bluuebunny/crossref_metadata_2025_split huggingface dataset:
A predictive regression model for mild cognitive impairment and Alzheimer´s disease using real‐world electronic health records
Authors: Yubero Raquel , Cobos Rocio García , Arcelay Elena Garcia , Algaba Alicia , Rebollo Pablo , Mauriño Jorge , Arroyo Rafael 
Published: January 2025

AbstractBackgroundIdentifying individuals with early Alzheimer’s disease, i.e. mild cognitive impairment (MCI) and mild dementia due to Alzheimer’s disease (AD) can facilitate the rapid initiation of pharmacological and non‐pharmacological therapies with the aim of achieving better clinical outcomes. However, an early and accurate diagnosis is still limited in clinical practice.This study aimed to identify factors associated to MCI and AD using a real‐world dataset from a memory clinic in Spain.MethodsThis non‐interventional, case‐control study used the Quirónsalud Madrid Database, which includes information from people who were seen for cognitive problems from 2007 to 2022.The dataset incorporated variables such as the Global Deterioration Scale (GDS), Neuropsychiatric Inventory Questionnaire (NPI), demographic characteristics such as age, educational level, profession, vascular risk factors (hypertension, diabetes mellitus, smoking), family history of dementia, alcohol consumption, and neurological diagnosis based on the International Classification of Diseases.Two regression models were built as Generalized Linear Mixed Models (GLMM): 1) 644 patients with MCI (GDS = 3) vs. 623 controls (GDS≤2); 2) 966 patients with AD (GDS≥3 and AD diagnosis) vs. 623 controls.ResultsAccording to GLMM, variables associated to MCI were age [OR = 1.222], apathy [OR = 2.650], depression [OR = 0.318] and education [OR = 0.232 (16‐20 years) and 0.217 (>20 years) vs. <15 years] (table 1) with an AUC of the ROC curve of 0.657, sensitivity of 0.82 and specificity of 0.45. In the GLMM adjusted for AD, variables included were age [OR = 1.490], family history [OR = 4.147 (first degree vs none)], apathy [OR = 8.247], anxiety [0.302], and education [OR = 0.103 (16‐20 years) and 0.119 (>20 years) vs. <15 years] (table 2) with an AUC of the ROC curve of 0.852, sensitivity of 0.84 and specificity of 0.73. No association with vascular risk factors was found.ConclusionsAge, education, and apathy were consistently associated with both MCI and AD. The AD constructed model demonstrated good classification performance, providing insights for diagnosis. Further studies are needed to develop a simple tool for MCI and AD detection.
A process mining approach to assessing diagnostic pathways in a memory clinic
Authors: Festari Cristina , Solorzano Claudio Singh , Orini Stefania , Buscarnera Simona , Rossato Francesco , Pievani Michela , Ramusino Matteo Cotta , MASSA FEDERICO , Gatta Roberto , Frisoni Giovanni B. 
Published: January 2025

AbstractBackgroundSeveral clinical guidelines and recommendations have been developed to improve the diagnostic process of patients with dementia, with the aim of optimising patient care and fostering a cost‐effective use of resources. However, patient characteristics and organizational factors in clinical practice can lead physicians to deviate from recommendations. In this context, process mining (PM) is a powerful technique for evaluating the compliance of actual to ideal diagnostic pathways, but has never been used in the cognitive field. This study aims to pilot the use of PM to study the diagnostic workup of patients with cognitive complains in an academic memory clinic.MethodWe retrospectively reviewed medical charts of 539 consecutive new patients referred to the University Hospitals of Geneva (Switzerland) between July 2021 and December 2022. The collected information includes socio‐demographic data, number and dates of clinical visits and biomarker exams (e.g., FDG‐, amyloid‐, tau‐PET, cerebrospinal fluid ‐ CSF). The pMineR package, a R library for PM, was used for data inspection and process discovery (e.g., First Order Markov Model ‐ FOMM, Careflow Miner ‐ CFM) to extract features of most frequent diagnostic pathway according to clinical stage.ResultPatients were 96 subjective cognitive decline (SCD; MMSE: 28.5±1.6), 308 Mild Cognitive Impairment (MCI; MMSE: 26.5±2.7), and 135 Mild Dementia (DEM; MMSE: 22.7±3.2). FOMM showed that all SCD patients received a syndromic diagnosis based on a detailed neuropsychological evaluation and a morphological imaging. CSF was the first‐line biomarker to ascertain the aetiology of cognitive impairment, used in 90 MCI (30%) and 32 DEM (24%). A second‐line biomarker (e.g., amyloid‐, FDG‐, Tau‐PET) was required in 23% of MCI and 16% of DEM. Differential PM with CFM revealed that DEM was more commonly referred to the first clinical assessment with morphological imaging than MCI (DEM:68/135vs.MCI:123/308, ratio:1.8; p = 0.047).ConclusionThese preliminary results demonstrate that the PM approach is appropriate for describing the diagnostic workup in memory clinics. Using the same approach and study design, a further project will evaluate the diagnostic pathways in 6 European academic memory clinics and contrast them to recommendations recently issued from a large European consensus effort (Frisoni, LancetNeurol 2024).
Dietary Patterns, Alzheimer’s Disease Mortality, and Psychometric Mild Cognitive Impairment: The National Health and Nutrition Examination Survey
Authors: Gong Yiying , Chen Hui , Shen Jie , Shen Ting , Ding Yihong , Lu Mengxi , Huang Liyan , Yuan Changzheng 
Published: January 2025

