bluuebunny/crossref_metadata_2025_split huggingface dataset:
Race, Gender, and Late‐life Productive Activities and Dementia in the Health, Aging, and Body Composition Study
Authors: Rooks Ronica Nicole 
Published: December 2022

AbstractBackgroundScholars have not addressed if productive activities, like working and volunteering, can mitigate Black vs. White racial disparities in incident dementia among older adults. We hypothesized: working vs. not, and volunteering vs. not, will reduce dementia risk and decrease racial disparities in the Health, Aging, and Body Composition (Health ABC) study.MethodHealth ABC is a 17‐year epidemiologic, prospective cohort study developed by the National Institute on Aging, including community‐dwelling, well‐functioning, Black (42%) and White, men and women (52%), aged 70‐79 in 1997‐98 (n = 3,069 at baseline). Full sample and gender‐stratified logistic regression model incident dementia risk among older adults with adjustments for socio‐demographics (e.g., race, age, education, family income, and site) and Apolipoprotein E genotype (APOE).ResultIn a full sample, unadjusted model, working vs. not (Yr1) was significantly related to 22% lower odds of dementia (OR = 0.78, p0.05) and volunteering vs. not (Yr1) was borderline‐significantly related to 16% lower odds of dementia (OR = 0.84, p = 0.059). In respective socio‐demographic and full model adjustments, working and volunteering were not significantly related to dementia. Black vs. White older adults had 31% (OR = 1.31, p0.05) and 29% (OR = 1.29, p0.05) higher odds of dementia in working and volunteering models with socio‐demographic adjustments, respectively. Race was not significant after APOE adjustment. Among older men, no significant relationships existed between dementia with work or race in any models. Similarly, no significant relationships existed between dementia with volunteering or race in any men’s models. Among older women, in the unadjusted model, working vs. not (Yr1) was significantly related to 30% lower odds of dementia (OR = 0.70, p0.05), but it was not significant in other models. Similarly, in an unadjusted model for women, volunteering vs. not (Yr1) was significantly related to 24% lower odds of dementia (OR = 0.76, p0.05), but it was not significant in other models. Black vs. White women had 35% (OR = 1.35, p0.05) and 32% (OR = 1.32, p = 0.052) higher odds of dementia in working and volunteering models with socio‐demographic adjustments, respectively, but race was not significant after APOE adjustment.ConclusionThis research provides insight about productive activities as possible contextual interventions to reduce racial disparities in incident dementia among older women.
Novel role of microRNA‐9 in stimulating mature BDNF and reducing cellular REST level in human fetal brain derived primary neuron culture.
Authors: Wang Ruizhi , Maloney Bryan , Counts Scott E. , Lahiri Debomoy K 
Published: December 2022

AbstractBackgroundAlzheimer's disease (AD) and Parkinson's disease are the most common neurodegenerative diseases. As of a 2021 report, the Alzheimer's Association estimates that the number of Americans with AD could be as many as 6.2 million. However, how the patho‐biochemical changes are regulated at the cellular level is still largely unknown.Our goal is to devise ways to arrest and/or reverse neurodegeneration. Our objective is to determine the molecular pathway in promoting neuronal survival. MicroRNA (miRNA), a group of small non‐coding RNAs, regulates multiple biological and pathological processes by binding to target mRNAs, the disruption of which could contribute to AD pathogenesis. Our hypothesis is to determine the role of a specific miRNA that can promote neural survival and neuronal gene expression. Our aim is two‐fold. First is to increase levels of BDNF, which is a neurotrophic factor. This protein promotes the survival of nerve cells by playing a role in the growth, maturation (differentiation), and maintenance of these cells. Second goal is to de‐repress neuronal gene expression by reducing REST protein. Can these aims be achieved by using one micro‐RNA? Here we show miR‐9's ability to exert both these actions in a beneficial way.MethodHuman primary cortical neurons, astrocytes and differentiated neuroblastoma were transfected with miR‐9. Cells lysate and culture media were harvested. Western blotting and ELISA were performed to determine target protein levels. Well‐defined human brain autopsy samples from AD patients and healthy elders were assayed for mature BDNF.ResultTreatment with synthetic miR‐9 mimics stimulated secretion of mature BDNF in human primary cortical ReN cells. Under the same condition, miR‐9 treatment decreased levels of nuclear Repressor Element 1‐Silencing Transcription factor (REST) protein. Treatment with antisense to miR‐9 (antagomiR) reversed the effect of miR‐9 on mBDNF and REST levels.ConclusionMiR‐9 increased mBDNF while reducing REST. REST is known to silence neuronal genes and BDNF to promote neural survival. Due to the twin impacts: increasing BDNF and decreasing REST, miR‐9 plays a vital role in neuron’s vitality and health. The further experiment would determine whether miR‐9 treatment would protect neuronal against insults that lead to neurodegeneration.
Olfactory dysfunction but not COVID‐19 severity predicts severity of cognitive sequelae following SARS‐CoV‐2 infection in Amerindian older adults
Authors: Gonzalez‐Aleman Gabriela , Zamponi Hernan P. , Juarez‐Aguaysol Leonardo , Kukoc Gabriela , Dominguez Maria Eugenia , Pini Belén , Padilla Eduardo G , Calvó Maria , Molina‐Rangeon Silvia Beatriz , Guerrero Gonzalo , Figueredo‐Aguiar Mariana , Fumagalli Emiliano , Vaca Fabiana , Yécora Agustín , Brugha Traolach S , Seshadri Sudha , Snyder Heather M. , de Erausquin Gabriel A. ,   Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS‐CoV‐2
Published: December 2022

