bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncovering superficial white matter changes in young‐onset Alzheimer’s disease
Authors: Veale Thomas , Malone Ian B , Poole Teresa , Parker Thomas D , Slattery Catherine F , Schott Jonathan M , Zhang Hui , Fox Nick C , Cash David M 
Published: December 2020

AbstractBackgroundSuperficial white matter (SWM), subjacent to the cortex, has unique vulnerabilities to Alzheimer’s disease (AD) but is understudied. The organisational complexity of SWM means conventional diffusion tensor imaging (DTI) has difficulty characterising both the degeneration and dispersion of fibres. We used both DTI and Neurite Orientation Dispersion and Density Imaging (NODDI) to assess AD‐related SWM changes while accounting for fibre density and dispersion.Method51 participants were included: 22 healthy controls (mean age 61 (+/‐6) years) and 29 individuals with young onset AD (YOAD: mean age 62 (+/‐5) years; 18 with typical AD, 11 posterior cortical atrophy). We used single‐shell (b=1000) and multi‐shell (b=300; b=700; b=2000) diffusion MRI (dMRI) data. Preprocessing involved correcting for eddy currents, motion and susceptibility artefacts followed by fitting DTI and NODDI models. DTI and NODDI metrics were sampled across the GM/WM FreeSurfer surface in 15 cortical regions of interest (ROI) (Figure 1). Linear mixed effect models of fractional anisotropy (FA), mean diffusivity (MD), neurite density index (NDI) and orientation dispersion index (ODI) were fit for each ROI while controlling for cortical thickness (correcting for multiple comparisons using False Discovery Rate of 0.05). Average Marginal Effects (AMEs) representing the change in YOAD versus controls, while holding other fixed effects constant, were calculated.ResultIn the GM, widespread significant differences were observed in both DTI and NODDI metrics (pFDR < 0.05) (Figure 2). In the SWM, YOAD patients had lower FA and/or changes in MD in five ROIs (pFDR < 0.05) (including parahippocampal gyrus and superior temporal cortex). NODDI metrics showed more widespread differences in the SWM, as the YOAD group had lower NDI and/or higher ODI across ten ROIs (pFDR < 0.05) (including parahippocampal gyrus and inferior parietal cortex).ConclusionDiffusion imaging can detect microstructural changes occurring within the SWM of YOAD individuals in regions associated with AD‐pathology. These changes in SWM not only persist, but are more prominent, when independently accounting for the density and dispersion of fibres using NODDI. These novel NODDI SWM measures may uncover previously under‐recognised degeneration and organisational WM alterations in AD.
A randomized controlled trial to evaluate the effectiveness and cost‐effectiveness of the FindMyApps intervention for improving self‐management and social participation of community‐dwelling people with dementia, compared to normal tablet use
Authors: Neal David Peter , Kerkhof Yvonne JF , Ettema Teake P , Muller Majon , Bosmans Judith , Finnema Evelyn , Graff Maud , Tanja‐Dijkstra Karin , Stek Max L , Droes Rose‐Marie 
Published: December 2020

AbstractBackgroundFor the rising number of people living with dementia, cost‐effective community‐based interventions to support psychosocial care are needed. The FindMyApps program helps people with dementia and their caregivers learn to use tablet computers and find user‐friendly apps that facilitate self‐management and engagement in meaningful activities. This definitive trial builds on previous feasibility pilot trials of FindMyApps and further evaluates cost‐effectiveness.MethodThis is a protocol for a non‐blinded randomized controlled trial (RCT) with two arms (intervention and usual care). 150 dyads (person with dementia and their carer) will be recruited. Participants must be resident in the community, with a diagnosis of Mild Cognitive Impairment or mild dementia (Mini Mental‐State Examination 17‐26, or Global Deterioration Scale 3‐4. Dyads will be randomly assigned in equal proportions to receive either the FindMyApps intervention (experimental arm) or usual care (control arm). Primary outcomes measured at 3 months will be: self‐management and social participation of the person with dementia; caregiver sense of competence. Data will be collected through questionnaires, filled in by the researcher or participants themselves. In addition to a main effect analysis, a cost‐effectiveness analysis will take place. In line with Medical Research Council (MRC) guidance for the evaluation of complex interventions, a process analysis will be undertaken, to identify factors that may influence trial outcomes. Semi‐structured interviews and remotely collected data regarding use of the FindMyApps app will support the process analysis.ResultResults of this study are expected in 2022. The study will be adequately powered to detect at least a moderate effect size of the intervention with respect to the primary outcomes.ConclusionThis study will investigate the effectiveness and cost‐effectiveness of the FindMyApps intervention. The results of the study will provide strong evidence to support or oppose scaling up implementation of the intervention. This is also an example of how the MRC framework for the evaluation of complex interventions can be implemented in practice. In a field which is often criticized for a lack of high quality evidence, randomized controlled trials should be applied more frequently designed for the robust and transparent evaluation of digital tools and technologies.
