bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating Dementia Prevalence in Rural South Africa with Remote Consensus Diagnoses and Algorithmic Modeling
Authors: Farrell Meagan T. , Bassil Darina T. , Guo Muqi , Glymour M. Maria , Langa Kenneth M , Wagner Ryan G. , Tollman Stephen , Brickman Adam M. , Berkman Lisa F. 
Published: December 2023

AbstractBackgroundThere is limited population‐based data on dementia epidemiology from sub‐Saharan Africa, precluding deeper understanding of global dementia burden. The Health and Aging in Africa Study (HAALSI) is designed to address this evidence gap through collection of high‐quality longitudinal data on cognition, health, and everyday function in older Black South Africans. Consensus‐based diagnoses have become a gold standard for ascertaining dementia status in research settings, however, this approach is resource‐intensive and difficult to implement at scale. Here, we utilize algorithmic methods to estimate dementia prevalence and risk factors in a population‐representative cohort in rural South Africa.MethodWe utilize data from 4,176 respondents who completed assessments of health, demographics, socioeconomic conditions, cognition, and activities of daily living (ADLs) as part of HAALSI Wave 2 (2018‐2019). An enriched sub‐cohort (n = 635) later completed clinical and neuropsychological assessments and received diagnostic classification of normal cognition, mild cognitive impairment, or dementia by an expert panel. Logistic regression was used to predict dementia status in the enriched sub‐cohort using predictor variables drawn from the parent HAALSI wave. Probability cut points were selected to achieve overall prediction accuracy of at least 80%, prioritizing specificity over sensitivity. Algorithm performance was evaluated across education‐level and age subgroups. Coefficients from best‐performing algorithms were applied to the full cohort to obtain dementia probability scores and calculate dementia prevalence.ResultWhen the enriched sub‐sample was reweighted to reflect the full HAALSI population, the estimated prevalence of dementia was 18%. Three models of increasing complexity were tested and showed good discrimination between dementia and non‐dementia (ROC = 0.76‐0.82). Models were generally more sensitive but less accurate in older and less educated respondents. Algorithmic estimates of dementia prevalence in the HAALSI population ranged from 15‐19%. Higher risk for dementia was associated with older age, lower education and wealth, hypertension, living alone, poor self‐rated health, widowhood, and immigration status.ConclusionThis is one of the first studies to utilize algorithmic methods to describe dementia prevalence in South Africa, producing higher estimates than most previous reports. These efforts may provide a foundation to expand understanding of dementia epidemiology in a region of the world currently experience rapid population aging.
The Feasibility of Digital Testing using a Smartphone Application for Precision Brain Health Monitoring in the Framingham Heart Study
Authors: Sunderaraman Preeti , Karjadi Cody , Devine Sherral A. , Hathaway Lindsay , Goyal Kriti , Monteverde Jose R , Ang Ting Fang Alvin , Gurnani Ashita S , Mez Jesse B. , Au Rhoda 
Published: December 2023

AbstractBackgroundEarly detection of cognitive decline is critical to identify effective treatments for Alzheimer’s disease and related dementias. The inherent heterogeneity of behaviors associated with brain health may obscure the signals derived from a typical neuropsychological evaluation, partly because of the limited frequency of assessment with which it can be conducted. This may lead to inaccurate or poor detection sensitivity. Digital health technology using smartphone applications enables frequent assessment and, thereby, more precise monitoring of brain health. The current study sought to examine the feasibility of using smartphone application‐based tasks in community‐based participants from the Framingham Heart Study (FHS).MethodThe smartphone application consists of three blocks of assessments, lasting approximately 15‐20 minutes (Figure 1). Block 1: Participants answer questions to ensure that they can see the stimuli and hear the instructions adequately. Block 2: Participants complete a series of cognitive tasks and respond to open‐ended questions which are voice recorded. Block 3: To ensure that performance is not influenced by external factors, participants respond to questions, for example, about their experiences with using the smartphone application.ResultTo date, 318 FHS participants have been enrolled into the study. Of these, as of 12/09/2022, 168 participants’ first assessment period has been completed within the two week period after being enrolled in the study. Of the 168 participants, a large majority (81%; n = 136) completed all the tasks, while the remaining 32 completed partial assessment. Table 1 reveals that the overall percentage of participants who have been enrolled in the study and the percentage of those who completed their first assessment are highly similar.ConclusionFindings reveal that older adults from a large, community‐based study are able to successfully download and complete the first set of tasks using their smartphone application. As data collection is ongoing, the number of older adults recruited into the study is expected to increase exponentially. These results indicate that it is feasible to monitor brain health on an on‐going basis using self‐administered smartphone applications, potentially creating an effective, lower cost, and scalable approach to detect significant changes in cognitive functions earlier and more accurately in the preclinical neurodegenerative process.
