bluuebunny/crossref_metadata_2025 huggingface dataset:
Capturing cognitive health disparities on the national and state level using 2023 proposed federal racial and ethnic categories: the case for a Middle Eastern and North African checkbox
Authors: Kindratt Tiffany B , Smith Alexandra
Published: January 2025

Background

Most research on cognitive difficulties in the US focus on minoritized groups that are part of the federal minimum reporting guidelines, include White, Black, Hispanic/Latino, Asian, American Indian/Alaskan Native (AI/AN), and Native Hawaiian/Other Pacific Islander (NH/OPI) individuals. Research has begun to describe cognitive difficulties among Middle Eastern and North African (MENA) adults, but it is limited because they are defined as White. In 2023, the Office of Management and Budget (OMB) proposed adding a separate checkbox for MENA individuals. Our objective was to estimate and compare the odds of cognitive difficulties among MENA adults compared to White, Black, Hispanic/Latino, Asian, AI/AN, NH/OPI adults in the US and four states (California, New York, Michigan, and Texas) after adjusting for sociodemographic characteristics.

Method

We analyzed data from the 2017‐2021 American Community Survey (ages≥45 years; n = 7,284,988). Cognitive difficulties (yes/no) among adults (ages 45+ years) who self‐identified their race/ethnicity from one of the six minimum reporting categories (White, Black, Hispanic/Latino, AI/AN, NH/OPI) were compared to those who reported a MENA ancestry/birthplace.

Result

MENA adults in the US had greater odds of reporting cognitive difficulties compared to White, Black, Hispanic, Asian and AI/AN adults, but there was no difference when compared to NH/OPI adults after adjusting for covariates. In California, MENA adults had higher odds of cognitive difficulties compared to White, Black, Hispanic/Latino, Asian, and NH/OPI adults. In New York, MENA adults had higher odds of cognitive difficulties compared to Asian adults. MENA adults in New York had lower odds of cognitive difficulties when compared to Black, Hispanic/Latino, and AI/AN adults. In Michigan, MENA adults had lower odds of cognitive difficulties than Black, but higher odds than Hispanic/Latino and Asian adults. In Texas, MENA adults had higher cognitive difficulties compared to White, Hispanic/Latino, and Asian adults.

Conclusion

This study expands on previous research uncovering cognitive difficulties among Arab Americans using the 2023 OMB proposal to include MENA as a checkbox as part of the minimum reporting standards for race/ethnicity in the US. It also provides the first state‐based estimates of cognitive difficulties among MENA adults living in California, New York, Michigan, and Texas.
Insulin resistance’s role in mediating physical activity’s impact on beta amyloid accumulation and tau phosphorylation: A scoping review
Authors: Slee Michael G , Scotney Joanne , Rainey‐Smith Stephanie R , Erickson Kirk I. , Sohrabi Hamid R. , Brown Belinda M.
Published: January 2025

Background

Type 2 diabetes (T2D) and Alzheimer’s disease (AD) are amongst the top 10 leading causes of death worldwide. T2D is associated with increased AD risk and brain beta amyloid (Aβ) burden, suggesting underlying mechanistic relationship between AD and T2D. Insulin signalling pathways, which can regulate the accumulation of Aβ and phosphorylation of tau in the brain, is a possible underlying mechanism of the T2D‐AD relationship. Insulin resistance, reduced responsiveness to insulin and T2D hallmark, has been found to impair insulin signalling pathway function. Animal studies show exercise reduces brain levels of Aβ. Whilst empirical evidence from human studies linking exercise to brain Aβ is somewhat limited, some studies have reported physical activity is associated with lower brain Aβ. Exercise has well established links to reductions in insulin resistance; thus, as physical activity can impact both insulin resistance and AD biomarkers, it is reasonable to hypothesise that a mediating relationship may exist. The objective of this review was to identify what evidence exists that examines the association between insulin, physical activity, and Aβ/tau in animals and human studies. Particularly, what is known about the potential mediating role insulin resistance has on the physical activity ‐ Aβ/tau relationship.

Method

A systematic search was performed in Cochrane library, PsycINFO, PubMed and World of Science to identify suitable publications. The search identified 343 articles with 21 articles meeting the full inclusion criteria.

Result

Most animal studies showed that exercise could simultaneously reduce insulin resistance and AD pathology. Limited human studies were identified and only a few found both reduced insulin resistance and Aβ/tau associated with higher physical activity. One study provided evidence that insulin resistance may mediate the physical activity ‐ Aβ relationship, however this was not derived through standard mediation analysis.

Conclusion

Exercise can simultaneously impact insulin resistance and AD pathology in animal models, suggesting similar underlying mechanisms. Results in human models are limited however, and no robust evaluation of insulin resistance’s mediating role in the physical activity ‐ Aβ/tau relationship exists. Future focus on mediation impact should be investigated to enhance our understanding of physical activity’s role in reducing AD risk.
Dementia risk reduction assessed with ANU‐ADRI in the Maintain Your Brain trial, an online multidomain intervention to prevent cognitive decline and dementia
Authors: Chau Tiffany , Briggs Nancy , Popovic Gordana , Anstey Kaarin J. , Heffernan Megan , Singh Maria A. Fiatarone , Valenzuela Michael , Millard Michael , Sachdev Perminder S. , Lautenschlager Nicola T , Jorm Louisa , Ginige Jeewani Anupama , Brodaty Henry
Published: January 2025

Background

The Maintain Your Brain (MYB) randomised controlled trial (RCT) aimed to prevent cognitive decline and dementia through a multidomain risk‐reduction intervention delivered digitally. The intervention targeted four modifiable risk areas (physical inactivity, poor diet, cognitive inactivity, and depression and/or anxiety). MYB ran for three years and targeted older Australians aged 55‐77 years. We previously reported significant benefits on cognition in the intervention group compared to the control group. Here we report the outcome on a validated dementia risk assessment tool.

