bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing the short‐term and long‐term impact of primary and secondary prevention strategies on population‐level dementia burden: A microsimulation modelling study
Authors: van Rosmalen Lynn , Brück Chiara C. , Wolters Frank J. , Handels Ron , de Kok Inge M.C.M.
Published: January 2025

Background

Dementia prevention can be achieved through modification of risk factors (primary prevention) or targeted therapy against pathophysiological hallmarks of disease (e.g., amyloid‐lowering medication (secondary prevention)). To compare the effectiveness of primary and secondary prevention approaches on population dementia burden over time, we used a microsimulation approach.

Method

We used the microsimulation model MISCAN‐Dementia to simulate 10 million people born between 1910‐1989, in absence and presence of dementia prevention (Figure 1). For primary prevention, we assumed it is effective if there is no brain pathology, and dementia was attributable to risk factors. We assumed that primary prevention delays the presymptomatic stage by 12 months. For secondary prevention, we assumed patients are eligible for amyloid‐lowering treatment if they are in MCI or early dementia stage and are amyloid positive. We assumed that treatment increases MCI and mild dementia stage durations by 10%. To simulate these primary and secondary interventions, we incorporated a presymptomatic dementia stage (pathology present, no cognitive decline), amyloid status, and risk factor status in the model. Both interventions are initiated in 2025. We calculated the number of life years lived with dementia per 100.000 persons <85 years by disease stage.

Result

Benefits of primary prevention accrued slowly over time, from no benefit at 5 years post initiation, to around 8‐9% reduction in the number of life years with moderate‐severe dementia at 25 years after initiation. After 5 years, secondary prevention showed a 4.8% decrease in years lived with moderate dementia and 2.6% with severe dementia. This reduction increases to 5‐6% in 25 years (Figure 2). In case both interventions are applied, the effect is 0.5‐1% weaker than additive. The two modes of prevention are equally effective 19 years after initiation.

Conclusion

Compared to secondary prevention, primary preventive strategies can yield a larger reduction in life years with dementia, but benefits take a much longer time to accrue. These findings underline the need for combined primary and secondary prevention initiatives and sustained, long‐term efforts to achieve the full potential of dementia prevention in the population. Sensitivity analyses to examine the robustness of the findings need to be complemented.
Optimizing blood biomarkers collection for Alzheimer’s disease among older adults in rural Kenya
Authors: Ndetei David , Nyamai Pascalyne , Musyimi Christine W. , Kasomo Diana , Mutiso Victoria
Published: January 2025

Background

Plasma/serum measurements, which stand as the clinical gold standard biomarkers for Alzheimer’s disease (AD) are minimally invasive, facilitating easy collection and processing particularly in low‐resource settings. Often, both laboratory and non‐laboratory medical personnel find themselves collecting these blood biomarker samples in remote hospitals characterized by a high influx of patients, leaving them with limited time and resources (e.g. freezers) for immediate sample processing, transport, and storage. This abstract describes blood biomarker sample collection and storage for AD research among older adults in Makueni County, Kenya.

Methods

In optimizing blood biomarkers collection for AD research among hard‐to‐reach older adults, a multidisciplinary team is crucial. Blood was collected into three Ethylenediamine tetraacetic acid (EDTA) of 10mls each. To ensure the preservation of biomarker integrity, we focused on refining sample handling processes, and maintained the required temperature for sample transportation.

Results

Following sample collection, one of the three EDTA blood tubes was immediately stored in dry ice (‐80 degrees) for Deoxyribonucleic acid (DNA) extraction. A volume of 0.5ml whole blood was taken from one of the remaining two EDTA tubes. The rest was centrifuged at 3400 rpm for 10 minutes and plasma aliquots obtained and put into the barcoded storage vials prelabeled. To preserve the integrity of the blood biomarkers, the collection and transportation process necessitated the use of dry ice (‐80 degrees) with continuous monitoring. This not only ensured the retention of blood biomarkers but also the importance of stability in these biomarkers. Subsequently, during storage, temperature monitoring becomes imperative. The options ranged from manual temperature monitors, albeit with inherent limitations, to more reliable yet costly data loggers. This monitoring was crucial to guarantee the integrity of the stored samples and maintain the accuracy of biomarker analysis.

