bluuebunny/crossref_metadata_2025 huggingface dataset:
Rural‐urban improvements in modifiable risk factors across Tasmania from an online, public health dementia risk reduction initiative: data from ISLAND (Island Study Linking Ageing and Neurodegenerative Disease)
Authors: Roccati Eddy , Bindoff Aidan , Kitsos Alex , Fair Hannah , Collins Jessica M , King Anna E , Doherty Kathleen , Alty Jane E , Vickers James C
Published: January 2025

Background

People living in diverse rural areas have shown higher rates of Alzheimer’s disease and related dementias (ADRD) compared with their urban counterparts. Further, individuals in rural areas have higher rates of modifiable risk factors for ADRD, such as physical inactivity and alcohol misuse, that account for up to 40% of dementia cases. This study aimed to investigate the efficacy of a novel public health initiative to reduce dementia incidence in both urban and rural settings in Australia’s island state: Tasmania. We hypothesized that: 1) rural participants would display greater ADRD via risk factors, four‐year risk factor trajectories and phosphorylated tau (p‐tau) 181; and 2) both rural and urban participants would reduce their risk profiles over time.

Method

Participants were from ISLAND (Island Study Linking Ageing and Neurodegenerative Disease) and were recruited from across Tasmania (n = 2,331, 70.9% female, average age 64.3 years, 26.6% APOE e4+). All participants were invited to complete yearly online surveys on background health, demographics, modifiable dementia risk via a custom Dementia Risk Profile (DRP), complete a free 6‐week Massive Open Online Course on Preventing Dementia (PD‐MOOC) and provide a blood sample for APOE genotyping and measurement of plasma p‐tau 181 (pg/mL). Multilevel longitudinal regression models assessed change in number and type of risk factors, with effects moderated by DRP and PD‐MOOC exposure.

Result

Over four years of follow up, both urban and rural participants significantly reduced their modifiable risk factor profiles as measured via the DRP (p < 0.001). This benefit was greatest for participants who completed the PD‐MOOC. There was no significant difference in plasma p‐tau 181 (pg/mL) between urban and rural participants. Urban participants (n = 1,752; 75.2%) were significantly more likely to have a university qualification and be socioeconomically advantaged than rural (n = 579; 24.8%) participants.

Conclusion

Our ISLAND public health dementia risk reduction initiative had a positive impact on modifiable risk factor adherence in both urban and rural Tasmanian Australians. This large‐scale cohort study shows that an online targeted public health campaign to reduce incidence and prevalence of ADRDs has the capacity to benefit both rural and urban populations.
Advancing Dementia Care: Memory Aid Technology and Data‐Driven Insights for Autonomy at Home
Authors: Sanchez Alyssia A , Mihailidis Alex
Published: January 2025

Background

Assistive technology (AT) plays a crucial role in empowering people living with dementia (PLWD) to perform tasks independently, enhancing their autonomy and dignity. To build on this foundation, our proposal introduces a home‐based reminder system designed to further support PLWD in their daily lives.

Hypothesis

Memory aid technology, in particular reminder systems, can be developed to prospectively provide PLWD with autonomy and independence, to alleviate responsibilities and time commitments of caregivers and clinicians, and to enable remote behavioral monitoring.

Method

Our project is grounded in existing research and focuses on the development and implementation of an innovative home‐based reminder system. This system comprises electronic reminder units and a central base station, enabling remote behavior monitoring and communication. Caregivers can transmit reminders through a mobile application, and the reminder units display these reminders and detect when they’re acknowledged by PLWD, allowing for the collection and analysis of behavioral data. Machine learning models are employed to understand daily schedules and identify deviations from routines. We engage dyads of PLWD and family caregivers through interviews and usability testing to refine the system.

Results

Preliminary stages of development involve system development, data simulation with approximately 1000 days of reminder usage, and interviews and useability demonstrations with 8 PLWD‐caregiver dyads. These efforts indicate the potential of memory aid technology to enhance communication between PLWD and caregivers, becoming a valuable aspect of daily routines. The reminder system can evolve to monitor and analyze behavior, providing crucial insights into the daily lives of PLWD and enabling timely support and intervention when needed.

Conclusion

Through the development and evaluation of this innovative reminder system, our aim is to improve the lives of PLWD, augment their autonomy, and assist caregivers in delivering effective and personalized dementia care. The system’s potential to enhance communication and provide behavioral insights aligns with the criteria for dementia care practice proposals, offering a promising avenue for advancing care practices and contributing to broader improvements in dementia care within our aging society.
Physical activity across the adult life course and incident dementia in the Framingham Heart Study
Authors: Hwang Phillip H , Lyu Chenglin , Liu Chunyu , Schon Karin , Mez Jesse , Au Rhoda
Published: January 2025

Background

Greater levels of physical activity are associated with improved cognition and decreased risk for dementia, but it is not clear when the potential benefits of physical activity on brain health are most beneficial throughout the life course. We examined associations between overall physical activity and incident dementia among adults in early adult life, midlife and late‐life.

Method

Participants from the Framingham Heart Study Offspring cohort were included. Those in the early adult life group (26‐44 years), midlife group (45‐65 years), and late‐life group (66‐80 years) were selected from Exam 2 (1979‐1983), Exam 4 (1987‐1991), and Exam 7 (1998‐2001), respectively, who were dementia‐free at their baseline exams. Overall daily physical activity was based on the physical activity index (PAI) and analyzed as quintiles (Q1‐Q5). Diagnosis of all‐cause dementia was adjudicated by a multi‐disciplinary consensus committee through 2020. Cox models were used to evaluate associations between higher PAI (Q2‐Q5) versus low PAI (Q1) among early adult life, midlife, and late‐life groups and incident dementia.

