bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of Mini‐Mental State Examination items to detect objective memory impairment in mild cognitive impairment
Authors: Ryu Seon Young , Lee Sang Bong , Lee Taek Jun , Jung Yu Jin 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is the main cause of cognitive impairment in late‐life, and the typical early presentation of AD in older adults is amnestic cognitive impairment. Mini‐Mental State Examination (MMSE) is widely used in screening cognitive impairment in elderly. The aim of this study was to examine which MMSE items would be more associated with the verbal memory impairment in individuals with mild cognitive impairment (MCI).Method249 MCI subjects (mean age: 73.67 ± 6.79 years) were included in this study. The participants underwent clinical assessments and completed detailed neuropsychological tests. The participants were divided into two groups according to Seoul Verbal Learning Test Delayed Recall (SVLT DR) scores: normal verbal memory performance (SVLT DR > = ‐1.5 SD) vs low verbal memory performance (SVLT DR < ‐1.5 SD) groups. Group comparisons between normal and low verbal memory performance were performed. In addition, associations between verbal memory performance and MMSE items were analysed.ResultLow verbal memory performance group (n = 91) had more males and a tendency to be older and more educated than normal verbal memory performance group (n = 158). For MMSE items, low verbal memory performance group had lower MMSE time orientation and lower MMSE recall subscores, and a tendency of higher MMSE copy score than normal verbal memory performance group. Multivariable analyses showed that male sex, MMSE time orientation and MMSE recall scores were associated with lower verbal memory performance.ConclusionIn MCI individuals, male sex, and MMSE time orientation and recall subscores among demographics and MMSE items were associated with low verbral memory performance. These results suggest that more consideration for MMSE sub‐items would be helpful for the clinical evaluation of individuals with MCI at first step.
Prediction of Mild Cognitive Impairment using eye movements and other easily accessible measures
Authors: Opwonya Julius 
Published: December 2023

AbstractBackgroundThe early identification of patients at risk of dementia and timely medical intervention can be effective in preventing disease progression and mitigate burdens and costs of health insurance. Although the current diagnostic tests for preclinical and prodromal Alzheimer’s disease (AD) using neuropsychological evaluation and biomarkers can accurately predict the progression to AD dementia, the high cost, invasive nature, and limited availability restrict their use to wealthy clinics only. Therefore, we developed a model to predict cognitive impairment based on non‐invasive information, including eye movement (EM) data.MethodEye‐tracking data was extracted from 594 subjects, 428 cognitively normal (CN) controls, and 166 patients with mild cognitive impairment (MCI) while they performed Prosaccade/Antisaccade (PS/AS) and Go/No‐go tasks. EM behavior was compared by task after stratification by cognitive status and controlling for age, sex, and education. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) from the EM metrics.ResultLogistic regression models suggested increased OR of MCI from EM metrics, including wider latency variability, fixation duration variability, a higher number of errors committed, anticipations, and omissions with 95% CI of OR between 1.213‐1.621.ConclusionEM metric changes linked with MCI are associated with deficits in attentional and executive functions. The models built from non‐invasive data allow the discrimination of patients with MCI from cognitively normal adults. In summary, our results suggest that eye tracking, in combination with demographics and brief cognitive tests, might significantly improve the diagnostic prediction of MCI.
Feasibility of the CART In‐Home Technology Platform in a Pilot Study of Hispanic Older Adults Residing in South Texas
Authors: Mathews Julia J. , Mulavelil Rachel M. , Rodrigues Nathaniel , Kautz Tiffany F , Cosgrove Kevin , Wang Chen‐Pin , Fernandez Roman A. , MacCarthy Daniel , Gothard Sarah , Sharma Nicole , Serrano‐Rubio Luis Humberto , Young Vanessa M. , Miller Lyndsey M. , Seshadri Sudha , Kaye Jeffrey A , Beattie Zachary T , Gonzales Mitzi M. 
Published: December 2023

