments at baseline, which included self‐reporting pre‐existing health conditions during a nurse‐led verbal interview. This was used to determine multimorbidity, defined as having two or more, out of a possible 42, chronic physical and mental health conditions used in recent large‐scale epidemiology studies to establish multimorbidity. Incident all‐cause dementia was ascertained using cohort‐wide hospital inpatient and death records collected up to 2020.ResultAfter excluding participants less than 60 years old at baseline (n=285,016), those with prevalent dementia (n=230), and those with missing covariate data (n=10,350) a total of 206,974 participants remained, of whom, 89,210 (43.1%) had multimorbidity. The five most common individual conditions in the analytic sample were hypertension (36.2%), pain (21.5%), cancer (10.7%), asthma (10.7%) and dyspepsia (10.1%). Over 2.28 million person years of follow‐up (mean = 11.0, standard deviation = 1.96), 4,813 participants developed dementia. In Cox proportional‐hazards models adjusted for age, sex, ethnicity, education, socioeconomic status and APOE‐e4, multimorbidity was associated with a 70% increased risk of developing dementia (Hazard Ratio [HR] = 1.70, 95% Confidence Interval [CI] 1.60‐1.80), compared to ≤1 conditions. The association remained consistent when restricting to incident dementia diagnosed after 3, 6 and 9 years respectively. There was evidence of a dose‐response effect, with HRs of 1.44 (95% CI 1.34‐1.55), 1.68 (95% CI 1.55‐1.82), 2.33 (95% CI 2.10‐2.59), 2.80 (95% CI 2.41‐3.24) and 3.43 (95% CI 2.84‐4.15) observed for 2, 3, 4, 5 and ≥6 conditions, respectively, compared to ≤1 conditions.ConclusionIn a population of more than 200,000 older adults, multimorbidity was strongly associated with an increased risk of incident dementia. Further research investigating which particular combinations of conditions contribute to dementia risk is warranted.
Heparan sulfate: In vitro and in vivo proof of efficacy of this new therapeutic strategy for halting Alzheimer disease‐related tauopathy development
Authors: Maïza Auriane , Douaron Gael Le , Soria Aida Muntsant , Li Yong , Ramakrishnan Kithika , Ouidja Mohand Ouidir , Fifre Alexandre , Chantepie‐Laborde Sandrine , Jospin Estelle , Laffray Xavier , Ramos Ivan , Fernig David , Llort Lydia Gimenez , Papy‐Garcia Dulce , Team ArrestAD Consortium 
Published: December 2021

AbstractBackgroundDeposition of amyloid plaques and neurofibrillary tangles composed of abnormally phosphorylated tau are the neuropathological hallmarks of Alzheimer's disease (AD). However, years before the accumulation of protein aggregates, the abnormal intraneuronal accumulation of heparan sulfates (HS) is observed. This phenomenon breaks a dogma, since HS are classically located on the cell surface and in the extracellular matrix, leading to a new cell autonomous concept in tauopathy, which is the conceptual core of the FET‐OPEN ArrestAD 737390 project. Previously, we provide evidence that inside the cell, HS act as molecular chaperones inducing in Tau conformational changes favoring its abnormal phosphorylation and aggregation (Sepulveda‐Diaz JE. Brain 2015, 138(Pt 5):1339‐54). Thus, molecules able to act on heparan sulfate pathway could represent a new class of compounds for the treatment of AD‐related tauopathies.MethodPAPS is the universal sulfate donor involved in HS biosynthesis and structurally related to ATP. Thus, we first screened kinase inhibitor libraries in a sulfotransferase enzymatic assay (Byrne et al., Biochem. J. 2018; 475:2417‐2433). This strategy, in addition to a HS mimetic, were evaluated for their ability to prevent tauopathy in cells. The best molecules were then evaluated in two transgenic mice model of AD. Thereafter, proof‐of‐concept of the efficacy of compounds selected with this strategy, as well as HS mimetic (Barritault D. Glycoconj J. 2017; 34(3):325‐338) for halting AD‐related tauopathies development was assessed first in vitro and then in vivo.ResultsThe screening of libraries allowed the identification of 3 hit compounds that, in addition to a HS mimetic, were evaluated for their ability to prevent tauopathy in cells. Two molecules, one HSSTs inhibitor and one heparan sulfate mimetic, were able to reduce tauopathy in cells and in 3xTg‐AD and rTg4510 mouse models of tauopathy. In the in vivo assessment in males and females 3xTg‐AD, the behavioral dose‐response of these molecules on the cognitive, neuropsychiatric‐like and motor AD‐phenotypes was determined.ConclusionOur results support the FET‐OPEN RIA ArrestAD cell autonomous hypothesis of tauopathy based in altered heparan sulfate biology and place HS and their biosynthetic enzymes as a potential therapeutic target for AD.
