bluuebunny/crossref_metadata_2025_split huggingface dataset:
Awareness of dementia risk and of brain‐healthy lifestyles in medical students implementing new brain health classes in French schools
Authors: Bayen Eleonore , de Langavant Laurent Cleret , Gouriou Clémentine , Pradat‐Diehl Pascale , Canoui‐Poitrine Florence , Yaffe Kristine , Lawlor Brian 
Published: December 2020

AbstractBackgroundResearch projects that up to 35% of dementia cases may be preventable by targeting modifiable risk factors. Yet, there is currently a low awareness among citizens of all ages about the link between lifestyles and dementia risk. MyBrainRobbie is a public health non‐profit initiative launched in 2019 to promote brain health among children aged 6 to 12 with support from the Global Brain Health Institute (GBHI) and the Alzheimer's Association. MyBrainRobbie includes 1)a video that helps children and teenagers learn about eight neuroprotective/risky lifestyles in a gentle and appropriate language (over 80000 YouTube views) 2)a website with scientific and educational resources: www.mybrainrobbie.org/ ,(1&2 freely available in four languages) 3)an implementation strategy to integrate brain health classes in schools’ curriculum 4)an international outreach development thanks to GBHI. Implementations of new brain health classes in French elementary and middle schools leveraging MyBrainRobbie’s tools were carried out during 2018‐2019 and 2019‐2020 academic years. Pilot monitoring of 303 school children showed a high satisfaction and a significant memorization of neuroprotective lifestyles after the class (AAIC2019). We now report on the monitoring of medical students who implemented these classes.MethodOver 400 students in second, third or fourth year of their medical studies were trained in three medical universities including 1) 2‐hours lecture on dementia risk 2) 2‐to‐6 hours of coaching in small groups to prepare their school interventions. Dyads of students then carried out their preventative educational class in schools. Before this training, medical students were asked 1) whether they thought that they could modify their own dementia risk 2) what neuroprotective/risky brain habits they were spontaneously aware of 3) to sort out a list of dementia risk factors. At the end of the training they were asked whether they thought they would now modify their personal behavior to protect their brain (and how). Six months later, after their practical teaching experience in schools, they were asked whether they had modified their behavior (how/why not) in order to protect their brain.ResultPre‐post results will be presented.ConclusionWe aim to evaluate how brain health promoted by medical students might ricochet on their own personal awareness and behaviors.
Haploinsufficiency of progranulin causes impairments in PINK/PARKIN mitophagy
Authors: Casey Jackie M. , Melandri Daniela , Arber Charles , Soutar Marc , Holler Christopher J. , Kukar Thomas , Isaacs Adrian M. , Rohrer Jonathan D. , Plun‐Favreau Helene , Wray Selina 
Published: December 2020

AbstractBackgroundGRN mutations, resulting in haploinsufficiency of progranulin, cause frontotemporal dementia (FTD) with TDP‐43 pathology. Impairments in mitophagy, the selective autophagy of damaged mitochondria, have been identified in several neurodegenerative diseases, and multiple neurodegenerative disease genes, including PINK1, Parkin, VCP and TBK1, have been shown to play a role in this pathway. A role for progranulin in the regulation of neuronal mitophagy has not been explored, however progranulin deficient mice exhibit reduced xenophagy (selective clearance of bacteria). We therefore hypothesised that loss of progranulin could lead to defective mitophagy.MethodWe used two in vitro models to investigate PINK1/Parkin mitophagy: SHSY5Y cells overexpressing Parkin (PoE‐SHSY5Y) +/‐ siRNA against GRN, and induced pluripotent stem cell (iPSC) derived cortical neurons from two patients with FTD‐associated GRN mutations (R493X and C31fs). PINK1/Parkin mitophagy was induced using a combination of Antimycin A (respiratory complex III inhibitor) and oligomycin (ATP synthase inhibitor), and PINK1 accumulation and levels of S65 phosphorylated ubiquitin (the substrate of PINK1 and a marker of its activity) were examined using western blot and immunofluorescence. Subsequent mitophagy was assessed by examining Mitofusin‐2 ubiquitination and degradation, and TIM23 levels by western blot.ResultA reduction in progranulin levels resulted in reduced accumulation of PINK1 and lower levels of mitochondrial phospho‐ubiquitin following oligomycin/antimycin treatment in both PoE‐SHSY5Y and iPSC‐neurons with GRN mutations. Ubiquitination and degradation of mitofusin‐2 was also decreased in cells with reduced progranulin.ConclusionThese results suggest that progranulin plays a role in mitophagy by regulating stability and/or activity of PINK1. Ongoing work aims to understand the mechanisms by which progranulin and/or individual granulins contribute to this process and to dissect cell‐type specific contributions of progranulin to mitophagy in iPSC‐ derived neurons, astrocytes and microglia.
Physical activity and brain volumes in older adults: The Washington Heights‐Inwood Columbia Aging Project (WHICAP)
Authors: Gu Yian , Manly Jennifer J , Schupf Nicole , Mayeux Richard , Brickman Adam M 
Published: December 2020