Method

The self‐reported short form of the Australian National University Alzheimer’s Disease Risk Index (ANU‐ADRI‐SF; 1) was used to assess dementia risk in MYB. To examine risk and protective factors, non‐modifiable factors (age and sex) were removed. Unrealistic values were also removed as part of the data cleaning process. A generalised linear mixed model with appropriate response distributions and link function was run to examine the group (intervention vs control) by time (baseline, 12‐, 24‐, and 36‐months) interaction. An additional analysis adjusted for baseline age, gender, and years of education was run.

Result

Of 14,064 participants who consented, 6,104 participants were eligible and completed baseline assessments. They were randomised 1:1 to the intervention (n = 3,051) or control (n = 3,053) group. Upon removing outliers (n = 58), 6,046 participants were included in the mixed model analysis. Analysis revealed significant intervention effects on dementia risk change over three years (0.56, 95%CI ‐0.88‐ ‐0.30, p<0.001). Results were replicated in the adjusted model (p<0.001).

Conclusion

An online intervention program confirmed results from a 24‐month follow‐up of in‐person multicomponent interventions (2,3) in lowering dementia risk. Overall, MYB has the potential to provide a realistic path towards scalable community‐based prevention of dementia, resulting in an improvement in public health and potential economic implications.

References:

1. Kim S et al, Alzheimers Dement: Translational Res & Clin Interventions 2016;2:93‐98

2. Barbera et al., Alzheimers Dement J Alzheimers Assoc. 2020; 16:S10

3. Deckers K et al. Alzheimers Dement. 2021;17:1205‐1212.
Associations between glucose metabolism measures and amyloid and tau load on PET 14 years later: Findings from the Framingham Heart Study
Authors: van Gils Veerle , Tao Qiushan , Ang Ting Fang Alvin , Young Christina B. , Mormino Elizabeth , Qiu Wei Qiao , Visser Pieter Jelle , Au Rhoda , Jansen Willemijn J. , Vos Stephanie J. B.
Published: January 2025

Background

Type 2 diabetes and glucose metabolism have previously been linked to cognitive decline and higher risk of developing Alzheimer’s disease (AD) dementia. Yet, the relation of glucose metabolism with amyloid and tau pathology remains unclear. This knowledge will help understanding the importance of glucose regulation in relation to AD. Therefore, we aimed to investigate whether earlier age glucose metabolism measures are associated with later age amyloid and tau measures on PET.

Method

We included 288 participants (mean age= 43.1, SD=10.7, range 20‐70 years) without dementia from the Framingham Heart Study (FHS), who had data available on glucose metabolism measures, i.e. continuous plasma glucose, elevated plasma glucose (>100mg/dl), plasma insulin, and homeostatic model assessment for insulin resistance (HOMA‐IR), and a PET measure of global amyloid and/or temporal tau 14 years later (range 11‐17 years). We performed linear regression analyses to test associations of each glucose metabolism measure with amyloid or tau uptake on PET, adjusted for age, sex, and exact years of time interval. For significant findings, we explored whether age, sex, ApoE‐ε4 allele carriership or amyloid load modified the associations.

Result

Demographics are shown in Table 1. Our findings indicated that elevated plasma glucose was associated with greater tau load in the brain 14 years later (B [95%CI] = 0.03 [0.01 – 0.05], p = 0.006). Findings were independent from age, sex, and amyloid load. The association was only observed in ApoE‐ε4 non‐carriers (B [95%CI] = ‐0.08 [‐0.12 – ‐0.03], p=0.001, Figure 1). Higher plasma insulin and HOMA‐IR were associated with decreased amyloid load after 14 years (B [95%CI] = ‐0.01 [‐0.02 – ‐0.00], p = 0.035 and B [95%CI] = ‐0.01 [‐0.02 – ‐0.00], p = 0.034, respectively), but this association attenuated after false discovery rate (FDR) correction (both p=0.07) and adjustment for ApoE‐ε4 carriership (insulin p=0.057 and HOMA‐IR p=0.053). No other associations were found (Table 2).

Conclusion

Our findings suggest that impaired glucose metabolism is associated with increased tau pathology later in life, independent from amyloid pathways. These findings suggest that glucose metabolism regulation is important to prevent neuropathology later in life.
Lewy body pathology exacerbates brain hypometabolism and cognitive decline in Alzheimer’s disease
Authors: Collij Lyduine E. , Mastenbroek Sophie E. , Mattsson‐Carlgren Niklas , Strandberg Olof , Smith Ruben , Palmqvist Sebastian , Ossenkoppele Rik , Hansson Oskar ,   the Alzheimer's Disease Neuroimaging Initiative
Published: January 2025

Background

Identification of concomitant Lewy Body (LB) pathology might be important for the diagnostic and prognostic work‐up of Alzheimer’s disease (AD) in clinical practice and trials. Here, we aimed to determine whether the presence of LB pathology exacerbates AD‐related disease progression.

