bluuebunny/crossref_metadata_2025_split huggingface dataset:
Better living with non‐memory led dementia: results from a pilot randomised clinical trial of an online training programme for carers of people with PCA, PPA and bvFTD
Authors: Gonzalez Aida , John Amber , Brotherhood Emilie V , Camic Paul , McKee‐Jackson Roberta , Melville Mel , Sullivan Mary Pat , Tudor‐Edwards Rhiannon , Windle Gill , Crutch Sebastian J , Hoare Zoe , Stott Joshua , Impact Rare Dementia Support 
Published: December 2023

AbstractBackgroundDementias starting with symptoms other than memory are low prevalent. Educational and training resources for caregivers of people living with these conditions are scarce and difficult to access. The aim of this trial is to test the feasibility of an online training program for carers of people with three non‐memory led dementias: Posterior Cortical Atrophy (PCA), Primary Progressive Aphasia (PPA) and behavioural variant FTD (bvFTD). The trial design is a randomised feasibility study.MethodSetting: Community. Participants were recruited from the organisation Rare Dementia Support (RDS). Participants: Carers of people with PCA, PPA and bvFTDIntervention: The experimental group was given access to an eight‐week online program consisting of 6 digital manuals addressing practical strategies to better support people living with PCA, PPA or bvFTD (depending on diagnosis of the care recipient). The control group was directed to RDS’s existing website (TAU).Outcome measures: Feasibility of recruitment, measurement tools (clinical outcomes, see Table 1) and acceptability. Measures were collected at baseline, immediate post intervention (8 weeks post‐randomisation) and 3 months post‐randomisation.Randomization: Allocation ratio was 2:1 (intervention: control) stratified by diagnosis carried out by a central computer system. Participants were unblinded to intervention. All measures were self‐reported online by the participants.ResultNumbers randomized: 31 participants were recruited. 30 participants were randomized (1/31 did not complete baseline) (21 to intervention, 9 to control group). Trial status: closed.Numbers analysed: 30 participants for intention to treat analysis (3 dropped out).Outcomes: Feasibility of recruitment (see Figure 1 Flowchart) is 40% (31 people consented/78 approached). Retention rate is 87%. The proportion of eligible participants who agree to participate is 97% (30/31).Assessment of feasibility of measurement tools (proposed clinical outcomes) shows 96% response rates at 8 weeks (29/30) and 90% (27/30) at 3 months. Acceptability: 100% of participants agreed to be randomised. Intervention coherence: 28% (6/21) participants interacted with facilitator during the intervention. Follow‐up qualitative interviews were conducted to gain a better understanding of how to improve intervention coherence.ConclusionThe trialled intervention shows excellent feasibility of recruitment, retention and measurement tools. Enhancement of intervention coherence is required.
What matters in everyday life for people living with dementia: a qualitative inquiry
Authors: Huizenga Jacoba , Scheffelaar Aukelien , Bleijenberg Nienke , Wilken Jean Pierre , Van Regenmortel Martine R.F. , Keady John 
Published: December 2023

AbstractBackgroundResearch on what matters to people with dementia in their everyday lives is crucial to develop tailored interventions and programs. However, they are rarely asked. A scoping review of studies with the perspective of people with dementia revealed that no study has explicitly examined everyday life as a whole (Huizenga et al., 2022). A conceptualization of everyday life is lacking. This qualitative study uses the lens of everyday sociology, which focuses on the ordinary mundane aspects of life that are often unseen and unnoticed. The aim of this study was to explore how people with dementia experience their everyday lives and what matters to them. This will provide insight into the essential ingredients for support to ensure the quality of everyday life.MethodUsing a phenomenological approach, open interviews were conducted with 15 people with dementia living at home. The topic list compromised the following topics: experience of activities, relationships, places, the condition of dementia, and health and social care. Respondents participated in 1‐3 interviews. The interviews were supplemented with home tours (Pink, 2009) and walking interviews. The analysis was performed in Atlas.Ti using a descriptive content analysis. The analysis followed the phases of open, axial and selective coding. During the analysis, an advisory board of people living with dementia was consulted to ensure the content validity of the findings.ResultPreliminary findings show that everyday life for people living with dementia is a continuing struggle to maintain balance in managing progressive disruptions. Helpful are meaningful activities, especially in meeting centers, feeling connected in relationships and a sense of feeling at home related to the house and the neighborhood. Everyday life is described as living in the present but is also influenced by life history. Furthermore, other conditions, such as financial problems and physical conditions hinder everyday life.ConclusionA preliminary conclusion is that this study gives insight in what matters to the daily life of people living with dementia at home. These insights help to gain a better understanding and better connect to needs.
Validation and comparisons of the Amnesia Light and Brief Assessment (ALBA), the door Picture Naming and Immediate Recall (PICNIR) and the Addenbrooke’s Cognitive Examination III (ACE‐III) for detecting cognitive impairment
Authors: Bartos Ales , Polanská Hana 
Published: December 2023