Result

A total of 1,740 participants comprised the early adult life group (mean age = 37 years), 2,385 participants comprised the midlife group (mean age = 54 years), and 953 participants comprised the late‐life group (mean age = 71 years). Higher PAI was associated with decreased dementia risk as compared to low PAI among the midlife group (HR = 0.72; 95% CI = 0.54 – 0.94; p = 0.02) and late‐life group (HR = 0.63; 95% CI = 0.45 – 0.87; p = 0.005), but not among the early adult life group (HR = 1.00; 95% CI = 0.53 – 2.26; p = 0.81).

Conclusion

Greater levels of overall physical activity are significantly associated with reduced risk of dementia in midlife and late‐life adults. This suggests that having a physically active lifestyle earlier in life may be beneficial to brain health, though the impact of physical activity early in life and in early adulthood warrants further investigation.
The Mediating Role of Social Participation in Depression and the Occurrence of Mild Cognitive Impairment among the Elderly in China: a prospective, case control, cross‐sectional study
Authors: Qiu Xiaoyuan , Zhang Lifeng , Ye Yifan
Published: January 2025

Background

Depression is common in the elderly, which is regarded as is an important risk factor for mild cognitive impairment (MCI), and social participation has been proved to be effective in improving the mental health of the aged, while the relationship and acting path among depression, social participation and the occurrence of MCI are still unclear.

Method

This study included 190 older adults with MCI and 190 matched older adults without cognitive impairment. All participants were asked to complete Montreal Cognitive Assessment (MoCA), the Participation and Autonomy Questionnaire (IPA), the Physical Activity Scale for the Elderly (PASE) and the Short Form Geriatric Depression Scale (GDS‐15). Binary regression and linear regression were used to investigate the relationship among depression, MCI and social participation. And RMediation was used to test mediating effect of social participation between depression and MCI.

Result

The occurrence of MCI was associated with more severe depression symptom (OR = 1.542,95%CI = 1.350 to 1.743), lower subjective and objective social participation level (OR = 1.204,0.987; 95%CI = 1.099 to1.319, 0.897 to 0.890), and those with more severe depression symptom showed lower subjective and objective social participation level (β = 0.582,‐0.229;95%CI = 1.832 to 2.467,‐4.981to ‐1.801)). RMediation analysis showed that both subjective and objective social participation played a significant role in mediating the depression and the occurrence of MCI (95% CI of a*b = 31.595 to 92.236, 95% CI of a*b = 0.814 to 25.039), and the indirect effects were 22.7% and 9.68%, respectively.

Conclusion

These findings imply that depression impacts MCI directly and indirectly through social Participation. Subsequent interventions should focus on improving social participation in the elderly to achieve greater outcomes for MCI management.
Single ascending dose results from an ongoing Phase 1 study of mivelsiran (ALN‐APP), the first investigational RNA interference therapeutic targeting amyloid precursor protein for Alzheimer’s disease
Authors: Cohen Sharon , Ducharme Simon , Brosch Jared R. , Vijverberg Everard G.B. , Sostelly Alexandre , Goteti Sasikiran , Farrugia Lynn , Avbersek Andreja , Kaspar Cristin , Mummery Catherine J.
Published: January 2025

Background

Mivelsiran (ALN‐APP) is an investigational, intrathecally administered RNA interference therapeutic designed to lower levels of amyloid‐β (Aβ) peptide, a key driver of Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA) pathogenesis, by reducing upstream production of amyloid precursor protein (APP). We report additional safety, pharmacodynamic, and biomarker data from the double‐blind, placebo‐controlled, single ascending dose part of the ongoing mivelsiran Phase 1 study (NCT05231785).

Method

Patients with early‐onset AD (symptom onset <65 years of age, Clinical Dementia Rating global score 0.5 or 1.0, and Mini‐Mental State Examination score >20) were randomized to single intrathecal doses of mivelsiran (25mg, 50mg, or 75mg) or placebo and evaluated for 6 months (plus up to 6‐months follow‐up if needed to achieve washout). Primary endpoint was frequency of adverse events (AEs). Pharmacological effects of mivelsiran (secondary endpoints) and exploratory biomarkers of disease progression were also evaluated.

Result

As of November 16, 2023, 20 patients (mean [range] age, 61.3 [53–73] years; 60.0% male; 80.0% white) were randomized to mivelsiran or placebo in 25mg (N = 6, 2:1 randomization), 50mg (N = 8, 3:1), and 75mg (N = 6, 2:1) cohorts. In these pooled cohorts, AEs were reported in 19 patients (95.0%), all of mild or moderate severity (Table 1). One patient experienced two mild AEs that were considered both study drug and procedure related. No serious AEs or deaths occurred. Reductions from baseline in cerebrospinal fluid (CSF) soluble APPα and APPβ levels were rapid and sustained through ongoing data capture (i.e., Month 6 with mivelsiran 50mg and Month 10 with mivelsiran 75mg; Table 2), and were accompanied by sustained reductions from baseline in CSF Aβ42 and Aβ40 levels available through Month 6 (Table 3). Safety and pharmacodynamic data of up to 6 months from additional mivelsiran dose cohorts will be presented at the meeting.