Methods

Cognitively impaired (Mild Cognitive Impairment [MCI] and dementia, n=795) individuals from the ADNI cohort with available CSF α‐synuclein amplification assay (SAA) and CSF p‐tau181/Aβ42 measures were included. Linear mixed models (LMMs) with random slope and intercept were run to assess group effects on longitudinal cognition and cortical metabolism using FDG‐PET, corrected for age, sex, and baseline cognitive state, and education in case of cognition models. To investigate potential non‐linear changes in cognitive functioning, LMMs additionally included an interaction between AD/LB group and time squared (time2). Differences between AD/LB groups (n=61) in pathological scores were assessed using ordinal logistic regression models, corrected for sex, age at death, measurement interval and post‐mortem interval.

Results

Participants were on average 75 years of age (SD=7.89), 40.8% were female, and 184 (23.1%) had no biomarker evidence of AD/LB pathology, 39 (4.9%) had isolated LB pathology (AD‐LB+), 395 (49.7%) had only AD pathology (AD+LB‐), and 177 (22.3%) had both pathologies (AD+LB+, Table 1/Figure 1). At baseline, the AD+LB+ group showed worst performance for most cognitive outcomes compared to the other groups, including the AD+LB‐ group (MMSE: p=0.008; PACC: p<0.0001). Over time, both the AD+LB‐ and AD+LB+ groups deteriorated faster in global cognitive function compared to the AD‐ groups. Importantly, this decline was more pronounced for the AD+LB+ group when compared to the AD+LB‐ group (MMSE: βAD/LB group*time2=‐0.15, p=0.005, PACC: βAD/LB group*time2=‐0.026, p=0.0015, Table 2/Figure 2). Furthermore, the AD+LB+ group showed more cortical hypometabolism at baseline and over time compared to the AD+LB‐ group, particularly in posterior brain regions (Figure 3). Neuropathological examination showed that the α‐syn SAA had 96.3% (26/27) sensitivity and 96.4% (27/28) specificity (Figure 1).

Conclusion

In a cognitively impaired AD population, co‐existing LB‐positivity exacerbates cognitive decline and cortical brain hypometabolism. In vivo detection of LB pathology could improve the prognostic work‐up of AD in clinical practice and might have implications for the design of clinical AD trials.
Assessing Alzheimer’s Disease Knowledge Among Caregivers Using the Alzheimer’s Disease Knowledge Scale
Authors: Guillén Núria , Sarto Jordi , Esteller Diana , Val‐Guardiola Andrea , Fernandez‐Villullas Guadalupe , Alberique Ainoa , Piñol‐Ripoll Gerard , Balasa Mircea , Sánchez‐Valle Raquel , Martínez Neus Falgàs , Lladó Albert
Published: January 2025

Background

Although Alzheimer’s disease (AD) is a common cause of dementia, whether patients and caregivers have notions of its risk factors, behavioral aspects or care considerations is unclear. Therefore, our study aims to evaluate caregiver’s knowledge of AD by using the Alzheimer’s Disease Knowledge Scale (ADKS).

Method

The ADKS is a comprehensive 25‐item true/false assessment tool that explores the understanding of AD. Comprising four subscales (Causes and characteristics, Communication and behavior, Considerations of care, and Risk factors and health promotion), it provides a nuanced evaluation of knowledge levels.

In this prospective consecutive observational study conducted between February 2021 and December 2023, we recruited 132 participants with clinically diagnosed MCI/dementia. Their caregivers completed the Spanish version of the ADKS. Scores for the entire test, its subscales, and the individual questions were normalized on a scale from 0 to 10, to facilitate result interpretation.

Result

The mean ADKS test score was 21.7 [SD 0.7], equivalent to 4.3/10 [SD 1.4]. Most of the subscales scored below 5, indicating a poor familiarity with aspects related to “Risk factors and health promotion” (4.3/10 [SD 1.8]), “Causes and characteristics” (4.2/10 [SD 1.9]), and “Communication and behavior” (2.0/10 [SD 1.6]) (Table 1). The only subscale with an average score over 5 was “Considerations of care,” (6.7/10 [SD 2.3]).

Conclusion

The findings underscore the limited knowledge of AD‐related aspects among caregivers of individuals suffering from cognitive impairment. It highlights the need to implement educational interventions in both the general population and diagnosed patients and their support networks.
EEG Cortical Sources Abnormalities During Transition Between Wakefulness and Light Sleep in Patients with Alzheimer’s Disease and Mild Cognitive Impairment
Authors: Salamone Enrico Michele , Carpi Matteo , Jakhar Dharmendra , Lopez Susanna , Noce Giuseppe , Lizio Roberta , Percio Claudio Del , Babiloni Claudio
Published: January 2025

Background

Alzheimer’s Disease (AD) and Sleep disturbances are closely linked in a bidirectional relationship. Indeed, sleep alterations represent a precipitating factor in early pathogenesis of neurodegeneration. Conversely, the accumulation of Aβ and tau proteins directly disrupts sleep‐wake cycles. Sleep disturbances are extremely prevalent in AD and the relationship between these disorders has been thoroughly investigated. Our study is the first to investigate the electroencephalographic cortical sources during the transitional stages between quiet wakefulness and light sleep in AD patients with MCI.