Highly palatable diet changes brain glucose metabolism in mice
Authors: Gehres Sarah Wehle , da Rocha Andreia Silva , Rodrigues Yuri Elias , Peixoto Guilherme G Schu , Carvalho Afonso Kopczynski , Carteri Randhall K , Venturin Gianina Teribele , Greggio Samuel , Costa daCosta Jaderson , Leonardi Bianca F , Zimmer Aline R , Souza Diogo O , Portela Luis V , Zimmer Eduardo R 
Published: December 2020

AbstractBackgroundObesity has become a global public health issue and is knowingly associated with several pathological conditions. Epidemiological data indicate it is an important risk factor for the development of neurodegenerative diseases, such as Alzheimer’s Disease (AD). However, the pathological mechanisms connecting these two conditions are still elusive. Current evidence points toward glucose metabolism dysregulation, as well as defective insulin signaling and low grade inflammation. Objective: Our main goal was to investigate the effects of a highly palatable diet (HPD) on brain glucose metabolism. Hypothesis: We hypothesized that the obesity induced by the HPD could lead to alterations in brain glucose metabolism similar to those found in AD.MethodsMale C57BL/6J mice (45 days old) were fed with HPD (rich in simple sugars and fat) for four months. They were then examined in vivo via microPET [18F]FDG. Data from images were used to assemble [18F]FDG‐derived brain metabolic networks. A glucose tolerance test (GTT) was also performed to assess peripheral insulin response. Post‐mortem, the brain tissue was used in a high resolution respirometry test to evaluate mitochondrial activity.ResultsHPD animals presented increased body weight (HPD= 37.17±4.38g; control= 28.72±1.23g; P<0.0001) and abnormal peripheral tolerance to glucose (peak blood glucose: HPD=421.93±47.13mg/dL; control=323.60±43.83mg/dL P<0.0001). HPD also induced [18F]FDG hypermetabolism in the prefrontal cortex and a hypersynchronicity in the metabolic network, where the hypothalamus appears to be more connected to the hippocampus, thalamus, prefrontal cortex, and striatum. Brain post mortem analysis indicated a less efficient mitochondrial oxidative phosphorylation in the hypothalamus of HPD fed animals as measured by the Respiratory Chain Ratio (HPD=0.640±0.022; control= 0.810±0.012 P<0.001).ConclusionThese preliminary results show that HPD causes peripheral and central disturbances in glucose metabolism, also altering brain mitochondrial activity. Interestingly, in vivo imaging indicates that the prefrontal cortex is highly active and the hypothalamus is unusually connected to other brain regions in these animals.
