bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal preventive trial for Alzheimer’s disease (MIND‐ADMINI): Pilot trial progress and results
Authors: Kivipelto Miia , Sindi Shireen , Thunborg Charlotta , Rosenberg Anna , Coley Nicola , Andrieu Sandrine , Broersen Laus M , Hartmann Tobias , Solomon Alina , Soininen Hilkka 
Published: December 2021

AbstractBackgroundInterventions simultaneously targeting multiple risk factors are most likely to prevent neurocognitive disorders. This was demonstrated in the 2‐year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). However, the feasibility and effects of multimodal interventions in individuals at an early symptomatic disease stage (prodromal AD) are unclear. The objective of the MIND‐AD trial was to evaluate the feasibility of an adapted FINGER‐based multimodal lifestyle intervention, with or without medical food, among individuals with prodromal AD.MethodsMIND‐ADMINI is a multinational proof‐of‐concept 6‐month randomized controlled trial (RCT, ClinicalTrials.gov NCT03249688), with four trial sites (Sweden, Finland, Germany, France). The target population is individuals with prodromal AD using the International Working Group‐1 criteria and vascular and/or lifestyle‐related risk factors. The parallel‐group RCT includes three arms: 1) multimodal lifestyle/vascular intervention (diet, exercise, cognitive training and social stimulation, vascular/metabolic risk management); 2) multimodal lifestyle/vascular intervention+medical food (Fortasyn Connect); 3) regular health advice/care (control group). Primary outcomes: feasibility and adherence. Secondary outcomes: adherence to the individual intervention domains and healthy lifestyle changes,ResultsScreening began September 2017 and was completed May 2019 in all four countries. Altogether, 93 participants were randomized, and the 6‐month intervention was completed December 2019. Electronic data entry and processing was completed December 2020 (delays due to Covid‐19). The mean (SD) age of the entire sample was 72.9 years, education level was 12.8 years, and MMSE score 27.6 points. Vascular and lifestyle‐related risk factors were expected based on the inclusion criteria. Impaired fasting glucose (≥ 6,1 mmol/L) was seen in 29%, and 40% were overweight, with BMI ≥25 and, 12% had BMI ≥30. The intervention proceeded as planned and the preliminary results and participant experiences are positive, supporting the feasibility. Detailed results will be presented, and lessons learned will be discussed.ConclusionsFor the first time, MIND‐AD tests the feasibility of and adherence to a multimodal lifestyle intervention, alone or combined with medical food, among individuals with prodromal AD. The positive intervention experiences are important for this patient group currently lacking effective treatments. The trial also offers a model for pharmacological/non‐pharmacological combination therapies and informs larger efficacy prevention trials.
Prevalence of dementia among elderly in Latin America and the Caribbean: A systematic review and meta‐analysis
Authors: Ribeiro Fabiana , Santos Ana Carolina Teixeira , Leist Anja 
Published: December 2021

AbstractBackgroundOver the last decades, life expectancy in Latin America and the Caribbean showed a rapid increase, which led to a significant increase in the number of people with dementia. Moreover, 9% of the population in this part of the world are aged 65 or older, and by 2050 this percentage is projected to at least double. For this reason, it is essential to estimate the prevalence of dementia in LAC countries with the aim to determine suitable actions to enhance the quality of life of those affected.MethodsDatabase searches for articles were conducted September 2020 throughout Pubmed, Web of knowledge, Scopus, Lilacs, and SciELO. The inclusion criteria comprised population‐ or community‐based studies, published in English, Spanish, or Portuguese, reporting data on the prevalence of dementia collected in LAC countries. The complete data search retrieved 1719 non‐duplicates.ResultsA total of 58 studies met the high‐quality inclusion criteria, published 1991‐2020, including participants in the following countries: Brazil, Mexico, Argentina, Colombia, Peru, Cuba, Dominican Republic, Venezuela, Ecuador, Trinidad and Tobago, and Jamaica. The most common form of dementia studied was Alzheimer’s disease with prevalence ranging from 5.9% to 23.4%. Estimates differed by age, gender, and education, with oldest, women, and lower‐educated adults living in rural areas presenting higher dementia prevalence.ConclusionThis is the first study giving a comprehensive overview of dementia prevalence in LAC countries, which is relevant to estimate care needs and economic costs related to dementia treatment and care.
Profiling the metabolome of patients with dementia in the UK Biobank
Authors: Liu Jun , Amin Najaf , Arnold Matthias , Nho Kwangsik , Saykin Andrew J. , Newby Danielle , Winchester Laura M. , Nevado‐Holgado Alejo J. , Kastenmüller Gabi , Kaddurah‐Daouk Rima F. , Van Duijn Cornelia M. 
Published: December 2021