AbstractBackgroundAs Alzheimer’s disease (AD) prevalence rises, the development of effective screening tools is necessary to aid in earlier AD diagnosis. In the USA, Hispanic and Non‐Hispanic Black adults are at a disproportionately higher risk of developing dementia than non‐Hispanic whites but are poorly represented in AD research. A digital assessment system ‐ the Collaborative Aging Research using Technology (CART) platform, has been developed to remotely and continuously detect early declines in cognition by analyzing changes in everyday activity levels. Although the platform is promising, installing digital technology in a home can cause concerns over privacy and user friendliness, especially in older adults. In our CART pilot study at UTHSCSA, we sought to determine the feasibility of deploying the CART platform in an underrepresented, mostly Hispanic population and to gain insight from their experiences.MethodSeven cognitively intact participants were enrolled in our year‐long pilot study. The CART platform consisted of a watch‐actigraph, digital scale, electronic pillbox, bed mat (measuring sleep), and wall‐mounted motion sensors. Participants completed weekly online surveys including mood assessments, the UDS3 neuropsychological battery at baseline and one‐year follow‐up, and an end‐of‐study user experiences survey. Wilcoxon signed rank exact tests were used to determine significance.ResultOur cohort consisted of five Hispanic, one non‐Hispanic Black, and one non‐Hispanic white participant, ages 65‐80. There were no significant changes in cognition, daily steps, sleep, weight, or heart and respiratory rate measured during sleep over the course of the study (p>0.05). Self‐reported depressive symptoms decreased (p = 0.034) (Figure 1J). Weekly survey results supported this finding because self‐reported feelings of loneliness and “blue mood” also decreased. Responses to the user experience survey demonstrated that participants found the technology installation satisfactory (43%) or very satisfactory (57%) and thought that their privacy concerns were addressed satisfactorily (43%) or very satisfactorily (57%) (Figure 2).ConclusionOur results suggest that the CART platform was widely accepted by our mostly Hispanic older adult participants and that they were comfortable with the study devices. The findings support the feasibility of increasing representation of diverse older adults in dementia prevention research using digital devices.
Severe Impairment Rating Scale (SIRS) in assessing patients with severe dementia in Chinese Community
Authors: Wai‐Yin Chui Vivian , Ka‐Yee Fung Catherine , Man‐yung Wong Alice , Yeung Man Yat , Shan Li Wai , Ho‐yin Lai Frank 
Published: December 2023

AbstractBackgroundLike other advanced countries, Hong Kong is facing the challenges of an aging population, reduced fertility, and increasing longevity. Most older people who diagnosed with moderate to severe dementia would need institutional care. Nevertheless, the current instruments available in the Chinese population are having flooring effects in measuring the functional conditions for this specific group of population.MethodThis study aims to validate the 14‐item Chinese Severe Impairment Rating Scale (C‐SIRS), as an instrument designed to measure functional condition of older people with moderate and severe dementia. The development of this validation study was under classical test theory to examine and test (1) the degree of clarity, understandability, and relevance (i.e. content validity), (2) the test‐retest reliability score of SIRS, (3) the degree of the inter‐relatedness among SIRS items like internal consistency, and (4) the correlation between SIRS score and the functional measures by Hong Kong Montreal Cognitive Assessment (HK‐MoCA) and Modified Barthel Index 100 (MBI‐100).ResultWhen assessing the relevance and sensitivity of the question with the universal agreement calculation method, the scale‐level content validity index (S‐CVI/UA) of C‐SIRS received relevance ratings of “almost agree” or “absolutely agree” by all the experts. The Fleiss' kappa showed that there was moderate agreement between the panellists’ judgements, with at least 8 years of experience, κ = .326 (95% CI, .319 to .343), p < .001. 105 older people with moderate to severe dementia recruited from nursing home were enrolled in the validation, the C‐SIRS had a high level of internal consistency, as determined by a Cronbach’s alpha of 0.99 with F = .005, p = .831. The SIRS shows significant correlation with both cognitive, as measured by MoCA (with r = .337, p < .001), and functional measures as measured by MBI (with r = .64, p < .01).ConclusionC‐SIRS is sensitive in measuring the functional condition in older people with moderate to severe dementia. Moreover, C‐SIRS is easier to administrate with shorter time required. Further study should help by investigating the sensitivity of C‐SIRS to assess the change over a longer period of time.
Resilience of family caregivers of PwD in Korea: A scoping review
Authors: Seo Hyun‐Ju , Park Song‐I , Choi Yu Mi , Choi Min‐Jung , Choo IL‐Han , Park Jeong‐Hwan 
Published: December 2023