Conclusion

In this ongoing Phase 1 single ascending dose study, mivelsiran 50mg and 75mg were well tolerated and produced robust, durable reductions in CSF levels of soluble APP and downstream Aβ42 and Aβ40, key proteins implicated in progression of AD and CAA. These interim results support further evaluation of mivelsiran in patients with AD or CAA.
Characterization of the first TREM2 small molecule agonist, VG‐3927, for clinical development in Alzheimer’s disease
Authors: Mirescu Christian
Published: January 2025

Background

TREM2 is a lipid‐sensing receptor expressed by microglial sub‐populations within neuropathological microenvironments, whose downstream signaling promotes microglial survival, plasticity, and migration. Multiple loss‐of‐function variants strongly implicate TREM2 as a key regulator of Alzheimer’s disease (AD) risk. Accordingly, TREM2 antibodies are currently in development to evaluate the therapeutic potential of TREM2 agonism in neurodegenerative diseases. Small molecule TREM2 agonist could represent a significant advancement for patients by providing potential key advantages in route of administration, superior brain penetration, and alternative mechanisms of action versus monoclonal antibodies. Herein, we share recent in vitro and in vivo preclinical data identifying VG‐3927, the first and only small molecule TREM2 agonist in clinical development as a potential disease‐modifying therapeutic.

Method

The agonist pharmacology of VG‐3927 was determined across an array of human cellular systems. Human iPSC‐derived microglia, astrocytes and neurons tri‐cultures were utilized to measure changes in microglia function and impact on neurodegeneration biomarkers in response to pharmacological and genetic modulation. Additionally, a humanized TREM2 amyloidosis mouse model (hTREM2‐5xFAD) was employed to determine the impact of VG‐3927 on AD‐associated neuropathological endpoints.

Result

Pharmacologic data suggest VG‐3927 is a highly potent, selective and brain penetrant TREM2 agonist with a favorable functional profile. In human tri‐cultures, VG‐3927 promoted anti‐inflammatory microglia activation and suppressed a broad spectrum of neurodegeneration‐associated biomarkers. Mutagenesis mapping studies demonstrated that the activity of VG‐3927 is on‐target, and results in functional effects via the coordinated clustering of TREM2. Following only 6 weeks of oral dosing in humanized TREM2 plaque‐bearing mice, VG‐3927 also reduced pathological forms of Aβ, insoluble ApoE levels, and peri‐plaque dystrophic neurites. Additional PKPD studies in non‐human primates further confirmed the brain penetrance and pharmacological activity in CNS.

Conclusion

VG‐3927 represents the first potent, selective small molecule TREM2 agonist able to favorably tune human microglia activation and impart a broadly neuroprotective profile across preclinical model systems. Initial PKPD studies have confirmed brain penetrance and pharmacological activity in CNS; an ongoing clinical study aims to further interrogate the potential of VG‐3927 as an AD modifying therapeutic with transformative potential as an orally bioavailable treatment.
Cardiovascular Health and Cognitive Function in Early Midlife: A Cross‐Sectional Analysis of the 1970 British Cohort Study
Authors: Chiesa Scott T , James Sarah‐Naomi , Hughes Alun D
Published: January 2025

Background

Poor cardiovascular health in midlife increases risk of dementia in later years. At least some of this risk may stem from early decrements in cognitive ability in those with poor cardiovascular health that are already evident by midlife. Whether such associations are causal, however, or develop in tandem due to shared factors encountered earlier in life, remains unclear.

Method

A modified version of the American Heart Association Life’s Essential 8 (LE8) cardiovascular health score was constructed in 8,226 participants (age 47 years) recruited to the 1970 British Cohort Study. Four biological (BMI, blood pressure, glucose, total cholesterol) and four behavioral (diet, physical activity, smoking, sleep) metrics were each categorized as 0 (poor), 1 (intermediate), or 2 (ideal) and summed to create the LE8 score. A cognitive test battery assessing immediate and delayed memory recall, executive function, processing speed, and overall cognitive function were chosen as outcomes. Multiple linear regressions employing multiple imputation and adjusting for a range of early (childhood socioeconomic status, household overcrowding, childhood IQ, and highest education level) and mid‐life (current socioeconomic status and malaise) factors were used to conduct analyses whilst accounting for missing data.

Result

Overall cognitive function in those classed as having ideal (LE8>13 points) cardiovascular health was 0.15 (0.04–0.27) z‐scores higher than those with intermediate (LE8 9‐13 points) and 0.42 (0.30–0.55) z‐scores higher than those with poor (<9 points) cardiovascular health. In age‐ and sex‐adjusted analyses, each 1‐point increase in LE8 was associated with a 0.02–0.06 z‐score higher cognitive function in all domains (p<0.001 for all). These associations became null for executive function and processing speed once accounting for early‐life factors, however, and were substantially attenuated for both memory domains. Further adjustment for midlife factors had little further impact on estimates. Follow‐up analyses suggested stronger relationships between midlife cardiovascular health behaviors and cognitive ability than biological factors.

Conclusion

Much of the observed relationship between cardiovascular health and cognitive ability in early midlife is likely explained by other shared early‐life factors. While a modest association still persists after accounting for these factors, the directionality of this relationship remains to be determined.
Understanding the Complexities of Caregiving for Alzheimer’s Disease and Related Dementias in Uganda: A Qualitative Insight
Authors: Onoria Joy
Published: January 2025

Background

In Uganda, caregivers of Alzheimer’s disease and related dementias (ADRD) face complex challenges, often lacking specialized skills for effective caregiving. Despite the growing prevalence of ADRD in the country, there’s a significant literature gap on caregiver selection and obstacles faced in urban and rural areas. This study aims to provide insights into the experiences of Ugandan caregivers, enhancing understanding of ADRD caregiving.

