bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential synaptic marker involvement in the different genetic forms of frontotemporal dementia
Authors: Esteve Aitana Sogorb , Nilsson Johanna , Swift Imogen J. , Heller Carolin , Russell Lucy L. , Peakman Georgia , Convery Rhian S. , van Swieten John C. , Seelaar Harro , Borroni Barbara , Galimberti Daniela , Sanchez‐Valle Raquel , Laforce Robert , Moreno Fermin , Synofzik Matthis , Graff Caroline , Masellis Mario , Tartaglia Maria Carmela , Rowe James B. , Vandenberghe Rik , Finger Elizabeth , Tagliavini Fabrizio , de Mendonca Alexandre , Santana Isabel , Butler Christopher , Ducharme Simon , Gerhard Alexander , Danek Adrian , Levin Johannes , Otto Markus , Sorbi Sandro , Le Ber Isabelle , Pasquier Florence , Zetterberg Henrik , Rohrer Jonathan D. ,   GENetic FTD Initiative
Published: December 2021

AbstractBackgroundApproximately a third of frontotemporal dementia (FTD) is genetic with mutations in three genes accounting for the majority of the inheritance: C9orf72, GRN and MAPT. Synaptic dysfunction is a common mechanism in all of them and the use of fluid biomarkers could be helpful to improve the diagnostic accuracy and useful as a readout of cellular dysfunction within therapeutic trials.MethodA total of 193 cerebrospinal fluid samples from the GENetic FTD Initiative including 77 presymptomatic (31 C9orf72, 23 GRN, 23 MAPT), 55 symptomatic mutation carriers (26 C9orf72, 17 GRN, 12 MAPT) and 61 mutation‐negative controls were measured using a microflow LC PRM‐MS set‐up targeting 15 synaptic proteins: 14‐3‐3 proteins (eta, zeta/delta and epsilon), AP‐2 complex subunit beta, beta‐synuclein, gamma‐synuclein, complexin‐2, neurogranin, neuronal pentraxin receptor (NPTXR), neuronal pentraxin 1 (NPTX1), neuronal pentraxin 2 (NPTX2), phosphatidylethanolamine‐binding protein 1 (PEBP‐1), rab GDP dissociation inhibitor α (rab GDIα), syntaxin‐1B and syntaxin‐7. Mutation carrier groups were compared to each other and to controls using a bootstrapped linear regression model, adjusting for age and sex.ResultEight proteins were increased only in symptomatic MAPT mutation carriers (compared with controls) and not in symptomatic C9orf72 or GRN mutation carriers: 14‐3‐3‐eta, beta‐synuclein, gamma‐synuclein, neurogranin, PEBP‐1, rab GDIα, syntaxin‐1B and syntaxin‐7. In contrast, NPTX1 and NPTX2 were affected in all three genetic groups (decreased compared to controls), with NPTXR being affected in C9orf72 and GRN mutation carriers only (decreased compared to controls). No changes were seen in presymptomatic mutation carriers in these proteins. Figure 1 contains p‐values for all significant changes.ConclusionDifferential involvement of synaptic markers is seen in the genetic forms of FTD, with impairment particularly in those with MAPT mutations, with only the neuronal pentraxins affected in GRN and C9orf72 mutation carriers. Further work is needed to explore correlations with clinical and imaging biomarkers, whether there are changes in the late presymptomatic period, and how these markers change over time.
When is more better? Modeling the effect of dose on the efficacy of the MAPT multidomain intervention as a function of individual characteristics
Authors: Belleville Sylvie , Cloutier Simon , Mellah Samira , Willis Sherry L , Vellas Bruno , Coley Nicola , Andrieu Sandrine , Ngandu Tiia ,   MAPT/DSA Group
Published: December 2021

