bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endogenous control miRNAs for normalization in plasma samples of Alzheimer’s disease patients from a discovery and validation cohort
Authors: Dakterzada Faride , Targa Adriano , Benitez Ivan David , Torres Gerard , ElKhayat Leila Romero , Moncusi Anna , Huerto Raquel , Barbe Ferran , Piñol‐Ripoll Gerard 
Published: December 2021

AbstractBackgroundSeveral studies had explored the role of miRNAs in Alzheimer’s disease (AD). The identification of endogenous controls (ECs) would contribute to the standardization of these biomarkers in AD but they have not yet been established. The objective of the study was to identify miRNAs that can be used as ECs in AD.MethodWe evaluated 145 patients divided into two different cohorts. One was a discovery cohort of 19 women diagnosed with mild to moderate AD (Mini‐Mental State Examination (MMSE) score ≥ 20) and with confirmed pathologic levels of Aβ42 in CSF. The stability assessment cohort consisted of 126 individuals: 24 control subjects, 25 subjects with MCI and negative for CSF biomarkers, 22 subjects with MCI and positive for CSF biomarkers and 55 subjects with AD and positive for CSF biomarkers.In the discovery cohort, a profile of 384 miRNAs was determined in plasma by TaqMan Low Density Array. The best EC candidates were identified by mean‐centering and concordance correlation restricted normalization methods. The stability of the EC candidates was assessed using the GeNorm, BestKeeper and NormFinder algorithms.ResultNine miRNAs (hsa‐miR‐324‐5p, hsa‐miR‐22‐5p, hsa‐miR‐103a‐2‐5p, hsa‐miR‐362‐5p, hsa‐miR‐425‐3p, hsa‐miR‐423‐5p, hsa‐let‐7i‐3p, hsa‐miR‐532‐5p, and hsa‐miR‐1301‐3p) were identified as EC candidates in the discovery cohort. The validation results indicated that hsa‐miR‐103a‐2‐5p was the best EC, followed by hsa‐miR‐22‐5p, hsa‐miR‐1301‐3p, and hsa‐miR‐425‐3p, which had similar stability values in all three algorithms.ConclusionWe identified a profile of four miRNAs as potential plasma ECs to be used for normalization of miRNA expression data in studies of subjects with cognitive impairment.
Lifestyle and behavior changes during the COVID19 pandemic in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER)
Authors: Lehtisalo Jenni , Ngandu Tiia , Mangialasche Francesca , Hemiö Katri , Solomon Alina , Laatikainen Tiina , Strandberg Timo , Antikainen Riitta L , Tuomilehto Jaakko , Soininen Hilkka , Kivipelto Miia 
Published: December 2021

AbstractBackgroundFinnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a randomized trial that showed beneficial effect on cognition with a 2‐year multidomain lifestyle intervention. During the post‐intervention follow‐up, COVID19 pandemic emerged resulting in lockdown and reduced services. Our aim is to investigate how lifestyle and behavior changes during the pandemic are related to lifestyle earlier in the study.MethodThe FINGER cohort included 1260 individuals aged 60‐77 years at baseline and at risk of dementia, randomized into multidomain intervention or control groups. A postal survey was sent to all eligible participants from the FINGER study in June 2020 (end of the first wave of the pandemic in Finland), on average 10 year after the baseline. 859 (68%) were still alive and eligible for the survey.ResultTotal of 735 responders (85% of the eligible participants) were on average 78 years old. They were younger, had higher baseline cognition, and were more often from the former control group than non‐responders (p<0.05 for all). The intervention allocation showed no association with self‐reported lifestyle changes during the pandemic in diet, exercise, or cognitive activity. Among older participants (>78 y), the intervention group reported more increase in remote contact with friends and relatives (p=0.013) and health care (p=0.042) than the control, and also less pandemic‐related reduction in overall contact with friends (p=0.045). Among all, reductions in physical exercise were reported among those who were less physically active earlier in the study. Both increase and decrease in contact with friends and family were reported by those more cognitively active earlier in the study. They also had more increase in remote contacts. Changes in diet were positive (increase in fruit and vegetable intake), but they were not related to earlier diet.ConclusionThe FINGER participants reported only minor change in their lifestyle and behavior during the first wave of the COVID pandemic related lockdown. For physical activity, the pandemic appeared to have negative effect particularly among those with lower levels earlier, possibly adding inequalities. Intervention was related to more remote contacts, probably due to better computer literacy after the cognitive training.
Exposure to ambient air pollution and cognitive decline: Results of the prospective Three‐City study
Authors: Duchesne Jeanne , Gutierrez Laure‐Anne , Chen Jie , Vienneau Danielle , de Hoogh Kees , Helmer Catherine , Tzourio Christophe , Jacquemin Benedicte , Berr Claudine , Mortamais Marion 
Published: December 2021

