bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal assessment of cognitive decline in the Amish
Authors: Song Yeunjoo E. , Miskimen Kristy , Laux Renee A. , Fuzzell M. Denise , Fuzzell Sarada L. , Sewell Jane L. , Miller Sherri D. , Adams Larry D. , Caywood Laura J. , Prough Michael , Close Jason E. , Herington Sharlene D. , Slifer Susan H. , Ramos Jairo , Vance Jeffery M. , Cuccaro Michael L. , Ogrocki Paula` K. , Lerner Alan J. , Scott William K. , Pericak‐Vance Margaret A. , Haines Jonathan L. 
Published: December 2020

AbstractBackgroundThe Modified Mini‐Mental State (3MS) is a widely used measure of global cognition. The Old Order Amish are both genetically and environmentally homogeneous, with similar years of formal education across the population. Here, we investigated the longitudinal course of cognitive function as measured by the distribution of 3MS in the Mid‐Western Amish.MethodAfter extensive QC, the 919 subjects with both baseline 3MS and AD status were analyzed. The change from 1st to 2nd measurement was used as the main longitudinal trait of interest. Mean decline differences in 4 baseline age groups (<70, 70‐80, 80‐90, >=90) were assessed. The differences in the average longitudinal decline of 3MS between AD cases and controls was assessed using Kolmogorov‐Smirnov tests and ANCOVA adjusted for age at exam and sibship.ResultThe overall baseline mean 3MS score was 89.52 [42, 100] at the mean age of exam 75.52 [60, 99]. The overall annual rate of decline was ‐0.3 [‐5, 5] from 1st to 2nd measurement (n=242) and ‐0.6 [‐2.1, 1.3] from 2nd to 3rd measurement (n = 23). The annual rate of decline was ‐0.96 [‐4, 1.7] in AD cases (n=18), ‐0.01 [‐5, 5] in AD controls (n=180) and ‐1.08 [‐5, 0.7] in an ‘Unclear’ group (n = 44). The most rapid annual decline of the 3MS was in age 80 to 90 group and the decline rate was significant (p‐value=0.004) compared to the lowest age group (<70) overall and in AD cases. In the Unclear group, the rate of decline was greatest in age 70 to 80. However, in the control group, cognition improved, with a 1.29 [‐1, 5] annual increase in age 80 to 90. The age and sibship adjusted differences in decline were significant (p‐value<2e‐10) between AD cases vs. controls as well as between Unclear vs. controls.ConclusionWe explored the changes of 3MS scores over time and demonstrated different patterns of decline by age and AD status in the Amish. Our study is the first in this homogeneous Amish population, providing a better understanding and insight into the cognitive decline examining the change in 3MS over time.
Association of depressive disorder with the cognitive performance of Mexican older adults with type 2 diabetes mellitus
Authors: Ortega‐Ramos Alicia , Salinas‐Contreras Rosa Maria , Acosta‐Castillo Gilberto Isaac , Sosa‐Ortiz Ana Luisa 
Published: December 2020