AbstractBackgroundCOVID‐19 has affected more than 380 million people. Infections may result in long term sequelae, including neuropsychiatric symptoms. In older adults COVID‐19 sequelae resemble early Alzheimer’s disease, and may share risk factors and blood biomarkers with it. The Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS‐CoV‐2 infection (CNS SC2) established harmonized definitions, ascertainment and assessment methodologies to evaluate and longitudinally follow up cohorts of older adults with exposure to COVID‐19. We present one year data in a prospective cohort from Argentina.MethodParticipants (n = 766) are older adults (≥60 years) recruited from the provincial health registry containing all SARS‐CoV‐2 testing data. We randomly invite older adults stratified by PCR COVID‐19 testing status regardless of symptom severity, between 3 and 6 months after recovery. Assessment includes interview with the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and Clinical Dementia Rating scale (CDR); neurocognitive assessment; emotional reactivity scale; and neurological assessment including semiquantitative olfactory function test, motor function, coordination and gait.ResultWe assessed 88.4% infected participants and 11.6 % controls. Education is 10.36 ± 5.6 years and age is 66.9 ± 6.14 years. Level of care during COVID‐19 is described in Figure 1. Normalized cognitive Z‐scores categorize the cohort in 3 groups with decreased performance compared to normal cognition: memory only impairment (Single‐domain,11.7%); impairment in attention+executive function without memory impairment (Two‐domain, 8.3%); and multiple domain impairment (Multiple domain,11.6%). Logistic regression showed that severity of anosmia, but not clinical status, significantly predicts cognitive impairment. No controls had olfactory dysfunction. Cognitive impairment is defined as Z‐scores below (‐ 2) (Table 1). Clinical assessment with SCAN revealed functional memory impairment in two thirds of infected patients (CDR ≥ 1), which was severe in half of them. Phone‐based follow up at 1 year revealed high adherence (4 participants declined). Five were deceased at follow up. Rates of re‐infection (between 10 and 23%) were not affected by the vaccination schedule (Table 2).ConclusionThe longitudinal cohort had very high adherence. Persistent cognitive and functional impairment after SARS‐CoV‐2 infection is predicted by persistent anosmia but not by the severity of the initial COVID‐19 disease.
Associations between local area deprivation and physical activity in cognitively impaired people: an accelerometry study
Authors: Ardle Ríona Mc , Hamilton Calum , Din Silvia Del , Kingston Andrew , Robinson Louise , Galna Brook , Thomas Alan J , Rochester Lynn 
Published: December 2022