AbstractBackgroundLeisure time physical activity (LTPA) has been shown to be protective against cognitive decline, dementia, and Alzheimer's disease. Understanding whether LTPA is associated with MRI‐assessed brain measures will help elucidate the underlying mechanisms.MethodThis cross‐sectional study included 1557 older participants of the Washington Heights‐Inwood Columbia Aging Project study, a community‐based, multi‐ethnic elderly cohort. Current LTPA level was measured using metabolic equivalent of energy expenditure (MET‐minutes/2‐wk), calculated from self‐reported Godin Leisure Time Exercise Questionnaire. Total brain volume, gray matter volume, white matter volume, hippocampal volume, and white matter hyperintensity volume were derived from MRI scans with established methods and were adjusted for intracranial volume. We examined the association of LTPA with these imaging markers using multivariable regression models.ResultsThe participants of the study had a mean (SD) age of 74.9(6.0) years, 64% were women; 26%, 34% and 38% were non‐Hispanics whites, African‐Americans, and Hispanics, respectively; and 28% carried Apolipoprotein ɛ4 allele. One SD (2860 MET‐minutes/2‐wk) increase in LTPA was significantly associated with 4.02 (95%CI=1.15‐6.88; p=0.006), 2.87 (95%CI=1.13‐4.62; p=0.001), and 0.043 (95%CI=0.004‐0.082; p=0.032) cm3 larger total brain, gray matter, and hippocampal volumes, respectively. Compared to those in the lowest tertile of LTPA, those with the highest tertile of LTPA had larger (in cm3) total brain volume (b=13.23, p=0.001; p‐trend=0.001), total gray matter volume (b=8.41, p<0.0001; p‐trend=0.001), and total white matter volume (b=7.25, p=0.005; p‐trend=0.013), hippocampal volumes (b=0.11, p=0.04; p‐trend=0.08), after adjusting for age, sex, race/ethnicity, education, Apolipoprotein E4 status, intracranial volume, and recruitment waves. The effect size comparing the highest to the lowest tertile LTPA was equivalent to about 3 years of aging (b for 1‐year older=‐3.14, ‐2.72, ‐2.16, ‐0.059 for total brain, gray matter, white matter, and hippocampal volumes, respectively). The associations were attenuated slightly but remained similar after further adjusting for body mass index and vascular comorbidities. LTPA was not associated white matter hyperintensity volume. The results remained similar after excluding 296 participants with mild cognitive impairment.ConclusionMore physical activity is associated with larger brain volumes in the elderly. Future longitudinal studies are needed to establish a temporal relationship between physical activity and brain health.
Quantitative sodium imaging using ultra‐high field magnetic resonance imaging in patients with Alzheimer's disease
Authors: Haeger Alexa , Coste Arthur , Lerman‐Rabrait Cécile , Lagarde Julien , Schulz Jörg B. , Vignaud Alexandre , Sarazin Marie , Bottlaender Michel , Reetz Kathrin , Romanzetti Sandro , Boumezbeur Fawzi 
Published: December 2020