Conclusion

The transportation of blood samples from the rural hospital to centralized facilities with adequate freezers demands meticulous cold chain maintenance. Clear guidelines encompassing sample collection, transport, processing, and storage, in hard‐to‐reach older adults should be delineated for future biomarker research in AD research.
Brazilian Subjective Cognitive Decline (BRASCODE) Cohort: baseline sociodemographic and clinical data
Authors: de Albuquerque Ana Letícia Amorim , Giordani Manuella Edler Zandoná , Souza Victória Tizeli , da Mota Simone Sieben , De Marchi Bruno De Olive , Rivas Gabriela Raquel Paz , Carvalho Guilherme Da Silva , De Souza Haniel Bispo , Beltrami Lucas Bastos , Santos Rhaná Carolina , Borelli Wyllians Vendramini , Carello‐Collar Giovanna , Chaves Marcia L Fagundes , Zimmer Eduardo R.
Published: January 2025

Background

Subjective cognitive decline (SCD) is the self‐perceived impairment of cognitive function and has been studied as a risk factor for objective cognitive impairment. Monitoring patients with SCD can aid in understanding the risk factors for dementia in low‐ and middle‐income countries. We aimed to describe the baseline sociodemographic and clinical data of the Brazilian Subjective Cognitive Decline (BRASCODE)

Methods

BRASCODE is an observational, prospective cohort study of cognitively unimpaired individuals with > 65 years‐old with cognitive complaints conducted at the Hospital de Clínicas de Porto Alegre, Brazil. The baseline evaluation was performed from March 2022 to January 2024. Exclusion criteria were previous diagnosis of dementia or cerebrovascular disease and uncontrolled neuropsychiatric/clinical illness. Sociodemographic, memory complaint scale (MCS), Mini‐Mental State Examination (MMSE), Clinical Dementia Rating (CDR) Scale and Cognitive Reserve Scale (CRS) were collected. Blood, cerebrospinal fluid, and imaging Alzheimer’s disease (AD) biomarkers were also performed.

Results

A total of 144 patients were included, with 72.2% being female. The majority were of white ethnicity (92.1%), belonging to middle‐class socioeconomic status (B and C ‐ 79.9%). The median age was 69 years, and the median education level was 15 years. The most prevalent comorbidities were arterial hypertension (46.5%), diabetes mellitus (14.6%), and smoking (6.9%). The median score on the MMSE was 29 [27, 30] points. Regarding the CDR scale, 109 patients (75.7%) had a CDR of 0, and 35 (24.3%) had a CDR of 0.5. CRS scores exhibited a positive correlation with MMSE (rho = 0.304; p = 0.0002) and years of formal education (rho = 0.408; p<0.0001). Age correlated negatively with MMSE (rho = ‐0.188; p = 0.024) and MCS (rho = ‐0.245; p = 0.003). MCS score of the subject and informant also correlated (rho = 0.305; p = 0.0002) and exhibited no correlation with CRS scores and MMSE.

Conclusions

Our results show an association between the patient’s cognitive reserve and education and formal cognitive testing (MMSE). The future availability of AD biomarkers and follow‐up data will provide additional information about cognitive progression of the SCD participants.
Abdominal Obesity (Waist‐to‐Hip Ratio) is Superior to Body Mass Index as an Indicator of Cognitive Health in Older African Americans
Authors: Niraula Sophee , Fausto Bernadette A. , Osiecka Zuzanna , Gluck Mark A.
Published: January 2025

Background

Recent studies suggest that body mass index (BMI) may overestimate obesity and related cognitive health consequences in some populations due to racial differences in body shape and composition. Conversely, waist‐to‐hip‐ratio (WHR) may better capture cognitive health, because this measure accounts for where body fat accumulates. However, few studies have compared the influence of BMI vs. WHR on cognitive function in older African Americans. As such, this study aimed to identify the relative contributions of BMI and WHR to cognitive function in older African Americans.