AbstractBackgroundDose is a critical factor examined in pharmacological treatment. However, little is known about the optimal dosage for non‐pharmacological multidomain interventions as well as the function that relates dose to improvement. These gaps have been assessed in this present study in interaction with individual characteristics, which may moderate the effect of dose. Magnification models predict that healthier individuals will benefit more from prolonged practice, whereas reserve models predict that training will reduce cognitive disadvantage.MethodThe data from the Multidomain Alzheimer Preventive Trial (MAPT) was used to determine the relationship between cognitive training dose and cognition, and its interaction with sex, age, education, entry criteria, CAIDE risk score, frailty and Apoe4 status. The MAPT is a three‐year randomized controlled trial, which includes cognitive training, physical activity, nutrition and omega‐3 polyunsaturated fatty acids in at‐risk individuals. The number of hours of cognitive training attended (max.=28) was used as a measure of dose in the 749 participants randomized to the multidomain intervention.ResultFirst, polynomial regression analysis modelled cognitive performance over time on memory, verbal fluency and composite cognitive score. Mixed model analyses measured the effect of dose on expected scores, and interaction with individual factors were assessed. A cubic function explained the relationship between dose and performance indicating benefits up to 12‐14 training hours followed by a plateau. Interactions were found with individual characteristics. Older participants and those with a higher CAIDE score reached their plateau more rapidly. Individuals with lower education and frail individuals benefited more from increased exposure.ConclusionA non‐linear dose‐response function indicates that more is not necessarily better. Here, the optimal dose was found to be 12‐14 hours of training, about half of what was potentially available to participants. A magnification effect is found for age and vascular risk factors as younger and healthier participants show larger benefit. However, a reserve effect is found in frail or less educated participants as they benefitted more from additional training experience than their more privileged counterparts.
Late‐onset epileptic seizures in adults with Down syndrome are linked to Alzheimer’s disease
Authors: Altuna Miren , Fernandez Susana , Carmona‐Iragui Maria , Barroeta Isabel , Simon‐Talero Manuel , Benejam Bessy , Videla Laura , Valldeneu Sílvia , Pegueroles Jordi , Illán‐Gala Ignacio , Garzón Diana , Gironell Alexandre , Escola Concepción , Giménez Sandra , Estellés Teresa , Iulita M. Florencia , Padilla Concepción , Blesa Rafael , Lleó Alberto , Fortea Juan 
Published: December 2021

AbstractBackgroundIndividuals with Down syndrome have a high risk of epilepsy and this risk increases with age. We aimed to determine the prevalence and characteristics of epileptic seizures and their link with symptomatic Alzheimer’s disease (AD).MethodPopulation‐based observational longitudinal study from the Down Alzheimer Neuroimaging Initiative. All adults with Down syndrome underwent a neurological and neuropsychological evaluation that included a structured questionnaire on epilepsy. Participants were classified as asymptomatic, prodromal AD or AD dementia patients. A subgroup had an electroencephalogram performed.ResultWe recruited 810 adults with Down syndrome, of whom 66.9% were asymptomatic, 7.2% had prodromal AD and 25.9% AD dementia. 143 (17.65%) had a history of epileptic seizures with a median age of onset of 41.20 years and a bimodal distribution (modes at 1 and 51 years). Clinical AD was associated with a higher risk of epileptic seizures: prevalence of 9.4% in asymptomatic individuals vs 28.04% in prodromal AD and 53.40% in AD dementia patients. Generalized tonic‐clonic seizures and myoclonic seizures were the most frequent seizure type, especially in patients with symptomatic AD. Epilepsy was associated with an earlier AD dementia diagnosis (p=0.016) and lower age at death (p=0.025).ConclusionSymptomatic AD is associated with a high risk of epileptic seizures in DS. Epilepsy in the context of Down syndrome associated Alzheimer´s disease shortens survival.
Can engagement in socially and cognitively stimulating leisure activities compensate for other dementia risk factors? A prospective cohort study
Authors: Duffner Lukas , Deckers Kay , Cadar Dorina , Steptoe Andrew , de Vugt Marjolein , Koehler Sebastian 
Published: December 2021