AbstractBackgroundDietary factors play a major role in cognitive aging, but few study has compared the associations of major dietary patterns with Alzheimer’s disease (AD) mortality and psychometric mild cognitive impairment (p‐MCI).MethodWe included 27,773 participants (mean age = 57.0 years, 52.9% female) from the US National Health and Nutrition Examination Survey (NHANES), 1998‐2016. We calculated five dietary pattern scores from repeated one day 24‐hour recalls, including the Healthy Eating Index (HEI‐2015), alternate Mediterranean diet score (AMED), Dietary Approach to Stop Hypertension score (DASH), the Mediterranean‐DASH Intervention for Neurodegeneration Delay diet score (MIND), and the healthful plant‐based diet index (hPDI). AD mortality was ascertained from linkage to the National Death Index through December, 2019. P‐MCI is defined as a composite cognitive function score being 1.0 standard deviation (SD) lower than the age‐, sex‐, and education‐specific norm measured in 2,713 participants in 2011‐2014. We applied Cox proportional hazard models and logistic models to assess the relations of the dietary scores to AD mortality and p‐MCI, respectively.ResultDuring follow‐up (median = 9.8 years), 260 participants died of AD. Higher AMED was associated with lower risk of AD mortality (HR per SD: 0.87, 0.76 to 0.99). In 2011‐2014, 432 out of 2713 participants had prevalent p‐MCI. Higher HEI‐2015 (OR per SD: 0.89, 95%CI: 0.80 to 1.00), AMED (0.84, 0.75 to 0.95), and MIND (0.81, 0.72 to 0.92) scores were associated with lower odds of p‐MCI.ConclusionAdherence to the Mediterranean diet is associated with both lower risk of AD mortality and lower odds of p‐MCI. Our findings highlight the importance of health dietary patterns in the healthy cognitive aging.
How Much Time Can be Saved in Cognitive Decline? the Internet‐based Conversational Engagement Clinical Trial (I‐CONECT)
Authors: Wu Chao‐Yi , Yu Kexin , Arnold Steven E. , Das Sudeshna , Dodge Hiroko H 
Published: January 2025