Digital Cognitive Phenotyping using a Smartphone Application Among Community‐Dwelling Older Malaysians in the Transforming Cognitive Frailty in Later‐Life Self‐Sufficiency (AGELESS) Study
Authors: Tan Maw Pin , Rosli Roshaslina , Kumanan Sobiitraa , Xu Xiang‐Jiang , Low Spencer , Devine Sherral A. , Kim Nicole , Hermanto Michael , Au Rhoda 
Published: December 2023

AbstractBackgroundThe WHO’s dementia research blueprint highlighted assessment tools of cognition and function development as a strategic goal with specific need for validated tools in lower‐ to middle‐income countries (LMIC). The limited availability of such tools in LMICs is attributed to the population diversity. Malaysia is a multi‐ethnic, multi‐cultural, and multi‐religious LMIC within Southeast Asia. Challenges include cultural and educational bias and requirement for multiple translations for written tools. This study, therefore, aimed to develop and evaluate a digital tool using a smartphone application within an existing ageing cohort in Malaysia.MethodThe Transforming Cognitive Frailty into Later‐Life Self‐Sufficiency (AGELESS) study combined three pre‐existing longitudinal studies of ageing from 2013, involving individuals aged 55y recruited through electoral rolls and sampling frames. Individuals attending AGELESS health checks were invited to download a smartphone application digital protocol developed as part of a collaboration established through the Davos Alzheimer’s Collaborative. Participants were assisted in registration and assessment completion (Figure 1).ResultRecruitment commenced in October 2022 through four mass screening activities each involving 100 participants. 141 were recruited into a pilot to test feasibility. Twenty‐three of the 141 (16.3%) completed all 10 tasks delivered in‐person (5 tasks) and remotely (5 tasks). The protocol was modified so two tasks were completed in‐person and an additional eleven tasks were completed remotely. The fourth screening recruited 53 participants of whom 22 (41.5%) completed all assessments. The basic characteristics of the participants recruited are summarized in Table 1. Issues identified were shared with the Boston University team following each session. Initially, registering or issues with starting tasks occurred with Android smartphones. Other difficulties included environmental noise and difficulties with instructions provided.ConclusionThe recruitment and initial cognitive assessment using a smartphone application of older Malaysians appear feasible, but adaptions are required to facilitate this process. Changes in the apps Android software and protocol adjustments enhanced completion rates by 150%. Future developments will focus on processes to ensure completion of the assessment not just at baseline but also at regular follow‐up intervals.
Cognitive, functional, and neuropsychiatric correlates of regional tau in autopsy‐confirmed chronic traumatic encephalopathy
Authors: Faheem Farwa , Alosco Michael L , White Micaela , Bell Carter , Tripodis Yorghos , Yhang Eukyung , Baucom Zachary H. , Martin Brett M , Palmisano Joseph N , Goldstein Lee E , Katz Douglas I , Dwyer Brigid , Daneshvar Daniel H , Nowinski Christopher , Cantu Robert , Kowall Neil W , Stern Robert A , Alvarez Victor E. , Huber Bertrand R. , Stein Thor D. , McKee Ann C. , Mez Jesse B. 
