bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of sleep efficiency and rapid eye movement sleep in early Alzheimer's disease (AD): Results of the RADAR‐AD study
Authors: Atreya Alankar , Conde Pauline , Doherty Aiden , Vairavan Srinivasan , Muurling Marijn , de Boer Casper , Curcic Jelena , Grammatikopoulou Margarita , Nikolopoulos Spiros , Brem Anna‐Katharine , Coello Neva , Fröhlich Holger , Narayan Vaibhav , Wittenberg Gayle , Aarsland Dag , Duijn Cornelia M Van , Hinds Chris ,   the RADAR‐AD Consortium
Published: January 2025

Background

The relationship between sleep and AD is unclear: sleep problems may contribute to AD pathogenesis, but the spreading of AD pathology across the brain may also de‐regulate sleep. What aspect of sleep is relevant in which disease phase is also unclear, as many studies are based on questionnaires. We study sleep efficiency and rapid eye movement (REM) sleep, objectively measured using an activity tracker to shed light on sleep disturbances across the AD spectrum.

Method

The RADAR‐AD is a cross‐sectional study (N=204), including healthy controls (HC, n=67), preclinical AD (preAD, n=34), prodromal AD (proAD, n=56) and mild‐to‐moderate AD (MMAD, n=47) participants (Table 1). Participants wore a Fitbit Charge‐3 activity tracker on their non‐dominant wrists for eight weeks, measuring REM sleep (in hours) and sleep efficiency (sleep duration/total time in bed). CSF amyloid and phosphorylated Tau (pTau) levels were determined in the subset (N=117) and stratified into biomarker groups (A‐T‐, A+T‐, and A+T+). We evaluated the difference in these mean sleep features among AD stages and biomarker groups.

Result

Compared to HC, we observed reductions in daily mean REM sleep for proAD (Estimate±SE=‐0.24±0.08, p=0.002) and MMAD (Estimate±SE=‐0.23±0.08, p=0.001) (Figure 1), and in sleep efficiency for preAD (Estimate±SE=‐0.012±0.005, p=0.016), proAD (Estimate±SE=‐0.011±0.004, p=0.015), and MMAD (Estimate±SE=‐0.009±0.004, p=0.046) participants. Compared to A‐T‐ participants, sleep efficiency was reduced for A+T‐ (Estimate±SE=‐0.016±0.006, p=0.022) and A+T+ (Estimate±SE=‐0.013±0.006, p=0.019) participants (Figure 2), while REM sleep was lower for A+T+ participants only (Estimate±SE=‐0.32±0.11, p=0.004).

Conclusion

Sleep efficiency is altered across the AD spectrum, including the early pre‐clinical AD stage. There is a trend toward lower REM sleep among subjects at more advanced stages of AD and elevated amyloid and tau that may suggest an association between AD pathology and REM sleep.

This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (grant No 806999). www.imi.europa.eu. This communication reflects the views of the RADAR‐AD consortium, and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein.
New real‐time PCR test for APOE genotyping in patients with Alzheimer’s disease before anti‐amyloid therapy
Authors: Meißner Dirk , Denker Annika , Stallmann Sonja , Milbredt Sarah , Venkataraman Iswariya , Saschenbrecker Sandra , Steller Ulf
Published: January 2025

Background

In 2023, the FDA approved LEQEMBI, a monoclonal antibody therapy targeting beta‐amyloid plaques, for patients with early‐stage Alzheimer’s disease (AD). However, anti‐amyloid drug trials demonstrated an elevated risk for amyloid‐related imaging abnormalities with cerebral edema (ARIA‐E) in carriers of the AD risk allele apolipoprotein E epsilon 4 (APOE‐ɛ4), especially in ɛ4/ɛ4 homozygous individuals. Here, we report on the evaluation of a new real‐time polymerase chain reaction (PCR) test for APOE genotyping.

Method

The EURORealTime APOE (EUROIMMUN), which enables simultaneous testing for all six APOE genotypes (ɛ2/ɛ2, ɛ2/ɛ3, ɛ2/ɛ4, ɛ3/ɛ3, ɛ3/ɛ4, and ɛ4/ɛ4) by real‐time PCR, was performed using genomic DNA (gDNA) isolated from EDTA blood samples. The PCR amplification results were evaluated using the EURORealTime Analysis Software (EUROIMMUN). Samples from healthy blood donors (HBD) were used to assess intra‐assay, inter‐assay and between‐lot precision (n=6) as well as analytical sensitivity (n=21), with each APOE genotype represented by at least one sample. Assay accuracy was analyzed by comparing genotype assignments to the results of the CE‐IVD‐marked EUROArray APOE (EUROIMMUN) and bidirectional Sanger sequencing using 110 samples (100 AD, 10 HBD). APOE genotype frequencies were compared between patients (100 AD) and controls (250 HBD).

Result

Precision testing of the EURORealTime APOE resulted in 100% correct genotype calls. Assessment of the analytical sensitivity revealed valid and correct genotype assignment in all 21 samples, confirming 1 ng/µl as the recommended minimum gDNA concentration. The analytical accuracy amounted to 100% based on agreement with the two reference methods in 110/110 cases. Comparison of the APOE genotype distribution showed a higher proportion of ɛ4 allele carriers (i.e., ɛ2/ɛ4, ɛ3/ɛ4, and ɛ4/ɛ4) in AD patients than in HBD (50.0% vs. 25.2%). The prevalence of the ɛ4/ɛ4 genotype in these cohorts was 25.0% for AD patients compared with 2.8% for HBD.