Method

122 older African American participants (mean age = 72.19; SD = ±6.65) from the Pathways to Healthy Aging in African Americans study completed demographic and mood questionnaires, cognitive assessments of attention, memory, executive function, and language, and anthropometric measurements (height, weight, waist and hip circumference). Participants were categorized into four BMI groups per established cut offs (normal weight = 18.5 to 24.9 kg/m2; overweight = 25 to 29.9 kg/m2; class 1 obese = 30.0 to 34.9 kg/m2; class 2 obese or greater = > 35.0 kg/m2). We also used the World Health Organization’s proposed cutoffs for WHR to classify participants with and without abdominal obesity (men ≥ 0.90 cm; women ≥ 0.85 cm). ANCOVA was employed to investigate the main effects of BMI and WHR groups while controlling for age, sex, education, depressive symptomatology, and APOE‐e4 carrier status.

Result

The WHR group with abdominal obesity had significantly poorer attention and executive function performance via the Digit Span test, F(1, 75) = 7.37, p = 0.01, η2
p = .09). There were no significant differences in cognitive test performance across the BMI groups when controlling for WHR, F(3, 75) = 54.10, p = .12, η2
p = .07.

Conclusion

Abdominal obesity (WHR) is superior to BMI as an indicator of cognitive health in older African Americans. The lack of independent association between BMI and cognition highlights the importance of considering more nuanced measures of body weight such as WHR and abdominal obesity in older African Americans
Association of Pesticide Use with Cognition in Aging Community‐Dwelling Rural Adults in South India
Authors: Panchawagh Suhrud , Mitra Sumedha , Sundarakumar Jonas S.
Published: January 2025

Background

Emerging evidence suggests environmental factors, such as chronic pesticide exposure, may influence cognitive functioning, yet research in this area remains limited, particularly in rural Indian settings. Our objective was to investigate the potential link between pesticide exposure and cognitive performance in an aging population from rural India.

Method

This cross‐sectional analysis included 4320 participants from the Srinivasapura Aging NeuroSenescence and COGnition (SANSCOG) cohort. They are predominantly farmers, recruited from the rural areas of Srinivaspura in southern India. Pesticide exposure was assessed based on self‐reporting of usage. Cognitive performance was evaluated using a comprehensive, culturally adapted, computerized neurocognitive battery (COGNITO), which encompasses various domains of cognitive function, such as attention (reaction time, visual attention, auditory attention), memory (immediate and delayed episodic memory, implicit memory, name‐face recognition), language (reading & comprehension, phoneme comprehension, phonemic fluency, semantic associations, vocabulary), visuospatial ability (visuospatial span and visuospatial construction), and executive function (form matching, fluid intelligence, semantic fluency). We used multivariate regression models, adjusting for potential confounders such as age, gender, education, diabetes mellitus, and hypertension to test the association between pesticide use and cognition. Multiple comparisons were handled using the Bonferroni correction.

Result

In our study, 3661/4320 participants (85%) were involved in agriculture, of which 1136/3661 (31%) used pesticides. (Table 1) The median duration of pesticide usage was 10 years (IQR: 5, 15). Our study did not find a statistically significant association between high pesticide use and cognitive performance scores in any domain after adjusting for multiple comparisons. (Figure 1)

Conclusion

Our analysis reports that moderate‐term pesticide use did not significantly impact cognitive function in this population of aging rural Indian adults. However, the cross‐sectional nature, lack of objective information on the severity of exposure, and potential confounders suggest caution in interpretation. We intend to follow up these participants with periodic cognitive monitoring to examine if long‐term pesticide exposure could be linked to accelerated cognitive decline and increased risk for dementia.
A new class of neurodegenerative disease‐fighting drugs: morADC (Morphomer®‐ antibody drug conjugates)
Authors: Nampally Sreenivasachary , Adolfsson Oskar , Martin Camille , Ollier Romain , Menant Sebastien , Tsika Elpida , Fenyi Alexis , Ait‐Bouziad Nadine , Aeschbach Lorene , Pautet Sylvain , Fuchs Aline , Ribas David , Derouazi Madiha , Pfeifer Andrea , Kosco‐Vilbois Marie
Published: January 2025

Background

Antibody‐drug conjugates (ADCs) represent a major advancement in oncology to deliver selectively cytotoxic drug to tumor cells while reducing their exposure to normal tissues. Each ADC consists of a monoclonal antibody (mAb) selective to a tumor specific/overexpressed surface antigen conjugated to the cytotoxic agent. In this study, we are investigating the potential of an ADC approach in neurodegenerative diseases (NDD) to increase the exposure of therapeutic mAbs in the brain using small molecules known to be brain penetrant.