AbstractBackgroundTwo unique very brief tests are easily administered and cognitively demanding. The Amnesia Light and Brief Assessment (abbreviated from the initial letters as ALBA) lasting 3 minutes and the door PICture Naming and Immediate Recall (PICNIR) lasting 4 minutes were validated and compared with the seven times longer Addenbrooke’s Cognitive Examination III (ACE‐III) (20‐30 minutes).MethodsThe ALBA, PICNIR and ACE‐III were administered to 155 elderly individuals in 2 groups comprising 40 patients with neurocognitive disorders according to DSM‐5 criteria and 116 normal elderly adults. The ALBA was evaluated using the memory ALBA score (MAS). The PICNIR was assessed using numbers of naming errors (NE) and correctly recalled picture names (PICR).ResultsAll the tests were significantly different between the two age‐ and education matched groups (ACE‐III: 73±11 vs. 96±4 points) and showed excellent accuracy as assessed by the area under the ROC Curve (AUC): 0.89 for MAS, 0.81 for NE, 0.96 for PICR and 0.98 for the ACE‐III. The AUCs of PICR and ACE‐III were comparable and larger than those of MAS and NE. The ACE‐III strongly correlated with MAS and PICR (0.8, R2 = 60% each) and NE (‐0.7, R2 = 48%) in the whole sample.ConclusionsThe innovative and efficient ALBA and PICNIR tests have high discriminant validity for cognitive impairment and high convergent validity with the ACE‐III. Moreover, they can reliably predict total ACE‐III scores. Brevity and simple administration and evaluation are major advantages of the ALBA and the PICNIR over much longer ACE‐III for busy clinical practice.Supported by grant COOPERATIO Neuroscience, Charles University, GAUK 268321 a SVV 260599 and grant NU20‐07‐00100.
Brain Function Entropy Analysis during Dual‐Tasking: Application of Functional Near Infrared Spectroscopy to Screen Alzheimer’s Disease
Authors: Petrillo Kelsi , Flores Hector , Mayoral‐Ortega Isabellah , Javed Bilaval , Dagar Meenakshi , Toosizadeh Nima 
Published: December 2023

