bluuebunny/crossref_metadata_2025 huggingface dataset:
CNN for a Regression Machine Learning Algorithm for Predicting Cognitive Impairment using qEEG
Authors: Simfukwe Chanda , Youn Young Chul
Published: December 2023

Background

Electroencephalogram (EEG) signals give detailed information on the electrical brain activities occurring in the cerebral cortex. They are used to study brain‐related disorders such as mild cognitive impairment (MCI), and dementia. Brain signals obtained using an EEG machine can be a neurophysiological biomarker for early diagnosis of dementia through quantitative EEG (qEEG) analysis. This paper proposes a machine learning methodology to detect MCI and dementia from qEEG time‐frequency (TF) images of the subjects in an eyes‐closed resting state (ECR).

Method

The dataset consisted of 16,910 TF images from 890 subjects: 269 healthy controls (HC), 356 MCI, and 265 dementia. First, EEG signals were transformed into TF images using a Fast Fourier Transform (FFT) containing different event‐rated changes of frequency sub‐bands preprocessed from the EEGlab toolbox in the MATLAB R2021a environment software. The preprocessed TF images were applied in a convolutional neural network (CNN) with adjusted parameters. For classification, the computed image features were concatenated with age data and went through the feed‐forward neural network (FFN).

Result

The trained models’, HC vs. MCI, HC vs. dementia, and HC vs. CASE (MCI + dementia), performance metrics were evaluated based on the test dataset of the subjects. The accuracy, sensitivity, and specificity were evaluated: HC vs. MCI was 83%, 93%, and 73%, HC vs. dementia was 81%, 80%, and 83%, and HC vs. CASE (MCI + dementia) was 88%, 80%, and 90%, respectively.

Conclusion

The proposed models trained with TF images and age can be used to assist clinicians as a biomarker in detecting cognitively impaired subjects at an early stage in clinical sectors.
Remote assessment of functional impairment in Alzheimer’s disease: results of the RADAR‐AD study
Authors: Muurling Marijn , de Boer Casper , Vairavan Srinivasan , Curcic Jelena , Scebba Gaetano , Atreya Alankar , Hinds Chris , Conde Pauline , Grammatikopoulou Margarita , Lazarou Ioulietta , Nikolopoulos Spiros , Brem Katy , Coello Neva , Narayan Vaibhav A , Wittenberg Gayle , Aarsland Dag , Visser Pieter Jelle ,   the RADAR‐AD consortium
Published: December 2023

Background

Remote monitoring technologies (RMTs), such as smartphone apps and smartwatches, are changing the way functional and cognitive performance are measured in Alzheimer’s disease (AD). Due to their sensitivity, objectivity, and the option of long‐term and continuous measurement, RMTs have the potential to detect a subtle decline in the earliest stages of AD. Here, we present the results of the European RADAR‐AD project (Remote Assessment of Disease and Relapse – Alzheimer’s disease), which aims to test feasibility, acceptability and validity of RMT measures across all stages of AD, from cognitively normal to mild dementia.

Method

Four study groups (amyloid negative healthy controls, and amyloid positive preclinical AD, prodromal AD, mild‐to‐moderate AD) were included in this cross‐sectional study (N = 175). During 8 weeks, participants wore two activity trackers (Fitbit and Axivity) measuring physical activity, heart rate and sleep continuously, and used two interactive smartphone apps (Mezurio and Altoida’s research algorithm: DNS‐MCI) measuring cognition daily/weekly. At baseline, participants underwent extensive neuropsychological, physical examinations, and did two sensor‐based tests (banking app and walk test). Features were extracted for all RMTs (Figure 1) and compared across groups using ANCOVA, with adjustment for relevant confounders. This study is part of an ongoing investigation into high‐end multimodal analyses for real‐world functional performance of continuous RMT data streams.

Result

Compliance was high, but decreased with cognitive impairment (feasibility). User experience did not differ between groups but was lower for smartwatches compared to interactive smartphone apps (Table 1) (acceptability). Various individual sensors discriminated symptomatic AD participants from asymptomatic participants (p<0.05), for example the two active apps, but did not discriminate preclinical AD from healthy controls (Table 1) (validity).

Conclusion

The RADAR‐AD study provides unique insights in the feasibility, acceptability, and validity of remote monitoring of functional abilities in AD and their potential to differentiate between syndromic stages.