Conclusion

The well‐established high prevalence of the APOE‐ɛ4/ɛ4 genotype in AD patients, together with the increased risk of ARIA‐E in these homozygous carriers, substantiates the relevance of APOE genotyping prior to anti‐amyloid treatment. The EURORealTime APOE test provides sensitive and reliable determination of APOE alleles, thus presenting a suitable tool to improve risk stratification for potential LEQEMBI recipients.
The impact of the 6‐month adapted Otago Exercise Program on clinical measures of physical function relative to usual care alone in people living with dementia in residential care facilities: A pilot randomized controlled trial
Authors: Jones Melanie T , Dong Yanbin , Zhu Haidong , Soares Andre , Patel Charmi , Hergott Colleen , Waller Jennifer L , Young Lufei , Robinson‐Johnson Dawnchelle , Sams Richard , Hamrick Mark , Jehu Deborah A
Published: January 2025

Background

Dementia compromises physical function, posing risks for falls. People living with dementia (PWD) have been historically excluded from intervention trials due to researchers’ eligibility criteria. Exercise shows potential in enhancing physical function, but more evidence is needed. This pilot randomized controlled trial aimed to assess whether the adapted Otago Exercise Program improves physical function relative to usual care alone in PWD.

Method

42 PWD (Montreal Cognitive Assessment<19/30) were randomized (1:1) into the exercise (n = 21) or usual care (n = 21) group at two residential care facilities [NCT05488951]. The adapted Otago Exercise Program was a physical therapist‐led strength, balance, and walking program for 1 hour, 3x/week for 6 months in groups of 5‐7 participants. Physical function was evaluated by the short physical performance battery (balance, gait speed, and chair stands), timed‐up‐and‐go (TUG), and strength at baseline and 6 months. Gait speed (m/s) was measured over 4m. The single‐task TUG involved getting up, walking 3m, walking back, and sitting down (s); the dual‐task TUG involved simultaneously performing a category task. We used dynamometers to measure leg and grip strength (kg). We performed intent‐to‐treat (ITT; n = 42) and per protocol (n = 21 usual care and n = 9 exercisers with 2/3 adherence) generalized mixed models, controlling for age, race, sex, and the MoCA.

Result

For the ITT analysis, left leg strength increased in the exercise group (baseline = 13.4kg; follow‐up = 16.7kg) and decreased in the usual care group (baseline = 14.4kg; follow‐up = 13.7kg; p = 0.03). Exercise provoked faster dual‐task gait speed (baseline = 0.4m/s; follow‐up = 0.5m/s; p<0.01) and decreased TUG dual‐task duration (baseline = 37.3s; follow‐up = 27.6s; p = 0.01) with no change following usual care. The per protocol analysis showed no differences.

Conclusion

The improvements in strength, gait speed, and functional mobility in the exercise group, plus the decline in strength in the usual care group suggest that exercise may prevent decline and improve physical function among PWD. There were no differences in the per protocol analysis, however, this could be due to our small sample of only n = 9 participants with ≥2/3 exercise adherence. Our results suggest that implementing any level of exercise into care plans may improve physical function in PWD, but further research should confirm these preliminary findings.
What Happens When the Honeymoon is Over? Sustaining Community Partner Relationships After Recruitment
Authors: Terry Melita H , Williams Lilcelia A. , Shaaban C. Elizabeth , Lingler Jennifer H
Published: January 2025

Background

Increasing calls for diversity in Alzheimer’s disease and related dementias (ADRDesearch have fueled significant investments in recruitment personnel and activities. However, the essential work of identifying and authentically engaging communities of color in relationship‐building begins well before, and continues long after, study recruitment activities take place. The purpose of this presentation is twofold: 1) to differentiate the work of trust‐building and relationship cultivation from that of research study recruitment, and 2) to describe the necessary steps to ensure that relationship cultivation is ongoing and supported beyond the timeline of a singular research study.

Method

This presentations draws on our team’s experience developing, implementing, and evaluating community engagement programming at a federally funded Alzheimer’s Disease Research Center (ADRC). We outline key features of relationship cultivation and contrast these efforts from the narrower, yet related, activity of study recruitment. We will offer real‐life exemplars to delineate the steps necessary for effective relationship cultivation, particularly in a post‐pandemic era. The importance of intentional actions to sustain partnerships, programming and participant relationships beyond the research recruitment phase will be demonstrated. The relevance of this work for individuals along the spectrum of participant readiness to enroll in ADRD research or consent to brain donation will be explained.

Result

Relationship cultivation efforts at our Center have led to: a) sustained community partnerships, including a multi‐decade presence in a predominantly Black and African‐American neighborhood despite changes in local governance, businesses, and service organizations; b) sustained programming, including a lecture series honoring a prominent local historical figure; and c) sustained longitudinal research participation among individuals identifying as Black or African American, as exemplified by a case study of a participant who was active in our cohort for 28 years and ultimately provided brain donation.