AbstractBackgroundThere is increasing interest in early metabolic changes in dementia, which may reflect the effects of genetic determinants of dementia, medical history and co‐morbidity, environmental risk factors, and aging. We studied the relation of blood‐based metabolites to the risk of dementia.MethodThe analyses are conducted in 121,389 participants of the UK Biobank (UKB) and include over 1172 incident dementia patients who developed dementia during the follow‐up. The metabolome was characterized using Nuclear Magnetic Resonance of the Nightingale Health platform. The platform covers 249 metabolic measures, including small molecules, fatty acids and detailed lipoprotein lipids. We integrated metabolic data measured before dementia onset with genetic data to determine whether the metabolites associations reflect causal pathways or rather consequences of the disease process. After log transformation of metabolites, scaling, and quality control, data were analysed using Cox‐regression. We adjusted for age, sex, BMI, technical variables ethnicity, smoking, alcohol, education, metabolic and neuropsychiatric medication and APOE genotypes.ResultWe identified 36 novel metabolites that are significantly associated with incident dementia (FDR<0.05), with positive associations of ketone bodies to the future risk of dementia and negative associations of fatty acids, various amino acids, and cholesterol subfractions. The metabolic pattern is remarkably similar for incident patients with Alzheimer disease and vascular dementia and overlaps substantially with the metabolic profile identified for incident Parkinson’s disease. We found evidence that a number of metabolites may mediate the association between the APOE e2 and APOE e4 variants and dementia.ConclusionOur findings suggest that changes in the metabolism that occur before the onset of disease are associated to the future risk of dementia.
Resting‐state functional connectivity of basal forebrain is associated with training gains in normal aging
Authors: Faraza Sofia , Dyrba Martin , Wolf Dominik , Fischer Florian U , Fellgiebel Andreas , Teipel Stefan J 
Published: December 2021

AbstractBackgroundCognitive training can improve cognitive performance in healthy older adults. The effectiveness of a training is considered as a maintenance of training skills outside of a training context. Research data indicate an association between cognitive decline and changes of brain function in normal aging. A better understanding of the brain mechanisms that can enhance or preserve cognitive training skills could help identifying healthy older adults who will benefit from cognitive interventions. The cholinergic basal forebrain is involved in several aspects of cognition including attention. In our study, we aimed to assess the association of functional connectivity of the basal forebrain with maintained training skills.MethodA sample of 60 healthy older adults (mean age: 68 years) underwent a 4‐week multi‐modal cognitive training and neuropsychological assessments before and after the training. A second follow‐up assessment was applied 12 weeks after the training. Baseline resting‐state functional magnetic resonance imaging was used to derive the global functional connectivity of the anterior‐medial and posterior‐lateral compartments of the basal forebrain. We focused on attention capacities using the Test battery for Attention Performance (TAP), which assesses a variety of attentional aspects, including alertness. Maintenance of training gains was defined as higher improvement in the alertness tasks after 12 weeks than a no‐training control group.ResultA high functional connectivity of anterior basal forebrain was a significantly associated with maintenance of training gains in the phasic arousal tasks, i.e. the reaction time in response to a critical stimulus preceded by a cue stimulus presented as a warning tone. There was no significant association for the posterior basal forebrain.ConclusionFunctional activation patterns of basal forebrain contribute to maintenance of training gains of alertness tasks.
Effects of healthy aging on internal brainstem structure
Authors: Mueller Susanne G 
Published: December 2021

