bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of COVID‐19 and Positive Interactions on Children’s Mental Representations of the Elderly and Dementia: A Drawing‐based Study
Authors: Bormans Kasper , Zwakhalen Sandra
Published: January 2025

Background

Amidst the global impact of COVID‐19, this study delves into how restrictions and positive interactions shape children’s mental images of the elderly and dementia. We organized drawing sessions with three groups to investigate the malleability of children’s perceptions, offering crucial insights for future Alzheimer’s research.

Method

This study gathered 848 children’s drawings from 106 ten‐year‐old children in Flanders and the Netherlands. Participants were asked to make four drawings: an older person, a healthy older person, an unhealthy older person, and their grandparent. The same drawing session is conducted before and after sixteen weeks. The children were divided into three groups: one group (N = 30) drew the elderly after a peak of COVID‐19 with strict restrictions, resulting in significantly smaller drawings (up to 33% on average). Another group (N = 34) drew the elderly after positive interactions with their grandparents and individuals with dementia, leading to considerably larger drawings (up to 21% on average), with more vibrant colours and more social elements. The third group (N = 42) drew the elderly without COVID‐19 restrictions and any specific intervention, resulting in a lack of changes in terms of size, colour usage, and content.

Results

The findings suggest that the mental landscape of children is malleable. The different interventions, including exposure to COVID‐19 restrictions and positive interactions with elderly individuals, have a substantial impact on the size, colourfulness, and social aspects of the children’s drawings.

Conclusion

This research provides important insights for future Alzheimer’s studies, particularly in the area of nuanced imagery surrounding ageing and dementia. The findings showed that children’s perceptions of the elderly may be influenced by various factors, highlighting the potential for interventions to shape their mental representations.
READD‐ADSP Kenya: Opportunities for recruitment of participants for Alzheimer’s Disease genetic research in Sub‐Saharan Africa
Authors: Musyimi Christine W. , Mutiso Victoria , Akinyemi Rufus O. , Kalaria Raj , Ndetei David
Published: January 2025

Background

The recruitment of individuals for Alzheimer’s disease (AD) genetic studies particularly those with low socioeconomic status, and living in rural areas remains a challenge in Sub‐Saharan Africa (SSA), due to stigma‐related cultural beliefs that hinder their participation. The Recruitment and Retention of Alzheimer’s Disease Diversity Genetic Cohorts in the ADSP (READD ‐ ADSP) project is a case‐control genetic epidemiological study involving individuals who are living with AD and disease ‐ free healthy control individuals. The aim is to build a resource that greatly expands Alzheimer’s disease genetic studies in the currently underrepresented African ancestry populations and Hispanic/Latinx individuals.

Method

The READD‐ADSP study uses a comprehensive and community‐sensitive approach towards recruitment. We employed a four‐level systematic community approach to recruitment of cases of AD and matching healthy controls of individuals aged 60 years and above. We employed the following steps: (i) Creating awareness and reducing stigma through implementation of a dementia anti‐stigma intervention; (ii) Dementia screening to promote early detection of dementia, (iii) Clinician confirmatory diagnosis, and (iv) Ascertainment of AD through a battery of neuropsychological assessments by a clinician and psychologist.

Result

Stigma reduction efforts resulted in reduction in negative beliefs and attitudes related to treatment, living well with dementia and care for the general public. This provided an opportunity for Community health workers to screen 3,546 older adults for dementia in community settings in Makueni County, Kenya. Confirmatory diagnosis was provided by a mental health nurse, resulting in a database for recruitment of 200 cases of AD and 200 controls to understand AD genetic architecture. By leveraging on this community‐based participatory research approach, 23 cases of AD and 21 controls have been recruited within the READD‐ADSP project in Kenya.