Conclusion

The value of relationship building as the primary step for powerful community engagement and participant partnership should not be underestimated by researchers. This work should be considered a critical aspect of research infrastructure. The foundation laid by building and sustaining the meaningful relationships is essential to bridging trust between community members and ADRD researchers and continues long beyond the recruitment honeymoon.
A Multi‐Modal Approach to Establish Trust and Provide Value within Communities in the Deep South
Authors: Allen Laquetta F. , Bowen Pamela , Hatch Maria L , Roberson Erik D , Geldmacher David S. , Clay Olivio
Published: January 2025

Background

Black/African Americans in the Deep South have been subjected to social segregation, discrimination, and other forms of systematic injustices that continue to negatively impact this population’s social determinants of health (SDoH). Healthy People 2030 has outlined a framework describing how adverse SDoH are associated with health inequities including higher rates of Alzheimer’s disease and related dementias (ADRD). Historically, it has been challenging to recruit citizens from this region to participate in brain aging‐related research studies.

Method

Our Outreach, Recruitment and Engagement Core (ORE) utilizes a diverse team of investigators and staff to cultivate and establish trust and build a vast network of community partners. These community partners include local churches, chapters of fraternities and sororities, civic and professional organizations, library branches, business owners, and other community leaders. The ORE team has worked to create a culture of providing value in Black/African American community by using a community‐based approach to engage individuals identified by others as “hard‐to‐reach,” maintain a constant presence within these communities, provide information on access to services, and increase ADRD knowledge. This model makes it easier to build trust and get residents involved in our studies.

Result

Our team demonstrates a strong commitment to actively engage communities allowing us to exceed our initial target of recruiting >40% Black/African American participants and achieve a Black/African American enrollment rate over 50%.

Conclusion

Achieving greater participation by Black/African American participants in ADRD research can be accomplished through the implementation of a multi‐modal strategy that fosters community trust and instills value.
Favorable cellular alterations in cortex and hippocampal regions of mice brain by Quercetin & Naringenin: Promising role in insulin resistance induced Alzheimer’s disease
Authors: Kaur Sukhmanpreet , Kumar Anil
Published: January 2025

Background

Alzheimer’s disease is a brain disorder that causes neurodegeneration and is linked with insulin resistance at molecular, clinical, and demographic levels. Defective insulin signaling promotes Aβ aggregation and accelerates Aβ formation in the brain leading to Type III diabetes.

Objective

The objective of this research project is to demonstrate a linkage if any between the risk of developing Alzheimer’s disease and insulin resistance. This linkage would be addressed with Quercetin & Naringenin as a test substance using the behavioral model of Alzheimer’s disease.

Method

Diabetes was induced in mice by injecting Alloxan (100mg/kg i.p.) & orally administering sucrose 35% solution. Behavioral models employed in the present study were the Morris water maze (MWM), actophotometer, and novel object recognition (NOR) test. Biochemical estimations were carried out by measuring mitochondrial, glutathione, catalase, SOD, lipid peroxidase activity, and acetylcholinesterase activity in the brain tissue. Histopathological evaluation of the hippocampal region was carried out under a bright field microscope.

Result

Alloxan (100mg/kg i.p.) & sucrose 35% solution (p.o.) administration produced significant hyperglycemia in mice as compared to the control group. Alloxan administration did not produce any significant effect on weight change and locomotor activity. During the acquisition test (learning), alloxan‐treated mice significantly enhanced the escape latency time taken to reach the submerged platform. However, Naringenin administration decreased the escape latency time indicating a significant improvement in memory performance. In the Novel Object Recognition test, alloxan‐treated mice spent more time near the familiar object, and the Naringenin‐treated group spent more time near the novel object. Alloxan treatment also disrupted the mitochondrial levels and lowered the catalase, glutathione, and SOD levels, and increased the lipid peroxidase and acetylcholinesterase activities. Whereas the Quercetin & Naringenin‐treated animals restored these pathological alterations.

Conclusion

Administration of Quercetin & Naringenin significantly reversed alloxan‐induced behavioral, biochemical, and cellular alterations in both the frontal cortex as well as in hippocampus. These findings suggest that quercetin may be looked upon as a promising memory‐enhancing agent in preclinical studies. Therefore, clinical trials may be undertaken to establish the memory‐enhancing property of quercetin.
Analysis of MicroRNA‐502‐3p and MicroRNA‐501‐3p in the Cerebrospinal Fluid of Alzheimer’s Disease and its Corresponding Neuropathology: Potential Biomarkers
Authors: Devara Davin , Sharma Bhupender , Kumar Subodh , Torres Melissa , Rodriguez Sheryl , Rodarte Daniela
Published: January 2025

Background

Alzheimer’s disease (AD) continues to be the leading cause of dementia. Few treatment options exist to manage AD. It is essential to diagnose AD early to slow its progression; however, there are very limited diagnostic tools to accurately diagnose AD. MicroRNAs (MiRNAs) are currently being studied for their biomarker potential in many diseases, including AD. This study explores the biomarker potential of miR‐502‐3p and miR‐501‐3p in the cerebrospinal fluid (CSF) exosomes of AD patients and their relationship to the severity of amyloid plaques and neurofibrillary tangles (NFTs) in affected brain regions.