AbstractBackgroundEmpowering people with cognitive impairment (PwCI) to maintain physical activity (PA) supports functional independence. PwCI participate in less PA than recommended; disease‐specific factors (e.g. cognitive changes) do not sufficiently explain this. In older adults, most habitual PA takes place in the home or local neighbourhoods. Targeting PA in both the home and local community may be more impactful than creating external opportunities (e.g. exercise classes).Regular participation in PA requires time, money, security, and access. Area deprivation may contribute to inequalities in PA participation through environmental factors; less deprived areas may have safer walkable routes and more immediate socialisation opportunities which support PA. Understanding the complex relationship between local area deprivation and PA may support personalised care for PwCI. We aimed to explore associations between local area deprivation in the North East of England and PA in PwCI and cognitively‐intact older adults (controls).MethodWe recruited 82 PwCI (mild cognitive impairment, dementia) and 26 controls. Daily step count was measured using an accelerometer worn on the lower back continuously for seven days. We derived mean daily step counts for each individual day. Individuals’ neighbourhoods were linked to UK government area deprivation statistics. Hierarchical Bayesian models assessed the association between area deprivation and daily step count in PwD and healthy older adults.ResultPreliminary results indicated that greater area deprivation is associated with lower daily steps for cognitively‐healthy older adults (12,308 (8,302‐19,111) steps/day for controls in least deprived areas, vs 9,349 (5,178‐17,444) steps/day in most deprived areas), but not for PwCI (9,018 (7,042‐11,565) steps/day for PwCI in least deprived areas vs 9,124 (6,553‐12,435) steps/day in most deprived areas), who had consistently low step counts across neighbourhoods (Figure 1).ConclusionCognitive impairment may impose a barrier to maintenance of habitual PA which supersedes the positive or negative influences of area deprivation on PA in cognitively healthy older adults. Findings are limited by lack of regional diversity and statistical power; further research should examine area deprivation across the whole of the UK to ensure accurate representation of area deprivation. PA interventions should consider multiple socio‐ecological factors, including personal, organisational, environmental and policy‐related components.
Cognitive impairment in COVID‐19 Survivors: Analysis and Extensions on Population Studies in Greece
Authors: Vavougios George D. , Stavrou Vasileios , Mysiris Dimitrios , Boutlas Stylianos , Papayianni Eirini , Koromboki Eleni , Mavridis Theodore , Astara Kyriaki , Biagi Nicolo , D'Avossa Giovanni , Katshu Mohammad Zia Ul Haq , Artemiadis Artemios , Hadjigeorgiou Georgios M. , Xiromerisiou Georgia , Zarogiannis Sotirios G , Daniil Zoe , Gourgoulianis Konstantinos 
Published: December 2022

AbstractBackgroundThe aim of our study was to investigate the prevalence and associations of cognitive impairment in COVID‐19 survivors in the post‐acute setting.MethodOur study is conducted in three post‐COVID‐19 outpatient clinics in tertiary hospitals in Greece. Eligible subjects included previously hospitalized COVID‐19 survivors with mild to moderate disease, returning for follow‐up at least two months post‐discharge. Exclusion criteria included intensive care unit admission, intubation, a history of neurodegenerative disease and other significant comorbidities. Study measurements included demographics, clinical evaluation, medical, family history, anthropometrics, 6‐minute walk test (6MWT), 30 seconds sit‐to‐stand (30STS), handgrip strength, spirometry, Pittsburgh Sleep Quality Index (PSQI), the Montreal Cognitive Assessment (MoCA), reactive oxygen metabolites (dROMs) and plasma antioxidant capacity (PAT). Cognitive impairment was considered on MoCA ≤24.Result142 COVID‐19 survivors were included in the study (110 Male, 32 Female; Mean age of 56.16±10.92). A total of 47.2% presented with cognitive decline (CD) as indicated by a MoCA score ≤24. Cognitive decline prevalence by SARS‐CoV‐2 variant of concern (VOC) was 39.5%, 50% and 62.5% for Alpha, Beta and Delta, correspondingly. A binary logistic regression model controlling for age, gender and VOC indicated that the diffusing capacity for carbon monoxide (DLCO) was independently associated with MoCA ≤24 (p = 0.014, OR = 0.669, 95%CI: 0.484‐0.923). Compared to severe untreated OSAS (n = 28), distinct domains but similar prevalence of cognitive impairment was noted.ConclusionDiffusion capacity abnormalities for carbon monoxide in COVID‐19 survivors as noted in other studies, may be implicated in the development of cognitive impairment.
Enabling implementation of Blood based biomarkers in our healthcare systems
Authors: Teunissen Charlotte E. , Hansson Oskar , van Harten Argonde C. 
Published: December 2022