AbstractBackgroundType 2 diabetes mellitus (T2D) and depression have both become pandemics over the last years. Both of these conditions have also been associated with signs of systemic inflammation, decreased insulin sensitivity, and autonomic dysfunction, all identified as risk factors for cognitive impairment and dementia. Our aim in this study was to explore the effect of depressive symptoms in the cognitive performance of Mexican older adults diagnosed with with T2D.MethodWe analyzed differences in global cognition (using the COGSCORE instrument) of adults aged 65 and over, with T2D, with a three‐year follow up within the 10/66 Dementia Research Group protocols in Mexico. T2D was diagnosed with glucose levels at baseline equal or greater than 126 mg/dl, and/or with self‐report of diabetes. Depression diagnosis was based on the International Classification of Diseases glossary version 10 (ICD‐10).ResultsThe total sample consisted of 441 older adults people with T2D. 65% were women. The majority (72%) were outside glycemic control levels, 45% were overweight and 27% were depressed. In termos of cognitive performance, there was no significant difference in subjects with diabetes and depressive symptoms (p>0.47). When comparing the cognitive performance, there were differences between 1) the ages of 75 and 79 (p<0.052) and 80 or more (p<0.013) with the group of 65‐69 years; and 2) between those with low or normal BMI compared to those with obesity (p>0.56). Variables such as depression, area of study, educational level, marital status, and mass index showed no statistical significance.ConclusionIn this study, we found that in a Mexican population with T2D the presence of depression did not show a significant effect on cognitive performance, which is controversial with other studies. Interestingly, those who were underweight or had a normal BMI had a decrease in cognitive function, so we must pay attention to mental health but also complement it with nutrition and establish prioritary intervention measures that allow weight control, decrease chronic degenerative diseases, and that could consequently reduce cognitive impairment.
Recruitment strategies for the genetics of Alzheimer disease in the Puerto Rican population
Authors: Silva Concepcion , Mena Pedro Ramon , Tejada Sergio , Adams Larry D , Rodriguez Vanessa C , Celis Katrina , Prough Michael , Bussies Parker , Sierra‐Lopez Carolina B , Contreras Maricarmen , Manrique Patricia , Feliciano Nereida I , Chinea Angel , McCauley Jacob L , Acosta Heriberto , Vance Jeffery M , Cuccaro Michael L , Beecham Gary W , Pericak‐Vance Margaret A , Feliciano‐Astacio Briseida E 
Published: December 2020

AbstractBackgroundWith over 5.1 million individuals, the Puerto Rican population makes up over 1.5% of the US population and is the 2nd largest Hispanic/Latino population in the continental US. There are an estimated of 60,000 cases of AD on the island. The Puerto Rico Alzheimer's and Related Dementias Initiatives (PRADI) cohort will both leverage and complement existing AD Resources, the Alzheimer Disease Sequencing Project (ADSP) with the inclusion of a diverse and underrepresented population. At present, the cohort consists of a total of 935 total participants including individuals from 115 multiplex AD families. There are 418 cases of dementia, 217 mild cognitive impairment, and 300 unrelated and family‐based controls.MethodWe examined the most successful strategy to recruit cases and controls as well as multiplex families for both case/control and family‐based genetic studies. We began by engaging a wide range of stakeholders across the island. The core activities of our team include relationship building, partnership development and maintenance, and coalition building. For the community outreach, we utilize mass media like newspapers, radio interviews, and focal group presentations and engaged the following stakeholder groups: Alzheimer disease day care centers, elderly housing in San Juan, senior day care centers, non‐profit organizations, private neurology offices, and other community‐based organizations such as the Alzheimer’s Association.ResultThe percent of patients recruited through each stakeholder group were 45.76% (428/935) from community outreach, 34.33% (321/935) from private neurologist practices, 18.93% (177/935) from senior day care centers and 0.96% (9/935) from Alzheimer disease day care centers. The mean age and standard deviation of cases and controls were 78.22 years (±9.37) and 70.84 years (±7.92) respectively. Examining the data with respect to multiplex family structure, we found that 53.77% of the families (including the largest families) came from private physician referral.ConclusionPartnering with diverse stakeholders and building coalitions proved to be effective as an outreach method for recruitment. Private physicians remain an excellent source for the identification of multiplex AD families for family‐based genetics study. Outreach community‐based approaches are highly successful mechanisms to educate and engage participants in genetic research.
Use of lipid lowering drugs in cognitively impaired patients
Authors: Van Gils Aniek M , Wiersinga Julia HI , de Schraaf Sara AJ Van , Trappenburg Marijke C , Peters Mike JL , Meester Hanneke FM Rhodius‐ , Muller Majon 
Published: December 2020