Method

CSF samples from AD patients (n=26) and unaffected controls (UC) (n=10) were obtained from NIH NeuroBioBank. We then isolated exosomes from CSF and analyzed the expression of miR‐502‐3p and miR‐501‐3p. Results were compared with CSF Aβ1‐40, Aβ1‐42, Tau and p‐Tau levels. We also evaluated the relationship of miR‐502‐3p and miR‐501‐3p with the neuropathology reports of the CSF samples.

Result

MiR‐502‐3p and miR‐501‐3p expression levels were upregulated in the AD CSF exosomes relative to the UC CSF exosomes. MiR‐502‐3p level was positively correlated with CSF Aβ1‐40 level while miR‐501‐3p was positively correlated with CSF p‐Tau levels. The expressions of miR‐502‐3p and miR‐501‐3p were significantly associated with the severity of amyloid plaques and NFTs in the entorhinal cortex, hippocampus, amygdala, middle frontal gyrus, inferior parietal lobule, and superior temporal gyrus.

Conclusion

MiR‐502‐3p and miR‐501‐3p could potentially be useful CSF biomarkers for AD in the future. They may also be used to track the progression of AD in patients.
Susceptibility based magnetic resonance imaging for development of neuroimaging biomarkers
Authors: O'Donnell Lauren F , Khan Suleiman , Goldman Hannah , Murray Sean , Szabo Jakub , Soliman Muhammad T , Llanos Michael , Cho Olivia , Kingsley Charles , Swain Jody , Gray Stanton B , Hopkins William D , Wisniewski Thomas , Veraart Jelle , Scholtzova Henrieta , Zaim‐Wadghiri Youssef
Published: January 2025

Background

Amyloid related imaging abnormalities (ARIA), a group of neuropathological features seen in anti‐amyloid immunotherapy patients, arises partly from CAA (Aβ buildup in blood vessels). Squirrel monkeys (SQMs), developing prominent age‐related CAA exceeding brain Aβ, offer a unique NHP model for ARIA study. Evaluating edema‐related neurobiological defects (ARIA‐E) involves preferential use of T2‐weighted (T2‐w) and flow‐attenuated inversion recovery (FLAIR) MRI while T2*‐weighted (T2*‐w) MRI is better suited for investigating iron‐related pathology like microbleeds, hemorrhaging, and iron‐homing in plaques. Further insights can be gained by mapping tissue magnetic susceptibility, which boosts sensitivity and specificity. Susceptibility‐weighted imaging (SWI) achieves this by combining magnitude and phase images to enhance contrast from iron containing structures. Notably, quantitative susceptibility mapping (QSM) goes a step further by utilizing phase information with field inversion computation to generate quantitative magnetic susceptibility values in the imaged tissue. This ability to differentiate between paramagnetic (iron) and diamagnetic (calcification) signal contributions makes QSM valuable for potentially quantifying iron content more accurately. Here we present the sensitivity of conventional T2* weighted and quantitative R2* (QR2*) imaging to SWI and QSM analysis in this SQM model.

Method

In Vivo MRI scans were acquired on a cohort of geriatric SQMs using a multi‐sequence protocol: a multigradient echo (MGE) sequence for susceptibility mapping, a 2D T2‐w Turbo‐spin‐echo for edema assessment, and 2D FLAIR for improved white matter and edema visualization. Susceptibility maps were generated from the MGE data using both SWI reconstruction (PV6.0.1, Bruker) and the QSM processing in STI Suite for Matlab by Liu et al. (2013).

Result

Expanding on QR2*'s success in aging SQM iron pathology, we compared QSM and SWI to it and T2*‐w, uncovering latent pathologies. QSM revealed iron in hyper‐intense regions with heightened SWI contrast, and conversely, identified unspecific hypo‐intensities, likely calcification, in some subjects. Immunohistochemistry then characterized these MRI anomalies.

Conclusion

Susceptibility imaging leverages tissue's magnetic properties to reveal subtle iron deposits, microbleeds, and calcifications that often escape detection. This unveils invaluable insights into iron‐related pathologies in the brain, invisible to conventional MRI's proton‐based techniques.
A Cross Cultural Understanding of Diverse Dementia Journeys
Authors: Michael Mary Chi
Published: January 2025

Background

Over the past 3 years, the Global Council on Alzheimer’s Disease (GCAD) has conducted research on lived experience and care partner journeys. Specifically, this research has focused on the experiences of individuals from historically underrepresented populations, including LGBTQ+, Black, Hispanic/Latino, and Asian communities. The goal has been to identify how these journeys might diverge across communities, understand various nuances that exist across cultures, and recognize the impact these might have on seeking diagnosis, care, and support.

Method

To understand the experiences of community members living with dementia, we undertook qualitative primary research, complemented by secondary research. Primary research consisted of dozens of one‐on‐one interviews with people living with dementia and their care partners. Secondary research consisted of a review of existing literature on each community’s experiences with dementia.

Result

An output of this work is a visualization that maps and overlays distinct journeys that members of each community experience. These journey maps illustrate how one community’s journeys might overlap and diverge compared to others. The maps capture the challenges each community faces, resources that have been developed, and how care is managed along the disease progression.