Method

This qualitative study involved 14 caregivers from Nansana and Busukuma, suburban areas of Wakiso District, Uganda. A purposive sampling strategy ensured representation across diverse age and sex groups. In‐depth interviews, each lasting to 60‐90 minutes, were conducted in Luganda to ensure cultural relevance. The interviews were meticulously transcribed verbatim, forming the basis of thematic analysis. This analysis involved a detailed coding process to compare and examine participants’ responses regarding uniformity, emerging patterns, and contradictions, thereby offering nuanced insights into the caregiving experience in ADRD.

Result

The study identified three primary themes within the caregiving experience for ADRD: relational foundations, multidimensional struggles, and the positive outcomes of caregiving. Caregiver selection is primarily influenced by existing family dynamics, with emotional bonds and patient preferences as crucial factors. Caregivers reported experiencing a spectrum of challenges, including emotional tolls, physical demands, and considerable financial sacrifices such as role reversals and the physical burden of care. Despite these challenges, many caregivers identified positive aspects, including enhanced empathy, acquisition of professional caregiving skills, and deepened sense of reciprocity. The thematic analysis provided a nuanced view of these complexities and benefits.

Conclusion

This study offers vital insights into the experiences of caregivers of patients with ADRD in Uganda, highlighting the need for culturally sensitive support systems that integrate familial dynamics and caregiver experiences into healthcare policies. Recommendations include tailored training, community‐based networks, and digital platforms for remote support. Future research should broaden caregiver demographics and employ longitudinal studies. These findings are crucial for enhancing caregivers’ and patients’ quality of life, emphasizing the indispensable role of caregivers in ADRD management in Uganda and similar settings.
Regional and national heatmaps of dementia and mild cognitive impairment over time in Greece: Recent past and current status along with predictions for 2035 and 2050
Authors: Skolariki Konstantina , Exarchos Themis , Machairaki Vasiliki , Lyketsos Constantine G. , Vlamos Panagiotis , Scarmeas Nikolaos ,   Hellenic Initiative Against Alzheimer’s Disease (HIAAD)
Published: January 2025

Background

Greece has among the largest proportions of elderly worldwide and is among the fastest aging countries in Europe. Consequently, the population suffering from mild cognitive impairment (MCI) or dementia is one of the largest in Europe. This population varies significantly within the different regions in Greece.

Method

We estimated the number of patients living with MCI or dementia in Greece and created heatmaps, by prefecture, for 4 different census periods, 1991, 2001, 2011 and 2021 (due to COVID results for 2021 were obtained in 2023). The prevalence of MCI and dementia, for men and women of different age categories (65‐69, 70‐74, 75‐79, 80‐84, 85+) were obtained from the The Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). Each prevalence for age and sex was multiplied by the respective number of people from the census, based on sex and age category.

Result

The analysis showed an increase in numbers in all prefectures, ranging for MCI from 177,898 in 1991, to 223,982 in 2001, 274,872 in 2011 and 311,189 in 2021 and for dementia from 103,535 in 1991, to 113,144 in 2001, 166,774 in 2011 and 206,939 for 2021. Projected estimates for the number of people with MCI or dementia with heatmaps were generated for 2035 and 2050, based on a Greek census projection estimating the number of people above 65 and above 85, for the above years. The projection indicates a great increase in number of persons with MCI to 375,000 in 2035 and 440,000 in 2050 and for dementia to 250,000 in 2035 and 310,000 in 2050.

Conclusion

Considering the fact that each person requires care over time from at least 2 other caregivers, the above numbers demonstrate the impact that the dementia pandemic will have in Greece. These heatmaps can be used as a tool in policy making, aiming to organize the setup and development of memory clinics and day care centers in the different prefectures in Greece, where the need is higher based on the number of patients.
Racial/Ethnic Differences in Physical Activity Participation of Dementia Caregivers in the US: Findings from the 2017 BRFSS Survey
Authors: Liang Jiaming
Published: January 2025

Background

It is well documented that participating in physical activity can help dementia caregivers alleviate stress and enhance well‐being. However, few studies have examined dementia caregivers’ needs for exercise, and the feasibility of promoting their physical activity amidst heavy caregiving responsibilities. This study compared the participation of physical activity between dementia caregivers and non‐caregivers, and examined effects of racial/ethnic identities and other sociodemographic factors on dementia caregivers’ physical activity participation.

Method

A cross‐sectional study was conducted using the 2017 Behavioral Risk Factor Surveillance System (BRFSS) Survey. Participants’ physical activity engagement was measured using four indicators: hours of (1) all physical activities, (2) moderate activities, and (3) vigorous activities in the last 30 days, and (4) whether meeting the WHO aerobic exercise recommendation. Regression and interaction analyses were used to examine associations between being dementia caregivers and physical activity participation, and factors related to physical activity status of dementia caregivers.