AbstractBackgroundClinical trials should strive to yield results that are clinically meaningful rather than solely relying on statistical significance. However, the determination of clinical meaningfulness of dementia clinical trials lacks standardization and varies based on the trial’s nature. To tackle this issue, a proposed approach involves assessing the time saved before reaching a specific threshold in cognitive status. In this study, we investigated the time saved in cognitive decline among the top responders based on the individual‐level treatment responses (ITR) analysis, using data from the Internet‐based Conversational Engagement Clinical Trial (I‐CONECT; NCT02871921).MethodI‐CONECT is a randomized controlled trial to examine the effects of conversational interactions on cognition among socially isolated participants aged ≥ 75 years old. The experiment group engaged in video chats with study staff 4 times/week for 6 months; the control groups received weekly check‐in phone calls. We focused on cognitive outcomes that exhibited significant treatment effects at 6‐month follow‐up: the Montreal Cognitive Assessment (MoCA) for global cognition and Category Fluency Animals (CFA) for semantic fluency. To assess ITR, we employed 300 iterations of 3‐fold cross‐validated random forest models. We estimated treatment heterogeneity by conducting permutation tests on the area between curves (ABC) statistics derived from the ITR scores. We estimated time saved in cognitive decline as the difference in the number of months required for the top responders (top 25%; 33%) and the remaining participants to reach the same cognitive level at 6‐months follow‐up.ResultABC statistics showed substantial heterogeneity in treatment response with MoCA but modest heterogeneity in treatment response with CFA. For global cognition, assuming a treatment effect size between 30‐50%, the top 25% and 33% of responders exhibited potential cognitive delays ranging from 4.1 to 10.8 months and 5.9 to 13.9 months, respectively (Figure 1). For semantic fluency, large effect sizes (70‐100%) are required to show potential cognitive delays ranging from 0.5 to 6.7 months.ConclusionIndividual differences in the time saved for cognitive decline through the ITR analysis are meaningful outcomes in clinical trials. Future trial outcomes should consider both quantity and quality concepts such as quality‐adjusted time saved.
Physical Activity and Acute Care Utilization in Older Adults Living with Mild Cognitive Impairment and Dementia in the Upper Midwest of the United States
Authors: Bartley Mairead M. , St. Sauver Jennifer , Schroeder Darrell R. , Khera Nandita , Fortune Emma , Griffin Joan M. 
Published: January 2025

AbstractBackgroundPeople living with dementia have high rates of emergency department (ED) use and hospitalizations. Identifying factors that influence acute care utilization is important. We examined the influence of physical activity levels on risk of hospitalization and emergency department (ED) use in a population of older people living with mild cognitive impairment (MCI) or dementia.MethodsWe included people with a diagnosis of MCI or dementia followed in Community Internal Medicine at Mayo Clinic, age 55 years and older, who had a clinic visit between June 1, 2019 and June 30, 2021 and had completed a social determinants of health questionnaire about physical activity levels. Physical activity was classified based on responses to questions about time spent exercising per week and rated as sufficiently active (≥150 minutes per week), insufficiently active (10‐140 minutes) or physically inactive (0 minutes). The risk of hospitalization and ED visits across physical activity levels was examined using quasi‐Poisson regression and presented as rate ratios (95% confidence interval (CI)), with adjustment for demographics, Charlson Comorbidity Index, marital status, living arrangement and body mass index.ResultsA total of 3090 persons living with MCI (n = 1308) or dementia (n = 1782) were included. People who were physically inactive were more likely to be older, female, not married, obese, have higher comorbid burden and a dementia diagnosis (p<0.001). Hospitalization and ED visit rates in those who were physically inactive were approximately double the rates for the sufficiently active group (p<0.001). Compared with those who were sufficiently active, people who were physically inactive had a significantly higher risk of hospitalization (rate ratio 1.73, 95% CI 1.30‐2.31) and ED visits (rate ratio 1.59, 95% CI 1.26‐2.01).ConclusionsPhysical inactivity in older people living with MCI or dementia is associated with an increased risk of ED visits and hospitalization. Targeted physical activity interventions could potentially impact on acute care utilization in this population. Our findings emphasize an area for public health promotion in people living with MCI or dementia.
The association between a pro‐inflammatory diet and machine learning‐based brain age in middle‐aged and older adults: Findings from the UK Biobank
Authors: Dunk Michelle M. , Huang Huijie , Wang Jiao , Dove Abigail , Sakakibara Sakura , Guo Jie , Carballo‐Casla Adrián , Bennett David A. , Xu Weili 
Published: January 2025