Conclusion

This work has revealed many nuances that exist across the dementia journey, including: different manifestations of stigma, bias, medical inequity, unequal access to care and treatment; how care is managed both institutionally and in the home; impacts of the presence or absence of traditional family care structures; and varying availability of resources for living well with dementia. It also revealed areas in which each community is overcoming that stigma as well as opportunities for support and resources. The project concludes with a call to action that outlines how the dementia community can better support people affected by dementia from the underrepresented communities; it also emphasizes the importance of applying culturally competent approaches to understanding these journeys and ultimately providing better care and support.
The Patient And family member Reactions to biomarker‐informed ADRD DiagnosEs or PARADE Study
Authors: Witbracht Megan G. , Knox Melissa L , Lingler Jennifer H , Grill Joshua D
Published: January 2025

Background

Amyloid imaging biomarkers serve an increasingly important role in diagnosing Alzheimer’s disease and determining eligibility for treatment with new disease‐modifying therapies. Yet, psychological and behavioral reactions to receiving a biomarker informed diagnosis remain relatively unstudied, especially in diverse and underserved populations where the burden of disease is high and resources for support are often insufficient. We developed the Patient And family member Reactions to biomarker‐informed ADRD DiagnosEs (PARADE) Study to address two key gaps in our understanding: 1) the range and trajectory of psychological and behavioral responses to a biomarker informed diagnosis and 2) the support needs of these individuals and their families.

Method

Leveraging the infrastructure of New IDEAS, a coverage with evidence development study of amyloid PET, we developed a longitudinal study to quantify responses to receiving an amyloid PET biomarker test as part of a clinical work up for a diagnosis of cognitive impairment. Patients enrolled in the New IDEAS study are referred through the Alzheimer’s Association’s TrialMatch and then invited to participate with their study partners in 4 remote structured interviews performed prior to their amyloid PET scan and then 4‐, 12‐, and 24‐weeks after result disclosure. The primary outcome of the study is the Impact of Events Scale (IES), a measure of intrusive thoughts. Along with the IES, the interviews include questionnaires to assess the “value of knowing”, anxiety, depression, social support, loneliness, coping style, and discrimination. The goal of the study is to enroll 500 English or Spanish speaking dyads residing in the continental US. We will oversample Latinx and Black/African American participants as a reflection of the New IDEAS population.

Result

Data collection began in May 2023 at the University of Pittsburgh and the University of California, Irvine and is expected to be complete the fourth quarter of 2026. Interviews have been completed by telephone and video conference in Spanish and English with relatively low rates of attrition.

Conclusion

As the field advances to improve diagnosis and treatment, data from studies like this one will be essential to better understanding the patient and family experience of receiving a biomarker informed diagnosis.
Relationships between medical comorbidities and plasma biomarkers of Alzheimer's disease reflect increased pathological markers as well as biological variabilities
Authors: Lee Eun Hye , Kang Sung Hoon , Kim Young Ju , Zetterberg Henrik , Blennow Kaj , Gonzalez‐Ortiz Fernando , Shin Daeun , Yoo Heejin , Cheon Bo Kyoung , Kim Jun Pyo , Kim Hee Jin , Na Duk L. , Jang Hyemin , Seo Sang Won
Published: January 2025

Background

Plasma biomarkers for Alzheimer’s disease (AD) have demonstrated their accuracy as diagnostic tools, suggesting their impending integration into clinical practice. Medical comorbidities might not only affect AD pathological burdens but also cause variability of plasma biomarkers by affecting their transfer via blood brain barriers. In the present study, we aimed to determine which comorbidities might affect plasma biomarkers with (real effects) or without (biological variability) AD pathological burdens measured by β‐amyloid (Aβ) uptakes on PET.

Method

We recruited 2,935 participants including cognitively unimpaired (n=673), mild cognitive impairment (n=1439), dementia of Alzheimer’s type (n=611), and subcortical vascular cognitive impairment (n=190) from Korea‐Registries to Overcome and Accelerate Dementia research. All of them underwent amyloid PET imaging. Their plasma Aβ40, Aβ42, p‐tau217, GFAP and NfL levels were measured by a single molecular assay on a single platform.

Result

Various medical comorbidities were predictive of decreased or increased plasma biomarker levels after controlling for Aβ uptakes on PET. By using these medical comorbidities as predictors and Aβ uptakes as mediators, we performed the mediation analyses. Aβ uptakes partially mediated the relationships between various comorbidities and plasma biomarkers: APOE ε4 for Aβ42/40 ratio, p‐tau217, GFAP and NfL; body mass index (BMI) status for p‐tau217 GFAP and NfL. Various comorbidities also directly affected plasma biomarkers levels: estimated glomerular filtration rate (eGFR) for Aβ42/40 ratio, p‐tau217, GFAP and NfL; chronic kidney disease, hemoglobin, C‐reactive protein, and T3 for p‐tau217, GFAP and NfL; erythrocyte sedimentation rate (ESR) for GFAP and NfL. Finally, adding the comorbidities with direct and indirect effects to the covariates increased the AUCs of Aβ42/40 ratio (0.851 to 0.882) and NfL levels (0.764 to 0.853), but not those of pTau217 and GFAP. However, adding the comorbidities with only direct effects to the covariates did not increase the AUCs of any plasma biomarkers.