AbstractBackgroundDementia and cardiovascular disease(CVD) are closely linked and share common risk factors. High cholesterol levels are a major risk factor for CVD and lipid‐lowering drugs(LLD) have proven to reduce this risk but are also associated with multiple side effects. Frail older patients, among them patients with cognitive impairment, are possibly less likely to experience benefit from LLD due to shorter life‐expectancies. However, there is a lack of consensus whether to continue or withdraw LLD treatment in this patient group. In this study, we examined LLD prescribing patterns for older patients(frail/non‐frail, with/without CVD) at different levels of cognitive impairment.MethodWe included data of 271 memory clinic patients with a diagnosis of dementia(n=146), mild cognitive impairment(MCI,n=80) and subjective cognitive decline(SCD,n=55) from the Amsterdam Ageing Cohort(AAC); mean age was 80(±5) yrs, 49% was female. Prevalence of LLD use was assessed for patients with and without CVD and stratified according to age(≤80,>80yrs), polypharmacy(<5,5‐8,>8 drugs) and physical frailty(gait speed<0.8,≥0.8m/s). LDL‐c levels were measured; patients with an LDL‐c level<2.5mmol/L were considered ‘on‐target’.ResultIn patients with CVD, LLD use in SCD, MCI and dementia patients was 45%, 61% and 69%; 78‐90% of these patients were on‐target. In patients without CVD, LLD use in SCD, MCI and dementia patients was 20%, 41% and 19%; 60‐71% of these patients were on‐target. No significant differences were found after stratification. Logistic regression analyses showed that, compared to SCD patients with CVD, dementia patients with CVD were more likely to use LLD; OR(95%CI) 3.2(1.0;9.8). Further, MCI patients without CVD were more likely to use LLD, compared to SCD patients without CVD; OR(95%CI) 8.6(2.1;35.1). These associations were independent of age, sex and multiple confounders.ConclusionContrary to our expectations, patients with cognitive impairment(with/without CVD) used more LLD than patients with SCD. This relation was not explained by old age, polypharmacy, or physical frailty. Our study provides insight in the current prescribing patterns of LLD in older patients visiting a memory clinic. Future research should focus on the efficacy of LLD use in older patients with cognitive impairment, in order to make a more applicable guideline in whether and when to continue or withdraw LLD in cognitive impaired patients.
Cognitive and clinical outcome measures for Alzheimer's disease prevention trials in adults with Down syndrome
Authors: Strydom Andre , Baksh Asaad , Hithersay Rosalyn , Aschenbrenner Andrew J. , Jaeger Judith , Carter Ben , Wijeratne Peter A , Alexander Daniel C. , Hassenstab Jason ,   Horizon21 Consortium
Published: December 2020

AbstractBackgroundAdults with Down syndrome (DS) are at ultra‐high risk for developing Alzheimer’s disease (AD) due to APP gene triplication on chromosome 21. There is interest in conducting trials of treatment that can delay or prevent onset of disease in at‐risk individuals with DS. Reliable outcome measures are required to demonstrate clinical benefit of treatment in a population with premorbid cognitive impairments that affect their performance on cognitive outcome measures. We aimed to identify the most efficient clinical and cognitive outcomes for prevention trials of AD in DS.MethodsAnalysis of cognitive data based on different test batteries from several recent longitudinal cohort studies of AD in DS in Europe and the US (n >300 with 2 years of follow‐up data), using staging and E‐Max models and other statistical methods.ResultsThe age range within which cognitive decline can be first reliably observed in DS adults who do not yet have dementia is around age 45; this varies by outcome measure, with memory, attention, orientation and some verbal tasks being the most feasible and reliable tests for prevention trials. We will report effect sizes for these outcome measures to inform trial design.ConclusionsTrials of treatment to prevent or delay AD in DS individuals using cognitive measures as primary outcomes are feasible if targeted at individuals within age ranges where decline can be first observed, but effect sizes (and sample sizes) vary by outcome measures selected.
Differential association between tau pathology and longitudinal cortical atrophy in subtypes of Alzheimer’s disease
Authors: Mohanty Rosaleena , Ferreira Daniel , Westman Eric 
Published: December 2020