Conclusion

The adoption and implementation of novel and systematic recruitment strategies in SSA could address local barriers to recruitment, improve best practices in AD research and ultimately advance development of targeted interventions in underrepresented community settings. This context‐specific approach could also allow researchers to be more fully empowered to respond to challenges within the recruitment process in order to enhance enrolment and retention low‐resource settings.
Racial Disparities in Cognitive Function & Mild Cognitive Impairment: Effects of Income, Education, and Discrimination in the Midlife in the United States (MIDUS) Study
Authors: Mann Frank D , Cuevas Adolfo G , Ong Anthony D , Corley Samantha S , Freilich Colin D , Markon Kristian E , Clouston Sean A.P. , Krueger Robert F.
Published: January 2025

Background

Racial differences in the prevalence of mild cognitive impairment (MCI) and Alzheimer’s Disease and related dementia (ADRD) are well documented in aging populations. Using data from a large longitudinal study of adults, Black‐White disparities in mild cognitive impairment (MCI) were estimated and putative mediators of Black‐White disparities in cognitive function were examined.

Method

The prevalence of MCI was determined algorithmically for Black and White adults, and longitudinal indicators of income, educational attainment, and interpersonal discrimination were used to conduct a parallel mediation analysis of Black‐White disparities in executive function and episodic memory.

Result

As expected, there was a statistically significant racial disparity in the prevalence of MCI, such that MCI was more prevalent among Black adults (6.4%) than White adults (3.0%), which was statistically significant according to Fisher’s exact test (OR = 2.20, p = .041). Continuous distributions of executive function, episodic memory, and general cognition also differed significantly for Black and White adults (range of Cohen’s d = [0.38, 0.76], p‐values < .01), as did putative mediators of Black‐White disparities in cognitive outcomes, including income, educational attainment, and exposure to discrimination (range of Cohen’s d = [0.26, 1.07], p‐values < .01). Parallel mediation analyses indicated that household income, educational attainment, and interpersonal discrimination were all statistically significant (p‐values < .005) mediators of Black‐White disparities.

Conclusion

Approximately 1/3 of the observed Black‐White disparity in executive function, episodic memory, and general cognition was accounted for by racial group differences in income, education, and cumulative exposure to interpersonal discrimination, which included lack of support from coworkers and supervisors. Conversely, the remaining 2/3 of the Black‐White racial disparity was neither explained by group differences in income, education, nor exposure to discrimination. Future research should focus on identifying additional socioeconomic and modifiable interpersonal factors that account for Black‐White disparities in cognitive dysfunction and mild cognitive impairment in aging populations.
Cost‐effectiveness analysis of the multimodal intervention for dementia prevention: post‐hoc sub‐group analyses of the J‐MINT
Authors: Takashi Naoki , Ohtera Shosuke , Kuroda Yujiro , Arai Hidenori , Sakurai Takashi ,   J‐MINT study group
Published: January 2025

Background

This post‐hoc subgroup analysis aimed to estimate the potential cost‐effectiveness of a Japanese multimodal intervention trial for the prevention of dementia (J‐MINT) from a societal perspective.

Method

Using a Markov model, we estimated the economic impact of J‐MINT on disease prevention, drawing on data from the 2019 J‐MINT trial and relevant published literature. The trial, a randomized controlled trial (RCT), focused on participants aged 65 to 85 years with mild cognitive impairment. Participants were randomly assigned either a multidomain intervention group (comprising management of vascular risk factors, physical exercise, nutritional counseling, and cognitive training) or a standard care group (involving vascular risk factor management and receipt of health‐related information every two months). The Markov model consists of five states: at‐risk, mild, moderate, severe dementia, and death. By simulating care costs and quality‐adjusted life years (QALYs), we estimated the incremental cost‐effectiveness ratio (ICER). The simulation spanned from ages 65 to 100, utilizing the Simpson 1/3 rule for correction, with a discount rate of 0.02. The intervention effect was assumed to persist for the remaining lifetime post‐program. Care costs encompassed medical care, public long‐term care, and informal care. The intervention cost was derived from the J‐MINT trial data. In addition to the base case analysis, sensitivity and scenario analysis were conducted to evaluate uncertainty and heterogeneity.