AbstractBackgroundPro‐inflammatory diets have been associated with cognitive decline and dementia, but their impact on overall brain aging is unclear. We aimed to investigate the relationship between a pro‐inflammatory diet and a machine learning‐based measure of brain age, taking into account age, genetic risk for Alzheimer’s disease (AD), and systemic inflammation.MethodFrom the UK Biobank, 21,473 participants aged 40‐70 years and free of chronic brain diseases were included. Baseline Dietary Inflammatory Index (DII) scores were calculated from participants’ average intake of 31 nutrients, assessed up to five times between 2009‐2012 using the Oxford WebQ. Participants were categorized into DII tertiles (low [anti‐inflammatory], moderate, or high [pro‐inflammatory]). An AD polygenic risk score (PRSAD; tertiled as low, moderate, and high) and high‐sensitivity C‐reactive protein (hsCRP; a biomarker of systemic inflammation) were measured from baseline blood draw. We used least absolute shrinkage and selection operator (LASSO) regression to estimate brain age from 1,079 structural and functional magnetic resonance imaging (MRI) measures, obtained approximately 9 years after baseline. We calculated brain‐predicted age difference (BPAD; the difference between brain age and chronological age), where BPAD >0 indicates accelerated brain aging. Data were analyzed using linear regression and mediation analysis.ResultAmong all participants, DII scores ranged from ‐6.22 to 5.38 (low: ‐6.22 to ‐1.34; moderate: ‐1.35 to 0.49; high: 0.50 to 5.38). In multi‐adjusted linear regression, each unit increase in DII score was associated with older brain age by β = 0.07 (95% confidence interval: 0.02, 0.12) years and greater BPAD by 0.06 (0.02, 0.11) years. Compared to the low DII tertile, high DII was associated with older brain age by 0.35 (0.12, 0.58) years and greater BPAD by 0.34 (0.13, 0.55) years. These associations were pronounced in adults aged ≥60 years, attenuated in adults aged 40‐59 years, and did not differ by PRSAD. HsCRP levels mediated 10% of the DII‐brain age association and 14% of the DII‐BPAD association.ConclusionA pro‐inflammatory diet is associated with accelerated brain aging, especially in older adults and independently of genetic risk for AD. Systemic inflammation may partially mediate the association between a pro‐inflammatory diet and brain age.
Geo‐cultural Variation in MMSE Score Changes from Screening to Baseline in Alzheimer’s Disease Trials
Authors: Machizawa Sayaka , Appleman Erica R. , Stenclik Jessica , Iacob Andrei , Hackebeil Amanda , Barbati Gila , Massa Jacqueline 
Published: January 2025

AbstractBackgroundThe Mini‐Mental State Examination (MMSE) is a common screening tool in Alzheimer’s disease (AD) clinical trials. MMSE score inflation at inclusionary visits poses challenges by potentially amplifying placebo responses and complicating the detection of treatment effects. Despite these concerns, prior research (e.g., Echevarria, 2023) has reported instances of MMSE score inflation when it is utilized as an inclusion criterion. Little is known, however, whether this phenomenon is observed universally in AD trials across geo‐cultural regions.This study examined whether MMSE score changes from Screening to Baseline differ across geo‐cultural regions in global AD trials. The regions compared included North America, Asia, Eastern Europe, Western Europe, Latin America, and the Middle East/Africa.MethodData from two multinational Phase 3 AD trials, where MMSE was an inclusionary criterion at Screening but not at Baseline, were analyzed. Both studies used the same MMSE cut‐off for the inclusionary criterion. All raters underwent uniform training and certification for MMSE administration. An enhanced eMMSE scale was employed to minimize rater errors, and a data quality surveillance program included central audio review of eMMSE administration and scoring. Kruskal‐Wallis and Dunn’s tests were used to compare score changes across regions.ResultsTable 1 displays the mean score changes from MMSE Screening to Baseline for each region. A Kruskal‐Wallis H‐test revealed statistically significant heterogeneity in MMSE score changes across regions, χ2 (5) = 16.709, p<.001. Dunn’s tests indicated significantly smaller score changes in North America (p<.001) compared to other regions.ConclusionsThis study observed geo‐cultural variances in MMSE score changes from Screening to Baseline in AD trials. North America demonstrated a significantly smaller score decrement than other regions, indicating potential lesser MMSE score inflation at inclusionary visits. The geo‐cultural differences in MMSE score inflation might reflect cultural impacts on placebo responses. Previous research underscores cultural effects on placebo and nocebo phenomena as cultural factors impact therapeutic expectations, disease perceptions, and treatment interactions (Cundiff‐O'Sullivan et al.). Further investigation is essential to comprehend the factors driving these geo‐cultural disparities in MMSE Screening score inflation and their implications in AD trials.
The effects of six months of exercise on single‐ and dual‐task gait and functional mobility relative to usual care alone among people living with dementia: A pilot randomized controlled trial
Authors: Langston Ryan L , Dong Yanbin , Zhu Haidong , Soares Andre , Patel Charmi , Hergott Colleen , Waller Jennifer L , Young Lufei , Robinson‐Johnson Dawnchelle , Carrick Ryan M , Sams Richard , Hamrick Mark , Jehu Deborah A 
Published: January 2025