Conclusion

Our findings revealed that various medical comorbidities could influence plasma biomarker levels, both directly and through mediation of AD pathology. Therefore, it is important to consider in terms of clinical application and interpretation of plasma biomarkers results in clinical practice.
Serum non‐targeted metabolomic and lipidomic analyses reveal potential biomarkers to predict cognitive impairment for subcortical ischemic vascular disease
Authors: Yin Yunsi , Zhang Yifei , Wang Fan , Tang Yi , Qin Qi
Published: January 2025

Background

It is challenging to distinguish which subcortical ischemic vascular disease (SIVD) patients will present with cognitive impairment. A blood‐based biomarker to distinguish SIVD patients with cognitive impairment would be superior to neuropsychological measures and neuroimaging measures in terms of cost, time, and feasibility for repeated measures. Metabolomics profiling studies could help identify blood‐based biomarkers for SIVD patients with cognitive impairment.

Method

100 SIVD patients without cognitive impairment,70 SIVD patients with cognitive impairment, 30 DLB patients and 30 AD patients were recruited from three Chinese research hospitals. 34 SIVD patients without cognitive impairment and 34 SIVD patients were follow‐up for 2 years. Patients’ serum samples were assessed using non‐targeted metabolomics and lipidomics analyses.

Result

Six metabolites including TG(52:2)‐FA18:1, DHCer(d18:0_24:0), ChE(22:4), Cer(d18:1_18:0), SM(d18:1_26:0) and Hex2Cer(d18:1_24:0) were identified as informative biomarkers for cognitive impairment in SIVD patients. The performance was stable after 2 years follow up and in differential diagnosis among AD and DLB patients.

Conclusion

Our study has developed an accurate and accessible means based on blood samples to identify SIVD patients at high risk of cognitive impairment. Dysregulation of sphingolipid metabolism was involved in the neurobiological pathways that contributed to cognitive impairment in SIVD patients.
Social environment of people living with dementia: Characteristics, facilitators and barriers
Authors: Knecht Hanna Lea , Rodriguez Francisca S
Published: January 2025

Background

The number of people with dementia increases worldwide. Previous studies have shown that social integration and high‐quality social relationships are beneficial for reducing dementia risk and improving symptoms. Our project aimed at identifying characteristics of the social environment of people with dementia (PWD) and their relevance for PWDs’ wellbeing, and at determining facilitators and barriers of the PWD’s social integration.

Method

A total of N = 497 participants (86% female, mean age of 53 years, 53% urban), of whom 3% had dementia, 16% cared for family members, 17% cared for someone outside of family, 15% were professional caregivers, 16% were counsellors, and 33% were otherwise connected to dementia care, answered our survey questions. We performed descriptive data analyses.

Result

The majority of participants (72%) reported that those caring for PWD initiated social interactions and more than half of the participants (57%) showed that these interactions are often experienced at home. Most participants (85%) felt that simply spending time with the PWD has a great positive impact on their well‐being. Partners of the PWD were considered as the most important social contact to reduce fears (score 4.8/5), to support them in managing everyday life (score 4.6/5), and to contribute to general well‐being (score 4.6/5). Regarding facilitators, most participants (89%) stated that family members are crucial for undertaking social activities. All participants (100%) felt that meeting face‐to‐face is necessary to maintain a relationship with a PWD and indicated that it is highly important (score 4.7/5) to show understanding for dementia symptoms. Concerning barriers, many participants (84%) felt that other people’s inability to cope with dementia symptoms is a significant reason for the downsizing of PWD’s social network. Moreover, the majority of the participants (52%) assumed that social stigma keeps PWD from being socially active.

Conclusion

The results signify that partners and family members play an important role in initiating social experiences of PWD and in determining the benefits that result from it. Barriers seem to lay mainly in the understanding of dementia in the community, which should be addressed in future community awareness projects.
Exploring Sleeping Patterns of Patients with Dementia Based on Different Sleep States
Authors: George Dalene Ephme Ben
Published: January 2025

Background

Sleep patterns and disruptions may associate with increased dementia risk and contribute to its progression and cognitive decline. Understanding the complexity of the sleep‐dementia relationship is crucial for developing interventions that may delay cognitive decline and enhance the well‐being of individuals with dementia. This study seeks to explore how the sleeping patterns of patients with dementia impact them and aims to provide insights to help improve the sleep patterns of individuals affected by dementia.

Method

The study uses the sleep data from TIHM project (Surrey and Borders Partnership, NHS Foundation), encompassing records of 17 dementia patients. The dataset contains details including sleep states, heart rate, respiratory rate, and snoring. Firstly, the average heart rate and respiratory rate are analyzed over time for each patient. Sleep transition states are explored to show patterns of transitions between different sleep states. The study explores circadian aspects by calculating average hours for each sleep state, and it provides additional insights, including average heart rate and respiratory rate based on sleep state and snoring.