This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (grant No 806999) and their associated partners. www.imi.europa.eu. This communication reflects the views of the RADAR‐AD consortium and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein.
Primary care training needs about dementia. A Qualitative study
Authors: Leon Tomas , Troncoso Deiza , Barria Soledad , Slachevsky Andrea
Published: December 2023

Introduction

The prevalence of dementia in Chile is 1.06%, and it is expected to triple in the next 30 years. The current regulations establish that over 80% of the people living with dementia and their care partners should receive care in primary care with only the hard or atypical cases. However, the knowledge and confidence of primary care teams are low, and there is no current training scheme for them.

Objectives

To identify the training needs of primary care teams, people living with dementia and their care partners, gathering information to create a course on dementia for primary care teams.

Methodology

Qualitative research methods were used, including focus group interviews for health professionals and individual interviews for people living with dementia and their care partners. A complete analysis of the recorded interviews was performed.

Results

Disregarding their previous training or background, all primary care professionals recognise the importance of continuous instruction. There is also a lack of preparation for interpersonal skills, like providing bad news and empathy. Caregivers and people living with dementia highlight a lack of continuity in their care team, being unaware of their diagnosis and low support.

Conclusions

Our study supports the need for training for primary care on dementia. Even more, it finds some areas, like interpersonal skills, that are usually not covered in dementia education. Adding the patient’s and care partners' voices will allow our course to be adapted to their reality and expectations.
Variations in metabolic risk factors for dementia do not affect APOE‐mediated cognitive or functional decline in patients with Alzheimer’s disease from São Paulo, Brazil
Authors: Oliveira Fabricio Ferreira , Chen Elizabeth Suchi , Smith Marilia Arruda Cardoso , Bertolucci Paulo Henrique Ferreira
Published: December 2023

Background

Midlife cerebrovascular risk, low education and copies of APOE‐ε4 are risk factors for Alzheimer’s disease (AD), whereas metabolic derangements have been associated with dementia onset. This prospective study aimed to explore the impacts of variations in metabolic risk factors on progression of AD in São Paulo, Brazil.

Methods

Outpatients with late‐onset AD according to National Institute on Aging – Alzheimer’s Association criteria were assessed for APOE haplotypes (rs7412 & rs429358 genotyped by way of TaqMan® Real‐Time Polymerase Chain Reaction technology) and variations in one year of the following potential metabolic predictors: fasting glycemia, TSH, free T4, vitamin B12, and folic acid. Metabolic variations were assessed in accordance with concurrent variations in the Clinical Dementia Rating Sum‐of‐Boxes, the Index of Independence in Activities of Daily Living, Lawton’s Scale for Instrumental Activities of Daily Living, and the Mini‐Mental State Examination in multiple linear regression models for all patients, and after stratification according to APOE‐ε4 carrier status, with the threshold of significance set at p<0.05.

Results

Of 122 patients, there were 81 women (66.4%) and 41 men (33.6%), 69 APOE‐ε4 carriers (56.5%) and 53 APOE‐ε4 non‐carriers (43.5%). The mean estimated age at AD onset was 73.13±7.1 years‐old. Overall, 120 patients used a cholinesterase inhibitor (98.4%), and 90 patients used Memantine (73.8%). All test scores were significantly different at the end of one year (p<0.01), except for the Mini‐Mental State Examination (p = 0.13). None of the potential metabolic predictors varied significantly after one year (p>0.16), and no variations in metabolic risk factors were concurrently associated with variations in the Clinical Dementia Rating Sum‐of‐Boxes (p>0.17), the Index of Independence in Activities of Daily Living (p>0.09), Lawton’s Scale for Instrumental Activities of Daily Living (p>0.22), or the Mini‐Mental State Examination (p>0.40), neither for APOE‐ε4 carriers (p>0.28), nor for APOE‐ε4 non‐carriers (p>0.07).