Incident stroke in patients with Alzheimer’s disease: A meta‐analysis
Authors: Pinho João , Miguel Quintas‐Neves , Imis Dogan , Reetz Kathrin , Reich Arno , Costa Ana Sofia 
Published: December 2021

AbstractBackgroundWe aimed to describe the risk of stroke in patients with Alzheimer´s disease (AD) and to compare it with matched controls without AD.MethodWe conducted a systematic review of all studies reporting incident stroke in AD patients according to the PRISMA guidelines. We included studies which: 1) reported ≥50 patients with a diagnosis of AD; 2) reported a retrospective or prospective follow‐up period; 3) specifically reported the occurrence of ischemic stroke and/or non‐traumatic ICH and/or stroke (all types) during the follow‐up period. We assessed the quality of studies using the Quality Assessment Tool for Observational Cohort and Cross‐Sectional Studies provided by the National Heart, Lung and Blood Institute. Using random effects meta‐analyses, we pooled the incidence rates and incidence rate ratios (IRR) of ischemic stroke, intracerebral hemorrhage (ICH) and stroke (all types) in AD patients.ResultTwenty‐nine (29) articles reporting incident ischemic stroke and/or incident ICH and/or incident stroke (all types) in patients with AD and were included in the meta‐analyses. The majority of studies was judged to have a fair quality. In patients with AD the incidence rates were 13.0 per 1000 person‐years for ischemic stroke, 3.4 per 1000 person‐years for ICH and 15.4 per 1000 person years for stroke (all types). When compared to matched controls without AD, incidence rate for ICH in AD patients was significantly higher (IRR 1.67, 95%CI 1.43‐1.96), but similar for ischemic stroke. Significant study heterogeneity was found in the meta‐analyses of incidence rates of ischemic stroke and stroke (all types) and moderate for studies reporting ICH.ConclusionIncident stroke is not a rare event in AD population. AD is associated with an increased risk of ICH which warrants further clarification. The significant risk of bias and heterogeneity among the studies, as well as the lack of information on possible confounding variables, does warrant the need for better quality studies on the overlap of the two neurological disorders with the highest disease burden worldwide.