AbstractBackgroundTau neurofibrillary tangle pathology and cortical atrophy progress at different rates when investigated cross‐sectionally or retrospectively (LaPoint 2017). However, convergence of the two over time remains unclear, especially in the subtypes of AD, which could inform about the underlying neural mechanisms. Here, we studied the association between tau pathology with positron emission tomography (PET) and cortical atrophy with retrospective and prospective structural magnetic resonance imaging (sMRI) in Alzheimer’s disease (AD) dementia. We identified subtypes using both modalities to compare their temporal evolution.MethodsWe identified 383 participants from the ADNI database, which comprised of 30 Aβ+ AD dementia patients, 54 Aβ+ prodromal AD patients, 99 Aβ+ preclinical AD and 200 Aβ‐ healthy individuals (HC). All subjects had tau PET (AV‐1451) and concurrent sMRI (T1‐weighted). Additionally, retrospective and prospective sMRI were available. Preliminarily, we analyzed data from the AD dementia group. Tau PET and longitudinal sMRI were preprocessed to generate regional measures (Desikan 2006) of partial volume corrected standardized uptake value ratio (SUVR) (Greve 2016) and cortical volume, thickness respectively. AD subtypes were characterized by regional volumes and tau SUVR as in a previous study (Byun 2015). Four subtypes were identified: typical AD (TAD), limbic predominant (LP), hippocampal sparing (HS) and minimal atrophy (MA). We investigated the association between tau SUVR and longitudinal cortical thickness in AD dementia and the four subtypes.ResultsIn the preliminary analysis, we observed a significant negative association between tau SUVR and longitudinal cortical thickness (baseline and prospectively) in the entorhinal cortex. Significant association between tau SUVR and cortical thickness was also observed in temporal and parietal areas prospectively. Additionally, subtypes identified based on tau PET and sMRI did not always coincide at baseline, but prospective tracking was indicative of potential convergence between the two (Figure 1).ConclusionThe association of increased tau PET binding with prospective cortical thinning suggests that including prospective imaging is critical to track disease progression. Preliminary evidence suggests that the convergence between tau pathology and cortical atrophy could occur at different rates in different subtypes. Learning subtype‐specific trajectory would be valuable for the design of disease‐slowing/modifying clinical trials.
Early alterations of hippocampal gabaergic synaptic properties induced by Aβ42 oligomers
Authors: Hidisoglu Enis , Chiantia Giuseppe , Franchino Claudio , Marcantoni Andrea , Carbone Emilio 
Published: December 2020

AbstractBackgroundSynaptic dysfunction is one of the earliest hallmarks of Alzheimer’s Disease (AD). It is well known that the oligomeric form of amyloid β protein (Aβ42) rather than fibrils or plaques is the cause of the synaptic abnormalities and cognitive impairments associated with AD. To date, there are no comprehensive electrophysiological studies that investigate the neuronal mechanism of Aβ42‐induced synaptic changes and there is an impressive lack of information on how Aβ42 affects the elementary parameters involving GABAergic synaptic function.MethodTo reveal the effects of Aβ42 on GABAergic synapses, we recorded miniature and evoked inhibitory postsynaptic currents (mIPSC and eIPSC, respectively) in c57bl6 mice embryo hippocampal neurons. mIPSC analysis and eIPSC related analysis such as paired‐pulse ratio, cumulative eIPSC amplitude and multiple probability fluctation analysis were performed to evaluate elementary parameters associated with synaptic transmission, such as unitary conductance of GABAAreceptors, number of release sites, release probability, and size of readily releasable pool.ResultWe found Aβ42 increased the frequency and amplitude of miniature currents as well as the amplitude of eIPSCs. When we focused on paired pulse ratio (PPR) we found that it was not changed by Aβ42, suggesting that GABA release probability was not affected by this oligomer. On the other hand, a more detailed study of the presynaptic effects induced by Aβ42 by mean of multiple probability fluctuation analysis (MPFA) and cumulative amplitude analysis has shown an increase in the size of the readily releasable pool (RRP) and number of release sites (N) without any changes of the release probability (p).ConclusionOur results clarify the early effects induced by Aβ42 on GABAergic synapses by focusing on their pre‐ and postsynaptic site and contribute to address the development of new therapies for the treatment of AD. This project was supported by the European Molecular Biology Organization (EMBO). Project ID: EMBO‐7835.
Review and analysis of the Spanish regulations on health and social care of people with neurodegenerative diseases and their families
Authors: Valverde Eva María Picado , Ortega Eva González ,   NEUROQUALYFAM Group
Published: December 2020