AbstractBackgroundWith the projected surge in global dementia cases, research is increasingly focusing on lifestyle factors as preventive measure. Social and cognitive leisure activities are promising targets, but have thus far received relatively little attention. This study investigates whether cognitive and social activities contribute to dementia risk, and whether engagement in these activities moderates the association between other known risk factors (education, wealth & lifestyle factors).MethodWe used data of the English Longitudinal Study of Ageing (ELSA) on engagement in social and cognitive activities in 6346 participants, followed up from 2008/2009 until 2014/2015. Dementia prevalence was assessed until up to 7 years after baseline. Self‐reported cognitive (e.g. “reading the newspaper”) and social (e.g. being a member of a social club) activities and social participation (e.g. “going to the cinema”) were clustered into high and low based on a median split. We then assessed their individual contribution to dementia‐risk as well as their interaction with the other risk factors, using Cox regression models, controlling for age, sex, education, wealth and lifestyle risk factorsResultWe found that higher engagement in cognitive (HR=0.476; 95% CI=0.27‐0.84) and social activities (HR=0.60; 95% CI=0.42‐0.87) as well as social participation (HR=0.59; 95% CI=0.38‐0.90) were associated with lower dementia risk, independently of the other risk‐factors in the model. We also found an interaction between the level of engagement in social activities and level of education with regard to dementia risk, but not with other risk factors.ConclusionCognitive and social leisure activities and social participation may be beneficial for overall dementia risk. The benefits of social activities may be larger for people with low education. Both should be taken into account when designing dementia prevention measures.
Tailoring recruitment message content to reach diverse communities for AD research participation
Authors: Edwards Dorothy Farrar , Dykema Jennifer 
Published: December 2021

AbstractBackgroundCOVID19 forced cessation of in‐person recruitment accelerating reliance on social media and other communication strategies. New strategies are needed to reach healthy controls who are typically recruited outside of clinical settings. Engaging diverse communities is also a priority given the disproportionate burden of AD and related dementias. Understanding the general and differential appeal of recruitment messaging to diverse groups will facilitate more effectively tailored messaging.MethodsThe Voices Heard Survey designed to identify factors associated with willingness to participate in biomedical research requesting biospecimens was administered to a diverse sample of 406 Wisconsin residents. Respondents include White (n=100), African American (n=105), Latino (n=100) and American Indian (n=101) adults. The 96 item survey assessed trust in medical research, along the continuum of study complexity and invasiveness relevant to AD studies, factors positively or negatively affecting willingness to participate in biomedical studies and clinical trials. Response frequencies indicated likelihood of participation were calculated for the full sample and by racial/ethnic group. Chi‐Square analyses were computed to determine significant differences across groups.ResultsSample characteristics are presented in Table 1. The factors most highly associated with willingness to volunteer for a study for the total sample were: Invited to Participate (85%), Research Goal (83%), Family Member with Disease (74%) and factors less likely to promote participation were: Share Results (48%), Paid for Participation (35%) and Transportation (34%) (see Figure 1). Significant differences were observed between the White and minority groups for the following factors: Black, Latino and American Indian respondents were: Significantly more likely to volunteer if asked by a a person of the same race (p<.0001), and more concerned than Whites about Disruption of work and family responsibilities (p< .001),Availability of transportation(p<.01), and If the results are used to help others (p<.01), and Childcare (p<.02). Remuneration for participation (p<.06) and sharing results with community (p<.07) approached significance. Specific priorities by racial and ethnic group will be presented.ConclusionAD study recruitment requires strategic communication and innovative methods of reaching groups traditionally underrepresented in biomedical research. We identified information opportunities for tailored messaging designed to increase awareness of the value and opportunities afforded of research participation.
Staying Sharp: A case study in virtual health education for aging brain health
Authors: Lazarus Rachel Carly , Rodman Zack 
Published: December 2021