AbstractBackgroundIn Alzheimer’s disease (AD), energy deficit is suspected to occur before clinical symptoms arise. Therefore, neuroimaging methods sensitive to metabolic alterations are attractive to improve diagnostics, therapeutics and follow‐ups of AD patients. An indirect measure of deficient Na+/K+‐ATPase‐activity during neurodegeneration is provided by the tissue sodium concentration (TSC) measured by Sodium‐(23Na)‐MRI.Method16 patients (7 Male, 71.7±8 years) diagnosed with AD (MoCA 15.1±7) were recruited from Ste. Anne Hospital in Paris as well as 16 cognitively healthy age‐matched control subjects (7 Male, 69±3.1 years; MoCA 28.1±1.8). Each subject underwent 23Na and 1H MRI examinations at the 7T MRI scanner (Siemens) at Neurospin, CEA. A dual‐resonance 1H/23Na volume coil (Rapid Biomedical) was used for a 23Na MRI protocol acquiring ultra‐short echo‐time images (3mm isotropic resolution) at two flip‐angles (a1=25º/a2=55º) (Coste et al., 2019). Briefly, processing steps comprised image reconstruction, denoising, motion‐ and B1‐inhomogeneities‐corrections, and a calibration step using 4 external references. Individual TSC maps were co‐registered to their T1‐weighted anatomical reference (MP2RAGE, 750 µm isotropic resolution) and a partial‐volume‐effect correction (Thomas et al., 2016) was implemented to limit the influence of sodium from cerebrospinal fluid. Anatomical and TSC images were normalized to the OASIS template using ANTs. A parameter free permutation analysis was performed voxel‐wise on normalized TSC images and on the LogJacobian of the deformation fields. After, region‐of‐interest‐analyses on hippocampus from VolBrain‐Atlas followed.ResultThe voxel‐based analysis showed significant widespread increases in TSC of AD patients, particularly in parietal, temporal and frontal regions. Interestingly, the observed TSC changes were located in areas not directly associated to significant structural changes (Fig 1). Furthermore, TSC in the hippocampus was found significantly higher in AD than in controls (42.9±4.3mmol/l; 35.8±3.9mmol/l; Wilcoxon‐rank‐sum; p=0.00015, z=3.8) and was correlated, after controlling for age, with both the MoCA‐scores (r=‐0.62; p=0.0002) and hippocampal volumes (r=‐0.39; p=0.032).ConclusionHigh‐field quantitative 23Na MRI in AD shows increased TSC values across a wide range of brain regions. These results may provide a deeper insight into metabolic alterations occurring during neurodegeneration. 23Na MRI could therefore serve as a useful tool to characterize disease progression or the impact of therapeutic intervention.
Vortioxetine use in demented patients
Authors: Valverde Ana H. , Campillo José M. , Godinho Filipe 
Published: December 2020

AbstractBackgroundVortioxetine is a new antidepressant with a distinctive pharmacological profile. It combines inhibition of serotinine transporter with modulation of various serotonine receptors. Its cognitive benefit in adults depressed patients has been previously demonstrated. There is evidence of its antidepressant effect in the elderly but not specifically of its utiliity in demented population. Effects in a group of different types of dementia patients are showed and hypothesis of its efficacy based on its properties are proposed.MethodA retrospective study was conducted. Eligible patients were those observed in our memory outpatient clinics during 2019. All patients had behavioural symptoms (BPSD), Main symptoms were anxiety, apathy, irritability and restlessness. Thirty‐two patients were reviewed.Result32 patients were included, of which 60,6% were women. Median age was 74 years (SD 12,070). Alzheimer´s disease was the most common type of dementia (51.5%), as expected. Median dose of vortioxetine used was 10 mg/day. Symptoms that led to vortioxetine initiation were anxiety (57,6%), apathy (48,5%) and irritability (42,4%). Depreesion was present in 33,3% of cases, but anxiety and apathy were the symptoms that improved the most after vortioxetine introduction. 60,6% of patients were concomitantly treated with antidementia drugs, mostly Rivastigmine (30,3%). Coexistent benzodiazepines or antipsychotics use in patients treated with vortioxetine was not significant (24,2% and 21,2% each one). No side effects were reported.ConclusionVortioxetine may be an useful option for BPSD in dementia population. Available evidence indicates that target receptors for vortioxetine play an important role in brain networks, and this could explain its efficacy regardless the antidepressive effect. No safety concerns were found in this group of patients with doses from 10 to 20 mg/day according with tolerability profile already described. Further studies with a more extensive number of eligible patients and prospective design are needed.
The association between health beliefs and attitudes towards dementia and the intention to change health behavior for dementia risk reduction: A cross‐sectional study in the Netherlands
Authors: Matulesseij Tessa , Joxhorst Tessa , Vrijsen Joyce , Smidt Nynke 
Published: December 2020