Method

Several ADCs were engineered by conjugating mAbs and small molecules (SME) derived from our Morphomer® platforms, resulting in molecules called morADC. The properties of those morADCs incorporating each different mAbs, morphomers and various linkers were assessed in an in vitro blood‐brain‐barrier (BBB) permeability, a primary neuron seeding and Thioflavin T (ThT) aggregation assays. In the latter, the aggregates were also analyzed by electron microscopy. The most promising molecules were injected in mice to monitor brain exposure and pharmacokinetic compared to the parental mAb.

Result

Over 30 morADCs were produced to target pathological proteins, e.g., Abeta, Tau and alpha‐synuclein. Drug‐to‐antibody ratios (DAR) from 2.5 to 4.5 were achieved exhibiting excellent purity and plasma stability. The morADC molecules demonstrated in vitro a synergistic effect quantified by isobologram analysis with 2 log higher potency in various seeding assays. When assessed in vitro for brain permeability, morADCs showed 3‐6‐fold enhanced BBB penetration as compared to parental mAb, dependent on the conjugated morphomer and the linker. Increased brain exposure of the morADC compared to the parental mAb was confirmed in mice: 3‐fold increase in vitro in the BBB permeability assay translated in 2.5‐fold increase of the mAb exposure in the mice parenchyma. The initial pharmacokinetic results indicate similar plasma concentration and stability of the morADC as the parental mAb.

Conclusion

Bioconjugating functionally active mAbs and SMEs provides therapeutic morADCs as a new treatment modality with synergistic potential to target NDD pathology. More work is ongoing to better characterize the unexpected synergistic effect observed as well as proof‐of‐concept studies in relevant model pathological models. Nevertheless, our morADC platform represents a promising breakthrough approach in NDDs.
Gender Differences in the Predictive Efficacy of Mayo‐PACC for Alzheimer's Disease Biomarkers: Results from a South American Cohort
Authors: Keller Greta , Mendez Patricio Chrem , Corvalan Nicolas , Clas Giulia Solange , Álvarez María Florencia , Pertierra Lucia , Allegri Ricardo , Sevlever Gustavo , Crivelli Lucia , Surace Ezequiel Ignacio
Published: January 2025

Background

With the increase in life expectancy and the rising prevalence of Alzheimer's Disease (AD), the integration of biomarkers for early diagnosis is crucial. The Mayo Preclinical Alzheimer's Cognitive Composite (Mayo‐PACC), encompassing the Rey‐Auditory Verbal Learning Test (RAVLT), Trail Making Test ‐ B (TMT B), and semantic fluency, is designed to detect cognitive changes in preclinical AD. This study investigates gender‐based differences in the predictive efficacy of Mayo‐PACC for AD biomarkers following the ATN (Amyloid, Tau, Neurodegeneration) criteria.

Method

The study included 112 patients diagnosed with Mild Cognitive Impairment (MCI), comprising 38% women and 61% men, matched by age (mean ± SD: 68.73 ± 10.70 years), education (14.21 ± 3.56 years), and cognitive performance (Mayo‐PACC p= 0.76). Neuropsychological assessments were conducted using the Mayo‐PACC, and cerebrospinal fluid biomarkers (amyloid β1–42, total tau, and phosphorylated tau at threonine 181) were quantified by ELISA (Fujirebio, Japan). Biomarkers were dichotomized using cutoff values previously determined in our laboratory.