AbstractBackgroundGrowing epidemiological evidence suggests an adverse relationship between exposure to air pollutants and cognitive decline. However, there is still some heterogeneity in the findings, with inconsistent results depending on the pollutant and cognitive domain considered. We aimed to evaluate if air pollution was associated with global and domain‐specific cognitive decline.MethodsWe used data from the French Three‐City prospective cohort on 6380 participants aged 65 and older at recruitment and followed up for 12 years. Participants did cognitive tests at baseline and every 2 years, to assess global cognition (Mini Mental State Examination, MMSE), visual memory (Benton Visual Retention Test, BVRT), semantic fluency (Isaacs Set Test, IST) and executive functions (Trail Making Tests A and B, TMTA/B). Land‐use regression models were used to estimate fine particulate matter (PM2.5), nitrogen dioxide (NO2) and black carbon (BC) exposure at participants’ residential address over the 5‐year preceding the baseline visit. Linear mixed models were performed for each pollutant to evaluate their association with cognitive decline.ResultsParticipants median age was 73.4 (IQR 8.0), and 61.5% were women. Baseline median scores were 28 (3) for MMSE, 12 (3) for BVRT, 48.0 (14.0) for IST, 0.5 (0.2) for TMTA, and 0.2 (0.2) for TMTB. We found a significantly worse decline in global cognition among participants with higher PM2.5 exposure: for PM2.5 levels ranging from 19.6 to 30.4 µg/m3, an IQR increment in PM2.5 (1.5) was associated with greater MMSE decline (β: 0.003 [0.0006;0.006] per year). Other associations were inconsistent in direction and of small magnitude. For instance, an IQR increment in PM2.5 was associated with a 0.03 (‐0.002;0.060) change in IST decline and a ‐0.0003 (‐0.0009;0.0003) change in TMTA decline.ConclusionWe found an adverse association between PM2.5 exposure and decline in global cognition. No significant associations were observed for the other pollutants and cognitive domains.
Estimating attrition in mild‐to‐moderate Alzheimer’s disease and mild cognitive impairment clinical trials
Authors: Ritchie Marina , Gillen Daniel L. , Grill Joshua D. 
Published: December 2021

AbstractBackgroundParticipant retention directly affects the validity and generalizability of clinical trial results. Investigators need information about expected attrition when planning trials of varying durations.MethodUsing the Alzforum and clinicaltrials.gov databases we reviewed 351 phase 2 and 3 placebo‐controlled trials conducted since 1998. Eighty‐six mild‐to‐moderate Alzheimer’s disease (AD) and eleven Mild Cognitive Impairment (MCI) trials met criteria for inclusion in this study. We first assessed the frequency with which trial arms differed in overall retention. When trials included more than one active arm, we combined those arms into a single group. To model associations between trial duration and retention, we used binomial regression.ResultFigure 1 illustrates differences in the observed proportion of participants completing in each trial between active and placebo arms for mild‐to‐moderate AD (Figure 1A) and MCI trials (Figure 1B). For each trial, a 95% confidence interval for the true difference between arms is provided. Since there was no consistent difference between arms, subsequent analyses combined active and placebo arms. Figure 2 illustrates the completion rate by trial duration for mild‐to‐moderate AD (Figure 2A) and MCI trials (Figure 2B). A local smoother along with uncertainty regions is added for visual aid. In general, trials with longer study duration had lower retention rates. Using binomial regression with robust variance estimates to account for within‐trial correlation, we estimated that a 6‐month increase in trial duration is associated with a 34% decrease in the odds of trial completion (OR=0.66; 95% CI: 0.58, 0.75; p<0.001) among mild‐to‐moderate AD trials and a 20% decrease (OR=0.80; 95% CI: 0.68, 0.93; p=0.004) among MCI trials. From the binomial regression model, the proportion of participants completing 6, 12, and 18‐month trials were estimated to be 82.9%, 76.3%, and 68.0% for mild‐to‐moderate AD trials and 82.6%, 79.1%, and 75.2% for MCI trials, respectively.ConclusionWhile decisions related to expected trial attrition are guided by several factors, these estimates may assist investigators designing trials and suggest that trial attrition is frequent and related to trial duration.
A phase 1b, randomized, double‐blind, placebo‐controlled, parallel cohort safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy study of intravenously infused BIIB092 in patients with four different primary tauopathy syndromes
Authors: Ljubenkov Peter A. , Vandevrede Lawren , Rojas Julio C. , Tsai Richard , Koestler Mary , Graham Danielle , Dam Tien , Boxer Adam L. 
Published: December 2021