Methods

We analysed data from an international database (www.pdwaves.org) comprising clinical, neuropsychological, EEG morning recordings (45 minutes), cerebrospinal fluid (CSF), structural and functional MRI data in n=36 ADMCI, n=20 showing transition to light sleep (t‐ADMCI) and n=16 without transition to sleep (nt‐ADMCI)(Table 1). The database also included clinical, neuropsychological, and EEG data of n=11 matched healthy elderly (Nold) persons transitioning to light sleep. The EEG traces were reviewed by researchers blinded to the diagnosis, divided in 4” epochs and categorised in four different vigilance conditions: Eyes Open, Wakefulness, Flattening of alpha (drowinsess), Ripples (light sleep), according to the sleep classification by Hori et al (1994). Individual alpha frequency (IAF) was used to determine the EEG delta, theta, and alpha bands. Regional EEG cortical sources were estimated using the eLORETA freeware.

Results

Compared to Nold subjects, the ADMCI subjects showed greater Frontal Delta Cortical source activity in all vigilance conditions (p<0,001) (Figure 1). Furthermore, when compared to nt‐ADMCI, t‐ADMCI showed an increased diffuse delta cortical source activity (p<0.0001) during the wakefulness period (Figure 2). No differences between these two last groups emerged in CSF neurodegeneration biomarkers, neuropsychological testing nor structural or functional MRI measures.

Conclusion

The higher Frontal Delta Cortical Source activity across all vigilance conditions in t‐ADMCI subjects as compared to Nold, and the persistence of this result when compared to matched nt‐ADMCI patients, likely reflects the presence of dominant local delta rhythms, normally found during N3 and REM sleep, due to a low dopaminergic and cholinergic tone. Our findings might reflect a “disconnection” of frontal regions due to the loss of projections from monoaminergic subcortical nuclei, affected by early neuronal loss from AD neuropathology.
Cerebral amyloid angiopathy differently impacts gray matter microstructure in patients with Lewy bodies dementia and Alzheimer’s disease
Authors: Bommarito Giulia , Griffa Alessandra , Hall Caroline , Aleman‐Gomez Yasser , Hagmann Patric , Allali Gilles
Published: January 2025

Background

Cerebral amyloid angiopathy (CAA) has been reported in patients with dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD), with a similar prevalence from pathology studies.1,2 CAA typically affects posterior regions, but amyloid deposits have been observed in the striatum in patients with DLB and with hereditary CAA.1,3 Here, we postulated that CAA‐related amyloid pathology results in a different spatial pattern of damage in DLB with respect to AD, and we tested this hypothesis in vivo, by characterizing gray matter imaging features in patients with DLB and AD with and without CAA (CAApos, CAAneg).

Method

In this retrospective case‐control study, we included patients referring to the Leenaards Memory Center (Lausanne University Hospital), with a biological diagnosis of AD and a clinical diagnosis of DLB. Co‐occurrence of CAA was defined according to Boston criteria 2.0. Structural and diffusion‐weighted MRI data were processed, deriving volume, average fractional anisotropy (FA) and mean diffusivity (MD) for 13 cortical and subcortical regions.4 Multiple comparison correction was applied to all statistical tests.

Result

Eighty‐eight AD patients AD and 87 DLB patients were included (Table 1). Among AD and DLB patients, 15 (17%) and 23 (26.4%) presented with probable CAA, respectively (p= .132). MD and FA values of putamen, caudate and thalamus were significantly higher in DLB compared to AD patients (t(173) ranging from 2.05 to 2.91, p values ranging from .027 to .033 after multiple comparison correction).

When comparing the 4 groups (AD‐CAApos, AD‐CAAneg, DLB‐CAApos, DLB‐CAAneg) subcortical microstructure significantly differed, and the ratio of limbic over basal ganglia FA values differentiated DLB‐CAApos from DLB‐CAAneg, AD‐CAAneg or AD‐CAApos (ANOVA F(3,171)= 3.44, p= .018, post‐hoc test corrected p values ranging from .021 to .041, Figure 1). No significant differences were found for posterior (occipital and parietal) regions metrics.

Conclusion

As expected, patients with DLB and AD present a similar prevalence of CAA co‐pathology. However, in DLB patients, CAA associates with an increased basal ganglia over limbic anisotropy that could reflect higher iron content5 and is not observed in AD and DLB without CAA. These results might suggest that alpha‐synuclein and plaque amyloid depositions differently interact with CAA pathogenic pathway.
Omega‐6/Omega‐3 Ratio in Dementia Prevention ‐ Study Design and preliminary data of a feasibility study on lifestyle intervention
Authors: Rostamzadeh Ayda , Sannemann Lena , Bohr Lara , Gerards Michelle , Egert Sarah , Ramirez Alfredo , Jessen Frank
Published: January 2025