Result

Costs were JPY 18,493,579 and JPY 18,056,997 and QALYs were 12.37 and 12.46 for standard of care and J‐MINT, respectively. This translated to savings of JPY 436,582 (US$ 2,952.01) and QALY gain of 0.09 per person, affirming the dominance of the J‐MINT.

Conclusion

Our estimation supports the potential cost‐effectiveness of multimodal intervention trials, exemplified by J‐MINT, for dementia prevention.
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

Background

Identifying 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.

Methods

This 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.

Results

According 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.

Conclusions

Age, 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

Background

Several 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.

Method

We 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.

Result

Patients 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).

Conclusion

These 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

Background

Dietary 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).

Method

We 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.

Result

During 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.

Conclusion

Adherence 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

Background

Clinical 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).

Method

I‐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.

Result

ABC 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.

Conclusion

Individual 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

Background

People 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.

Methods

We 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.

Results

A 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).

Conclusions

Physical 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

Background

Pro‐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.

Method

From 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.

Result

Among 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.

Conclusion

A 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

Background

The 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.

Method

Data 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.

Results

Table 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.

Conclusions

This 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

Background

Exercise 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.

Method

This 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.

Result

In 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).

Conclusion

Six 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

Background

Commonly 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.

Method

Using 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.

Result

Data 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).

Conclusion

SCIRS appears to be a valid measure of cognitive function, showing better variance among individuals with severe cognitive impairment, as compared to MoCA.
Evaluating DTI‐ALPS, an imaging surrogate for glymphatic clearance, in a large population‐based sample
Authors: Satpathi Siddhartha , Reid Robert I. , Przybelski Scott A. , Raghavan Sheelakumari , Gunter Jeffrey L. , Knopman David S. , Petersen Ronald C. , Cogswell Petrice M , Jack Clifford R. , Radford Jonathan Graff , Vemuri Prashanthi
Published: January 2025

Background

Diffusion tensor imaging along perivascular spaces index (DTI‐ALPS), which measures diffusivity increases in the perivascular spaces along the medullary veins, is being increasingly utilized as a surrogate marker of glymphatic clearance (Taoka et. al. Jpn J Radio 2017). Lower DTI‐ALPS index means higher measured diffusivity from the perivascular space, and so it is expected to decrease with age. However, correlation with aging and dementia markers have not been systematically evaluated. The goal of this work was to automatically estimate DTI‐ALPS in a large sample and evaluate the variance explained by various demographic and imaging markers.

Methods

We identified 2739 participants aged 30+ years (mean 69.6, 48% female, 88% CU) in the population‐based Mayo Clinic Study of Aging with diffusion MRI. We estimated DTI‐ALPS through automated placement of regions as published previously (Liu et al. AAIC 2023) and shown in Figure 1. We examined the associations of DTI‐ALPS with demographics (age, sex), vascular risk (cardiovascular and metabolic condition score), clinical data (diagnosis, global cognition) and imaging markers (white matter hyperintensity (WMH), global amyloid load from PIB‐PET, and the temporal meta‐ROI Tau‐PET SUVR) using partial Pearson correlations and ANCOVA with adjustments for age and sex.

Results

DTI‐ALPS was negatively correlated with age, higher in females, declined with vascular risk, and lower in MCI/dementia groups (Figure 2). Higher WMH and higher amyloid were associated with lower DTI‐ALPS whereas Tau‐PET SUVR was not associated with DTI‐ALPS.