Published: December 2023

AbstractBackgroundChronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by hyperphosphorylated tau (p‐tau) accumulation. The clinical features of CTE are heterogeneous and their association with CTE are unclear. We investigated the association of CTE p‐tau pathology density and location with cognitive and neuropsychiatric symptoms in brain donors with autopsy‐confirmed CTE.Method364 brain donors with autopsy confirmed CTE were evaluated to determine the density of p‐tau pathology in 10 cortical and subcortical regions using semi‐quantitative rating scales (score range: 0‐3). We summed ratings across 10 regions to form a global composite of p‐tau severity (score range:0‐30). Informants completed standardized scales of cognition (Cognitive Difficulties Scale, CDS; BRIEF‐A Metacognition Index, MI), activities of daily living (Functional Activities Questionnaire), neurobehavioral dysregulation (BRIEF‐A Behavioral Regulation Index, BRI; Barratt Impulsiveness Scale, BIS‐11), aggression (Brown‐Goodwin Aggression Scale), depression (Geriatric Depression Scale‐15, GDS‐15), and apathy (Apathy Evaluation Scale, AES). Multivariable linear regression analyses examined the association between global p‐tau severity and p‐tau severity in each region with each of the clinical scales, controlling for age at death, racial identity, education level, hypertension history, obstructive sleep apnea history, and substance use treatment history.ResultThe sample predominantly consisted of football players (333; 91.2%) and 140 (38.5%) had low CTE and 224 (61.5%) had high CTE (Table 1). Figures 1‐2 are Forrest plots of the estimated effects between regional p‐tau and clinical scales. Global p‐tau severity was associated with cognitive and functional scales: MI (beta = 0.46, 95% CI = 0.11‐0.81), CDS (beta = 1.08, 95% CI = 0.31‐1.85), and FAQ (beta = 0.32, 95% CI = 0.16‐0.49). After false‐discovery rate (FDR) correction, p‐tau in the frontal, inferior parietal, superior temporal cortex, and the amygdala was significantly associated with the CDS and FAQ; frontal and inferior parietal cortex and amygdala p‐tau also was significantly associated with MI. Frontal cortex p‐tau was significantly associated with the BRI. There were no significant associations with the other neuropsychiatric scales after FDR correction. Entorhinal cortex, hippocampus, and locus coeruleus showed no significant associations.ConclusionAccumulation of p‐tau aggregates, especially in the frontal cortex, are a driver of cognitive, function, and certain neurobehavioral symptoms in CTE.
Florbetapir amyloid PET in cognitively impaired former professional and college American football players
Authors: Stern Robert A , Trujillo‐Rodriguez Diana , Tripodis Yorghos , Pulukuri Surya V , Alosco Michael L , Adler Charles , Balcer Laura , Bernick Charles B. , Baucom Zachary H. , Marek Kenneth , McClean Michael D , Johnson Keith A. , McKee Ann C. , Stein Thor D. , Mez Jesse B. , Palmisano Joseph N , Cummings Jeffrey L. , Shenton Martha E , Reiman Eric M. ,   the DIAGNOSE CTE Research Project Investigators
Published: December 2023

AbstractBackgroundRepetitive head impact (RHI) exposure from the routine play of American football increases the risk of later‐life cognitive impairment and dementia from the neurodegenerative disease, chronic traumatic encephalopathy (CTE). Although neuropathological studies of CTE have found comorbid neurodegenerative and other pathologies, neuritic Aβ plaques are infrequent, particularly in early stages. However, amyloid PET imaging has not been fully characterized in cognitively impaired former American football players.MethodIn this cross‐sectional, observational cohort study from the DIAGNOSE CTE Research Project, florbetapir PET mean cortical standard uptake value ratios (SUVR) and positivity (defined by average SUVR >1.10, indicative of moderate‐to‐frequent neuritic Aβ plaques), were analyzed in 119 former professional (PRO) National Football League players, 60 former college football players (COL), and 58 men unexposed (UE) to RHI who were cognitively asymptomatic. Former players were categorized into one of four diagnostic groups: cognitively normal (CN), subjective memory complaints (SMC), mild cognitive impairment (MCI), and dementia (DEM). All participants were 45‐74 yo. Multivariable linear and logistic regressions were conducted, with race, education, age, and APOE4 genotype included as covariates. A priori power calculations demonstrated adequate power to detect significant findingsResultNo differences between the three exposure groups in average florbetapir SUVR or proportion of elevated florbetapir uptake were found. Pairwise group comparisons resulted in no differences in average SUVR between PRO and COL (‐0.01, 95% CI [‐0.033, 0.025], p = 0.95), PRO and UE (0.02, 95% CI [‐0.010, 0.029], p = 0.41), and COL and UE (0.02, 95% CI [0.0004, 0.039], p = 0.36). Analysis of covariance resulted in no differences among diagnostic groups (F = 0.94, p = 0.43). Neither years of playing football nor measures of cognition and daily functioning showed significant associations with florbetapir SUVR.ConclusionFormer professional and college American football players with cognitive impairment and dementia did not have elevated florbetapir amyloid PET compared to a group of men without RHI exposure. Their rates of florbetapir positivity in the football players were lower than expected for a group of men this age. These findings suggest that cognitive impairment in former elite football players may not be due to Alzheimer’s disease pathology.