AbstractBackgroundThe brainstem is a complex structure and is often affected in the earliest stages of a neurodegenerative diseases. However, internal brainstem structures are not delineated on standard MR sequences complicating the differentiation between healthy aging and an incipient neurodegenerative process in‐vivo. The overall goal of this project was to characterize age‐related atrophy of different brainstem structures using a modification of a previously published multi‐contrast brainstem segmentation approach (1) using standard MR sequences.MethodThe T1 and T2‐weighted images from 677 subjects (age range: 36‐100) of the Lifespan Human Connectome Project Aging were selected. Each subject’s T1w and T2w were co‐registered, re‐scaled and a T1/T2ratio image calculated. After extracting the brainstem/thalamus, a k‐mean cluster analysis was used to identify 4 different brainstem tissue clusters based on the intensities from the 3 images. DARTEL was used to generate a population template from the brainstem tissue‐maps of 100 randomly selected subjects covering the whole age range. Each subjects tissue‐maps were warped onto this template and the Jacobian determinants calculated (Figure 1). The subjects were then divided into 6 groups (4th, 5th, 6th, 7th, 8th, 9th decade). SPM with threshold‐free cluster enhancement (p<0.005, FWE) was used for group comparisons. 58 gray and white matter brainstem regions‐of‐interest were used to extract voxels surpassing this statistical threshold to further characterize the age‐related volume loss.ResultSee Figure 2 for abbreviations and detailed findings. Mesencephalic centers such as NR, CS, CI and PTPT showed age‐related volume loss starting at the age of 50. SN, VTA, and pontine centers such as NRPO, PB, NRPT, NRPC and medullary regions such as OI, NTS, VML, NRMOC and other major white matter tracts became atrophied starting at 60 and after 70 all 58 brainstem centers except for the DR and SC were atrophied.ConclusionAge‐related brainstem atrophy starts in the mesencephalon and progresses to the pons and medulla and also affects white matter tracts. The pattern of age‐related atrophy reflects the timing of typical age‐related brainstem dysfunctions, e.g., age‐related hearing loss. This method might be useful for the early detection of neurodegenerative diseases starting in the brainstem. Reference: Hum Brain Mapp.2020;41:2173‐2186.
TMS‐induced EEG perturbation as a marker of psychological resilience to deleterious mental health effects during the COVID‐19 pandemic
Authors: Perellón‐Alfonso Ruben , Redondo‐Camós María , Abellaneda‐Pérez Kilian , Cattaneo Gabriele , Delgado‐Gallén Selma , España‐Irla Goretti , Sánchez Javier Solana , Tormos‐Muñoz Josep M. , Pascual‐Leone Alvaro , Bartrés‐Faz David 
Published: December 2021

AbstractBackgroundSocial, economic and psychological hardships associated with the COVID‐19 pandemic are expected to result in a global burden on mental health outcomes. However, while some individuals suffer from increasing distress and reduced quality of life, others will show no negative effects. A better understanding of brain mechanisms subtending resilience would be helpful in informing future recommendations to individuals and societies facing the present pandemic and future similar events. Here, we compared neurophysiological brain markers between individuals who exhibited resilience or vulnerability to pandemic associated psychological stress.Method23 participants from the longitudinal study cohort of the Barcelona Brain Health Initiative (Cattaneo et al., Front. Aging Neurosci. 2018;10:321) who underwent concurrent transcranial magnetic stimulation with electroencephalography (TMS‐EEG), were classified as either resilient (n=16) or non‐resilient (n=7), based on their scoring in the PHQ‐4 questionnaire (Kroenke et al., Psychosomatics 2009;50(6):613–21) along four timepoints; one before COVID‐19 outbreak and three spanning 2.5 months during the pandemic. Individuals maintaining a score below 3 across all timepoints were deemed resilient, while those scoring below 3 before pandemic but higher than 2 at any pandemic timepoint were considered non‐resilient. TMS‐EEG data was collected by delivering 120 single TMS pulses to the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobule (IPL). TMS evoked global mean field amplitude and local response at the stimulation site were computed.ResultFigure 1 depicts time‐series for DLPFC and IPL responses for both groups of subjects. Overall, non‐resilient individuals exhibited a larger global response to TMS perturbation during DLPFC stimulation, as well as larger local current density estimates during IPL stimulation.ConclusionThese preliminary results revealed that non‐resilient individuals were more susceptible to TMS perturbation, shown by global DLPFC and local IPL reactivity. Notably, these targets are nodes of the default mode and cognitive control networks affected by stress (van Oort et al., Neurosci. Biobehav. Rev. 2017;83:281–97), and the left frontal cortex has been proposed as a cognitive resilience hub (Franzmeier et al., J. Alzheimer’s Dis. 2017;59(4):1381–92.). Future studies should investigate and confirm the possibility that these nodes constitute a shared neurophysiological substrate for psychological and cognitive resilience.
Wisconsin ADRC research education component: Fostering AD researchers via a virtual network
Authors: Spensley Sheryl , Kohli Akshay , Puglielli Luigi , Shah Manish N , Kind Amy J , Bendlin Barbara B 
Published: December 2021