Network analysis for studying the dynamics of affective symptoms and treatment adherence in APOE‐ɛ4 carriers with subjective cognitive decline following a multimodal intervention: Preliminary findings from the PENSA Study
Authors: Soldevila‐Domenech Natalia , Forcano Laura , Boronat Anna , Lorenzo Thais , Piera Iris , Puig‐Pijoan Albert , Knezevic Iva , Fauria Karine , Molinuevo Jose Luis , de la Torre Rafael 
Published: December 2021

AbstractBackgroundThe co‐occurrence of subjective cognitive decline (SCD) and anxiety critically increases the risk of developing mild cognitive impairment and dementia. Understanding the influence of life style changes on affective symptoms in individuals with SCD can help implementing successful multimodal interventions that benefit both cognitive and mental health. We studied the interaction between affective symptoms and treatment adherence over time in individuals meeting SCD‐Plus criteria and being APOE‐ ɛ4 carriers that were following a multimodal intervention in the framework of the PENSA Study.MethodWe report preliminary analyses of intensive longitudinal data (ILD) weekly collected for 20 weeks in 11 participants (Figure 1). Ecological momentary assessments (EMAs) were used to evaluate anxiety, depression, mood, Mediterranean diet (MedDiet) adherence and participation in social activities. Physical activity and sleep were measured with an activity tracker. Multilevel vector autoregressive models were used to obtain the full set of interactions.ResultThe mean response rate for EMAs was 89.6% (min‐max 80‐100%). There were within‐person temporal relationships between several variables as shown in Figure 2. Physical activity had a positive forward influence on sleep (β=0.32, P=0.016). In turn, higher hours of sleep predicted higher adherence to the MedDiet (β=0.28, P=0.034) and lower anxiety levels (β=‐0.302, P=0.005). Also, higher anxiety predicted negative mood states (β=‐0.12, P=0.012) and lower number of social activities (β=‐0.27, P=0.013), being such relationship bidirectional (β=‐0.19, P=0.005). Finally, the between‐person network (Figure 3) indicated that some variables co‐varied across persons. Individuals with high average minutes of physical activity tended to be more socially active (r=0.36) and those more socially active presented lower anxiety and depression symptoms (r=‐0.24). Finally, those that slept more hours presented more positive mood states (r=0.67).ConclusionThese preliminary findings suggest that social life, quality of sleep and physical activity could be critical to improve affective symptoms. Our findings also support the feasibility and value of ILD collection to better understand the effect of life style changes on cognitive and mental health at the individual and population levels. Finally, monitoring the mental health in ongoing clinical trials is important to understand the impact of the COVID‐19 pandemic on study outcomes.
Psychiatric misdiagnosis in behavioral variant frontotemporal dementia in Cali, Colombia
Authors: Zapata‐Restrepo Lina Maria , Possin Kate , Rivas Juan Carlos , Miranda Carlos , Miller Bruce L. , Allen Isabel Elaine 
Published: December 2021

AbstractBackgroundPsychiatric manifestations are common in the behavioral variant of frontotemporal dementia (bvFTD) with many patients misclassified with other psychiatric diagnoses. In this study, we described the initial neuropsychiatric symptoms and the psychiatric misdiagnoses in a diverse population of patients with probable bvFTD seen at a psychiatric public hospital in Colombia.MethodsWe retrospectively reviewed the medical records of 28 patients who met diagnostic criteria for probable bvFTD based on a multidisciplinary evaluation. Neuropsychiatric symptoms were rated using the NPI. Initial psychiatric diagnoses were made using the DSM‐V. The bvFTD diagnostic criteria of the international consortium were used. Stata 16.1 and SPSS 27.0 were used for the statistical analysis.ResultsUsing the NPI, we found that the most common symptoms were apathy in both genders. Delusions were present in 60.7% and hallucinations in 39.2% of the sample. 71.4% of the patients were misdiagnosed with psychiatric disease and not with dementia. In women, the most frequent psychiatric diagnoses were depression (26.3%), and bipolar disorder (26.3%), while in men it was anxiety disorders (33.3%) and psychotic disorders (22.2%).ConclusionPsychotic symptoms were higher in this sample than in previous studies. The presence of psychiatric symptoms and their possible overlap in patients with bvFTD make differential diagnosis difficult. The misdiagnosis could be related to factors such as a lack of knowledge about this type of dementia in the medical community. In the future, the implementation of specific biomarkers and genetic testing will help to improve the diagnosis of bvFTD.