AbstractBackgroundNeurodegenerative diseases (ND) constitute a problem of great magnitude, seriousness and complexity that require actions in the diverse areas of the Health and Social System (Ministerio de Sanidad, Servicios Sociales e Igualdad, 2016). These actions must cover the basic needs of patients and their families, while improving their care and quality of life. Given this situation, the aim of this study is to carry out a detailed review of the current national and regional regulations regarding health and social care of people with ND and their families.MethodAfter a systematic review of 102 regulatory measures in Spain and in the Autonomous Community of Castile and Leon, those failing to consider the family of the person with ND were discarded. Finally, 35 instructions related to ND in terms of health and social services were analyzed and classified according to their scope (9 state regulations, 16 autonomous community regulations and 10 approved strategies).ResultThe analyses showed that: (1) only 34% of the regulatory instructions include contents that are directly or indirectly related to the quality of life of the families of these patients; (2) analyzed instructions do not specify how to coordinate resources and services in the health and social welfare sector for the care of people with ND and their families.ConclusionThis study shows the lack of regulations in our region and country that specifically focus on the families of people with ND, as these relatives are not deemed to be direct beneficiaries. Likewise, there is a lack of specificity regarding the coordination of the services and resources for patients and their families. Reference: Ministerio de Sanidad, Servicios Sociales e Igualdad. (2016). Estrategia en Enfermedades Neurodegenerativas del Sistema Nacional de Salud. Madrid: Ministerio de Sanidad, Servicios Sociales e Igualdad.
Domiciliary Alzheimer visiting in Down syndrome pilot project: Preliminary results
Authors: Valldeneu Sílvia , Barroeta Isabel , Altuna Miren , Videla Laura , Benejam Bessy , Estellés Teresa , Fernandez Susana , Lleó Alberto , Blesa Rafael , Fortea Juan , Carmona‐Iragui Maria 
Published: December 2020

AbstractIntroductionPeople with Down syndrome (DS) are at ultra‐high risk of developing Alzheimer’s disease (AD). A comprehensive health care approach is needed to enable an early diagnosis and an individualized follow up. The Alzheimer‐Down Unit developed a health plan which is offered to every adult with Down syndrome in Catalonia and which includes annual neurological and neuropsychological assessments together with clinical support and social counseling when needed. Within this plan, the “Domiciliary Alzheimer Visiting in Down syndrome” (DAVIS) pilot project adds domiciliary visits to bring closer this plan to those candidates who are not able to come to our site. In the present study, we analyze the preliminary results of this project.MethodsPilot observational cross‐sectional study. We contacted occupational centers /residences which included users with Down syndrome and we organized the visit of a neurologist and a neuropsychologist from our team. Candidates and their caregivers were informed about the health plan and those who accepted to participate were assessed. According to their cognitive status, they were classified into 3 groups: without cognitive impairment (aDS), prodromal AD (pDS) or AD dementia (dDS). Subsequently, a physically present or telephonic follow‐up visit, together with the option of collaborating with Primary Care, was offered. Participation in biomarkers research projects was also proposed.ResultsBetween October 2018 and December 2019 we assessed 92 participants (mean age 42.5, 48.9% males) classified as aDS (77.1%), pDS (4.4%) or dDS (18.5%). The 67.4% and the 28.3% of the participants were recruited to continue with the physically present or telephonic follow‐up, respectively. A 10.9% of the participants agreed to collaborate on research projects.ConclusionsThe DAVIS pilot project facilitates the dissemination of our comprehensive health plan for adults with DS in Catalonia. Its clinical application allows the diagnosis of new cases of AD and brings closer research to the adult population with DS. The DAVIS pilot project emphasizes the need of social and health care improvements for adults with DS; however, an extended DAVIS project will generate solid data to influence on health policy and, potentially, to improve the people with DS and their caregivers quality of life.