AbstractBackgroundAggregation of insoluble tau is a key autopsy finding in several neurodegenerative conditions including corticobasal syndrome (CBS), non‐fluent variant primary progressive aphasia (nfvPPA), frontotemporal lobar degeneration due to microtubule‐associated protein tau (MAPT) mutation, and traumatic encephalopathy syndrome (TES). Monoclonal‐antibody (mAb) therapies may promote clearance of pathogenic tau species, but differing protein isoforms and conformations may limit the affinity of mAbs for tau epitopes in distinct tauopathy syndromes. A “basket trial” allows for efficient investigation of drug target engagement in distinct diseases sharing common causative molecular alterations. We assessed the safety, tolerability, pharmacokinetic profile, and pharmacodynamic effects of BIIB092 (gosuranemab), a mAb targeting an N‐terminal tau epitope, in a basket trial enrolling participants with 4 different tauopathy syndromes: CBS, nfvPPA, symptomatic MAPT mutations, and TES. We also explored BIIB092’s effects on CSF, MRI and clinical measures of disease severity.MethodN=25 participants were randomized approximately 3:1 to monthly intravenous infusions of 2000 mg BIIB092 (8 CBS, 4 nfvPPA, 4 MAPT, 2 TES) or placebo (CBS, 2 nfvPPA, 1 MAPT, 1 TES) for up to 6 months of double‐blind therapy. Subsequently 14 participants received monthly open label infusions for up to 6 months. Plasma, CSF, exploratory clinical measures, and volumetric imaging were collected at baseline, week 12, and week 24 of the double‐blind portion of the trial.ResultThe study was terminated by Biogen in December 2019 (following negative results in a phase 2 in progressive supranuclear palsy), prior to completion of planned enrollment or treatment in recruited participants. Adverse events were more frequent in participants randomized to BIIB092 (83%) compared to placebo (28%), though no adverse events were attributed to study drug. In all patients randomized to BIIB092, we observed 90% reduction in detectable CSF N‐terminal tau epitopes at weeks 12 (mean ‐96.9%, SD 2.0) and 24 (mean ‐97.0%, SD 1.9) of the blinded treatment period. Analyses of other secondary and exploratory endpoints are underway.ConclusionSix months of BIIB092 treatment was well tolerated and appears to bind to the N‐terminal epitopes in individuals with four different tauopathy syndromes.
Trajectories of self‐rated concerns in individuals developing cognitive decline
Authors: Gagliardi Geoffroy Pierre , Diez Ibai Palacio , Bueichekú Elisenda , Farrell Michelle E. , Kuppe Madeline K , Marshall Gad A , Amariglio Rebecca E. , Sepulcre Jorge , Sperling Reisa A. , Vannini Patrizia 
Published: December 2021