Result

Random Forest models indicated an overall area under the curve (AUC) of 0.67 for the Mayo‐PACC. In gender‐specific analyses, women showed a lower predictive capacity (AUC: 0.43), with TMT B (35.42%), RAVLT (32.84%), and semantic fluency (31.74%) as key predictors. For men, a higher AUC of 0.90 was observed, with TMT B (35.49%) and semantic fluency (34.91%) being the most influential. When examining individual ATN biomarkers, women showed an AUC of 0.25 for Aβ1‐42, 0.54 for N, and 0.40 for T, with RAVLT (40.51%) as a prominent feature. Men exhibited AUCs of 0.63 for Aβ1‐42, 0.83 for N, and 0.48 for T, with semantic fluency (33.95%), and RAVLT (33.12%) being significant predictors.

Conclusion

The study highlights notable gender differences in the predictive performance of neuropsychological composites for AD biomarkers. Biomarker prediction was more accurate in men. These findings suggest the importance of gender‐specific approaches in predictive modeling for AD diagnosis, underscoring the potential to enhance diagnostic precision in clinical practice.
Association between hippocampal volume and visual classification of hippocampal atrophy: an MRI study
Authors: Garrafiel Fabricio Nery , Vidaletti Vitor Verlindo , Soder Ricardo Benardi , Paganin Ricardo Pessini , da Silva Maria Rosa Alves , Aguzzoli Cristiano Schaffer , Schilling Lucas Porcello
Published: January 2025

Background

Hippocampus has a key role in the memory and cognitive functions and its volume tends to decrease during aging and is severely affected in neurodegenerative disorders such as Alzheimer’s disease (AD). The hippocampal atrophy can be assessed by quantitative volumetry or classified by the Mesial Temporal Atrophy Score (MTA). Here, we perform a comparison between the values of automatic hippocampal volumetry and the MTA score, to analyze possible variations through a correlation curve and their impacts on quantitative and qualitative measures.

Method

We analyzed 100 cranial Magnetic Resonance Imaging (MRI) images, T1‐weighted from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The hippocampal volume was obtained by Freesurfer analysis. All images were classified using MTA score by two experienced neuroradiologists. In the statistical analysis, a correlation curve was created, and the Pearson correlation coefficient was obtained between the volumetry and the degree of atrophy and between the interpretations of both radiologists.

Result

The hippocampus volumetric mean size was 2963.83 mm³ (standard deviation 495.16 mm³). As expected, the data exhibited a consistent inverse relationship between hippocampal volume and the MTA score (Figure 1A, B). The Pearson correlation showed a negative correlation between MTA score and hippocampal volume of ‐0.75 for one radiologist and ‐0.76 for the second radiologist and 0.89 between radiologists. However, we observed a variation ≥ 1 predominantly in higher MTA scores in 17 individuals when comparing the MTA scores between radiologists (Figure 2).

Conclusion

The results showed an inverse correlation between MTA score and hippocampal volume, but also indicates discrepancies in visual interpretation of data. Our findings highlight that in some situations the MTA classification has an important mismatch compared to volumetry, and future analysis could clarify in which situations MTA is less accurate and should be complementary to other analysis.
Associations Between Circadian Timing and White Matter Microstructure
Authors: Weimar Lisa S , Zhang Meina , Axelson Eric , Magnotta Vincent A , Burgess Helen J , Moon Chooza
Published: January 2025

Background

Individuals with Alzheimer’s disease often exhibit white matter microstructure degenerations observable through diffusion tensor imaging (DTI). The circadian system regulates sleep and wake cycles. As people age, sleep and wake cycles can be disrupted, which can worsen sleep quality. Circadian rhythm disruption can increase the risk of developing Alzheimer’s disease and damage white matter microstructures. However, few studies have investigated the relationship between circadian timing and the structural integrity of white matter among adults.

Method

Data was collected from 49 later‐life adults (51% female) with mean age 70.4 years (SD = 6.50). Diffusion‐weighted MRI sequences were acquired using a 3.0T scanner. Fractional anisotropy (FA) scalar maps were generated through FSL‐DTIFIT, and the Johns Hopkins University‐ICBM white matter atlas was utilized to assess FA values within white matter tracts. Circadian timing was determined by home‐based dim light melatonin onset (DLMO). A t‐test was used to compare FA values by mean DLMO (17: 46).