Result

The study included 10,158 participants (280 dementia caregivers and 9,878 non‐caregivers). Compared to non‐caregivers, dementia caregivers tend to be older (≥ 55‐year‐old, 67% vs. 55%), more likely to be women (63% vs. 51%), have a higher level of education (≥ Bachelor’s degree, 56% vs. 50%), and more likely to own houses (83% vs. 71%). Between‐group comparison found no difference between dementia caregivers and non‐caregivers on all four physical activity indicators. Regression analyses found that, Hispanic participants tend to report more hours of physical activity participation than non‐Hispanic Whites. However, interaction analyses revealed that Hispanic dementia caregivers have significantly fewer hours of participating in moderate physical activity (12.96±8.52 vs 23.20±1.10), and are less likely to meet the WHO aerobic recommendation (OR: 0.70±0.10 vs 0.83± 0.10) than Hispanic non‐caregivers. The analyses also found that dementia caregivers report fewer moderate activity hours if they are unemployed (15.71±5.92 vs. 23.44±0.99).

Conclusion

The findings suggest that dementia caregiving does not necessarily reduce physical activity hours of caregivers, unless they are Hispanic and unemployed. Future intervention development should focus on promoting moderate and aerobic exercise participation among dementia caregivers, especially in developing culturally and linguistically appropriate programs for Hispanic dementia caregivers.
Longitudinal associations between self‐reported exercise levels and Alzheimer’s related biomarkers in Autosomal Dominant Alzheimer’s Disease
Authors: Sewell Kelsey R , Doecke James D. , Sohrabi Hamid R. , Rainey‐Smith Stephanie R , Peiffer Jeremiah J , Bateman Randall J. , Morris John C. , McDade Eric , Martins Ralph N , Brown Belinda M. ,   The DIAN Study Group
Published: January 2025

Background

Accumulating evidence indicates exercise may delay or prevent the onset of Alzheimer’s disease (AD). To our knowledge, no study has investigated the longitudinal impact of exercise on AD‐related biomarkers in individuals with Autosomal dominant Alzheimer’s disease (ADAD) mutations who are destined to develop AD. This study examined longitudinal associations between self‐reported exercise levels and AD‐related biomarkers in a cohort of ADAD mutation carriers and investigated whether observed associations depended upon disease stage.

Method

This prospective cohort study included participants from the Dominantly Inherited Alzheimer’s Network (DIAN). Participants were n = 308 ADAD mutation carriers aged 39.7 ± 10.8 years (56.5% female) with data available for self‐reported exercise participation and either brain imaging (hippocampal volume, total volume, gray matter volume, white matter hyperintensities, brain Aβ), or biomarkers quantified from cerebrospinal fluid (Aβ40, Aβ42, p‐tau, t‐tau, p‐tau/Aβ42, and Aβ42/40). Associations between exercise and AD biomarkers (i.e., from brain imaging and CSF) were examined using linear mixed models.

Result

Greater weekly baseline exercise was associated with slower accumulation of brain Aβ at preclinical disease stages (β = ‐0.16, 95% CI ‐0.23 – ‐0.08), and slower decline of right and left hippocampal volume (β = 0.06, 95% CI 0.03–0.08; β = 0.06, 95% CI 0.02–0.09, respectively), total cortical volume (β = 0.03, 95% CI 0.01–0.05), total subcortical gray matter volume (β = 0.03, 95% CI 0.01–0.05), and total gray matter volume (β = 0.03, 95% CI 0.01–0.05), effects which became significant approximately 5 years before predicted cognitive symptom onset.

Conclusion

These findings demonstrate that exercise is associated with more favourable profiles of AD‐related biomarkers in those with ADAD mutations. The causal direction of this research is difficult to ascertain, thus future study designs investigating the therapeutic potential of exercise in both ADAD and late‐onset AD should be considered before clinical recommendation of exercise is implemented.
Comparing the dynamics of multiple cognitive markers for Alzheimer’s disease progression using a novel double anchoring events‐based sigmoidal mixed model
Authors: Kang Kaidi , Zhang Panpan , Dumitrescu Logan C. , Mukherjee Shubhabrata , Lee Michael L. , Choi Seo‐Eun , Scollard Phoebe , Gibbons Laura E. , Trittschuh Emily H. , Mez Jesse , Saykin Andrew J. , Buckley Rachel F. , Gao Xiaoting , Di Jianing , Crane Paul K. , Hohman Timothy J. , Liu Dandan
Published: January 2025

Background

Understanding the dynamics of markers throughout Alzheimer’s disease (AD) progression in a representative population is critical for early detection of AD. Most existing studies used a single cohort to model the dynamics of AD‐related markers, which may lead to biased and unreproducible results. The Alzheimer’s Disease Sequencing Project Phenotype Harmonization Consortium (ADSP‐PHC) harmonized rich endophenotype data across multiple cohort studies, providing valuable resources for ADRD research. Using harmonized cognitive markers from ADSP‐PHC, we modeled and compared dynamics of memory, language, and executive function over AD progression through a novel double anchoring events‐based sigmoidal mixed model (DSMM).

Method

The study included diagnostically irreversible participants with clinical diagnoses of mild cognitive impairment (MCI) and/or AD (n = 5,475; Table 1). A novel DSMM used time to the first diagnosis of AD as time scale, and extended the standard sigmoidal mixed model to include the participants with unobserved AD diagnosis by jointly modeling the duration between the first diagnoses of MCI and AD. The model provided inference about initial score, maximum decline (of score) and half‐life of decline (time from when score dropped by half) for the population. A log‐linear model characterizing the duration between clinical diagnoses of MCI and AD was adjusted for age (at MCI diagnoses), sex, apolipoprotein E‐ε4 status, and their interactions.