AbstractBackgroundSubjective perception of cognitive decline is identified as an important marker related to the risk of progression to Alzheimer's disease. However, loss of awareness has also been observed in predementia stages, potentially reducing the validity of the subjective experience. The aim of this study was to characterize the trajectories of complaints in cognitively normal (CN) individuals who later developed cognitive decline, as well as investigate differences in demographics, brain pathology and clinical progression between individuals aware and unaware of these changes.MethodWe included participants (CN at baseline) from the Harvard Aging Brain Study. Linear Mixed effect models were used to compute individual longitudinal changes of memory complaints (7 questions questionnaire) and cognition (Preclinical Alzheimer’s Cognitive Composite, PACC5). Participants who demonstrated a statistically significant PACC5 decline over time were divided into two groups: an Unaware (N=36) group defined as individuals with statistically significantly decreasing or displaying low (<2.5/7) complaints, and a Heightened (N=14) group defined as individuals with significantly increasing or displaying high (>2.5/7) complaints (Fig 1). Participants who did not decline in memory were assigned to the Stable group (N=248). Kaplan‐Meier survival analysis was performed to determine the rate of progression from CN to clinically impaired (MCI or dementia diagnosis) across groups.ResultNo group differences were found for gender, education, depressive symptoms or Apolipoprotein E4‐carrier status (Tab 1). Unaware participants were significantly older than the Stable group (p<0.001). The Heightened and Unaware groups demonstrated equivalent amyloid burden, which was significantly greater than the Stable group (p<0.01). The survival analysis revealed significant differences between all groups (p<0.001,Fig 2). Heightened participants had the fastest rate of clinical progression, followed by the Unaware group.ConclusionParticipants with heightened awareness demonstrated the fastest rate of progression from cognitively normal to MCI or dementia. Importantly, among the individuals with a subsequent cognitive decline, a number of individuals (72%) were unaware of their decline. These individuals had the same demographic profile and amyloid burden as the individuals with heightened awareness. Future research will investigate the mechanisms of self‐awareness and potential dysfunction of systems underlying the loss of awareness, as it can be essential for the preservation of individual autonomy.
Collaborative Approach for Asian Americans and Pacific Islanders Research and Education (CARE): A recruitment registry for Alzheimer’s disease and related dementias, aging and caregiver‐related research
Authors: Park Van Ta , Meyer Oanh L , Tsoh Janice Y , Vuong Quyen , Bang Joon , Hinton Ladson , Gallagher‐Thompson Dolores , Kanaya Alka , Gansky Stuart , Grill Joshua D ,   Collaborative Approach for Asian Americans and Pacific Islanders Research and Education (CARE)
Published: December 2021

AbstractBackgroundThere have been large investments in Alzheimer’s Disease and Related Dementias (AD/ADRD) research, but low AD/ADRD research participation from ethnically diverse individuals can hinder the facilitation and progress in the advancements of AD/ADRD prevention, treatment and care. The fastest growing racial group of older Americans at risk for AD/ADRD are Asian Americans and Pacific Islanders (AAPIs), but their research participation is limited. To address this disparity in AAPIs’ research participation, a recruitment registry, Collaborative Approach for AAPI Research and Education (CARE), was established to educate and engage AAPIs in AD/ADRD, aging, and caregiving related research in California, U.S.A. We will discuss an overview of CARE, completed/planned activities, and future vision.MethodsCARE created a recruitment registry of 10,000+ AAPIs. CARE has 25+ community/research partners, many of whom serve on CARE’s Community Advisory Board, who help to a) ensure that the outreach/conduct adheres to the principles of cultural humility/appropriateness; b) provide overall guidance/feedback about the registry’s development; c) provide input about research findings; and, f) provide perspectives/suggestions on community engagement. Focus groups (N=14) with AAPI cultural groups were conducted to identify best strategies for recruiting/retaining AAPIs’ CARE participation and establishing effective processes for connecting participants to studies. Based on focus group data, Discrete Choice Experiment (DCE) surveys will be conducted in early 2021 to examine AAPIs’ preferences on recruitment messages/strategies.ResultCARE’s theme is “Health Across the Lifespan”, which considers the intergenerational families and collectivist AAPI cultures. CARE’s full launch was on 10/15/20 and as of 01/09/21, 1,400 AAPIs have enrolled. CARE is promoting its use via CARE’s Brain Trust meetings and the National Institute on Aging. Several outreach materials have been developed including: AD/ADRD caregiver audio stories; animated video; flyers; community‐tailored presentations. CARE’s activities are available in five spoken languages (English, Mandarin, Cantonese, Korean, Vietnamese) and five written languages (English, Simplified Chinese, Traditional Chinese, Korean, Vietnamese).ConclusionCARE aims to meaningfully include AAPI in AD/ADRD/aging/caregiving‐related research; and, for CARE to serve as a national resource for ADRD prevention, caregiving, and treatment research. We envision CARE to become a national recruitment registry and expand to include additional AAPI languages.
Nutritional treatments for Alzheimer’s disease: A narrative review
Authors: Aschettino Liza A , Labyak Corinne A , Sealey‐Potts Claudia 
Published: December 2021