AbstractBackgroundDespite a high prevalence, over half of patients with dementia never receive an evaluation, indicating a need for a quick and objective routine test for screening cognitive decline in older adults. Due to neural death and disconnections, Alzheimer’s disease (AD) is associated with a low value of nonlinear complexity of brain function, which can be quantified using multiscale entropy analysis.MethodOur proposed solution is an upper extremity function dual‐task screening method, during which, brain function is measured by functional near infrared spectroscopy (fNIRS). The aim of this study was to investigate association between fNIRS entropy during upper‐extremity dual‐tasking and cognitive status in older adults. The sample population for this data includes 40 older adults with ages ranging from 65‐96 years. Participants were categorized into cognitive normal (CN), mild cognitively impaired (MCI), and AD based on MoCA test results. The fNIRS device took measurements over the frontal (right and left) and parietal (right and left) brain regions. Participants were first instructed to rest for three minutes, during which they were asked to relax and not think about any specific topic. Participants were then asked to flex and extend their right arm consistently for three minutes, while counting backwards by intervals of three.ResultWe used multivariable repeated measures analysis using mixed effects modeling to assess the effect of cognitive status on multiscale entropy, with task condition (rest and dual‐task) as within‐subject parameter and sex as covariate. We observed a significant effect of cognitive status on multiscale entropy of left frontal (p = 0.0196) and right frontal brain regions (p = 0.0448), with 0.198, 0.267, and 0.301 entropy values on average across AD, MCI, and CN, respectively. There was also a significant effect of task on multiscale entropy of right frontal (p = 0.0165), left frontal (p = 0.0209) and left parietal regions (p = 0.0011), with 39.79% higher entropy during dual‐task compared to rest trials.ConclusionThe results of this study indicate potential for the use of fNIRS multiscale entropy analysis as a screening tool for cognitive impairment. More research is necessary to better understand other potential confounding factors as well as validate this approach in a larger sample size.
Successful Recruitment of Low‐income and Minority Patients in the Southern United States: Implementation of Intensive Blood Pressure Control to Slow Cognitive Decline (IMPACTS‐MIND) Trial
Authors: Mills Katherine , Williamson Jeff D. , He Jiang 
Published: December 2023

AbstractBackgroundBlack communities, low‐income populations, and those living in the stroke belt bear a disproportionate burden of dementia and are underrepresented in previous trials on preventing cognitive decline and dementia. Improved methods to implement interventions to slow cognitive decline and reduce health disparities are needed. The Implementation of Multifaceted Patient‐Centered Treatment Strategies for Intensive Blood Pressure Control to Minimize Cognitive Decline (IMPACTS‐MIND) trial is testing a multifaceted strategy for implementing an intensive blood pressure (BP) intervention protocol on cognitive decline in racial minority and low‐income hypertensive patients in primary care.MethodThe IMPACTS‐MIND study is a cluster‐randomized trial in 10 primary care organizations with 40 clinics in Louisiana and Mississippi. The included organizations predominantly treat low‐income and minority patients, and 9 of the organizations (with 36 included clinics) are federally‐qualified health centers (FQHCs). We are recruiting a goal of 1,260 patients who are at least 40 years of age (2/3s over age 60 years) with have uncontrolled systolic BP. Recruitment has been conducted in partnership with primary care organizations. Using electronic health record systems, potentially eligible patients based on BP are contacted via a letter and phone call to assess willingness and preliminary eligibility. Provider and staff referrals are also encouraged and incentivized.ResultWe have enrolled 581 participants in the study to date. Participants are an average of 63.0 years of age, 68% are Black, and 59% are female. More than 60% have a high school education or less, and 72.8% have an annual household income <$25,000. Over 44% have diabetes, 28.9% depression, and mean body mass index of 33.6 kg/m2. Mean baseline Montreal Cognitive Assessment (MoCA) score is 19.7. Successful recruitment of low‐income and minority participants has hinged on strong relationships with primary care partners through study steering committee membership for each organization and state FQHC organizations, manuscript co‐authorship for all members, monthly meetings to support study conduct, and building research capacity and opportunities for partnering organizations.ConclusionEffectively recruiting low‐income and minority patients is possible through partnership with primary care providers who treat these patients. Building relationships with these organizations around common interests and priorities is critical to effective recruitment.
Amyloid models for quantitative x‐ray brain amyloid imaging
Authors: Suresh Karthika , Dahal Eshan , Badano Aldo 
Published: December 2023