AbstractBackgroundWorldwide, 47 million people have Alzheimer’s disease or related dementias (Alzheimer’s Association). The National Institute on Aging has introduced Alzheimer’s Disease Research Center Research Education Components (RECs) to “support research educational activities to complement the training of a workforce to meet the nation's research needs in AD and related dementias.” By recruiting and training promising researchers, the goal of RECs are to increase the pool of researchers studying ADRD, advance the mission of translating research advances into improved diagnosis and care, as well as treating and preventing ADRD.MethodThe Wisconsin Alzheimer’s Disease Research Center (ADRC) REC, funded in 2019, aims to deliver a rigorous training program to ensure research proficiency in AD research, infuse research concepts into predoctoral to junior faculty training programs, and measure the effectiveness of the REC. The REC sponsors didactic learning, facilitates networking for ADRD research trainees across campus, identifies ADRC REC Scholars who engage in mentored, 2‐year, research projects, and created a REC junior fellowship to reach students who are underrepresented in AD research. Using a previously created database, survey methods were used to assess trainee career promotions, demographics, and awards. During the COVID‐19 pandemic, the REC modified its strategies to use virtual methods to ensure continued availability of training opportunities. An E‐newsletter was introduced to communicate training and funding opportunities.ResultsOur REC Scholars (N=3) secured an R01, NIH R21/R33 and Beeson K76. Attendance at ADRD‐focused didactic events grew by nearly three‐fold using virtual methods. The E‐newsletter is shared with 550 individuals weekly and has a 35% open rate. The REC held a virtual introduction to ADRD research with UW Madison Precollege Enrichment Opportunity Program for Learning Excellence students via Zoom. Planned internships for the REC junior fellows were not completed due to the pandemic.ConclusionTraining during the COVID‐19 pandemic presented several opportunities for new initiatives. We observed that virtual tools increased the number of individuals engaged in training activities, although level of engagement and learning has not been assessed. Assessment of virtual training will be formally evaluated in collaboration with the UW Learning through Evaluation, Adaptation, and Dissemination Center.
Improved methods for recruiting Latino participants for Alzheimer’s disease research using the Brain Healthy Registry
Authors: Camacho Monica R , Weiner Mike W , González Hector M , Mayeda Elizabeth Rose , Alaniz Roxanne , Ashford Miriam T , Nosheny Rachel L 
Published: December 2021