AbstractBackgroundKnowledge is limited about ways to treat, manage and slow the progression of Alzheimer’s Disease (AD). It is suspected that there are potential nutrition‐related components that may contribute to the pathology of AD. This includes nutrient deficiencies and/or dietary factors that may lead to comorbidities, increasing the risk for development. Thus, many nutrient‐specific, dietary and medical food treatments are continually being researched. Some studies even combine both nutrient and dietary interventions to treat AD. The purpose of this review is to explore and discuss the efficacy of several macro‐ and micronutrients, antioxidants, dietary therapies and combined components to treat or slow the progression of AD while providing valuable insight into the role that nutrition may play in the treatment of this disease.MethodsUsing PubMed, Google Scholar, EBSCOhost and Science Direct, databases were searched using pertinent keywords. A total of 33 research articles were included, primarily consisting randomized, double‐blind, placebo‐controlled clinical human research trials with the addition of few animal studies. Full‐text studies in detail were obtained, assessed with data extracted and summarized.ResultsOverall, it was determined that folate in conjunction with Donepezil, may improve cognitive function and inflammatory markers. Omega‐3 fatty acids (FA) with ɑ‐lipoic acid may reduce cognitive and functional decline rates. Adequate B‐vitamin status is needed to obtain the benefits of omega‐3 FAs. Vitamin D supplementation and medical food Souvenaid may be considered for cognitive benefits in patients with AD. Medium‐chain triglyceride (MCT) supplementation is not yet supported. Antioxidant treatment is not recommended as it may accelerate cognitive decline. DASH, Mediterranean Diet, MIND and ketogenic diet therapy may be considered as dietary treatments in AD patients. Nutrient supplementation requires more research to determine appropriate dosages.ConclusionAlzheimer’s disease remains a major health concern to the aging public. The anti‐inflammatory properties, antioxidative and neuroprotective effects of several nutrition‐related treatments have been shown to be beneficial in combating the progression of this disease. Patient individualization must be considered prior to treating. It is recommended that future studies determine appropriate dosage amounts to minimize adverse effects.
Cognitive change by anxiety and depressive symptoms in subjective cognitive decline: An implication to prevent Alzheimer's disease
Authors: Ahn Sangwoo 
Published: December 2021

AbstractBackgroundWhile anxiety and depressive symptoms frequently exist in subjective cognitive decline (SCD), how anxiety or depressive symptoms and their co‐existence differentially map onto particular cognitive domains is unknown among older adults with SCD. The purpose of this study was to evaluate longitudinal associations between baseline psychological symptoms (anxiety [A] and/or depressive [D] symptoms) and changes in global cognition, episodic memory, attention, language, and executive function.MethodData were from the National Alzheimer’s Coordinating Center for this longitudinal, observational study. A total of 1,401 older adults with SCD (ages: 74.0 ± 8.2 years) were assessed over 4.1 ± 2.4 years. Linear mixed‐effects regression models were used to evaluate longitudinal cognitive changes by baseline psychological symptoms among older adults with SCD. Reference was the group without any psychological symptoms (A–/D–).ResultThe presence of anxiety symptoms only (A+/D–) was not associated with any cognitive changes. Whereas, the presence of depressive symptoms only (A–/D+) was associated with a greater decline in episodic memory and executive function, cognitive domains that are affected early in Alzheimer’s disease. The presence of both anxiety and depressive symptoms (A+/D+) was associated with a greater decline in attention. No psychological symptoms predicted changes in global cognition and language.ConclusionBased on the finding that depressive symptoms predicted lower episodic memory and executive function, managing depressive symptoms may help protect against cognitive decline more typical of early Alzheimer’s disease among older adults with SCD.