Decrease in olfactory cortex volume and alterations in caspase expression in the olfactory bulb in the pathogenesis of Alzheimer’s disease
Authors: Alotaibi Majed , Lessard‐Beaudoin Mélissa , Loudghi Amel , Chouinard‐Watkins Raphaël , Plourde Melanie , Calon Frederic , Castellano Christian‐Alexandre , Cunnane Stephen , Gaudreau Pierrette , Graham Rona 
Published: December 2020

AbstractBackgroundAlzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Symptoms include memory dysfunction, and also alterations in attention, planning, language and overall cognitive function. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may therefore lead to the discovery of potential biomarkers and/or treatments for neurodegenerative diseases.MethodFor the human study, quantitative olfactory tests (UPSIT and OMT) have been done on 93 subjects from the Quebec Longitudinal Study on Nutrition and Successful Aging cohort accepting to participate in the ORCA secondary study. The telephone Modified Mini Mental State examination (t‐MMSE) was used to assess cognition levels, and an olfactory self‐report was also collected. In a separate cohort, olfactory cortical volume was calculated using MRI results from healthy old adults (n=25) and patients with AD (n=14) using the AAL single‐subject atlas and performed with the PNEURO tool.ResultHuman Study: Based on the self‐report, 81% of the participants claimed to not suffer from any problem with olfaction. However, based on the UPSIT, 94% of those subjects showed a poor olfactory performance and different forms of microsmia. Moreover, our results confirm that olfactory function declines with age. We also detected a significant decrease in olfactory cortical volume in AD individuals compared to controls. Murine study: Preliminary data demonstrate there is a significant decrease in expression levels of the proform of caspase‐3 and the caspase substrate STK3, in the olfactory bulb of mice expressing human APOE4 compared with controls. The data also suggest that Iba‐1 immunostaining is increased in the olfactory bulb of APOE4 mice compared to wild type mice.ConclusionThe activation of caspase‐3 may be the cause of the decreased levels of STK3 through caspase cleavage and may play a role in the inflammation observed. In the clinical study, our results suggest that seniors are unaware of their olfactory function status and therefore it is not sufficient to measure olfaction using the self‐report in the elderly. Studying olfactory function in the aging population will help to discover biomarkers in the early stage of the AD.
The impact of green care farms and other innovative nursing home models on BPSD symptoms in everyday life for people with dementia
Authors: Verbeek Hilde , De Boer Bram , Zwakhalen Sandra , Hamers Jan 
Published: December 2020

AbstractBackgroundMany countries are introducing small‐scale, home‐like care facilities that represent a radically new approach to nursing home care for people with dementia. These facilities emphasize person‐centered care, focus on remaining strengths and value autonomy. Originated outside of the healthcare sector, green care farms (GCFs) are a new type of nursing home in the Netherlands. GCFs provide care in small‐scale, homelike environment, in which agricultural activities are combined with care and support services for a variety of client groups, including people with dementia. This study investigated effect of GCFs on residents, in particular on behavioral and psychological symptoms.MethodIn total, 115 residents with a formal diagnosis of dementia were included, living at GCFs (n=34), regular small‐scale living facilities (n=52) and traditional nursing homes (n=29). Residents were matched regarding cognitive status (S‐MMSE). Ecological momentary assessments (n=16,860) were conducted using the Maastricht Electronic Daily Life Observation Tool, assessing activity engagement, social interaction and emotional well‐being. Furthermore, neuropsychiatric symptoms (NPI‐NH), agitation (CMAI), depressive symptoms (CSDD), quality of life (Qol‐AD and QUALIDEM) and social engagement (RISE) were measured.ResultThe daily life of residents living at GCFs was significantly different compared with traditional nursing homes. Residents were significantly more active (p<0.05, SE=0.9) and socially engaged (p<0.05) at GCFs compared with traditional nursing home wards. Furthermore, residents living at GCFs scored significantly higher on the Qol‐AD (p<0.05, ES=0.8) and on three domains of the Qualidem: positive affect, social relations and having something to do (p<0.05, ES>0.7) compared with traditional nursing homes. No significant differences were found regarding neuropsychiatric symptoms (mean NPI‐NH score 15.4), agitation (mean CMAI score 41.9) and depressive symptoms (mean CSDD score 5.4).ConclusionThis study showed that GCFs provide an attractive, homelike environment and activities that positively influence engagement and social interaction. GCFs appear to be a valuable alternative to existing nursing homes. This is important as people with dementia are a heterogeneous group with varying needs. In order to provide tailored care there also is a need for a variety of living environments.