Conclusions

DTI‐ALPS can be automatically computed in large samples. Vascular risk and WMH had stronger associations with the computed DTI‐ALPS compared to AD biomarkers (amyloid and tau) suggesting that the surrogate was more likely linked to vascular injury.
Insights from Functional MRI: Understanding the Mechanisms underlying Reserve and Brain Maintenance
Authors: Bartrés‐Faz David , Cabello‐Toscano María , Andersson Micael , Vidal‐Piñeiro Didac , Pascual‐Leone Alvaro , Walhovd Kristine B , Fjell Anders M , Nyberg Lars , Vaqué‐Alcázar Lídia
Published: January 2025

Background

Cognitive reserve (CR) and Brain Maintenance (BR) are constructs defined at a theoretical level (Stern et al., Neurobiol Aging, 2021 Apr, 124:100‐103). Our aim was to propose a reproducible procedure to compare CR‐like of BR‐like mechanisms underlying interindividual differences in memory stability.

Method

Leveraging data from the Lifebrain consortia (Walhovd et al. Eur Psychiatry. 2018 Jan;47:76‐87) we gathered information regarding 1) episodic memory (EM) stability, defined as those subjects showing no negative memory changes across two time point assessments (i.e., change ≥0), 2) brain structure and 3) brain functionality (resting‐state functional magnetic resonance imaging [MRI]) changes). We designed a unified approach where at each step an analysis between EM and multimodal MRI‐based measures provides a general metric, referring to either associations between EM and hippocampal (HC) volume changes, or to EM and fMRI connectivity changes (see Figure). This aimed to distinguish a ‘BM – Pathway 1’ identifying those subjects presenting a correspondence between both stability of EM and of HC volumes (i.e x≥0 & y≥0 quadrants of the upper left scatterplot) and a, ‘BM ‐ pathway 2’ reflecting a correspondence between stability of EM and HPC fMRI functionality (i.e x≥0 & y≥0 quadrants of the bottom right scatterplot). Finally, a CR ‐ pathway (‘deviant cases’ in Figure) was defined for subjects where a discrepancy between EM stability and their neural substrates was found (i.e. x>0 and y<0 quadrants in both scatterplots).

Result

Findings obtained from N = 532 participants (67.8 years at baseline, 294 women) revealed that N = 275 exhibited memory stability over time. Present analyses show that from those, N = 166 (60%) could be classified as BM ‐pathway 1 at the first step, whereas N = 109 (40%) cases were classified as CR ‐ pathway. Further results from a subsample, indicate that CR ‐ pathway cases exhibited a positive change in EM and negative in HC volumes, evidencing reductions in functional connectivity between HC and the Medial Prefrontal node from the dorsal Default Mode Network.

Conclusion

The present approach combining structural and functional MRI to study CR and BM constructs shall provide new relevant empirical data helping to clarify the conceptual boundaries between these categories.
Association between anticholinergic burden and volumes of the basal forebrain and hippocampus across the Alzheimer’s disease spectrum ‐ data from the DELCODE study
Authors: Kilimann Ingo , Peltner Jonas , Levin Fedor , Spottke Annika , Peters Oliver , Düzel Emrah , Jessen Frank , Haenisch Britta , Teipel Stefan
Published: January 2025

Background

Drugs with desirable and undesirable anticholinergic effects influence cognitive performance and increase the risk of dementia later in life. MRI imaging studies showed structural effect of these substances on basal forebrain and hippocampus, key regions of Alzheimer’s disease pathology.

Methods

We analyzed data from 787 participants of the DELCODE study with a diagnosis of subjective cognitive impairment (SCD), mild cognitive impairment, Alzheimer’s disease dementia, 1st degree relatives of people with dementia and cognitively healthy controls. We tested for associations between basal forebrain and hippocampal volume and anticholinergic medication exposure using the anticholinergic burden (ACB) score, modified for drugs approved in Germany. Furthermore, we investigated the influence of ApoE 4 status on possible effects.