AbstractBackgroundThe novel blood based biomarkers have shown such promising results, and these developments coincide with the approval of the first AD drugs. This needs to consider clinical implementation. Are we there yet? What steps need to be undertaken to make that happen? Can we implement these biomarkers, as single markers or as combinations in secondary care, primary care, or in‐between to avoid health care system overload?MethodThis presentation will give an overview of steps be taken and currently ongoing.ResultI will address clinical studies in different settings, technical developments on the level of assays and standardization of lab‐protocols and regulatory approval. In addition, i will discuss possible context of use and definition of appropriate use recommendations by the Alzheimer Association working group.ConclusionThe exact context and appropriate use of BBB are to be defined in the next few years.
A methodology for normalizing fluid biomarker concentrations across reagent lots
Authors: Henson Rachel L. , Volluz Katherine , Saef Benjamin A. , Sutphen Courtney L. , Herries Elizabeth M. , Morris John C. , Fagan Anne M. , Xiong Chengjie , Schindler Suzanne E. 
Published: December 2022

AbstractBackgroundLongitudinal studies of cerebrospinal fluid (CSF) and plasma biomarkers typically require the use of different assay reagent lots over time. Measured biomarker concentrations may drift from lot to lot, adding variability that may bias estimates and decrease the statistical power of biomarker analyses. Including lot as a covariate in models may not adequately adjust for lot effects, particularly if cohort characteristics change over time.MethodCSF and plasma samples were collected from participants enrolled in studies of memory and aging. CSF Aβ40, Aβ42, total tau (t‐tau), and phosphotau‐181 (p‐tau181) were measured using a fully automated assay platform (LUMIPULSE, Fujirebio). CSF and plasma NfL were measured using a plate‐based ELISA (UMAN Diagnostics) and Simoa‐HDX assays (Quanterix), respectively. “Bridging” samples were measured using an initial lot of reagents and were subsequently re‐analyzed using a different lot of reagents. Biomarker concentrations were transformed with the natural logarithm and compared via linear regression. If the slope (tested against 1) or intercept (tested against 0) were significantly different, the equation for the initial values as a function of the subsequent values was used to normalize the subsequent values, putting all values on one common scale.ResultMeasured concentrations for all analytes were highly correlated between lots. Slopes and/or intercepts for a linear regression of the log(initial value) as a function of the log(subsequent value) were significant for CSF Aβ40 (intercept: p<0.0001), t‐tau (slope: p<0.0001), p‐tau181 (intercept: p<0.0001), and plasma NfL (intercept: p=0.001), but were not significant for CSF Aβ42 or NfL.ConclusionThere is significant systematic variation in measured biomarker concentrations by reagent lot, even when using fully‐automated assay platforms. Running samples in larger batches with fewer lots is preferable to reduce lot effects. Using biomarker data unadjusted for lot effects or adjusted using simple correction factors may be problematic. Including two or three certified reference standards may not adequately control for these differences; measuring more samples across a wide range of values is likely necessary. Normalization of measured values between reagent lots may decrease variability in longitudinal data collected over several years, increase statistical power and improve the validity of biomarker analyses.
Association between PTSD and Cognitive Performance: A Longitudinal Twins Study
Authors: Kulshreshtha Ambar , Shah Amit , Ko Yi‐An , Goldberg Jack , Smith Nicholas , Jajeh Nour , Ahmed Hashir , Marof Biwar , Murrah Nancy , Shallenberger Lucy , Driggers Emily , Bremner Douglas , Vaccarino Viola 
Published: December 2022