Result

The three cognitive markers have similar initial scores (memory: 0.33, 95%CI: 0.08‐0.54; language: 0.29, 95%CI: 0.14‐0.41; executive function: 0.31; 95%CI: 0.18‐0.40). Memory has the largest decline (β = 1.45, 95%CI: 1.01‐1.90), followed by language (β = 1.33, 95%CI: 0.81‐1.82) and executive function (β = 1.20, 95%CI: 1.01‐1.39). The half‐life of decline is the shortest for memory (β = ‐0.69, 95%CI: ‐1.72‐0.34), followed by language (β = 0.08, 95%CI: ‐0.88‐1.01) and executive function (β = 0.26, 95%CI: ‐0.41‐0.94; Figure 1).

Conclusion

A novel DSMM was used to characterize the dynamics of multiple harmonized cognitive markers related to AD progression using multiple harmonized cohorts from ADSP‐PHC, empirically determining the temporal order of decline of harmonized cognitive markers: memory, then language, and lastly executive function. The study improved the representativeness of the research sample by using multiple cohorts and harmonized cognitive markers, and DSMM helped reduce selection bias by including participants without observed clinical diagnosis of AD.
Randomised Controlled Crossover Trial Evaluating Two Caregiver‐Delivered Music Listening Interventions for Community‐Dwelling People with Dementia
Authors: Hofbauer Lena M , Rodriguez Francisca S
Published: January 2025

Background

Given that the majority of people with dementia live in their homes in the community and are primarily cared for by informal caregivers, there is a growing interest in developing interventions suitable for this setting. Further, it is important to establish how music selections can differentially affect PwD. In this pilot trial, we thus compare two caregiver‐delivered music listening MBIs with care‐as‐usual.

Methods

17 PwD‐caregiver‐dyads were randomised to receive 6 weeks of ‘MBI A’ and ‘MBI B’, the order was crossed over. As control, half of the participants also underwent 6 weeks of care‐as‐usual. MBI A consisted of fast, positively valenced music while MBI B consisted of slow, positively valenced music. The music was provided on tablet or CD. Quantitative outcomes were cognition, well‐being, quality of life, and caregiver‐reported behavioural and psychiatric symptom severity and related distress. Outcomes were analysed in separate mixed‐effect models adjusted for baseline values, period, and intervention adherence. Dyads’ descriptions of experiences were narratively summarised.

Results

Music listening was associated with an initial increase in quality of life. Further, MBI A was associated with superior delayed recall compared to MBI B (MBI A‐B: 1.04 [95% CI: 0.16, 1.92], Hedge’s gav = 0.70). Dyads’ descriptions highlight differential positive effects of MBI A and B ‘in‐the‐moment’ of listening. Positive effects of MBI A included heightened mood and movement, MBI B was associated with relaxation. Dyads suggested that future iterations of the MBI may (i) be usable by PwD on their own, (ii) contain longer playlists, and (iii) be individualised.

Conclusion

Overall, the music listening intervention created value for PwD, increasing quality of life and inducing positive experiences ‘in‐the‐moment’. The recall‐enhancing effect of listening to fast, positively valenced music over a prolonged period should be investigated further and may be relevant to targeted uses of music with PwD. While the MBI design used in the present investigation can be described as feasible overall, adapting it so that PwD may use the intervention independently may be a valuable next step.
Neighborhood social cohesion, racial composition, and walkability and dementia risk: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study
Authors: Besser Lilah M , Zanwar Preeti Pushpalata , Meyer Oanh L. , Sohn Elisabeth K. , Yen Irene H. , Kandula Namratha R. , Kanaya Alka M.
Published: January 2025

Background

Prior studies suggest that neighborhood socioeconomic status, neighborhood walkability, and neighborhood social cohesion are associated with cognitive function and dementia risk. However, little is known about how neighborhood social and built environments influence dementia risk in South Asian populations residing in the US.

Methods

We used data from 745 South Asian individuals ≥40 years in the US who completed Exam 2 (2015‐2018) of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study. Neighborhood characteristics at Exam 1 (2010‐2013) included neighborhood percentage of Asian residents (range: 0‐87%), neighborhood Walk Score (i.e., walkability) (range: 0‐100), and neighborhood social cohesion (range: 5‐25). We calculated a modified Washington Heights/Inwood Columbia Aging Project (WHICAP) dementia risk score (range: 0‐52) for Exam 2 based on age, gender, education, diabetes, hypertension, current smoking status, low high‐density lipoprotein, and high waist‐to‐hip ratio. Multivariable linear regression examined associations between neighborhood characteristics and the dementia risk score, controlling for age (in years), marital/partner status, family income, study site, years residing in the neighborhood at Exam 1, neighborhood socioeconomic status, and percentage of life lived in the US. Interaction terms tested whether associations differed by gender.

Results

Our sample was comprised of 45% women, 90% achieved a bachelor’s degree, and 84% were born in India, while the remainder originating from Pakistan, Sri Lanka, Sub‐Saharan Africa, the US, and other countries. Mean age was 59 years old (SD = 9). The mean dementia risk score was 8.4 for women (SD = 5.3) and 10.0 for men (SD = 4.8) (overall sample range: 0‐31). In multivariable analyses, greater neighborhood social cohesion at Exam 1 was associated with lower dementia risk scores at Exam 2 (estimate: ‐0.15, 95% CI: ‐0.28, ‐0.03). In stratified analysis, greater neighborhood social cohesion was associated with lower dementia risk scores for women (estimate: ‐0.28, 95% CI: ‐0.46, ‐0.10) but not men (estimate: 0.02, 95% CI: ‐0.15, 0.19) (interaction p‐value: 0.01). No associations were observed between neighborhood walkability or neighborhood percentage of Asian residents and dementia risk score.