Results

Among all cases, we found no statistically significant association between the ACB sum score and volume of hippocampus or basal forebrain. Within diagnostic groups, an association between ACB score and hippocampus volumes was only detectable in participants with a diagnosis of SCD; all other diagnostic groups showed no association. Dividing the SCD group into ApoE 4 positive and negative status, the significant effect on hippocampus volume only remained in the ApoE 4 negative group. Additionally, there was a significant effect on the basal forebrain volume. No associations were seen in the ApoE 4 positive group.

Conclusion

A structural effect of anticholinergic load was shown in this cohort as in previous studies. It is interesting to note that the association can only be mapped in the group of people with a subjective cognitive disorder without an ApoE 4 risk allele. An effect of the anticholinergic burden could therefore be particularly relevant if no other risk factors such as ApoE 4 are present.
An atypical clinical phenotype is a risk factor for higher mortality in Alzheimer’s disease
Authors: Bader Ilse , Groot Colin , van der Flier Wiesje M. , Pijnenburg Yolande A.L. , Ossenkoppele Rik
Published: January 2025

Background

Survival estimates for individuals with Alzheimer’s disease (AD) are informative to understand the full disease trajectory. A previous meta‐analysis estimated the mean survival of AD patients at 5.8 years from diagnosis, but precise estimates for atypical AD variants are scarce. Atypical AD variants are characterized by a non‐amnestic phenotype, a relatively early‐onset and lower prevalence of APOE4, which are all possible modulators of clinical trajectories. Here we aimed to evaluate how phenotypical atypicality affects mortality for posterior cortical atrophy (PCA; visual‐AD), logopenic variant primary progressive aphasia (lvPPA; language‐AD) and behavioral‐AD (bvAD) versus a typical AD reference group while taking other risk‐modulators into account.

Method

2084 amyloid‐positive cases from the Amsterdam Dementia Cohort were grouped into typical AD (n = 1802) versus atypical AD (n = 282; PCA [n = 112], lvPPA [n = 88], and bvAD [n = 82]) cases. Kaplan‐Meier analysis was performed to obtain survival estimates from diagnosis to death. Cox proportional‐hazard models were performed to assess effects of atypical AD on mortality, using typical AD as the reference group. We modeled atypical AD subtypes separately (model‐1) or combined (model‐2) while accounting for the potential effects of age, sex, education, MMSE and APOE4 on mortality. A Likelihood‐ratio test was performed to assess whether model‐2 with atypical AD provided a better model‐fit than model‐2 without atypical AD.

Result

Table‐1 provides sample characteristics. Median survival times were 6.3[95%CI:5.7‐7.6] for lvPPA and 6.0[5.4‐6.9] for PCA, compared to 7.0[6.7‐7.2] for typical AD. The median survival time for bvAD 5.9[4.3‐9.0] could only be extrapolated given that 44% had deceased (Figure‐1a). Adjusted median survival times were 7.0[6.7‐7.2] for typical and 6.1[5.7‐6.5] for atypical AD as a combined group (Figure‐1b). In model‐1, PCA (HR = 1.37[1.06‐1.78]), male sex (HR = 1.44[1.28‐1.62]), age (HR = 1.02[1.01‐1.03]), and lower MMSE (HR = 0.93[0.92‐0.94]) were associated with increased mortality risk (Table‐2). All atypical AD variants combined were associated with increased mortality risk (HR = 1.36[1.14‐1.63]) compared to typical AD, and addition of atypical AD to the model significantly improved the model‐fit (X2 = 10.5;p<0.01).

Conclusion

Survival in atypical AD is shorter compared to typical AD, even when correcting for other risk‐modulators. Hence, atypicality is an important risk factor for mortality beyond age, sex, education and MMSE.
FDA Over‐The‐Counter Hearing Aid (OTC HA) Rule guides innovation to assist those with risk of cognitive decline
Authors: Gupta Elora
Published: January 2025

The recent ACHIEVE study (https://www.achievestudy.org/) demonstrated the substantial benefit of hearing aid use in those with mild‐moderate hearing loss and at increased risk for cognitive decline. The FDA’s OTC HA Rule provides a reliable basis for technology innovation to improve accessibility, affordability and wear of quality hearing aids in this population.