Late‐stage dementia is associated with decreased likelihood of successful discharge to community after home health care
Authors: Knox Sara , Downer Brian , Haas Allen , Ottenbacher Kenneth J 
Published: December 2021

AbstractBackgroundSeveral studies have established the efficacy of home health in meeting the health care needs of people with Alzheimer’s disease and related dementias (ADRD) and in assisting them to remain in their homes, which is a key goal for the majority of older adults. However, transitioning to the community after discharge from home health poses significant challenges to patient safety and quality of care. For individuals with ADRD, these challenges are compounded by cognitive limitations and behavioral and psychological symptoms inherent to their disease. The likelihood of a person with ADRD successfully discharging to the community may depend on the severity of their dementia. The purpose of this study was to examine the association between ADRD severity and successful discharge to community (DTC) after home health.MethodThis retrospective study derived data from 100% national CMS data files from October 1, 2016 through September 30, 2017. A cohort of 140,616 Medicare beneficiaries with ADRD who received home health was identified. Successful DTC rates with associated 95% confidence intervals (CIs) were calculated for each patient characteristic. Multilevel logistic regression was used to estimate the relative risk (RR) of successful DTC after home health, by dementia severity level, adjusted for patient and clinical characteristics.ResultOverall, 72.5% of individuals had a successful DTC. Individuals in the first 5 stages of the dementia categorization scale had successful DTC rates greater than the cohort average (75.3%‐ 80.3%). Individuals in the 6th dementia categorization stage (69.2%) had successful DTC rates 3% less than the cohort average and individuals in the 7th dementia categorization stage had successful DTC rates almost 20% lower (55.9%) than the cohort average. Individuals in the 6th and 7th dementia severity categories had significantly lower risk of successful DTC (RR=0.67, 95% CI=0.65‐0.69 and RR= 0.42, 95% CI= 0.38‐ 0.46) than those in the lowest dementia severity category.ConclusionMost older adults with ADRD had a successful DTC following home health, but the likelihood for successful DTC decreased considerably with greater ADRD severity. Strategies for increasing the likelihood for successful DTC following home health among older adults with ADRD need to consider disease severity.
What happens to the worried well? Follow‐up of subjective cognitive impairment
Authors: Sutherland Maggie , Kirk Andrew , Karunanayake Chandima P , O'Connell Megan E , Morgan Debra G 
Published: December 2021

AbstractBackgroundPerceived neurocognitive decline is becoming a more common concern, leading to an increased number of referrals to specialists for further investigation and increased stress and anxiety for patients. Subjective cognitive impairment (SCI) refers to the condition of having concerns about one’s memory but performing within the expected range on neurocognitive tests. People with SCI can also be referred to as the “worried well”. We aimed to explore how likely the “worried well” are to experience neurocognitive decline and develop a neurologic diagnosis.Method166 consecutive “worried well” patients who attended the Rural and Remote Memory Clinic (RRMC) in Saskatchewan, Canada between 2004 and 2019 were included. Demographic, health, social, and behavioural factors were recorded at the initial visit. Mini Mental Status Examination (MMSE) score, Center for Epidemiologic Studies Depression Scale (CESD) score, and Functional Assessment Questionnaire (FAQ) scores were measured and compared at initial assessment and at 1‐year follow‐up. MMSE scores overtime were assessed with a mean follow‐up of 2.95 years (SD 2.87). Case summaries were used to build the profile of 9 cases, which have been followed longer than one year and developed a neurologic diagnosis.ResultThere was no statistically significant difference in MMSE, CESD, or FAQ scores between clinic day and one‐year follow‐up, and no consistent pattern of MMSE score over time. Of the 166 patients with SCI on initial assessment, 5 were later diagnosed with AD at 8.5, 3.5, 5, 3, and 1.75 years; 2 were diagnosed with MCI at 1 and 2 years; 1 was diagnosed with vascular cognitive impairment at 5 years; and 1 was diagnosed with frontotemporal dementia (FTD) at 0.5 years.ConclusionThere is no pattern of neurologic decline observed in the “worried well”. Though the likelihood of a patient with SCI developing a neurological diagnosis is reassuringly low, (9/166), it is not irrelevant. The chance of an underlying neurological problem and subsequent neurologic diagnosis, along with the benefits of early diagnosis and treatment for dementia, leads us to believe that patients with SCI should still be seen in follow‐up at least at the one‐year mark.