AbstractBackgroundExercise may improve dual‐tasking and mobility impairments among people living with dementia (PWD), but more evidence is needed. The purpose of this pilot randomized controlled trial (RCT) was to determine the effect of six months of exercise on single‐ and dual‐task mobility compared to usual care alone in PWD.MethodThis assessor‐blinded RCT (1:1) included n = 21 PWD in the usual care and n = 21 PWD in the exercise group at two residential care facilities (Age = 82 years, 35% female, Montreal Cognitive Assessment (MoCA) = 10.2±5.9; NCT05488951). The physical therapist‐led adapted Otago Exercise Program involved 30 minutes of lower body strength and balance exercises and 30 minutes walking 3x/week for 6 months in groups of 5‐7. At baseline and 6 months, participants completed two trials of single‐ (walk 4m) and dual‐task gait (walk 4m while naming words), and single‐task timed‐up‐and‐go (TUG), and dual‐task TUG with a category task using APDM inertial sensors. We measured double limb support (%), gait speed (m/s), and stride length (m) for gait, and duration (s), turns angle (°), and turn velocity (m/s) for the TUG. Intent‐to‐treat (ITT) and per protocol (all usual care and exercisers with ≥2/3 adherence) analyses were performed. We controlled for age, race, sex, and the MoCA.ResultIn the ITT analysis, exercise provoked faster dual‐task gait speed (+0.03 m/s, p = 0.006), increased single‐task TUG turn velocity (+24.01 m/s, p = 0.001), decreased dual‐task TUG duration (‐11.54 s, p = 0.01), and increased dual‐task TUG turn velocity (+18.96 m/s, p<0.001). In the per Protocol analysis, both the exercise (‐22.04%, p = 0.007, n = 9) and usual care groups (‐18.90%, p<0.001, n = 21) decreased double limb support during single‐task gait. Additionally, only the exercise group increased stride length during dual‐task gait (+0.24 m, p = 0.007) and increased turn velocity during the single‐ (+28.27 m/s, p = 0.002) and dual‐task TUG (+17.75 m/s, p = 0.002).ConclusionSix months of exercise improved both single‐ and dual‐task mobility in PWD compared to usual care. Similar findings in both ITT and per protocol analyses indicate that exercising in any amount can improve dual‐task mobility in PWD. Our findings may inform therapeutic interventions for improving dual‐task mobility in PWD in residential care facilities.
Validity and psychometric properties of the Severe Cognitive Rating Scale‐English version, among individuals with dementia
Authors: Harikrishnan Shreya , Soffer Matan , Alhabbal Hiba , Burhan Amer M. , Colman Sarah , Chu Li , Davies Simon , Derkach Peter , Elmi Sarah , Gerretsen Philip , Graff‐Guerrero Ariel , Hussain Maria , Ismail Zahinoor , Kim Donna , Krisman Linda , Moghabghab Rola , Mulsant Benoit H. , Pollock Bruce G. , Nair Vasavan , Rajji Tarek K. , Rej Soham , Rostas Aviva , Van Bussel Lisa , Kumar Sanjeev 
Published: January 2025

AbstractBackgroundCommonly used screening measures of cognitive function such as the Montreal Cognitive Assessment (MoCA) are not sensitive to assess cognitive function among individuals with severe cognitive impairment due to floor effect. The Severe Cognitive Impairment Rating Scale (SCIRS) was designed to assess cognitive function in those with severe cognitive impairment, however, psychometric properties of its English version have not been reported.MethodUsing the existing data from StaN and tTED studies, floor and ceiling effects (percentage of minimal or maximal scores) of SCIRS and MoCA were examined, and the association between SCIRS and MoCA was evaluated.ResultData from 141 participants (mean age = 78.7, 56% females) who completed either the SCIRS (n = 122) or MoCA (n = 80) were collected (n = 61 completed both). There was robust association between SCIRS and MoCA, supporting criterion validity of the SCIRS as a measure of cognitive function. SCIRS had a lower floor effect (13.1% minimal scores) as compared to the MoCA (27.5% minimal scores). Out of 22 participants with minimal scores on the MoCA, 16 participants completed the SCIRS with mean score of 9.8 (SD = 7.5).ConclusionSCIRS appears to be a valid measure of cognitive function, showing better variance among individuals with severe cognitive impairment, as compared to MoCA.