AbstractBackgroundFamily caregivers play a important role in living the journey of life of person with dementia through their involvement in caregiving as in informal carers in South Korea. The aim of this scoping review was to examine research theory, measurement instruments, correlates, interventions, and outcomes of resilience for family caregivers of persons with people with dementia (PwD).MethodThis scoping review was conducted according to Arksey and O'Malley’s scoping review framework and Joanna Briggs Institute’s manual for scoping reviews. Multiple databases, including Ovid‐MEDLINE, Ovid‐EMBASE, PsycINFO, CINAHL and Korean databases were searched using controlled vocabulary and text words. Two review authors independently screened and selected relevant studies.ResultMultiple database search identified 18 studies, published between January 2000 and February 2022. Most studies (72.2%) used theoretical framework, such as modified McCubbin and McCubbin’s Family stress, adjustment, and adaptation model and Walsh’s Family resilience model. Eight measurement instruments have been applied to measure the resilience for family caregivers of PwD. However, all the used instruments were not conducted the cross‐cultural adaptation and construct validation in Korean family caregivers of PwD. Moreover, some studies (4 of 18 studies) were used resilience tool focused the individual level rather than family and community levels.ConclusionThis review findings indicate that more rigorous research is needed to measure family resilience using cross‐cultural adapted and validated tools and to test the guided theory for family caregiver of PwD, considering Korean cultural and social context. Moreover, family resilience enhancement programs, considering identified correlates in this review are needed to develop and implement to help family caregiver achieve coping and adaptation with persistent distress in caregiving for their PwD.
A case of reversible isolated cognition impairment in meningoencephalitis without abnormal MRI findings
Authors: Hwang Jungyun 
Published: December 2023

AbstractBackgroundWe report a case of meningoencephalitis with reversible isolated cognition impairment without abnormal MRI findings.MethodA 75‐year‐old man presented with confusion including bizarre behavior 2 days ago. Before visiting the hospital, his son found the patient naked and under the blanket saying it was cold. Fever didn’t occur. Mental status was alert without awareness. On neurologic examination, mutism was found. Muscle power on both upper and lower limbs was normal. Routine laboratory test showed that leukocytes count was normal but eosinophils were increased to 14.0%. Initial brain MRI including DWI and contrast enhanced image revealed no enhanced structural lesions. Initial K‐MMSE score was 4 points while the previous K‐MMSE score 3‐months‐ago was 25 points. There was no epileptic form discharge in EEG. CSF study demonstrated that WBC count was 18/L. protein was 42.6mg/dL, and glucose was 103mg/dL. CSF opening pressure was 5cmH2O. Culture study including gram stain, AFB stain, PAS stain showed no growth of aerobe, anaerobe, fungus and hyphae. Mycobacterium tuberculosis PCR and HSV PCR were negative. ADA was under 3 IU/I. Serum paraneoplastic antibodies were all negative.ResultThe patient showed only isolated cognition impairment without fever and there was no evidence of meningoencephalitis on the contrast enhanced MRI. Although the patient revealed CNS infection with unknown cause in CSF profile, it has some possibilities; 1) Aseptic meningoencephalitis with viral infection, 2) Bacterial meningoencephalitis with early stage, 3) Parasitic meningoencephalitis, 4) Autoimmune meningoencephalitis. Because of the negative findings in autoimmune antibody test, autoimmune meningoencephalitis was less likely. After treatment with acyclovir 0.6g for 7days, ceftriaxone 4g, vancomycin 2.5g and Ampicillin 8g for 10 days, confusion and mutism were improved with K‐MMSE 18 points.ConclusionMany reports have been published on meningoencephalitis accompanied by fever, altered mentality, seizure, muscle weakness and abnormal MRI findings respectively. However there have been few cases of meningoencephalitis with isolated cognition impairment and normal MRI simultaneously. If it is a change of consciousness and cognition impairment caused by meningoencephalitis, it can be reversible with proper treatment. Therefore, if only sudden onset isolated CNS symptom with normal brain MR finding, it is essential to check CSF profile.
Estimating Treatment Effects of Disease‐modifying Drugs: Traditional Methods vs. Accelerated Failure Time Models and Progression Analysis
Authors: Atri Alireza , Ivkovic Milana , Jönsson Linus , Gustavsson Anders , Léon Teresa , Hahn‐Pedersen Julie Hviid , Handels Ron , Raket Lars Lau 
Published: December 2023