Conclusion

Neighborhood social cohesion may help reduce the risk of dementia among South Asian middle to older‐age women in the US.
Systemic medications and dementia risk: an umbrella review
Authors: Mukadam Naaheed , Belessiotis Clara , Yap Ying Feng , Talwar Shivangi , Bruun Andrea , Li Wenqianglong , Ward Harry , Letrondo Pilar , Morelli‐Batters Madeleine , Lin Rongyu , Eskinazi Michelle , Wright Talen , Hayes Joseph
Published: January 2025

Background

Dementia is a growing global public health challenge. Previous meta‐analyses have found that systemic medications may modulate dementia risk. We aimed to provide an overview of this evidence.

Method

We conducted an umbrella review of meta‐analyses (PROSPERO CRD42021226307). MEDLINE, AMED, PsycINFO, and Embase were searched from inception to 25th January 2023. Only peer‐reviewed meta‐analyses examining dementia risk and systemic medications in humans were included, with no restrictions on language. Studies examining cognitive decline were excluded. Participant details, study types, diagnostic criteria, publication bias, heterogeneity, and summary effect estimates were extracted from publications. Study quality was assessed using the AMSTAR‐2. Data extraction and quality ratings were carried out independently by two authors.

Result

60 studies were included in the final review. Included meta‐analyses examined anti‐hypertensives (n = 17), statins (n = 7), antacids (n = 7), non‐steroidal anti‐inflammatory drugs (NSAIDs) (n = 6), diabetes medications (n = 4), hormone replacement therapy (n = 4), androgen deprivation therapy (ADT) (n = 4), psychotropic medications (n = 4), anticholinergics (n = 3), anticoagulants (n = 2), and vitamin E (n = 2). Number of participants in each review ranged from 842 to 9,162,509. Mean age ranged from 59 to 78 years, and between 0 and 100% of participants were female. There was a trend towards decreased risk of dementia with antihypertensives, statins, NSAIDs, anticoagulants, and vitamin E, and towards increased risk with ADT, benzodiazepines, and anticholinergic medications.

Conclusion

Available data were primarily observational, leading to biases such as confounding by indication, and few studies met a high number of critical quality criteria. Randomised‐controlled data were rare but supported an association between treatment of hypertension and reduced dementia incidence and a possible association between hormone replacement therapy and increased risk of dementia. Our review provides an overview of what kinds of medication are associated with dementia risk, to guide clinical practice and future research. Currently there are no systemic medications that should be prescribed with the primary aim of reducing dementia risk.
Sleep Patterns in Midlife and Brain Age
Authors: Cavaillès Clémence , Dintica Christina S. , Habes Mohamad , Leng Yue , Carnethon Mercedes , Yaffe Kristine
Published: January 2025

Background

Previous studies have linked sleep disturbances with an increased risk of dementia among older adults. However, the association between sleep patterns and brain health earlier in life is less understood. We aimed to determine how sleep in early midlife relates to an MRI‐derived indicator of brain age in late midlife.

Method

We analyzed 619 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study. At the study baseline (2000‐2001), participants answered six binary questions about their typical sleep patterns, including general sleep quality, sleep duration, daytime sleepiness, trouble falling asleep, waking up at night, and early awakening. We quantified the number of poor sleep characteristics (range from 0 to 6) and categorized them into three groups (0‐1; 2‐3; >3). On average 15 years later (2015‐2016), brain MRIs were obtained, and a high dimensional pattern analysis was used to determine brain age by quantifying individual differences in age‐related atrophy. We used multivariable linear regressions to examine the association between sleep patterns and brain age.

Result

At baseline, the participants’ mean age was 40.4 (±3.4) years, 52% were women, and 38% were Black. Around 70% of participants reported 0‐1, 22% reported 2‐3, and 8% reported >3 poor sleep characteristics. After adjusting for demographics, lifestyle factors, and comorbidities, participants reporting 2‐3 and >3 poor sleep characteristics had 1.9‐year (95% confidence interval (CI) = 0.54;3.16) and 3.1‐year (95%CI = 1.14;5.11) greater brain age, respectively, compared with participants reporting 0‐1 poor sleep characteristic. Of the individual questions, sleep quality, trouble falling asleep, early awakening, and waking up at night were associated with a 1.7 (95%CI = 0.25;3.16), 1.6 (95%CI = 0.06;3.08), 2.1 (95%CI = 0.71;3.50), and 1.2 (95%CI = 0.08;2.23) years older brain age, respectively.

Conclusion

These findings suggest an association of poor sleep in early midlife with advanced brain age 15 years later. Further research is needed to clarify the underlying mechanisms linking sleep to brain aging earlier in life.
EEG utilization to assess the efficacy of Person‐Centered Communication Intervention
Authors: Kim Dongseon
Published: January 2025

This study employs electroencephalography (EEG) to assess the efficacy of a person‐centered communication intervention in the context of dementia care. Seventy‐seven individuals in the early stage of dementia, attending day care centers, were divided into experimental and control groups following a non‐equivalence control design. The communication intervention consisted of 30 minutes of semi‐structured, topic‐specific in‐person interactions, incorporating elements of self‐introduction, rapport‐building, emotional exploration, reminiscence, and cognitive stimulation. To enhance communication with peopel with dementia, techniques such as acknowledgment, validation and other communication skills were employed, aligning with the principles of person‐centered care. Data comprises of EEG measurements on the points of prefrontal lobe before and after the intervention, and assessment of emotional changes and agitated behaviors using the Observed Emotion Rate Scale (OERS) and Agitational Behavior Scale (ABS).