Background

Alzheimer’s disease (AD) is the most common etiology of dementia. As the progression of the disease may be slowed down by disease‐modifying therapies, but not stopped, research identifying further therapeutic approaches is necessary. Due to the multifactorial etiology of AD, targeting modifiable risk factors for dementia, including diet, is a starting point for preventive interventions. Currently, dementia prevalence is highest in North America and Western Europe, which correlates with an excess of saturated fat in the Western diet (WD). How precisely fatty acid dietary composition contributes to AD pathogenesis is poorly understood. Polyunsaturated fatty acids (PUFA), which account for 18% of total fat intake, include the essential fatty acids ω‐6‐linolenic and ω‐3‐alpha‐linolenic acid, which cannot be synthesized de novo and must be consumed in the diet. Omega ω‐6 and ω‐3 PUFA are found in high concentrations in the brain. Current findings indicate that a high ω‐6/ω‐3 ratio may contribute to a dysbalance between pro‐ and anti‐inflammatory processes and consequently accelerate or trigger neurodegenerative processes.

Method

This randomized‐controlled feasibility study investigates the effects of a 10‐week dietary intervention in a sample (n = 60) of cognitively healthy individuals from the Cologne Dementia Prevention Registry, who follow a WD. The dietary intervention consists of both a change in diet to reduce ω‐6 PUFA and supplementation with fish oil capsules to increase ω‐3 PUFA intake. The primary endpoint of the study is the reduction of the ω‐6/ω‐3 ratio, measured in serum phospholipids, including levels of ω‐6 and ω‐3 fatty acids. Secondary, exploratory endpoints include changes in dietary behavior, cognitive performance, markers of inflammation and oxidative status, epigenetic analyses (DNA methylation), and changes in lifestyle and well‐being.

Result

We present the rationale, design and preliminary results of a 10‐week dietary intervention trial in a cognitively healthy cohort.

Conclusion

This study investigates the feasibility and effects of a lifestyle‐based intervention on the ω‐6/ω‐3 ratio and further biological and cognitive‐behavioral secondary outcomes. The results can inform future trials aimed at a deeper mechanistic understanding of the reduction of the ω‐6/ ω‐3 ratio in humans; eventually targeting clinical primary outcomes, such as cognition, over time.
The gut microbiome and pathology of Alzheimer’s disease
Authors: Dissanayaka Sithara Udeshini , Rainey‐Smith Stephanie R , Martins Ralph N , Fernando Warnakulasuriya Mary Ann Dipika Binosha
Published: January 2025

Background

Current literature focuses on the association between gut dysbiosis and the aggregation of Aβ, the development of tau protein, as well as neuroinflammation and oxidative stress associated with AD. Since the brain and gut are connected (gut‐brain axis), gut microbiota and their metabolites may influence AD progression, or vice versa, if AD pathogenesis impacts the microbiome. Observational studies have shown an altered taxonomic composition of gut microbiota in AD patients compared to cognitively normal (CN) controls.

Method

This perspective study will explore taxonomic composition and gut microbial function (using metagenomic analysis) compared with Aβ aggregation, deposition of tau, and inflammatory biomarkers in cognitively normal individuals and preclinical AD individuals. We will also address the effect of dietary intake on gut dysbiosis to assess the effectiveness of healthy diet patterns as preventive approaches in AD.

Results

The faecal samples of people with AD have been shown to have decreased microbial diversity and compositionally distinct microbiota. At the same time, correlations were found between gut microbiome differences and cerebrospinal fluid (CSF) tau levels, and plasma β‐amyloid (Aβ) biomarkers levels early in the progression of the disease. However, research into the gut and brain concerning AD progression and AD pathology remains very inconsistent with the reported data. Therefore, evaluation of the potential role of microbiota taxonomy in stool in the early detection of preclinical AD may lead to the development of novel directions in the investigation of the potential role of the gut in AD progression.

Conclusion

The altered gut microbiota can influence increased Aβ deposits, tau phosphorylation, and neuroinflammation. Therefore, it is necessary to gain a better understanding of microbial community diversity at the species level and the function of these communities due to AD pathology as well as the effect of confounding factors like dietary intake.
Digital Healthcare Applications for Preventing Risk Factors in Dementia: Requirements Engineering in the German Healthcare System
Authors: Gerdes Marius , Schinle Markus , Stock Simon , Stork Willhelm
Published: January 2025

Background

The increasing prevalence of dementia globally, including Germany, necessitates effective strategies to reduce the burden on patients, caregivers, and healthcare systems. Risk factor prevention plays a crucial role in delaying the onset of severe symptoms and alleviating the strain on resources.

Method

This study focuses on identifying the requirements of a digital healthcare application for risk factor prevention in dementia within the German public healthcare system. A requirements engineering process was employed, involving the identification of user needs and regulatory constraints, the generation of clickable mockups, and user testing with individuals at risk for dementia through semi‐structured interviews (N = 30).

Result

The target group, consisting of individuals at risk for dementia, exhibited a strong interest in using digital healthcare applications. Most demonstrated a high affinity for technology and already utilized digital products in their daily lives. Interventions related to exercise and nutrition were well‐received, while interventions targeting sleep encountered skepticism. The German regulatory framework currently only allows for the development of independent applications, although the preference for a human coach was expressed. However, participants indicated that an AI coach could be a viable alternative in the future, as regulations evolve.