AbstractBackgroundAARP's Staying Sharp program is a digital platform dedicated to educating users on how to learn, practice, and apply holistic, lifestyle‐based behaviors that may impact cognitive aging. The Staying Sharp program has been active for several years, and currently has a userbase of over 800,000 members. This past year, COVID necessitated a massive shift in the way we live our lives; this particularly impacted older adults, who are especially vulnerable to COVID. Consequently, Staying Sharp pivoted in several ways in order to best serve as a valuable health education tool. Here, we will (1) discuss the lessons learned during this COVID‐driven pivot; and (2) present preliminary data analyses of the impact of COVID / social distancing on measures of behaviors in the domains of sleep, stress, and social interaction.MethodA retrospective analysis of >200,000 self‐reported lifestyle surveys from the platform evaluated responses regarding sleep hygiene, social isolation, and stress management. Responses were categorized across three periods: prior to April 1, 2020 (pre‐social distancing), from April 1 ‐ August 1 2020 (acute social distancing), and from August 1 2020 ‐ January 1 2020 (chronic social distancing). Demographic factors were also analyzed for potential correlation with self‐reported changes in lifestyle behaviors.ResultPreliminary results indicate age‐associated changes in sleep hygiene habits and stress management over the chronological progression of pandemic‐driven social distancing. Furthermore, changes in self‐reported habits of social media use and contact with family / friends were associated with total time elapsed since April 1; these behavior changes were also associated with age.ConclusionThe Staying Sharp platform carried out a significant pivot at the beginning of the COVID pandemic in order to best serve its userbase. With a cultural shift towards virtual health education, the digital Staying Sharp platform became positioned as an optimal source for health education related to cognitive aging. A preliminary analysis of retrospective data indicates pandemic‐associated shifts in self‐reported habits in sleep, stress, and social interaction as a function of age. These findings may represent an interesting line of future investigation in older populations, who are particularly affected by social distancing during the COVID era.
The shift to virtual, Part 2: Implications for neuropsychological health and well‐being in older populations
Authors: McGuire Lisa C 
Published: December 2021

AbstractBackground2020 brought a pandemic that placed older adults at risk for severe illness and outcomes.MethodBecause of their increased risk, older adults were advised to limit interactions as much as possible with other people and consider avoiding activities where taking protective measures may be difficult, such as activities where social distancing can’t be maintained.ResultsThe result for many older adults was feelings of social isolation, loneliness, and depression. Through the pandemic, there has been a shift from face‐face interactions to virtual interactions as a delivery mechanism for medical interactions and also social ones.ConclusionThis presentation will explore outcomes of this virtual shift with respect to physical health and well‐being utilizing the latest CDC data.
Bilingualism is associated with lower cognitive decline and with lower levels of AD biomarkers in a cognitively unaffected cohort
Authors: Dauar Marina Tedeschi , Picard Cynthia , Rosa‐Neto Pedro , Breitner John , Villeneuve Sylvia , Poirier Judes ,   PREVENT‐AD
Published: December 2021

AbstractBackgroundSpeaking two or more languages has been shown to contribute to cognitive reserve and to delay the onset of Alzheimer’s disease (AD). However, little is known about the effect of bilingualism on the progression of AD biomarkers. In this study, we intended to investigate the effect of bilingualism on cognitive scores and on AD biomarkers in a cohort of cognitively unaffected individuals.MethodWe analyzed data from participants of the PREVENT‐AD cohort. This cohort comprises cognitively normal participants over the age of 55 who have a first degree relative with AD. Cognition was assessed with the RBANS scale, Tau burden was measured with [18F]‐AV1451 PET, and CSF biomarkers were measured with Innotest’s enzyme‐linked immunosorbent assay kit (Fujirebio, Ghent, Belgium). Analyses were performed comparing participants who speak one, two or three languages and comparing participants who speak one or more than one language.ResultA total of 327 participants were included, with 89 that speak one language, 195 that speak two languages, and 43 that speak three languages. We found that participants who speak more than one language have significantly higher attention scores (p=0.041) (Fig. 1a) and total RBANS scores (p=0.021) (Fig 1b) than participants who speak only one language. Participants who speak two languages have a lower tau burden in the entorhinal cortex than participants who speak one language (p=0.047) (Fig. 2). For total Tau, participants who speak more than one language have lower CSF levels than participants who speak one language. This difference increases over time and becomes statistically significant on follow up visits 36 months (p=0.049) and 48 months (p= 0.031) (Fig 3a). Participants who speak more than one language have lower CSF levels of phospho‐Tau (p= 0.017) (Fig 3b), and neurofilament light (p=0.041)(Fig 3c) compared to participants who speak one language.ConclusionOur results show that bilingualism is associated not only with less cognitive decline, but also with lower levels of AD biomarkers in pre‐symptomatic AD.
Can a digital scientific conference function as a platform for facilitating two‐way learning between researchers and participants?
Authors: Walter Sarah , Wheaton Bonnie , Hummel Cynthia Huling , Tyrone Jamie , Chan Dennis , Ziolkowski Jaimie , Shaffer‐Bacareza Elizabeth , Aggarwal Neelum T 
Published: December 2021