AbstractBackgroundProgression models for repeated measures (PMRM1) are a class of statistical models that enable estimation of slowing of progression of Alzheimer’s disease, expressed as percentage or time delay. Similarly, accelerated failure time (AFT) models can estimate relative expected time until progression when evaluating disease‐modifying therapies. We compared these methods to mixed‐effects models for repeated measures (MMRM) and Cox time‐to‐event analysis on simulated trial data, evaluating their power and the difference in interpretation when expressing outcomes as a measure of time.MethodPrimary outcomes were Clinical Dementia Rating (CDR) Sum of Boxes (MMRM and PMRM) and time to progression to dementia as assessed by CDR global (Cox regression and AFT models). Weibull and log‐logistic distributions were assumed for random error distribution in AFT models.Subject‐level placebo arm trajectories were jointly simulated based on estimated CDR mean trajectories and joint temporal correlation structure of 538 amyloid‐positive MCI patients meeting typical disease‐modifying trial inclusion criteria from the ADNI study. Active arm trajectories were simulated to show an average 20% slowing of disease progression vs placebo at each visit. A thousand simulations were conducted across scenarios, varying number of subjects per arm (200‐700) and clinical trial duration (18‐36 months).ResultPower of PMRM was shown to be consistently greater than that of MMRM (Table 1). The AFT and Cox models’ power rarely exceeded 40%.PMRM accurately estimated the underlying 20% slowed progression. With greater sample sizes and at least 2 years of follow‐up, the AFT models indicated a slowing of progression, but the median estimated slowing was 5%. The MMRM and Cox model found median estimated reduction in decline of 25% and median estimated hazard ratios of 0.88‐0.91, respectively.ConclusionsPMRM and AFT models estimate slowing of progression. Compared to the MMRM and Cox model, these time‐based models better capture the effect of disease‐modifying therapies and facilitate translation of results to patients and their care partners. Among all methods studied, the PMRM offered the best combination of interpretability and power.
References: 1. Raket, LL. Progression models for repeated measures: Estimating novel treatment effects in progressive diseases. Statistics in Medicine. 2022; 1‐ 21. https://doi.org/10.1002/sim.9581
The effect of prion protein expression on amyloid‐beta pathology
Authors: Mistry Beenaben , Farmer Michael , Purro Silvia , Collinge John 
Published: December 2023

AbstractBackgroundWe have developed multiple knock‐in mouse models that express humanised Aβ (AppNL‐F) with varying levels of PrPC expression (AppNL‐F, AppNL‐F_Tg20, AppNL‐F_PrPKO, AppNL‐F_hTauKI and AppNL‐F_hTauKI_PrPKO) to investigate the role of PrPC in knock‐in mice before and after inoculation with human AD brain homogenates.MethodUninoculated knock‐in mice with varying levels of PrPC were characterised using biochemical and histological techniques. We went on to characterise AppNL‐F, AppNL‐F_Tg20, AppNL‐F_PrPKO, AppNL‐F_hTauKI and AppNL‐F_hTauKI_PrPKO mice after inoculation with human brain homogenates.ResultAn age‐dependent increase in Aβ42 levels in all animals at 10 months old was observed compared to their 6 month old counterparts. We saw an accumulation of activated astrocytes around the Aβ plaques with higher levels of astrogliosis seen in the AppNL‐F_Tg20 animals at all ages compared to AppNL‐F, AppNL‐F_PrPKO, AppNL‐F_hTauKI and AppNL‐F_hTauKI_PrPKO mice. Synaptic protein fractions extracted from AppNL‐F_Tg20 mice inoculated human AD brain homogenate showed a significant increase in Fyn and Pyk2 protein phosphorylation when compared to vehicle and control human brain homogenate inoculated AppNL‐F_Tg20 mice. This effect was statistically significant for both proteins at 8 months post‐inoculation (mpi) and was further exacerbated at 12 mpi. The results at 8 and 12mpi were independent of guanidine hydrochloride‐soluble Aβ42 levels and Aβ plaque coverage in the mouse brains. We went on to find significant differences in tau hyperphosphorylation and Aβ plaque coverage between inoculated AppNL‐F_hTauKI and AppNL‐F_hTauKI_PrPKO mice which was independent of guanidine hydrochloride‐soluble Aβ42 levels.ConclusionThe level of PrPC expression in two knock‐in mouse models inoculated with human brain homogenate was shown to have an effect on synaptic protein phosphorylation at 8 and 12mpi. This was independent of Aβ42 levels and Aβ plaque coverage in the mouse brains.
Outcome imbalance in clinical trials: Mitigating loss of statistical power
Authors: Tam Angela , Laurent César , Dansereau Christian 
Published: December 2023