Conclusion

By providing a digital healthcare application for risk factor prevention in dementia, scalability to a wider population can be achieved. This approach bridges the gap between specialized care, which requires significant resources, and the limited resources available in the public healthcare system. The study highlights the potential of digital healthcare applications to increase accessibility and facilitate the integration of risk factor prevention strategies into routine care. Furthermore, it underscores the need for regulatory adaptation to accommodate the evolving landscape of digital healthcare solutions.
Utilization of Wearable Devices as means for Remote Digital Biometric Data Collection in a community‐based, rural randomized controlled trial among Alzheimer’s disease dyads
Authors: Rhodus Elizabeth K. , Onim Md Saif Hassan , Roberts Celeste , Kumar Sanjeev , Burhan Amer M. , Thapliyal Himanshu
Published: January 2025

Background

Use of remote measurement of physiological parameters using digital biometrics (i.e., Electro Dermal Activities, heart rate, oxygen saturation, blood volume pulse, etc.) has a multitude of opportunities in rural contexts that have not yet fully been explored in Alzheimer’s disease (AD) clinical research. This study assessed feasibility and acceptability of advanced digital biometric data collection among rural, community‐dwelling adults living with Alzheimer’s disease with support from primary caregivers (dyad).

Methods

Initial feasibility and acceptability of a wrist‐worn wearable device (Empatica E4) as means for digital biometric data collection were assessed among participants of a larger randomized controlled trial which was aimed to assess a non‐pharmacological care intervention improving behavioral symptoms of AD. Following consent, dyads were mailed an E4 device and behavior tracking journal to companion digital recordings for one week of data collection. Caregivers assisted the person with AD in wear and care of the E4 device and completed time‐stamped behavior tracking. Feasibility was assessed based on completeness of digital biometric data recordings and acceptability was determined based on wear schedules for the device in participants with AD (worn >50% of allotted time).

Results

Digital biometric data collection via remote, wearable devices is feasible and acceptable among participants with AD in rural settings among 16 dyads (person with AD age x̄=77±2.4 years, 10 female; caregiver age years x̄=57±2.9 years, 8 female). The E4 correctly captured biometric signals (Electro Dermal Activities, blood volume pulse, Skin Temperature, etc.). The device was acceptable as 14 of the 16 participants with AD wore the device >50% of allotted time with proper completion of the caregiver‐reported behavior tracking. Further, we observed that unsupervised machine learning models were able to create digital biometrics that mirrored caregivers’ notes.

Conclusion

Advances in technology, evolution of health status surveillance, and vast needs in rural areas create an ideal scenario to advance research in digital biometrics. With goals to use digital biometrics as primary outcome measures in AD clinical trials, the findings presented here illustrate feasibility and acceptability among geographically remote communities. Additional research is needed to assess context‐aware machine learning applicability in intervention‐based clinical research.
Care Setting Trajectories in Last Three Years of Life for People with Dementia
Authors: Montaner Olga F Jarrín , Xia Weiyi , Zafar Anum , Kim Hyosin , Lopez Maria J. , Lin Haiqun
Published: January 2025

Background

Most older adults prefer aging in place; however, patients with dementia and advanced illness often need institutional care, even if only for a brief period of time. In the context of the aging US population and the increasing number of individuals living with dementia, understanding place of care trajectory patterns is important for patient‐centered care planning and health policy decisions. The purpose of this study was to characterize place of care trajectories during the last three years of life among Medicare beneficiaries diagnosed with dementia.

Method

The analytic cohort included a 20% random sample (n = 186,723) of Medicare beneficiaries who died in 2019 with a diagnosis of dementia, aged fifty or older, and continuously enrolled in Medicare during their last five years of life. Group‐based trajectory modeling was used to identify dual trajectories of inpatient/institutional care, and skilled home healthcare/home hospice.

Result

Ten distinct trajectory classes and their associated sociodemographic and clinical characteristics were identified. The first two classes were characterized by brief use of both skilled home care and institutional care concentrated in the last six‐months of life (40%, 11%); the next three classes were characterized by long‐term use of skilled home healthcare/hospice and low use of inpatient/institutional care (15%, 4%); the next three classes were characterized by long‐term use of inpatient/institutional care and low use of skilled home healthcare/hospice (2%, 2%, 5%), the final three classes were characterized by intermittent use of both institutional and skilled home care during the last two or three years of life (9%, 8%, 3%). We investigate the association between care trajectories and socio‐demographic and clinical factors. Our findings may help to inform dementia care planning and related health and aging policy.

Conclusion

This study identified distinct patterns of care setting trajectories during the last three years of life. While half of older adults with dementia spent their final years at home with minimal use of skilled home care or institutional care until the last six months of life, half had significant skilled care needs over two or more years.
Digital access for non‐memory‐led and inherited dementias: How to optimise blended digital/human interventions
Authors: Brotherhood Emilie V , Baou Celine El , Fearn Caroline , Hayes Oliver S , Zimmermann Nikki , Tsipa Anastasia , Stott Joshua
Published: January 2025

Background

How people affected by non‐memory‐led and inherited dementias (NMLDs) interact with online health resources is poorly understood. We conducted the world’s largest survey exploring ‘digital access in non‐memory‐led dementias’ to learn directly from people with NMLD, their care partners and NMLD Healthcare Professionals (HCPs) about the NMLD experience interacting with web‐based health resources.