AbstractBackgroundA range of human neurological disorders are related to amyloid fibrillar deposits including Alzheimer’s disease (AD). AD is linked to the presence of amyloid‐β (Aβ) fibrils and those are comprised of β‐sheet motifs. The precise mechanism through which Aβ leads to AD are not completely understood. The scarcity of human derived Aβ fibrils and high cost of recombinant Aβ fibrils further restrict the research in this area. However, intrinsically disordered proteins (IDPs) have been reported as amyloid model proteins. Even though, these models qualitatively mimic β‐sheet structure of Aβ fibrils but often fail to quantitatively match the β‐sheet content. Therefore, this study aimed to develop model proteins to closely mimic Aβ fibrils structure and produce them in a large quantity to evaluate emerging X‐ray methods to detect and quantify amyloid plaques.MethodsWe used a commercially available β‐lactoglobulin A and B genetic mixture (LGAB) protein as our amyloid model to mimic the structural properties of Aβ fibrils. Here, the alteration in the protein conformation was induced by altering the net charge on the polypeptide chain by changing the pH from 2 to 7. Additionally, we studied the fibrillization of these proteins in presence of more cooperative transitions at 90°C. The secondary structural compositions of LGAB were studied using attenuated total reflectance Fourier transform infrared (ATR‐FTIR) spectroscopy. The nanostructures of LGAB fibrils were characterized using small angle X‐ray scattering (SAXS). We further varied the mass fraction of LGAB fibrils (amyloid model) and quantitatively measured their amyloid content using a SAXS based method.ResultsATR‐FTIR (Fig.1) and SAXS (Fig.2) studies confirm that thermally aggregated LGAB fibrils exhibited parallel β‐sheet secondary structure similar to Aβ fibrils. Systematic variation in LGAB fibril concentration in the tissue mimicking environment showed a linear correlation between protein mass fraction and area under the curve of a peak (∼ 6 nm−1) corresponding to inter β‐sheet spacing (Fig.3).ConclusionOur study suggests that the amyloid model based on LGAB fibrils can likely be used to simulate Aβ fibrils in phantom studies for the evaluation of emerging X‐ray methods to detect and quantify amyloid plaques.
The Prevalence of Leg Spasticity and it’s Clinical Correlates among a Cohort of persons carrying ADAD mutations
Authors: O'Dowd Connor Daniel , Sagare Abhay P , Zlokovic Berislav V , Montoya Lucy , Chui Helena C , Ringman John M 
Published: December 2023

AbstractBackgroundMotor deficits, including gait problems due to dysfunction of the pyramidal tracts, become increasingly problematic as Alzheimer’s disease (AD) advances. Leg spasticity can be more common and severe in the early stages of autosomal dominant AD (ADAD), particularly in association with specific PSEN1 mutations. We sought to define the frequency of leg spasticity in ADAD and its relationship to other features of the disease.Methods103 carriers of ADAD mutations (MCs, 84.4% PSEN and 15.6% APP) underwent comprehensive cross‐sectional clinical phenotyping including the Clinical dementia rating scale (CDR), assessment of leg tone using the Ashworth scale (n = 99 MCs), and measurement of walking speed standardized to meters per second (n = 46 MCs). Subjects’ ages were characterized relative to the median age of dementia diagnosis in their families (adjusted age).ResultsAmong non‐demented (CDR < 1) MC’s with severe spasticity (Ashworth ≥ 2), 4 had the A431E mutation and 1 had the F388S mutations in PSEN1. Carriers of A431E showed a high prevalence of increased leg tone prior to the age of dementia onset with 12/25 (48%) of A431E carriers exhibiting mild spasticity (Ashworth > 0) at an adjusted age < 0. Carriers of this mutation showed an increased prevalence of spasticity after the onset of cognitive symptoms. Every individual (N = 3) bearing the F388S PS1 mutation displayed severe spasticity. Of these MC’s, CDRs were 0.5, 1, and 3. Among MC’s, walking speed correlated significantly with Ashworth score (r = ‐0.765, p < 0.01) and verbal fluency (r = 0.304, p < 0.05) and Ashworth scores also correlated significantly with CDR sum of box scores (r = 0.414, p < 0.01).ConclusionsPhysical signs of pyramidal dysfunction may manifest before cognitive symptoms in association with some PSEN1 mutations. The correlation of spasticity with slowed cognition suggests a common underlying pathophysiology. Understanding the natural history of ADAD subgroups is helpful in delineating this underlying pathophysiology and therefore our ability to treat it.This study was funded by NIH P30AG066530, U01AG051218, R01AG062007
The effect of APOEƐ4 on neurocognitive decline is accentuated by female sex and menopause: Identification of mitigating interventions
Authors: Saleh Rasha , Hornberger Michael , Pontifex Matthew , Vauzour David , Ritchie Craig , Minihane Anne‐Marie 
Published: December 2023