AbstractBackgroundTraditional strategies have been largely unsuccessful in recruiting Latinos and other underrepresented groups for Alzheimer’s disease and related dementias (ADRD) clinical research. Online registries are a promising approach to recruit hard to reach populations. This project, funded by the California Department of Public Health Alzheimer’s Disease Program, aimed to use internet advertising and culturally‐tailored messaging to enroll participants in the Brain Healthy Registry (BHR), an online registry for ADRD research.MethodsResearchers collaborated with marketing professionals experienced in marketing to Latinos. A community advisory board, comprised of professionals from different industries who identify as Latino and/or have knowledge and experience within local Latino communities, was formed to guide recruitment strategies tailored to Latinos’ values and beliefs. Custom audience targeting displayed Facebook and Google ads to Latinos living in California zip codes with large Latino populations. Recruitment strategies, including “look‐alike” audience targeting, ad retargeting, simplification of the BHR enrollment process, and revamped email campaigns to individuals that did not complete enrollment, were employed.ResultsInternet advertising from September 2020 and mid‐January 2021 resulted in email addresses from 5,095 individuals, of which 2,560 (50%) joined BHR. Seventy four percent of new participants self‐reported Latino ethnicity. Prior to this, there were only 3,761 Latino participants (out of total sample size of > 70,0000) since BHR’s inception in 2014. A larger percentage of new participants also self‐reported being non‐White/Caucasian compared to previously enrolled participants (Table 1). The cost to enroll a participant recruited from these efforts ranged from approximately $35 – $80.ConclusionInternet advertising with culturally tailored recruitment messaging substantially increased representation of Latino participants in BHR during a short timeframe. Future efforts include a Spanish‐language BHR website, Spanish digital ads, and messaging to improve engagement and retention of Latino participants once they are enrolled.
The relationship between blood‐brain barrier permeability and cerebral blood flow in cognitive impairment
Authors: Barisano Giuseppe , Montagne Axel , Nation Daniel A. , Sagare Abhay P. , Joe Elizabeth B. , D'Orazio Lina , Buennagel David P. , Harrington Michael G. , Ringman John M. , Schneider Lon S. , Chui Helena C. , Pa Judy , Law Meng , Toga Arthur W. , Zlokovic Berislav V. 
Published: December 2021

AbstractBackgroundThe contribution of cerebral microvascular dysfunction to early cognitive impairment and dementia is increasingly recognized. Here we investigated cerebral blood flow (CBF) and blood–brain barrier (BBB) permeability in relation to early cognitive decline in APOE3‐homozygotes (ε3/ε3) and APOE4‐carriers (ε3/ε4; ε4/ε4).MethodA total of 237 participants underwent neuropsychological evaluations, venipuncture, and magnetic resonance imaging (MRI). The global Clinical Dementia Rating (CDR) was used to classify participants in cognitively unimpaired (CU, CDR=0) and mild cognitive impairment (CDR=0.5). APOE genotyping was performed via polymerase chain reaction‐based retention fragment length polymorphism analysis on DNA extracted from buffy coat. BBB permeability and CBF were estimated from dynamic contrast‐enhanced and 3D pseudo‐continuous arterial spin labeling (pCASL) MRI data, respectively, using in‐house pipelines. After excluding APOE2‐carriers and participants with CDR>0.5, 143 participants (86 females [60.1%]) were included in the analysis. (Table 1)ResultStandardized CBF levels in grey matter (GM), hippocampus (HC), and parahippocampal gyrus (PHG) were not significantly different in APOE3‐homozygotes and APOE4‐carriers, after controlling for age and sex. (Figure 1) Our results of BBB permeability in 52 CU participants (27 APOE3‐homozygotes and 25 APOE4‐carriers) confirm a significantly higher BBB permeability in the HC of APOE4‐carriers compared with APOE3‐homozygotes (p<0.001), as previously reported (Montagne et al., Nature, 2020), and show no relationship between BBB permeability and CBF. (Figure 2) In a subgroup of 46 participants (21 CU APOE3‐homozygotes, 18 CU APOE4‐carriers, and 7 APOE4‐carriers with CDR=0.5) who underwent a second MRI approximately 2 years after the first MRI, we observed a significant reduction (p=0.008) of CBF in APOE4‐carriers with mild cognitive impairment, but not in CU individuals.ConclusionAPOE4 is associated with higher BBB permeability in CU participants compared with APOE3‐homozygotes, but CBF is not different between the two genotypes. In the future, longitudinal data will be collected to confirm whether BBB breakdown precedes CBF alterations and to assess their relationship with cognitive decline, amyloid‐β and tau pathology.