Continuous palliative sedation in nursing home residents with dementia suffering from extreme refractory BPSD symptoms: A qualitative study
Authors: Koopmans Raymond , Veldwijk‐Rouwenhorst Annelies , Smalbrugge Martin , Zuidema Sytse U , Hanssen Suzan , Gerritsen Debby L 
Published: December 2020

AbstractBackgroundBPSD are highly prevalent in nursing home (NH) residents with dementia. Sometimes these BPSD are very severe or even extreme resulting in the application of continuous palliative sedation (CPS) CPS is defined as “the deliberate lowering of a patient’s level of consciousness in the last stages of life”. The aim of this study was to explore the trajectory leading to CPS and its application NH‐residents with dementia and case of so called ‘refractory BPSD’.MethodA qualitative interview study on dementia special care units of three NHs in the Netherlands was performed in 2017. Relatives, elderly care physicians and other staff members involved with three NH‐residents with dementia and extreme refractory NPS who received CPS. We used consecutive sampling to select participants. Medical files were studied. Semi‐structured interviews were conducted. Transcriptions were analyzed with thematic analysis, including directed content analysis.ResultNine in‐depth interviews with fourteen participants were held. Analysis resulted in five main themes with several subthemes reflecting phases of the trajectory leading to CPS and the CPS application itself, a sixth main theme concerned evaluations thereof. According to the first theme (run‐up), the suffering of the NH‐resident was described as unbearable/an inner struggle. Participants still had hope for improvement. Concerning the second theme (turning point), hope was lost, participants were convinced they had tried everything and experienced feelings of powerlessness and failure. Regarding theme three (considering CPS), intermittent sedation was applied in all three cases and peer consultation was employed. Honoring the wish of the NH‐resident and therapeutic uncertainties, among others, were important subthemes. According to theme four (decision to start CPS), in each case one specific aspect was a decisive trigger for administering CPS. Concerning theme five (applying CPS) feelings of relief were experienced after starting with CPS.ConclusionThe trajectory leading up to CPS in NH‐residents with dementia and extreme refractory BPSD was complex and burdensome, but the application led to relief and contentment of all those involved. We recommend to include external consultation in the decision process and to apply intermittent sedation as a preceding step when CPS is considered.
Effectiveness of Reducing Disability in Alzheimer’s Disease among dementia patients and their family caregiver
Authors: Perales Jaime , Barton Kelli , Ptomey Lauren , Niedens Michelle , Vidoni Eric D 
Published: December 2020

AbstractBackgroundDementia impacts the mental health of individual‐caregiver dyads. Interventions such as Reducing Disability in Alzheimer’s Disease (RDAD) improve dyad mental health, but to implement it locally community agencies in Kansas City suggested three changes: 1) reduced reliance on licensed social workers, 2) centralized exercise interventionists and 3) more flexible delivery. We aimed to assess the effectiveness of the Kansas City RDAD implementation (RDAD‐KC), which addressed these three gaps. We hypothesized that dyads’ mental health would improve from baseline to the end of the intervention.MethodThis is a secondary‐analysis of an in‐home dementia support services quality improvement project amongst a collaborative of nine community agencies in the Kansas City region. Agencies administered RDAD‐KC to a non‐probabilistic sample of dyads they recruited in their service areas. Eligibility criteria included living in the community, having moderate dementia, with enough home space to exercise, ability to walk across the room with or without assistive devices and no physical activity restrictions. The original RDAD is a 12‐module dyad home‐based multicomponent intervention that focuses on exercise for people with dementia and coping with behavioral symptoms for caregivers. RDAD‐KC 1) allowed non‐licensed interventionists, 2) included exercise videos and contact of a centralized exercise team and 3) allowed fitting the intervention delivery to the dyads’ situation, needs, and time available. Data analyses included paired samples t‐tests. Final data analysis included those who had a family caregiver, no intellectual disability and completed nine of the 12 modules.ResultAmong the 157 screened dyads, 66 completed ≥9 modules. People with dementia were 77.4 years in average, 72.9% identified as White, 19.7% as Black, 17.0% rural and 71.2% had their partners as caregivers. All outcomes improved statistically (p<0.01) from pre to post‐intervention: Behavioral symptom severity (range 0‐36) decreased from 11.3 to 8.6, caregiver unmet needs (range 0‐34) decreased from 10.6 to 5.6, caregiver behavioral symptom distress (0‐60) decreased from 15.5 to 10.4 and caregiver strain (0‐26) decreased from 11.1 to 9.7.ConclusionA more flexible implementation of RDAD leads to clinically meaningful improvement of mental health outcomes among dyads. RDAD‐KC might inform the scaling‐up of RDAD in the region.