Result

This study provided significant insights into the sleep patterns of individuals living with dementia. The heart rates of patients vary from 50.87 to 69.43 with an average 60.57, slightly elevated from the normal. The respiratory rates range from 11.80 to 18.34, with an average 14.83 (Figure 1). Notably, individuals who snore exhibit a lower average heart rate (56.4) compared to non‐snorers (61.03). Sleep state analysis indicates slightly higher heart and respiratory rates during Awake and Rem states compared to other states. Sleep state transitions highlight a predominant shift from Awake to Light, followed by Light to Awake (Figure 2). Patients primarily spend time in the Awake state (6 hours), followed by Deep (5 hours), and then Light and Rem states (4 hours) (Figure 3).

Conclusion

The study provides significant insights about the relationship between sleep patterns and dementia. Elevated heart and respiratory rates during Awake and Rem states underscore physiological aspects in individuals with dementia, with prevalent transitions from Awake to Light in sleep state analysis. These findings contribute to a deeper understanding of sleep in dementia, suggesting implications for enhanced care.
Effect of Social Interaction Intervention on the Elderly:A Systematic Review
Authors: Yoo Soo Yeon , Han Jung Min , Park Ji‐Hyuk
Published: January 2025

Background

Exercise or cognitive interventions have already been sufficiently provided to the elderly, and their effectiveness has been proven. However, interventions in the context of promoting social interaction have not been well‐implemented for the elderly, and few studies have considered the effectiveness of interaction mediation for the elderly. This study therefore sought to examine the effectiveness of interactive interventions by examining studies that provide interventions focusing on social interactions.

Methods

We conducted a systematic search spanning the period from 2013 to 2023, utilizing databases such as RISS, DBpia, Embase, and Web of Science. The primary search terms employed were (“elderly” OR “geriatric”) AND “social interaction” AND intervention.” Four carefully selected studies were subjected to detailed analysis.

Result

Among the four selected studies, three specifically evaluated cognitive function and confirmed the results. The interventions demonstrated a notable increase in both social interaction and cognitive function, coupled with a decrease in depression.

Conclusion

This study examined interventions targeting social interaction among older adults. These findings serve as foundational data for designing effective social interaction interventions within the context of occupational therapy for the elderly.
Simple fully convolutional network to estimate Brain Age
Authors: Aithal Ninad , Sinha Neelam
Published: January 2025

Background

Data‐driven methods, particularly deep learning, are transforming neuroimaging by accurately estimating Brain Age using diverse modalities. Discrepan‐ cies between predicted and actual age unveil potential health risks. Utilizing a training set of healthy subjects, a regression algorithm correlates brain features to age, allowing inference for unseen patients. Deviations, termed brain age delta, correlate with brain health. This Simple fully convolutional network (SFCN) model draws inspiration from the work of Peng H et al. and is trained on the openly available ADNI dataset.

Method

We trained the SFCN model on 908 MRI skull stripped and linearly registered MRI images using fsl belonging to Cognitively normal (CN) group, where each scan was of dimensions 1×91×109×91. The SFCN model has 7 blocks, The first five blocks extract features rapidly, reducing dimensions, and the sixth block introduces non‐linearity, while the final block functions as dense layers to capture the feature map. The model is trained with Mean Squared Error loss with Adam optimiser and early stopping.

Result

The dataset exhibited an age range from 56 to 96 years, with 71 being the mode. The model achieved a Mean Absolute Error (MAE) of 2.23 years on the validation set and 2.22 years on the test set, comparable to State‐of‐the‐ Art (SOTA) techniques. Applying the same model to Alzheimer’s Disease (AD) subjects, totaling 396, yielded a MAE of 6.89 years.

Conclusion

Accurate brain age prediction, revealing disparities between chronological age and brain age, serves as an early marker for diseases. This approach, showcasing a MAE of 2.22 years on T1‐weighted MRI images with minimal preprocessing, holds promise for precise brain age prediction, contributing to early disease detection and intervention.
Cognitive Impairment and Its Risk Factors Among South Asians Living in India: Findings from the P‐CARRS Cohort Study
Authors: Pai Rima , Kondal Dimple , Mohan Deepa , Komal Rani , Subramani Poongothai , Alladi Suvarna , Mohan Sailesh , Ali Mohammed K , Goldstein Felicia , Levey Allan I. , Tandon Nikhil , Prabhakaran Dorairaj , Mohan V , KM Venkat Narayan , Jagannathan Ram
Published: January 2025

Background

To estimate the prevalence of cognitive impairment in a population‐based cohort from India and assess the potential modifiable factors of cognitive impairment.

Method

We used the population‐representative data from the longitudinal Precision‐CARRS study from Delhi and Chennai, India. The cohort was recruited in two waves, CARRS‐1 in 2010‐11 and CARRS‐2 in 2015‐16. We administered the Mini‐Cog screening test during the 7th follow‐up visit in CARRS‐1 and the 2nd follow‐up of the CARRS‐2 in participants over 50 years old. The Mini‐Cog test is a three‐minute screening instrument that consists of two components: a three‐item recall test for memory and a clock drawing test that yields high sensitivity and specificity for detecting cognitive impairment. In models accounting for age, we tested the association between seven hypothesized modifiable risk factors (education level, tobacco use, alcohol use, sleep duration, fruit and vegetable daily intake, presence of moderate to severe depression, type 2 diabetes, and high blood pressure) and cognitive impairment (Mini‐Cog ≤2 points/5 total points).