Method

Four surveys [for individuals diagnosed with NMLD, care partners, care partner proxy for person with NMLD, HCP proxy] were co‐developed with people with NMLD experience. Surveys contained standardised scales and open‐ended short‐form questions relating to: behavioural intention to use web‐based resources (Venkatesh, 2012), attitudes towards web‐based resources, gerontechnology‐related anxiety, control beliefs, health and quality of life (Chen & Lou, 2020) digital health literacy (Nelson, 2022) and web‐related privacy/security concerns (Hong & Thong, 2013). The survey was administered either: online via Qualtrics, or in hard copy via post/in‐person data collection at Rare Dementia Support (RDS) meetings.

Result

Initial inspection of the data indicates 572 responses were collected from 481 individuals. Responses were received from: people with NMLD (N = 65; years since diagnosis mean±sd = 2.81 ± 2.56 years); care partners (N = 291); care partners providing proxy NMLD responses (N = 111); and NMLD HCPs providing perspectives from their experience of service users’ interactions with digital health resources (N = 105). From preliminary inspection of partial data (see Table 1) the proportion of positive responses to the question ‘Have you (proxy: person with NMLD) ever used web‐based resources (e.g., Zoom, websites) for your health and psychological wellbeing?’ is similarly reported between people living with NMLD (80.0%) and proxy HCP responses (79.0%), but a lower proportion reported in proxy caregiver responses (51.3%). In the proxy NMLD responses, the proxy estimation of people with NMLD accessing online resources in the past 3 months is low (71.2% not accessing any web‐based health resources three months prior to survey completion).

Conclusion

Initial analyses indicate this dataset will provide insight for practitioners, clinicians and research academics in the development of online health resources for people affected by NMLD.
Community recruitment of underrepresented populations to a preclinical AD trial using novel partnerships with nursing organizations: Lessons and outcomes
Authors: Salazar Christian R , Tallakson Melanie B , Corona Maria , Duran Edwin , Russ Eunji , Hoang Dan , Romero Romina A , Sultzer David L , Grill Joshua D , Shin Hye‐Won
Published: January 2025

Background

Alzheimer’s disease (AD) disproportionately affects minoritized populations, who are consistently underrepresented in clinical trials. We aimed to recruit underrepresented adults aged 55‐80 to an ongoing preclinical AD trial.

Method

A community‐based strategy was used to recruit Filipino, Hispanic/Latino, and Korean adults into the AHEAD study, a preclinical AD trial testing the anti‐amyloid treatment lecanemab, at the University of California, Irvine. We forged partnerships with nursing and community‐based organizations to facilitate educational and engagement events tailored to each community’s cultural and linguistic needs. The educational content provided a comprehensive overview of the AHEAD Study, its objectives, methodology, and eligibility criteria, alongside an in‐depth explanation of dementia, AD, its risk factors, and lifestyle modification strategies for risk reduction. During pre‐screening, potential participants underwent a brief in‐person or telephone review of qualifications and were referred to the study site for formal screening.

Result

Through 21 community education and engagement events we reached 654 individuals, leading to the pre‐screening of 71 individuals, of whom 11.2% were Hispanic/Latino adults, 21.1% were Filipino adults, and 67.6% were Korean adults. Among Hispanic/Latino adults who pre‐screened, 50% were deemed ineligible primarily due to age requirements. Approximately 47% of the Filipino adults who pre‐screened did not proceed to in‐person screening, with the primary reasons being withdrawn interest and loss to follow‐up. Of the Korean adults who pre‐screened, 69% were found ineligible, predominantly due to challenges with English fluency and loss to follow‐up. A total of 25 participants, representing 3.8% of those reached, were successfully enrolled in the AHEAD Study. Of these, 2 (8%) were Hispanic/Latino, 8 (32%) were Filipino, and 15 (60%) were Korean adults. The success of the study depended upon partnerships with nursing and community‐based organizations, leveraging existing trust and rapport. Continuous communication and early nurse leader involvement as well as participant feedback in refining educational content for cultural relevance were key.

Conclusion

Community‐based recruitment strategies that include trusted local organizations and culturally sensitive approaches were effective in engaging underrepresented groups in interventional AD research.
PAA, a novel metal chelator and metalloproteinase inhibitor significantly reduced amyloid plaque burden in an APP/tau mouse model of Alzheimer’s disease (AD)
Authors: Schmued Larry , Schmued Calvert , Maloney Bryan , Lahiri Debomoy K.
Published: January 2025

Background

Major contributors to AD pathogenesis include aggregates of amyloid‐β (Aβ) peptides, hyperphosphorylated tau protein, and neuroinflammation. No currently approved treatment stops or significantly slows the progression of AD. Nevertheless, one class of agents that has shown promise is metal chelators. For the assessment of a novel effect of oral administration of 1,10‐Phenanthroline‐5‐amine (PAA) on the severity of amyloid plaque load, we used a transgenic (Tg) mouse model with inserted human autosomally dominant (familial) AD genes: amyloid‐beta (Aβ) protein precursor (APP) and tau protein.