Conclusions

Lifetime metabolic risk factors may affect onset of AD, but concurrent variations in metabolic parameters seem to have no associations with cognitive or functional decline in such patients, regardless of APOE‐ε4 carrier status. (Supported by FAPESP grant #2015/10109‐5)
Carer Assessment of medicaTion management guidanCe for people living with dementia at Hospital discharge (CATCH): A national cross‐sectional survey
Authors: Sawan Mouna J , Clough Alexander J , Mirzaei Ardalan J , Jeon Yun‐Hee , Schneider Carl R , Gnjidic Danijela , Chen Timothy
Published: December 2023

Introduction

Transitions of care are a major contributing factor to medication‐related adverse events in people with dementia. There is limited knowledge on how well guidance on medication management is provided to carers at hospital discharge, and there is no tool that comprehensively reports on medication management guidance at discharge. The study aim was to evaluate carers’ experiences of medication management guidance for people with dementia at hospital discharge and explore the underlying factors of the CATCH tool as preliminary validation of the tool.

Methods

A cross‐sectional survey of the CATCH tool was distributed across Australia between March and November 2022. The CATCH tool contained 30 Likert‐type items and three dichotomous (yes/no) items. The results of the survey were analysed descriptively, and exploratory factor and regression analyses were performed.

Results

A total of 185 survey responses were completed (completion rate 66.8%). Most respondents were informal carers (n = 116, 62.7%), and were predominantly provided medication management guidance on the day of discharge (n = 79, 42.7%). One‐third (n = 61, 33.0%) responded that medication management guidance could be improved. Regarding the safe use of medications, respondents felt information was not well provided on: medications that may interact with each other (n = 30, 17.6%), possible side‐effects of medications (n = 28,16.1%), and medications that might act on the brain (n = 27, 15.8%). Thirty respondents (17.8%) reported that they were not included in decisions by hospital staff about medications for people with dementia. The CATCH tool contained two factors: 1) person‐centred guidance in the safe use of medications during and after discharge; and 2) support of carers in medication management. Internal consistency of all factors were acceptable with Cronbach’s alpha (>0.8). The carer reported measure of how medication management guidance is provided is positively related to their confidence in management of medications post‐discharge and satisfaction (p< 0.05 for both).

Conclusion

Opportunities to improve delivery of person‐focused medication management guidance involve provision of information on the safe use of medications to the carer and engagement in medication decisions. The CATCH tool is the first scale developed that evaluates person‐centred medication management guidance and support provided to carers of people with dementia at discharge.
Day care program for older adults with dementia: A multidiscipilinary approach for patients and family caregivers from Argentina
Authors: Feldberg Carolina , Tartaglini María Florencia , Guyet Gisela , Vilas Silvia , Jacoboni Marina , Buttazzi Melina , Kasten Sergio , Teran Claudio , Astudillo Manuel , Garcia Susana , Gimenez Ariel
Published: December 2023

Background

Day care programs for older adults with dementia is an effective strategy that allows prolonging the functionality of the elderly, their support and that of their family reducing home care costs and delaying the institutionalization of patients with cognitive impairment. The aim of the present work is to describe the main goals and the implementation of a multidisciplinary day care program for patients with dementia and their family caregivers in Argentina.

Method

Subjects: 22 patients and their family caregivers, who attend a day care program in Argentina. Instruments: socio‐demographic and psychosocial questionnaire of both patient and caregiver (built ad hoc) Patient: MMSE, GDS, HAD‐A, PANAS‐VRARG, EQ‐5D and instrumental and basic habilites of daily living. Family caregiver: Zarit Burden Interview. Procedure: The intervention for patients consists of two different lines of work, one for the patient, and another for the family member. The activities are coordinated by a multidisciplinary group of professionals. Regarding the caregiver, individual orientation interviews and therapeutic group spaces and psycho‐educational material are offered.

Result

Preliminary data of 22 patients and caregivers, who have taken part in the program so far, indicate that: Patient: median age was years 75,27 old (ds = 9,28), % 63,6 of which are woman. The values obtain in the instrument are: MMSE 22,45 (ds = 4,78) GDS 4,47 (ds = 3,73), HAD‐A 3,66 (ds = 3,39), (PANAS ‐E‐VRARG) Negative ítems 7,70 (ds = 3,11) (PANAS ‐E‐VRARG) Positive ítems 18,7 (ds = 3,13), EQ‐5D 77,35 (ds = 16,21) and BHDL 93,63 (ds = 13,10), IHDL 9,1 (ds = 3,31) . And for family caregivers the mean age was 65,27 old (ds = 11,37), % 66,71 of which are woman. Caregivers Zarit Burden Interview mean score was 40,18 (ds = 11,35).