Result

A total of 5,711 participants (mean age: 61.0 years; female: 59%) with the Mini‐Cog screening test were included in the analysis. Twenty‐five percent (female: 28.3%; men: 22.7%) of the participants showed indications of cognitive impairment on the Mini‐Cog. We identified an association between higher education levels and lower alcohol intake being linked to a lower risk of cognitive impairment. Additionally, higher tobacco use was directly associated with a greater risk of cognitive impairment. In sex‐stratified analysis, we observed that higher education attainment was protective against cognitive impairment in both men and women. Moreover, tobacco use was specifically associated with cognitive impairment in men, while higher fruit and vegetable intake exerted a protective effect against cognitive impairment only in females (Table).

Conclusion

Over a quarter of the P‐CARRS study participants presented with cognitive impairment. Future longitudinal studies are warranted to explore the association of risk factor control with improving cognitive function, particularly in populations and regions where dementia prevalence is projected to increase, such as in South Asia.
Exploring the Influence of Loneliness on Cognitive Decline: Differential Effects in White and Black Older Adults
Authors: Lin Quinn , Dadar Mahsa , Oliver Michael , Morrison Cassandra
Published: January 2025

Background

Approximately 25% of adults 65+ are socially isolated. Social isolation (i.e., loneliness), or the perceived absence of an available and acceptable social network, may be associated with increased cognitive decline. However, there is a limited understanding of how social isolation influences cognitive decline and if this relationship differs as a function of race.

Methods

A total of 3,082 participants (n = 1943 Whites, n = 1139 Blacks) with 20,882 follow‐ups over 10 years were included from the RUSH database. Participants completed the De Jong Gierveld Loneliness Scale and were identified as having either high or low loneliness using a median split of perceived social isolation. Participants were then divided into one of four groups based on race (White vs Black) and loneliness (High vs Low): 1) White‐High (n = 1030), 2) White‐Low (n = 913), 3) Black‐High (n = 493), 4) Black‐Low (n = 646). Linear mixed‐effects models examined group differences in cognitive change over time (global cognition, episodic memory, semantic memory, visuospatial ability, and working memory).

Results

White adults with high loneliness exhibited increased rates of cognitive change compared to low and high loneliness Black adults in all domains (p<.01). Compared to White adults with low loneliness, Whites with high loneliness exhibited increased decline in all domains except processing speed and visuospatial ability (p<.001). Black adults with high loneliness exhibited increased decline compared to Black adults with low loneliness in all domains (p<.01).

Conclusion

Our study reveals a robust association between loneliness and cognitive decline in older adults, with White individuals experiencing a more pronounced impact than their Black counterparts. These findings underscore the need for targeted interventions to address loneliness, particularly among White older adults, to mitigate cognitive decline and promote healthy aging.
Widespread neurite degeneration in mild cognitive impairment and Alzheimer's disease revealed using advanced diffusion MRI
Authors: Laporte John P , Gong Zhaoyuan , Guo Alex , Bae Jonghyun , Faulkner Mary E , Bouhrara Mustapha
Published: January 2025

Background

Neurite degeneration is increasingly suspected to represent a causal feature of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Therefore, sensitive and specific imaging biomarkers of neuronal degeneration are needed to elucidate the mechanisms underlying cognitive impairment in MCI and AD. However, the recently developed Neurite Orientation Dispersion and Density Imaging (NODDI) MRI technique, used to measure the neurite density index (NDI), has some limitations. To address these, we have introduced the constrained NODDI (C‐NODDI) analysis providing more accurate determination of NDI (PMC10435293). Here, we investigated neurite degeneration in MCI and AD using C‐NODDI and compared the results to those derived using NODDI.

Methods

We obtained Multi‐shell diffusion MR images from the ADNI study (Table 1) and calculated NDI using NODDI or C‐NODDI. We conducted a voxelwise two‐sample t‐test to compare NDI of control vs. AD, control vs. MCI, and MCI vs. AD groups. Further, we assessed the regional associations between NDI and overall cognition as measured using the Mini‐Mental State Examination (MMSE) score (dependent variable), controlling for age and sex. All continuous variables were Z‐scored.

Results

The AD group exhibited significantly lower NDI values as compared to control, with C‐NODDI exhibiting greater sensitivity in capturing regional NDI variations as compared to NODDI (Figure 1). Further, unlike NODDI, C‐NODDI was capable of detecting subtitle differences in NDI between control and MCI and between MCI and AD (Figure 1). Interestingly, NODDI exhibited higher NDI values in MCI or AD as compared to control in several brain regions (Figure 1), a physiologically implausible result that C‐NODDI corrected. Additionally, the associations between MMSE and NDI derived using C‐NODDI were significant in several white matter regions, with higher NDI values corresponding to expected higher MMSE scores (Figure 2). NODDI has failed to capture this anticipated association.

Conclusions

This study provides evidence of widespread neuronal degeneration in MCI and AD. Importantly, our results highlight the superior sensitivity of C‐NODDI analysis in detecting these differences in neurite density as compared to NODDI, making it a potent MRI method for clinical investigations and trials studying neuronal degeneration in aging and age‐related diseases.