Sleep changes during the COVID‐19 lockdown contribute to cerebrospinal fluid phosphorylated tau and neurofilament light increases independent of β‐amyloid
Authors: Akinci Muge , Palpatzis Eleni , Sánchez‐Benavides Gonzalo , Argiris Georgette , González Escalante Armand , Deulofeu Carme , Kollmorgen Gwendlyn , Carboni Margherita , Blennow Kaj , Zetterberg Henrik , Fauria Karine , Navarro Arcadi , Gispert Juan Domingo , Suarez‐Calvet Marc , Grau‐Rivera Oriol , Arenaza‐Urquijo Eider M 
Published: December 2023

AbstractBackgroundPrevious studies reported sleep alterations during the COVID‐19 lockdown. Disrupted sleep may influence and promote Alzheimer’s disease (AD) pathologies. In cognitively unimpaired adults at AD risk, we investigated the association of sleep duration changes during lockdown in relation to pre‐ and post‐lockdown AD‐related CSF biomarkers.MethodWe included 118 adults (52‐71 years, 61.9% women) with self‐reported data on sleep duration before and during the lockdown (May–July 2020). Participants completed a questionnaire on hours of sleep per night (<7h vs. ≥7h) at both timepoints and were classified into three groups: “No change (<7h or ≥7h before and during lockdown)”, “Increased (from <7h to ≥7h during lockdown)” or “Decreased (from ≥7h to <7h during lockdown)”. All had CSF biomarkers measured with Roche NeuroToolKit or Elecsys® immunoassays before (pre‐lockdown) and after (post‐lockdown) completing the questionnaire (average time lapse: 3.4±0.4 years). During the lockdown, 117 (99.1%) participants completed an anxiety/depression assessment (Hospital Anxiety and Depression Scale). ANCOVA models adjusted by pre‐lockdown biomarker values were run to investigate differences among the three groups in post‐lockdown AD pathology (Aβ42/40 and p‐tau), neuroinflammation (sTREM2), and neuronal injury (NfL) biomarkers. Covariates included age, sex, education (years), APOE‐ε4 status, anxiety/depression levels, and time variability between the biomarker assessments. We then performed sensitivity analyses to adjust the models by pre‐lockdown Aβ42/40 levels and sleep quality (Pittsburgh Sleep Quality Index, n = 90).ResultNinety‐four participants (79.7%) reported “No change (stable)”, 10 (8.5%) “Increased” and 14 (11.5%) “Decreased” sleep duration during lockdown. Irrespective of pre‐lockdown p‐tau and NfL levels, participants transitioning to decreased sleep showed higher p‐tau and NfL post‐lockdown compared with the increased sleep group. Further, those with stable sleep duration showed higher post‐lockdown p‐tau and NfL compared with the increased group (Table 1). Results were independent of pre‐lockdown Aβ42/40 levels (Table 2) and sleep quality (Table 3).ConclusionTransitioning to fewer hours of sleep during the lockdown was associated with greater tau pathology and neuronal injury levels post‐lockdown. Consequently, alterations in sleep duration during the pandemic may hasten pathological processes downstream amyloid pathology. These findings suggest that pandemic‐induced lifestyle changes may increase AD prevalence in the long term.