Result

In this preliminary analysis later DLMO time was associated with greater FA values in the corticospinal (Meanearly DLMO = 0.41 (SD = 0.04) vs. Mean later DLMO = 0.44 (SD = 0.04), p = 0.023, uncorrected), right corticospinal (Meanearly DLMO = 0.40 (0.05) vs. Meanlater DLMO = 0.44 (0.04), p = 0.01, uncorrected), left posterior thalamic radiation (Meanearly DLMO = 0.38 (0.03) vs. Meanlater DLMO 0.40 (0.03), p = 0.048, uncorrected), cingulum‐hippocampus (Meanearly DLMO = 0.26 (0.03) vs. Meanlater DLMO = 0.28 (0.03) p = 0.025, uncorrected), and left cingulum‐hippocampus tracts (Meanearly DLMO = 0.26 (0.03) vs. Meanlater DLMO = 0.29 (0.03) p = 0.01, uncorrected).

Conclusion

This preliminary data demonstrates that abnormally early circadian timing may be associated with reduced white matter integrity in specific tracts. Future research using a larger sample, longitudinal design, and multimodal imaging methods is needed to confirm these findings and identify the mechanisms underlying these associations.
Differential expression of miRNAs from circulating exosomes in Alzheimer disease and frontotemporal dementia
Authors: Orellana Paulina , Caviedes Ariel , Hernandez Hernan , Lillo Patricia , Villagra Roque , Cerda Mauricio , Zitko Pedro , Thumala Daniela , Gonzalez‐Billault Christian , Ibañez Agustin , de la Cruz Rolando , Chonchol Andrea Slachevsky , Duran‐Aniotz Claudia
Published: January 2025

Background

The content of circulating exosomes has been observed to be altered in response to changes in physiological and pathological conditions, and they are detectable in different human fluids such as blood. Studies focused on the quantification of Aβ and tau proteins, as molecules contained within exosomes, suggest that they are related with Alzheimer disease (AD) and frontotemporal dementia (FTD) development, demonstrated that plasma‐derived exosome analysis is a good approach for searching for biomarkers in the development of dementia. Our aim is to identify new blood biomarkers to detect the AD or FTD in the Chilean population using machine learning based on exosomal miRNAs.

Method

miRNAs were extracted from circulating exosomes from plasma samples of 25 healthy controls (HC), 25 AD patients and 10 FTD patients. miRNAs were sequencing to identify and measure the expression levels. Dysregulated miRNAs were analyzed to create machine learning algorithms. miRNAs obtained from algorithms were validated in a new population of subjects 30 HC, 30 AD and 10 FTD using qRT‐PCR.

Result

After the sequencing and machine learning analysis, we identified 8 miRNAs as potential predictors of AD and FTD. These miRNAs were further assessed in new samples using the qRT‐PCR technique. We identified 4 miRNAs with variable expression in patients with AD and FTD, with three miRNAs downregulated in AD and one upregulated in FTD. For the four miRNAs, significant differences in expression are observed between AD and FTD.

Conclusion

This is the first study in the Chilean population that evaluates miRNAs in patients with AD and FTD. The study of miRNAs as biomarkers of dementia provides the opportunity to develop low‐cost and easy‐to‐obtain diagnostic methods, in addition to the possibility of being implemented in a greater number of health centers, making them more accessible to the population.
Innovations in Dementia Empowerment and Action [IDEA]: First Dementia/Memory Loss RCT Intervention for Sexual and Gender Minority Older Adults and Their Care Partners
Authors: Fredriksen‐Goldsen Karen I , Kim Hyun‐Jun , Jones Brittany R , Hoy‐Ellis Charles Pitre , Oswald Austin G. , Teri Linda
Published: January 2025

Background

Sexual and gender minority (SGM) older adults experience disparities in subjective cognitive impairment when compared to heterosexuals of similar age. Yet, SGM older adults and their care partners living with dementia/memory loss face substantial barriers to accessing culturally relevant health and dementia care. To address the gap in culturally relevant interventions, we tested the efficacy of a first of its kind stigma reduction, cognitive behavioral intervention for SGM older adults living with dementia/memory loss and their care partners, Aging with Pride: Innovations in Empowerment and Action (IDEA). IDEA is a 6‐week, 9‐session culturally responsive intervention delivered by trained coaches built upon an efficacious dementia intervention, Reducing Disability in Alzheimer’s Disease (RDAD).