AbstractBackgroundApproximately one third of the dementia cases are attributed to modifiable risk factors, including physical inactivity, unhealthy diet, excessive alcohol use and smoking (Livingston et al., 2017). Positive health beliefs and attitudes towards dementia (risk reduction) may encourage adopting a healthy lifestyle. We aimed to investigate the association between health beliefs and attitudes towards dementia and the intention‐to‐change health behavior for dementia‐risk‐reduction among the Dutch general population.MethodA random sample of 4500 residents of the municipality of Groningen (The Netherlands), aged 30 to 80 years, was invited to complete an online survey. Health beliefs and attitudes were measured using the cross‐cultural validated Dutch Motivation to Change Lifestyle and Health Behavior for Dementia‐Risk‐Reduction scale (perceived susceptibility, perceived severity, perceived benefits and barriers, cues to action, general health motivation, self‐efficacy). The intention‐to‐change health behavior (physical activity, diet, alcohol consumption, and smoking) was measured using the stages‐of‐change (contemplation and preparation stage versus pre‐contemplation, action or maintenance stage). We used multiple logistic regression analyses adjusting for potential confounders (age, sex, education, employment).Results655 residents participated in the survey (mean(SD) age: 58(13.4) years, 54% female). Sixty percent were physically inactive, 44% were excessive‐alcohol‐users, 13% were smokers and all participants (100%) had a poor‐to‐moderate adherence to the Mediterranean‐DASH‐Intervention‐for‐Neurodegenerative‐Delay (MIND)‐diet. Older participants had higher scores on perceived severity and lower scores on perceived benefits, perceived barriers and self‐efficacy. Participants with a higher education level had higher scores on perceived benefits and self‐efficacy, but lower scores on perceived barriers. Overall, positive attitudes and health beliefs towards dementia‐risk‐reduction are associated with the intention‐to‐change physical activity (OR=1.058; 95%‐CI:1.031,1.087), diet (OR=1.049; 95%‐CI:1.024,1.073) and alcohol use (OR= 1.045; 95%CI:1.006,1.086).ConclusionAttitudes and health beliefs towards (dementia) risk reduction in the Netherlands are poor. People with positive health beliefs and attitudes towards (dementia) risk reduction have more often the intention‐to‐change their health behaviors. Dementia prevention should focus on education of the general population to improve their knowledge about dementia in general and the risk and protective factors for dementia. Further research should investigate the effectiveness of improving health beliefs and attitudes towards (dementia) risk reduction on health behavior change.
Stigma of Alzheimer's disease in healthcare professionals: Numbers that still surprise
Authors: Sarmento Ana Luisa Rosas 
Published: December 2020

AbstractBackgroundEven in high income countries , the general public and health care professionals still have some stigma about dementia. Despite campaigns people still delay seeking out help advice when they first start to forget and to worry about their own memory or that of a family member.MethodA simple multiple choice questionnaire, with questions about knowledge about Alzheimer's disease, evolution and prognosis and personal questions about perception, feelings and prejudices about the disease, was applied to physicians in the field of neurology and non‐neurologists. The sample was made up of 5 different groups of health professionals : second and third year neurology residents, general neurology assistants, neurologists specializing in dementia , non‐neurologists and nursing technicians working in a neurology ward.ResultDoctors are expected to have less prejudice and misconceptions about diseases, however, although rare, we still find some concepts inadequate and mainly, some responses from the questionnaires pointed out a certain stigma in relation to Alzheimer's disease, mainly in the group of non‐neurologists e some nursing technicians.ConclusionInformation is the better way to combat the stigma. More campaigns, more medical information and most importantly, more continuing medical education in dementia needs to be provided to health professionals.
Aβ42 mediated activation of the NLRP3 inflammasome predicts cognitive and gait performance in midlife type 2 diabetes mellitus (T2DM)
Authors: Dyer Adam H. , Batten Isabella , Woods Conor , Gibney James , Bourke Nollaig , Kennelly Sean 
Published: December 2020