Gut microbiome moderates the association between metabolic syndrome and the cerebrospinal fluid concentration of YKL‐40 in a cognitively unimpaired cohort
Authors: Peter Darby , Heston Margo B. , Ennis Gilda E. , Knight Rob , Kaddurah‐Daouk Rima F. , Johnson Sterling C , Asthana Sanjay , Carlsson Cynthia M. , Chin Nathaniel A. , Kollmorgen Gwendlyn , Carboni Margherita , Blennow Kaj , Zetterberg Henrik , Ulland Tyler K. , Rey Federico E. , Bendlin Barbara B 
Published: December 2023

AbstractBackgroundType 2 diabetes (T2D) and metabolic syndrome (MetS) are associated with increased risk of dementia, as well as altered gut microbiome composition (Ott et al., 1999; Ley et al., 2006). However, the extent to which gut microbiome alterations moderate brain pathology in these conditions remains unclear. Here, we examined the extent to which MetS associates with altered cerebrospinal fluid (CSF) biomarkers of Alzheimer’s Disease (AD), glial activation, and neurodegeneration, and whether MetS interacts with gut microbiome composition to impact brain pathology.MethodCognitively unimpaired adults (n = 88, Wisconsin Registry for Alzheimer’s Prevention and Wisconsin Alzheimer’s Disease Research Center; Table 1) underwent fasting blood collection and lumbar puncture, and provided a stool sample. Twenty‐six percent (n = 23) of participants met MetS criteria. Fecal microbiota composition was characterized using 16S rRNA sequencing. QIIME2 was used to denoise and classify features, followed by Phyloseq to filter rare taxa, agglomerate taxa at the phylum rank, and compute relative abundances. Analyses centered on Firmicutes:Bacteroidetes, given its previously observed alterations in T2D and MetS (Stadlbauer et al., 2015). CSF biomarkers were quantified using a robust prototype assay as part of the Roche NeuroToolKit research platform. Multiple regression models were used to determine associations between MetS and CSF biomarkers in addition to Firmicutes:Bacteroidetes, and any MetS by Firmicutes:Bacteroidetes effects on CSF biomarkers. Results are reported as significant when p < 0.05, uncorrected.ResultA significant negative association between MetS and CSF YKL‐40 was observed (Figs. 1a, 1b), but no significant association between MetS and Firmicutes:Bacteroidetes (Fig 1c), nor associations with other CSF biomarkers (Table 2). MetS showed a significant interaction with Firmicutes:Bacteroidetes on YKL‐40 (Fig. 1d), as control participants with a higher ratio showed increased YKL‐40.ConclusionIn a cognitively unimpaired cohort, MetS was associated with lower CSF YKL‐40 (a marker of astrocytic activation) and moderated the relationship between Firmicutes:Bacteroidetes and CSF YKL‐40. While the direction of the findings was unexpected, T2D is associated with inhibition of astrocyte activation (Jing et al., 2013), and astroglial function is modulated by gut microbiota. Follow‐up studies are currently testing how gut microbiome modulates neuroimmune function in the context of AD.
Acceptability of a Balance Rehabilitation Program Delivered via a Tele‐Remote Platform Among a Thai MCI Cohort
Authors: Utoomprurkporn Nattawan , Limkitisupasin Patcharaorn , Tundiew Noppawan , Magauina Gulnaz , Tunvirachaisakul Chawit , Tangwongchai Sookjaroen 
Published: December 2023

AbstractBackgroundPatients with mild cognitive impairment can have a decline in overall motor function and balance which are more severe than the normal older adult population. Balance rehabilitation should be offered consistently to maximize its effect. Telerehabilitation programs are emerging as a possible solution for customized balance exercises for older adults at home.However, the acceptability of such programs among cognitive decline cohorts should be explored. Modification may be needed to tailor to the need of this population. We conducted a public involvement and engagement session with the MCI cohort according to the user‐centred design approach to gather feedback from the cohort to better improve the platform to suit the cognitive decline of older adults' needs, especially in ASIAN culture.MethodTwenty MCI and carer volunteers from the memory clinic were invited to attend the session. The augmented reality equipment, sensors and telerehabilitation platform were shown to the group. Their opinions and feedback about the system were collected.ResultVolunteers were keen to adopt new technology. The user experience and system usability were collected along with additional feedback from the cohort to ease the use of the platform for the cognitively impaired population.ConclusionThe volunteer feedback promoted the customization of the platform to be more user‐friendly. Balance rehabilitation programs delivered via tele‐remote platform at home can be a potential solution among the MCI population in ASIA.