Method

APP/Tau transgenic mice that model AD were allotted into one of two groups. The control group received no treatment while the experimental group received 1,10‐phenanthroline‐5‐amine (PAA) in their drinking water, starting at 4 months. All animals were sacrificed at 1 year of age, and their brains were stained with 2 different markers of amyloid plaques, Amylo‐Glo+ and HQ‐O, as we have recently described (Schmued et al, 2023).

Result

PAA administered as a daily oral dose for 9 months resulted in no changes in weight or behavior and resulted in no observed pathologies. Control animals exhibited numerous dense core plaques throughout the neo‐ and allo‐cortical brain regions. PAA administered as a daily dose for 9 months resulted in roughly 2/3 the amyloid plaque burden compared to untreated transgenic mice.

Conclusion

Oral daily dosing with PAA significantly reduced the amyloid plaque burden in transgenic AD model mice. The mode of action of PAA may be attributed to its ability to chelate transition metals and to inhibit either metalloprotease enzymes or the metal‐seeded auto aggregation of Aβ. The underlying mechanism for this protection is not fully known; one possible mechanism would be to inhibit the “metal‐seeding” of Aβ. Dyshomeostasis of certain transition metals in brain microenvironment contributes to amyloidosis. Although this dysregulation may be attributable to impaired metal transporter function, there exists no known treatment that would modify such dysfunction. Further research is underway to confirm these results in another mouse model of AD (APP/PS1). Altogether, reducing regional metal levels via chelation with PAA may be a feasible and viable strategy for suppressing the formation of amyloid plaques in AD patients.
High cognitive reserve postpones dementia onset in older adults with cardiometabolic disease
Authors: Dove Abigail , Yang Wenzhe , Dekhtyar Serhiy , Guo Jie , Wang Jiao , Marseglia Anna , Vetrano Davide Liborio , Whitmer Rachel A. , Xu Weili
Published: January 2025

Background

Cardiometabolic diseases (CMDs) including type 2 diabetes, heart disease, and stroke have been linked to increased dementia risk. We examined whether high levels of cognitive reserve (CR) are associated with an attenuation in the CMD‐dementia association and lower levels of CMD‐related brain pathologies.

Method

Within the UK Biobank, 216,178 dementia‐free participants aged ≥60 were followed for up to 15 years for incident dementia via linage to medical records. At baseline, CMDs were ascertained from medical records and self‐reported medical history. Latent class analysis was used to generate an indicator of cognitive reserve (CR; low, moderate, and high) based on education, occupational attainment, confiding in others, social contact, leisure activities, and television watching time. A subsample (n = 13,663) underwent brain magnetic resonance imaging (MRI) scans 9 years after baseline. Volumes of total gray matter (GMV), hippocampus (HV), and white matter hyperintensities (WMHV) were ascertained, and mean diffusivity (MD) and fractional anisotropy (FA) in white matter tracts were collected through diffusion tensor imaging.

Result

CMDs were associated with 57% increased risk of dementia (HR 1.57 [95% CI 1.48, 1.67]). In joint effect analysis, dementia risk was 35% lower among people with CMDs and moderate‐to‐high CR (HR 1.78 [1.66, 1.91]) compared to low CR (HR 2.13 [1.97, 2.30]) (reference: CMD‐free, moderate‐to‐high CR). Having moderate‐to‐high compared to low CR significantly attenuated the association between CMDs and lower GMV and HV.

Conclusion

Moderate‐to‐high cognitive reserve may partially mitigate CMD‐related dementia risk. Resistance to neurodegeneration may account for this alleviating effect.
A national intervention to increase representation of Latinos/Hispanics in clinical trials on dementia: A mixed‐method evaluation
Authors: Perez Adriana , Portacolone Elena , Aranda Maria P.
Published: January 2025

Background

The lack of inclusion of Latinos/Hispanics in Alzheimer’s disease and related dementias (ADRD) clinical trials reduces the generalizability of study findings and hinders our understanding of the mechanisms of dementia, further widening cognitive health disparities. To address this growing public health concern, the purpose of this study is to leverage the national infrastructure of a Consortium between the National Association of Hispanic Nurses (NAHN) and the Alzheimer’s Association (ALZ) to increase the representation Latino/Hispanic participants in one clinical trial on dementia.

Methods

The study used a randomized controlled trial design and mixed‐method evaluation. Recruitment intervention strategies were tested across 4 cities with high Latino/Hispanic populations. Metrics of sites receiving the intervention vs. those using usual recruitment activity in a clinical trial on dementia. Focus groups and semi‐structured interviews captured the experiences and perceptions of recruitment procedures from the research team, officers of NAHN and ALZ and potential participants who chose to enroll in the clinical trial.

Results

Across the 4 intervention sites, a total of 145 Latino potential participants were referred to the clinical trial; however, none were enrolled. Themes that emerged from focus groups and interviews include: 1) Thirst for information about dementia in Latino communities; 2) A sense of being stronger and bigger together stemming from the partnership between NAHN and ALZ; 3) Importance of logistical support offered by the research team; 4) Importance of timely and thorough follow up with Latino adults who expressed intention to participate in the clinical trial.

Conclusion

Study findings underline the importance of focusing on structural mechanisms enhancing Latino representation. Findings can inform future recruitment science efforts among researchers, community leaders, and policymakers to capture and promote the beneficial roles of collaborations between academia and national organizations that are embedded within communities historically underrepresented in ADRD clinical trials.