For over 3 years, we have been collecting real‐world data on user needs from individuals with cognitive decline risks such as age, family history, prior brain injury, heart disease and diabetes, mental health concerns, employment in high noise hazard and fall hazard industries. These individuals also had diagnosed or self‐perceived hearing loss, one‐sided hearing loss, hyperacusis, tinnitus, balance problems. We sought input on (1) OTC HA expectations (2) meaningful product features and tools (3) willingness to try OTC HAs.

The key needs for purchase decision‐making and consistent wear were:

1. Education on user‐centricity: Understanding how the FDA effectiveness and safety requirements translate to daily lifestyle and individual hearing needs

2. Confidence in quality: Understanding scope of FDA’s technical and labeling requirements and ability to distinguish from misbranded products

3. Design supporting daily activities and lifestyle: Ease of use with limitations such as avoiding social engagement and healthcare appointments, remembering HA settings, judging loudness of environmental sounds, losing hearing aids, restricted mobility and dexterity, other hearing problems such as tinnitus

4. Caregiver engagement to improve hearing aid wear: Joint decision‐making for OTC purchase, setting realistic expectations, monitoring and supporting wear, detecting worsening in hearing abilities or red flags requiring ENT consult

5. Tools to protect remaining hearing: From noise, ototoxins, earwax, other risk factors and comorbidities

6. Improving overall health and quality of life: Reliable tools for monitoring and potentially improving physical and mental health, in conjunction with hearing health, individualized and self‐paced learning that is interactive with privacy protection

7. Cost‐effectiveness and convenience: Fair pricing with quality assurance per FDA requirements, payment flexibility, maintenance at home, communicating with manufacturer

These needs can be integrated into OTC HA design and functionalities, with tools to specifically benefit those with mild‐moderate hearing loss and cognitive decline risks.
Dementias Platform UK and other similar platforms to advance research into the global epidemiology of dementia
Authors: Bauermeister Sarah
Published: January 2025

Background

Dementias Platform UK (DPUK) is a global data repository and analysis environment for optimising the use of existing longitudinal clinical and population data resources for dementias research. The DPUK Data Portal provides secure storage and access for high‐quality, multi‐modal data from over 65 cohorts across 3.6 million individuals. Data include clinical, survey, imaging and genetic outcomes and measures which allow for multi‐cohort comparison and validation work. Importantly, Data Portal resources are are free to access from anywhere in the world and targeting participation and collaboration with LMICs is a key focus. The remotely accesses data, mentoring and training resources provided by DPUK are enabling increasingly diverse international representation from LMIC researchers ‐ democratizing a research landscape traditionally more accessible for HIC researchers. Here we present the DPUK programme of work for democratizing data access and training for LMICs.

Method

1. All bona fide academic and industry researchers may access the resources of the DPUK Data Portal.

2. Tools and guidance documents are provided for the identification of cohorts and data of interest.

3. An online application is completed and the median time for data owner response is 23 days.

4. Training workshops and academies are provided for researchers at very low cost or free to LMIC participants – providing online analytical and data management training.

5. A remote mentoring programme initiated between DPUK and the IHCC (International Health Cohorts Consortium) provides early career researchers (ECRs) with opportunity to work with senior researchers – especially beneficial for those in LMICs.

Result

Over 428 research applications with 1038 users across 48 countries (11 LMICs) have been received by the Data Portal. More than 200 international researchers have attended training events across 12 countries (3 LMICs).

Conclusion

DPUK is democratizing data access and training for all researchers, including those from LMICs where resources for research are difficult to acquire and bespoke training programmes are largely inaccessible. Only by making secondary data resources and training more easily accessible and affordable will it be possible to increase LMIC representation of researchers in dementia and neurodegeneration.