Results indicate a noteworthy reduction in theta waves which are known to be associated with emotional states, alongside significant alterations in alpha and beta waves, indicative of attention increase. Moreover, statistically significant emotional changes were observed, including increased happiness and attention, as well as decreased anger, anxiety, and agitation. Notably, behavioral symptoms were found to be correlated with emotional states of anxiety and agitation, both of which exhibited reductions post‐intervention. In conclusion, the person‐centered communication intervention yielded changes in brain wave patterns and improvements in emotional and behavioral states. This study contributes to the field by providing quantitative evidence of the efficacy of person‐centered communication in alleviating anxiety and behavioral symptoms among people with dementia.
Kimel Family Centre for Brain Health and Wellness: Protocol for a Naturalistic Longitudinal Personalized Multidomain Preference Dementia Risk Reduction Trial
Authors: Anderson Nicole D. , D'Amico Danielle , Rotenberg Shlomit , Gillen Jenna , Moore Daniel , Tan Brian , Binns Malcolm , Santarossa Melanie , Chertkow Howard ,   The Canadian Consortium on Neurodegeneration in Aging (CCNA), CAN‐THUMBS UP
Published: January 2025

Background

The Kimel Family Centre for Brain Health and Wellness is a research‐driven community centre testing the efficacy of a naturalistic longitudinal personalized multidomain preference dementia risk reduction intervention on dementia risk and cognition. The objective of this protocol is to validate this approach by following people for two years.

Method

Participants (n = 325) will be 50 years of age or older, without a diagnosis of dementia, and sufficiently fluent in English to complete the assessments and understand program instructors. Participants will receive a comprehensive dementia risk assessment, including both nonmodifiable and modifiable risk factors, from which they will receive a Personalized Dementia Risk Report and Program Strategy, indicating health conditions increasing dementia risk, and their risk level in five risk domains: physical activity, brain‐healthy eating, cognitive engagement, social connections, and mental wellbeing. Participants will select programs to meet their Personalized Program Strategy. We will examine the effects of this program on cognition (MoCA and Cogniciti’s Brain Health Assessment) and risk in the five domains, as a function of adherence (attendance), compared to those of 300 individuals who will complete the Canadian Consortium on Neurodegeneration’s CAN‐THUMBS Up online, educational program on modifiable dementia risk factors, called Brain Health PRO.

Result

We expect better maintenance of cognition and reduction in the five dementia risk domains in Kimel Family Center participants, compared to Brain Health PRO participants.

Conclusion

There is an urgent need to develop scalable multidomain programs for dementia prevention. This innovative approach overcomes a number of limitations present in prior multidomain dementia prevention trials. Once validated, the approach will be scaled to other community centres, to benefit a greater number of geographically dispersed individuals.
Significance of Donanemab Versus Placebo in Alzheimer’s Disease Pathogenesis. A Systematic Review
Authors: Ortíz Arid Barragán , Flores Marcos Arreola , Ortega Christan J Monge , Lara Sofia Andrade , Castillo David A Chávez , Rodríguez Sergio M Carrillo , Ortega Thania F Estrada , Posadas Maria F Estrada , Suárez Gilberto Mauricio
Published: January 2025

Background

Alzheimer’s Disease (AD) is a neurodegenerative disease, characterized by a decrease in cognitive and behavioral functions of patients. Between the multiple potential disease‐modifying therapeutics for AD, we have monoclonal antibodies as aducanumab, lecanemab, and donanemab. Recent results from the TRAILBLAZER‐ALZ trial, highlighted donanemab as a promising monoantibodies treatment of early symptomatic AD. Donanemab targets the N‐terminal region of pyroglutamate Aβ plaques. It is designed to bind selectively to these plaques. This targeting mechanism offers a focused approach in the treatment and potential amelioration of the disease’s symptoms.

Method

systematic search in the meta search engines of Pubmed and TRIP database, described in the diagram

Result

Donanemab follows a two‐compartment model with first order elimination and in several studies found that reduction of amyloid plaque is associated with maintenance of donanemab threshold serum concentrations above 4.43 µg/ml. The difference in iADRS score changed ‐6.86 in donanemab group and ‐10.06 in placebo group. Also amyloid plaques clearance measured by florbetapir PET was 85.06 centiloids more than in the placebo group, −84.13 centiloids for donanemab vs. 0.93 centiloids for placebo. In early stages of Alzheimer’s disease, donanemab as treatmenet, resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks. Among the side effects that were seen across studies were amyloid‐related edema or stroke (mostly asymptomatic) occurring with donanemab and no exposure threshold was identified as being associated with an increased risk of ARIA‐E. The apparent effect of donanemab on ARIA‐E was generated primarily in participants who were carriers of the APOE ε4 gene.

Conclusion

Preliminary data indicates its potential in effectively impeding the progression of the disease, as observed in the extracted articles. In order to comprehensively grasp the implications of the observed rise in CSF Aβ42 and its correlation with cognitive and clinical effects. While there is limited research available, the current evidence suggests that donanemab is indeed efficacious in halting the advancement of the disease. Donanemab has emerged as a promising option, yet its status is not definitive due to the associated risk of developing ARIA‐E during its administration.