AbstractBackgroundTwo thirds of those living with AD are female. Age‐standardised AD prevalence is consistently higher at all ages over 70 years in women versus men. The aetiology of the accelerated neurophysiological decline in females is poorly understood. Here we investigate the independent and interactive impact of APOE4 carrier status and menopause.MethodTargeted replacement (APOE3‐TR and APOE4‐TR) rodent models and human cohort studies (European Prevention of Alzheimer’s Dementia (EPAD) and UK Biobank (UKB)) were used to investigate the impact of APOE4, menopause and hormone replacement therapy (HRT) on cognition, brain volumes (assessed by MRI), omega‐3 fatty acid status and synaptic function. In rodents, menopause is elicited by the administration of 4‐vinylcyclohexene diepoxide (VCD), which induces a human‐like “perimenopausal” phenotype, whilst maintaining ovarian tissue integrity.ResultsIn EPAD, using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test battery, HRT use in APOE4 only was associated with higher overall cognition and (delayed) memory scores and larger entorhinal and amygdala volumes in APOE4 only. Earlier HRT introduction was associated with larger hippocampal volumes. In UKB, HRT use was associated with improved memory in APOE4/E4. In mice, VCD administration reduced recognition memory, brain docosahexaenoic acid (DHA, omega‐3 fatty acid) levels, and altered synaptic plasticity biomarkers in APOE4‐TR animals, which was mitigated by DHA supplementation (1).ConclusionAn increased penetrance of the APOE4 genotype during the menopausal transition is likely to contribute to the higher incident AD in females, and in APOE4 females versus non‐carriers. HRT and DHA intervention during the menopausal transition, as a critical window of opportunity, may represent effective strategies to support cognitive health into older age in this ‘at‐risk’ (APOE4 female) group, which typically represent 12% of Caucasian populations compared and 33‐50% of AD.1. Pontifex MG et al., FASEB J. 2021 May;35(5):e21583
Novel mechanisms to enhance omega‐3 brain metabolism with APOE4
Authors: Wang Shaowei , Ebright Brandon , Duro Marlon Vincent V. , Cai Zhiheng , Galvan Jasmin , Tsiknia Amaryllis A , Asante Isaac , Louie Stan G , Yassine Hussein N. 
Published: December 2023

AbstractBackgroundNeuroprotective nutritional interventions involving greater consumption of polyunsaturated fats (Mediterranean diet, fish consumption or DHA supplements) are less effective in APOE4 carriers with dementia compared to non‐carriers. We recently demonstrated greater activation of calcium dependent phospholipase A2 (cPLA2) in APOE4 compared with non‐APOE4 using both postmortem human brains and in brain tissues from APOE4 animal models. Activation of cPLA2 is associated with lower omega‐3 brain levels and lower measures of blood‐brain barrier (BBB) integrity as assessed using 7T DCE MRI to derive contrast transfer values (K trans).MethodHere, we present new data on aging (18 months) old APOE mouse models on a low DHA diet, APOE4‐TR mice treated with LPS and APOE knock out mice as a model of lower BBB integrity. All models were treated with the brain penetrant cPLA2 inhibitor ASB14780 at 10 mg/kg IP daily over 8 weeks in the aging model and acutely (7 days) in the younger LPS and APOE KO models.ResultcPLA2 inhibition was associated with increased brain omega‐3 levels in both the aging APOE4 model and in the younger APOE4 mice treated acutely with LPS. In the aging APOE4 mouse model, cPLA2 inhibition associated with better performance on novel object recognition, improved synaptic markers, and lower microglial activation. In the APOE KO model, treatment was associated with improved measures of BBB with lower K trans following treatment (Figure).ConclusionThe results here demonstrate how neuroinflammation associated with APOE4 depletes brain omega‐3s via activation of cPLA2 and how reducing cPLA2 activity can rescue this phenotype. The development of specific and potent brain penetrant cPLA2 inhibitors promises to enhance the brain effects of omega‐3 enriched diets by limiting the effects of neuroinflammation on the aging APOE4 brain.