AbstractBackgroundPosttraumatic Stress Disorder (PTSD) is a chronic psychiatric condition that develops after exposure to life‐threatening events. The negative impact of PTSD on a person’s emotions and behavior can have long‐term deleterious effects on cognitive performance. The association between PTSD and cognition however can be confounded by unmeasured factors such as shared genetic and environmental factors. Twin studies allow us to explore this potential causal pathway by controlling for genetic and familial confounding.MethodsWe examined 77 male monozygotic and 47 dizygotic twin pairs from the Vietnam Era Twin Registry in two examinations approximately 12 years apart. At both visits, we obtained information regarding demographic data, medical history, diagnosis of PTSD and cognitive tests. Memory and learning were measured by Trail making tests, Wechsler Memory Scale (Immediate and Delayed Memory tests and Visual Reproductive Test). Linear mixed‐effect regression models were used to examine the association between PTSD and cognitive tests accounting for twin pairing. Analysis was performed by treating twins as individuals and considering within twin pair differences (among twin pairs discordant for PTSD).ResultsThe mean age was 55 years (SD 3.0) at baseline, 96% were White, and 60% monozygotic twins. Lifetime history of PTSD was not associated with cognitive measures at baseline. At follow‐up, the mean age was 67.9 years (SD 2.5). In twins considered as individuals lifetime history of PTSD was associated with worse performance on Trails A (β = 4.9, 95% CI 8.6, 1.3, p‐value = 0.008) and Trails B (β = 14.6, 95% CI 26.8, 2.4, p‐value = 0.019). After adjusting for demographics, cardiovascular and behavioral risk factors, these associations persisted (Trails A, β = 5.4, 95% CI 9.4, 1.4, p‐value = 0.009; Trails B, β = 14.1, 95% CI 26.9, 1.2, p‐value = 0.032). The within‐pair estimates were similar to individual estimates. There was no association with Wechsler immediate or delayed story recall or Visual Reproductive Test. In stratified analyses, the results were similar by zygosity.ConclusionsLifetime history of PTSD is associated with poor cognitive performance, primarily in the executive function domain, which manifests at older age. This association is not confounded by shared genetic and other familial factors.
Antecedents of episodic memory in the oldest‐old: a population‐based NONAGINTA study with 45‐years of follow‐up
Authors: Vuoksimaa Eero , Varjonen Anni , Schwarz Claudia , Aaltonen Sari , Iso‐Markku Paula , Palviainen Teemu , Urjansson Mia , Rinne Juha O. , Kaprio Jaakko 
Published: December 2022

AbstractBackgroundWe have established NONAGINTA – Memory and Health in 90‐year‐olds –study in a population‐based sample with 45 years of follow‐up. Our study is aimed to understand both, the antecedents of cognitive impairment and successful cognitive aging in the oldest‐old (90 years or older).MethodParticipants were nonagenarians from a population‐based longitudinal older Finnish Twin Cohort study with baseline questionnaire in 1975. Ongoing 90‐year‐old data collection included postal questionnaire and telephone administered cognitive testing. Episodic memory (EM) was measured with total words recalled in three trials of 10‐word list. Predictors of EM included cognitive, health‐related, and psychological factors. Self‐reported educational attainment, body mass index (BMI), physical activity (METhours/day), life satisfaction and neuroticism were measured in middle age (N = 55, age M = 46.2, SD = 1.7 years) and in old age (N = 59‐67, age M = 91.3, SD = 1.9 years). Semantic verbal fluency (number of animals in 1‐minute) and depressive symptoms (Center for Epidemiological Studies – Depression (CES‐D)) were measured only in old age. We used individual level linear regression models with age and sex as covariates and adjusted for family structure.ResultTo date, 67 individuals have cognitive data. On average, women (N = 36, M = 11.97, SD = 4.70) had better EM than men (N = 31, M = 11.10, SD = 4.74), but this difference was not statistically significant (p = 0.49). Better verbal fluency was significantly related to better EM (r = 0.34, p<0.001). Compared to those with 6 years of education, those with 7‐11 years and those with 12 or more years of education had significantly better EM: 4.03 (95%CI: 1.27‐6.80) (p = 0.005) and 5.75 (95%CI: 3.75‐7.45) (p<0.001) words more, respectively. Mean CES‐D was 12.3 (SD = 8.7) and 16% scored above the cut‐off for clinically significant depressive symptoms, however, depressive symptoms were not related to EM (p = 0.15). Middle age or old age BMI, physical activity, life satisfaction or neuroticism were not significantly related to EM (p’s >0.32).ConclusionOur preliminary results suggest that cognitive, but not midlife or old age physical or psychological health‐related factors, are associated with episodic memory performance in nonagenarians. Good episodic memory goes hand in hand with good semantic fluency and cognitive benefits of early life educational attainment are still evident in nonagenarians.