Conclusion

Our findings concur with those presented in scientific literature and support the WHO recommendations regarding the need to implement multidisciplinary programs for patients with dementia and family caregivers, in order to moderate the impact that providing care for an elderly relative with a neurological disease has on them.
Dementia care navigation: A systematic review on different models and their prevalence
Authors: Giebel Clarissa , Reilly Siobhan , Gabbay Mark , Dickinson Julie , Tetlow Hilary , Hogan Hayley , Griffiths Alys Wyn , Cooper Claudia
Published: December 2023

Background

Dementia Care Navigators (DCNs) are professionals without clinical training, who provide individualised emotional and practical support to people living with dementia, working alongside clinical services. Navigator services have been implemented widely but the service offered vary without a consistent overview provided. The aim of this narrative systematic review was to describe and compare existing models, and to synthesise evidence regarding their implementation and impacts.

Methods

The review was registered on PROSPERO [CRD42021292518]. Three electronic databases were searched and included studies reported on a DCN model, defined as a service in which non‐clinically trained workers provide personalised advice and support to people with dementia and/or carers in the community. Two independent reviewers screened abstracts and titles and read through full papers for inclusion. Risk of bias was assessed using the Standard Quality Assessment QualSyst.

Results

We included 13 papers (six studies). All models were US‐based and only varied by integration and training provided. Studies reported different degrees of impact on service utilisation and on symptoms and mental well‐being of people with dementia and their carers, with too little evidence to draw substantial/meaningful conclusions. One study evidenced greater impacts on people with more advanced dementia compared to earlier stages.

Conclusions

DCN models have the potential to effectively provide non‐clinical support to people with dementia and carers from the point of diagnosis. Further research from countries other than the USA, focusing on the impact on social care and social support service access and utilisation, and utilising similar stablished outcome measures are required.
Application of Wavelet Leader Based Analysis to characterize different neurodegenerative disease
Authors: Azizi Tahmineh
Published: December 2023

Background

Neuro‐degenerative diseases influence significantly the gait behavior and the ability to move.

Method

To explore the etiology of neuro‐degenerative disease, it would be useful to characterize gait dynamics. The purpose of this study is to classify different neuro‐degenerative diseases using fractal geometry.

Result

We noticed that neither SPD nor FD alone were sufficient to separate different classes of patients and healthy people. In addition, when WLM and scaling exponent were used as a classifier, the three classes could not be well separated. However, this study revealed that we have a wide range of exponents for some of the recordings which indicates they have multifractal structure and need to be indexed by different exponents as decomposed into different subsets. In other words, these multifractal subjects require much more exponents to characterize their scaling properties compared to monofractal gait recordings which their spectrum displays a narrow width of scaling exponent.

Conclusion

Although SPD, FD and WLM may not be able to classify gait recordings, however, they can be used as comprehensive frameworks to characterize the fractal behavior of gait recordings of different neuro‐degenerative diseases.
The Effectiveness of Reminiscence Therapy in Improving Cognitive Functions And Psychological Wellbeing in Older Adults With Early Dementia ‐ The Randomized Control Trial
Authors: Ho‐Yin Lai Frank
Published: December 2023

Background

Reminiscence therapy (RT) is a trending type of non‐pharmacological intervention in dementia care. RT is using life histories recalling and re‐experiencing the life events in older people in order to improve their psychological well‐being through the volitional or non‐volitional process of recollecting memories from their past.

Method

Participants' selection inclusion criteria are: (a) aged 65 or above, (b) early stage of dementia that was screened by the Montreal Cognitive Assessment (MoCA) with scoring of 17‐19, and (c) can read written instruction and consent. Participants were randomly assigned by block randomization with randomized block procedure. The participants attended eight group sessions, with each session lasting for 60 minutes. Sessions were administered two times a week over a 4‐week period. Participants' depressive symptoms were evaluated by Geriatric Depression Scale (GDS), Subjective well‐being (the cognitive components) was measured by Satisfaction With Life Scale (SWLS), mood change as measured by Visual Analogue Mood Scale (VAMS). All these evaluation were conducted baseline, mid‐way evaluation and post‐evaluation by a registered Occupational Therapist.