AbstractBackgroundResponding to requests from research participants, we piloted a program to facilitate two‐way learning between researchers and participants through the platform of a digital scientific conference.MethodParticipants were invited to attend the Alzheimer’s Association International Conference (AAIC), through a digital platform, and were offered daily small group discussions. Support was provided in the form of daily emails, navigation tips, and a glossary of frequently used terms and acronyms.ResultThe digital conference was well attended, with participants attending a broad spectrum of talks. Convening daily small group discussions was critical in creating a space where two‐way learning could occur by allowing participants to interact and share with each other as well as with research professionals. Participants provided input on research design, recruitment, outcomes, and approaches, as well as applicability of research to clinical settings.ConclusionConferences that are remotely accessible offer a unique opportunity to support the engagement and participation of individuals with limited mobility or time. Future conferences should offer research participants either free or reduced registration, and allow them to select the topics they are most interested in. We recommend providing support and a glossary of frequently used acronyms and terms. Future work is needed to replicate this approach in a more diverse group of research‐naïve participants.
Distinct patters of associations between cognitive performance and Alzheimer’s disease biomarkers in a multinational cohort of clinically normal older adults
Authors: Tsoy Elena , Brugulat‐Serrat Anna , Vandevrede Lawren , Erlhoff Sabrina J , Casaletto Kaitlin B , Rankin Katherine P , Kramer Joel H , Possin Kate L ,   EPAD Consortium
Published: December 2021

AbstractBackgroundThere is growing evidence of early cognitive changes associated with Alzheimer’s disease (AD) biomarker burden. While changes in CSF phosphorylated tau (p‐tau) and Aβ42 levels have been shown to precede onset of clinical symptoms by 15‐20 years, preclinical cognitive changes remain poorly understood, particularly in multinational cohorts. In this study, we leveraged the data from the multisite European Prevention of Alzheimer’s Dementia (EPAD) consortium (France, Netherlands, Spain, United Kingdom) to investigate cross‐sectional and longitudinal associations between cognitive performance and gold standard AD CSF biomarkers (p‐tau/Aβ42 ratio).MethodParticipants were 811 clinically normal older adults (age: 65.1±6.8; education: 14.4±3.7; 57% female) who completed a battery of digital cognitive tests of working memory, inhibitory control, and associative memory (TabCAT, University of California San Francisco) in addition to CSF Aβ42 and p‐tau‐181 (Roche Elecsys®). Additionally, 114 of these participants completed both cognitive and biomarker studies at 1‐year follow‐up (age: 65.4±5.9; education: 13.2±3.5; 54% female). Cross‐sectional associations between p‐tau/Aβ42 ratio and cognitive performance were examined using multiple linear regression models, and longitudinal associations were examined using linear mixed effects models. All analyses covaried for age, sex, education, hippocampal volume, and APOE ε4 status. Longitudinal analyses additionally covaried for time since baseline.ResultAt baseline, greater p‐tau/Aβ42 ratio was related to poorer performance on tasks of working memory (B=‐0.57, SE= 0.24, t=‐2.31, P=.02) and inhibitory control (B=‐0.45, SE=0.25, t=‐1.82, P=.06), but not on a task of associative memory (B=‐0.30, SE=0.26, t=‐1.13, P=.23). Longitudinal analyses showed that increases in p‐tau/Aβ42 ratio were significantly associated with decline in associative memory performance only (B=‐1.14, SE=0.52, t=‐2.20, P=.03).ConclusionIn summary, we found that greater AD biomarker burden was cross‐sectionally associated with poorer executive performance, while longitudinal increase in biomarker burden was related to greater decline in memory. Our findings contribute to the growing literature on the cognitive characteristics of preclinical AD and provide support for the hypothesis of an early impairment in attentional/executive processes, followed by a breakdown in memory functions as the pathological changes progress. A particular strength of our results is their potential generalizability in international cohorts and global studies of preclinical AD.