Higher TREM2 levels and microglia activation associated with slower rates of amyloid PET increase in humans and a transgenic mouse model of beta‐amyloid
Authors: Ewers Michael , Franzmeier Nicolai , Brendel Matthias , Suarez‐Calvet Mark , Biechele Gloria , Sacher Christian , Blume Tanja , Haass Christian ,   Alzheimer's Disease Neuroimaging Initiative
Published: December 2020

AbstractBackgroundLoss‐of‐function mutations in the TREM2 gene, a key receptor molecule on microglia, are associated with a 2 – 3 fold increase in the risk of Alzheimer’s disease (AD). Biomarker‐levels of soluble TREM2 (sTREM2) are increased in AD and associated with slower cognitive decline, suggesting a protective role of sTREM2‐related microglia activity (Suarez Calvet et al. Science Trans Med, 2016; Ewers et al. Science Trans Med., 2019). However, whether microglia activity reduces the future accumulation of core AD‐pathology remains unclear. Here we 1) tested in elderly subjects whether higher cerebrospinal fluid (CSF) levels of sTREM2 are associated with slower longitudinal rates of global amyloid‐PET accumulation, and 2) in a transgenic mouse model of Ab, whether higher baseline microglia‐PET is associated with slower rates of amyloid‐PET accumulation.Method206 Ab‐positive participants (global 18F‐AV‐45‐PET SUVR > 0.79, Landau et al. 2015) comprising 55 cognitively normal, 136 amnestic mild cognitive impairment and 15 AD dementia participants, and in addition, 94 Ab‐negative CN were included from ADNI. CSF sTREM2 and 18F‐AV‐45 PET were measured at baseline, and 18F ‐AV‐45 PET was repeated during follow‐up (mean = 2 years, range = 1.71‐6.1 years). 15 APPNL‐G‐F transgenic mice and 43 age‐ and gender matched C57BL/6 control mice were assessed with 18F‐GE180 TSPO‐PET at age 5 months and 18F‐AV‐45 PET at ages 5 and 10 months.ResultIn linear mixed effects analysis across all participants, the rate of change in amyloid PET showed a quadratic curve as a function of baseline amyloid‐PET levels, peaking at SUVR = 0.95 (Fig. 1A). Baseline levels of CSF sTREM2 modulated the rate of change in amyloid‐PET, such that at higher CSF sTREM2, the rate of subsequent increase in amyloid‐PET was reduced, controlled for demographics, diagnosis, CSF p‐tau181, and ApoE e4 (Figure 1B). In the AppNL‐G‐F
mice, higher microglia‐PET at baseline was associated with slower rate of increase in global amyloid‐PET increase, controlled for baseline amyloid‐PET (Figure 2).ConclusionAcross humans and mice, higher microglia activation as measured by CSF sTREM2 or microglia PET showed protective effects on subsequent amyloid accumulation, supporting the critical role of microglia activation in the development of AD.