Result

Forty older people (29 male and 11 female) were eligible for the study. There was significant difference on depressive symptoms (p = .02, t = ‐2.38), mood change (p = .03, t = ‐3.38), but marginally significant in subjective well‐being (p = .05, t = ‐1.03) between intervention and control group. Further analyses were conducted whether depressive symptoms and mood change effect individuals' subjective well‐being. A two‐way ANOVA revealed that there was not a statistically significant interaction between the effects of depressive symptoms and mood change (F(3, 16) = 1.242, p = .311). Simple main effects analysis showed that depressive symptoms did not have a statistically significant effect on subjective well‐being (p = .975). Simple main effects analysis showed that mood change did have a statistically significant effect on subjective well‐being (p < .000).

Conclusion

The findings of this study affirmed the benefit of RT to older people with early stage of dementia through improving depressive symptoms, mood and marginally on their subjective well‐being. The research data available support the inclusion of a structured RT as a part of the routine care given to older people. There are some limitations of our study.
The association of bone mineral density and dementia: the Rotterdam Study
Authors: Xiao Tian , Ghatan Samuel , Mooldijk Sanne S. , Trajanoska Katerina , Oei Ling , Gomez M. Medina , Ikram M. Kamran , Rivadeneira Fernando , Ikram M. Arfan
Published: December 2023

Background

Low bone mineral density and dementia commonly co‐occur in the elderly, with bone loss accelerating in dementia patients due to physical inactivity and poor nutrition. However, uncertainty persists over the extent to which bone loss already exists prior to the onset of dementia. Therefore, we investigated how dementia risk was affected by bone mineral density at various skeletal regions in community‐dwelling older adults.

Method

In a prospective population‐based cohort study, bone mineral density at the femoral neck, lumbar spine, and total body and the trabecular bone score were obtained using dual‐energy X‐ray absorptiometry (DXA) in 3,651 participants free from dementia between 2002‐2005. Persons at risk of dementia were followed up until 1 January 2020. For analyses of the association between bone mineral density at baseline and the risk of incident dementia, we used Cox proportional‐hazards regression analyses, adjusting for age, sex, educational attainment, physical activity, smoking status, body mass index, systolic blood pressure, diastolic blood pressure, cholesterol level, high‐density lipoprotein cholesterol, history of comorbidities (stroke and diabetes mellitus), and APOE genotype.

Result

Among the 3,651 participants (median age 72.3±10.0 years, 57.9% women), 688 (18.8%) developed incident dementia during a median of 11.1 years, of whom 528 (76.7%) developed Alzheimer’s disease. During the whole follow‐up, participants with lower bone mineral density at the femoral neck (per SD decrease) were more likely to develop all‐cause dementia (Hazard ratio [HR] total follow‐up: 1.12, 95% Confidential interval [CI]: 1.02‐1.23) and Alzheimer’s disease (HR total follow‐up: 1.14, 95% CI: 1.02‐1.28). Within the first ten years following baseline, the risk of dementia was greatest for groups with the lowest tertile of bone mineral density (femoral neck bone mineral density, HR0‐10years 2.03; 95% CI, 1.39–2.96; total body bone mineral density, HR0‐10years 1.42; 95% CI, 1.01‐2.02; trabecular bone score, HR0‐10years 1.59; 95% CI, 1.11‐2.28).

Conclusion

In conclusion, participants with low femoral neck and total body bone mineral density and low trabecular bone score were more likely to develop dementia. Further studies should focus on the predictive ability of bone mineral density for dementia.
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

Background

Alzheimer’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).

Method

249 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.

Result

Low 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.

Conclusion

In 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

Background

The 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.

Method

Eye‐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.

Result

Logistic 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.

Conclusion

EM 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

Background

As 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.

Method

Seven 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.

Result

Our 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).

Conclusion

Our 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

Background

Like 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.

Method

This 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).

Result

When 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).

Conclusion

C‐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

Background

Family 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).

Method

This 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.

Result

Multiple 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.

Conclusion

This 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

Background

We report a case of meningoencephalitis with reversible isolated cognition impairment without abnormal MRI findings.

Method

A 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.

Result

The 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.

Conclusion

Many 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

Background

Progression 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.

Method

Primary 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).

Result

Power 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.

Conclusions

PMRM 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

Background

We 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.

Method

Uninoculated 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.

Result

An 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.

Conclusion

The 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

Background

Unequal 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.

Method

We 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.

Result

22.4% 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).

Conclusion

To 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

Background

In 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.

Method

The 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.)

Participants

Combined 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.

Results

The 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%.

Conclusions

In conclusion, race is associated with cognitive decline depending on age and state of residency.