AbstractBackgroundMidlife Type 2 Diabetes Mellitus (T2DM) is a potent risk factor for later development of dementia. However, putative mechanisms mediating this risk are poorly understood. The NLRP3 inflammasome receptor, which drives strong pro‐inflammatory responses, has been implicated in both T2DM and Alzheimer’s disease (AD) pathogenesis, and can be activated by Amyloid β1‐42 (Aβ42).MethodPeripheral Blood Mononuclear Cells (PBMCs) were isolated from participants with T2DM (N = 39; 52.04 ± 8.01 years) and matched controls (N = 21; 52.16 ± 7.82 years) without any evidence of cognitive impairment. PBMCs were incubated for 18 hours under the following conditions: (i) Lipopolysaccharide (LPS), (ii) Aβ42, (iii) LPS & Aβ42 and (iv) LPS & Nigericin (potent NLRP3 activator). Cytokine production was measured using ELISA and gene expression using qPCR. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Gait speed was measured under normal and dual‐task conditions (reciting alternate letters of the alphabet). Wilcoxon rank‐sum tests were used for univariate analysis and Poisson and linear regression models used for multivariate analyses, adjusting for important covariates.ResultsTreatment of PBMCs under all four conditions resulted in a significant production of the pro‐inflammatory cytokines IL‐1β and IL‐6, which did not differ between T2DM and healthy controls. Greater IL‐1β production (an NLRP3‐dependent cytokine) under both Aβ‐42 (ii) and LPS & Nigericin (iv) conditions was associated with greater likelihood of error on the MoCA (aIRR 1.01, p = 0.010; aIRR 1.01, p = 0.004). Further, greater IL‐1β production under both LPS & Aβ42 (iii) and LPS & Nigericin (iv) conditions was associated with a greater slowing effect (cost) on the dual‐task (adjusted: β = 0.31, 0.04‐0.58, p = 0.023; 0.029, 0.05 – 0.54, p = 0.019). Effects were seen in the cohort overall, regardless of T2DM status, but were stronger in those with T2DM.ConclusionsGreater activation of the NLRP3 inflamamsome by Aβ42 was associated with poorer cognitive and gait performance in midlife T2DM. Further work will follow this cohort longitudinally and assess the ability of innate immune NLRP3 activity to predict later cognitive trajectories in those with midlife T2DM.
Prolonged therapy of dementia with Lewy bodies with quaternary ammonium anti‐muscarinic/high‐dose cholinesterase inhibitor (QAAM/HDCI)
Authors: Rich Steven A. 
Published: December 2020

AbstractBackgroundDementia with Lewy Bodies (DLB) is the second most common human neurodegenerative disease and the most reduction in CNS choline acetyl‐transferase. This case series demonstrates beneficial effects from a level inhibition of cholinesterase inhibition that can only be achieved with concurrent peripheral muscarinic blockade.MethodPatients were selected from those seen in a single geriatric consultation clinic after 2010. DLB was diagnosed by the Consensus criteria of the third report (2005) or fourth (2017) of the DLB consortium by a geriatrician, with concurring neurologist in most cases. Patients received rivastigmine at doses greater that the upper limit of FDA approved dosing. Does greater than 12 mg oral, or 13.3 mg transdermal were paired with glycopyrrolate 1‐4 mg orally twice daily. Concurrent use of carbidopa/levodopa, selegiline was permitted but use of dopamine receptor agonists other than low dose quetiapine, other acetyl‐cholinesterase inhibitors or centrally acting anti‐muscarinic agents was not. Criteria for selection included treatment more than one year, the ability to perform a Mini Mental State Examination (MMSE) at the time of initiation and the availability of follow up data. The MMSE was performed in a standardized format. Functional Assessment Stage (FAST) was determined by nurse and physician after an interview with patient and caregivers.ResultMMSE values over time were compared to recently published rates of decline of DLB. All patients had MMSE and functional improvement, with most having a reduction in the rate of decline of MMSE scores.ConclusionThe results show that prolonged symptomatic, cognitive and functional improvement of dementia with Lewy Bodies is possible with the high‐level inhibition of central nervous system cholinesterase achievable when rivastigmine is combined with glycopyrrolate. The discussion correlates these observations with current experimental, clinical and epidemiological evidence regarding the mechanism and treatment of this, and other, neurodegenerative diseases.