AbstractBackgroundUnequal rates of decline between placebo and treatment arms reduce a trial’s power. We use machine learning to differentiate decliners from non‐decliners to mitigate the impact of outcome imbalance.MethodWe trained a model to classify decliners (i.e. individuals with higher CDR‐SB at 24 months of follow‐up) and non‐decliners on 1329 individuals with MCI or Alzheimer’s dementia from ADNI (adni.loni.usc.edu) and NACC (naccdata.org). Input features included baseline age, sex, APOE4 status, gray matter volumes of brain regions from MRI, MMSE, and CDR‐SB. We 1) simulated 100,000 trials by randomizing individuals to placebo and treatment (n = 250 per arm) and measured the proportions of decliners between the arms to assess the likelihood of imbalance, 2) measured the power to detect a 25% treatment effect across simulated trials with varying levels of imbalance (0‐5% more decliners in treatment, 1000 simulations per imbalance level), and 3) studied whether covariate adjustment and enrichment with predicted decliners alleviate imbalance‐related power losses.Result22.4% of our simulated trials had inter‐arm imbalances of 5% or more, which translated into reduced power (‐15%) and effect sizes (‐0.11) compared to balanced trials (mean ± sem 89.2 ± 0.6% power, 0.39 ± 0.006 Cohen’s d for balanced trials; 73.8 ± 0.9% power, 0.28 ± 0.004 Cohen’s d for 5%‐imbalanced trials). Covariate adjustment on prognostic factors (e.g. APOE4, diagnosis, baseline CDR‐SB) increased power, but imbalance still reduced power by 9% (balanced: 97.2 ± 0.3%; 5%‐imbalanced: 87.8 ± 0.7%). Subgroups analyses of the predicted decliners (excluding predicted non‐decliners) increased power, despite smaller sample sizes (balanced: 97.4 ± 0.3%; 5%‐imbalanced: 92.2 ± 0.5%). Using enriched samples with 250 predicted decliners per arm obtained the greatest power and constrained the power loss to only 3% (balanced: 99.1 ± 0.1%; 5%‐imbalanced: 96.2 ± 0.4%) (Figure).ConclusionTo improve a trial’s likelihood of success, covariate adjustment and enrichment with likely decliners should be used to mitigate power loss related to outcome imbalance.
Alzheimer’s Disease and Healthy Aging Indicators Cognitive Decline
Authors: Khuld Hamna 
Published: December 2023

AbstractBackgroundIn the United States (U.S.) and Puerto Rico, cognitive decline and resulting Alzheimer’s disease are major public health concerns for older adults. According to the Alzheimer’s Association (2021), by 2050, people ages 65 and above with Alzheimer’s are estimated to grow to 12.7 million—rising in prevalence and severity.MethodThe Alzheimer’s Disease and Healthy Aging Indicators Cognitive Decline study is an ecological study that documents cognitive decline or memory loss among adults ages 50 and above. The CDC collected data from 2015 to 2019 under the Behavior Risk Factor Surveillance System (BRFSS). The surveys documented cognitive decline or memory loss experienced by 16,799 older adults by age, race, sex, and state of residency. (Please note that sex and missing variables were excluded from the observation, and 2,498 participants were analyzed.)ParticipantsCombined data from 2015 to 2019 was obtained from older adults ages 50 and above. Participants were surveyed nationally on their cognitive decline by age, race, and sex. My analysis focuses on the correlation between race‐exacerbated cognitive decline or worsening memory loss in 12 months by age and state of residency.ResultsThe main findings examine the association of cognitive decline by comparing races, using White, non‐Hispanic as the reference group. This analysis shows adults ages 50‐64 are 1.91 times more likely to report cognitive decline compared to adults 65 and above.Association between cognitive decline and race showed Hispanic participants reported the highest rates of mean percentage of BRFSS for functional difficulties in both age groups—50‐64 years at 75% and 65 and older at 55%. Black, non‐Hispanics were the second highest group to report high rates of mean percentage of BRFSS for functional difficulties in both age groups—50‐64 years at 55% and 65 and older at 47%.Additional analysis on age and its association with participants' state of residency shows the highest rate of cognitive decline for Asian/Pacific Islanders is reported in the West—in the state of Hawaii at 26.6%.ConclusionsIn conclusion, race is associated with cognitive decline depending on age and state of residency.