Methods

Using a 2‐arm, single‐blind randomized controlled trial with a staggered multiple baseline design, we enrolled 161 dyads of SGM older adults living with dementia/memory loss and their care partners and randomized them to either the IDEA or RDAD intervention arms. For this presentation, we tested the short and long‐term effects in exercise, physical functioning, and depression, as well as the moderating effects of social support and microaggressions. We used linear mixed models with random intercepts and slopes to analyze our longitudinal data.

Results

Among the IDEA participants, those living with dementia/memory loss showed a significant increase in the number of days exercising post‐intervention, and care partners had decreased depression. The treatment effects for exercise among care recipients persisted at 30 weeks post‐intervention, while the treatment effects for depression among care partners persisted at both 30‐ and 52‐weeks post‐intervention. We also found moderating effects of social support and microaggressions on key outcomes.

Conclusions

IDEA, designed to be culturally tailored for underserved and stigmatized populations, including SGM older adults and care partners, was found to be an efficacious intervention. The IDEA intervention is poised to be responsive to the disparities in dementia care in our increasingly diverse and growing older adult population. Recognizing the importance of cultural responsiveness and stigma reduction in dementia and caregiving interventions, the study findings will be disseminated among care providers and within underserved communities.
Early CER Strategies to Recruit Black 80+ year olds in the SuperAging Research Initiative
Authors: Timpo Phyllis , Maher Amanda Cook , Zolliecoffer Chandler , Rahman‐Filipiak Annalise , Lincoln Gabrielle A , Moore Sophia , Awosika Avemaria , Devine Rebecca , Peirce Hannah , Engelmeyer Janessa , Morhardt Darby J. , Okonkwo Ozioma C , Bruce Monica , Lose Sarah R , Goldstein Felicia , Trammell Antoine R , Locke Mary , Parker Monica W , Culum Ivan , Finger Elizabeth , Roberts Angela C , Rogalski Emily J
Published: January 2025

Background

Community engaged research (CER) has been critical for increasing diversity in Alzheimer’s studies. However, the effectiveness of CER for engaging a diverse population of ‘SuperAgers,’ has been largely unstudied. SuperAgers are individuals age 80+ with superior episodic memory. The multi‐site SuperAging Research Initiative (SRI) seeks to recruit at least 500 SuperAgers and similarly aged controls, including 40% who identify as Black. This report summarizes initial CER strategies, implementation of new strategies, and enrollment success across the first ∼18 months.

Method

Semi‐structured interviews were conducted at each site to assess current CER strategies and perceptions of facilitators/barriers to CER approaches. Interviews were transcribed and concept mapping was used to identify key themes across sites. Key themes are reported here along with recruitment outcomes across the sites over the first ∼18 months. Initial responsive actions are described.

Result

SRI sites were selected based on their historical success engaging and recruiting Black older adults in cognitive aging research; however, identification and recruitment of SuperAgers was new for most sites. Results revealed strong current community engagement practices across sites. Emergent themes included prioritizing diverse staff, barriers to CER, strengths of the multi‐site design, the value of research to participants. Sites also implemented several CER strategies including building/enhancing community partnerships, providing community presentations, and engaging community members and enrolled participants in feedback sessions related to recruitment methods. Responsive actions of the SRI included development of participant informed culturally tailored recruitment flyers, videos, and photos, which incorporated site‐level feedback. Holiday‐themed appreciation gifts were provided to enrolled participants.

Initial enrollment included 173 participants (mean age: 86.6 years). Diverse recruitment across sites ranged from 0‐27%. Diverse recruitment increased over the second half of the year, potentially suggesting early success with CER strategies.

Conclusion

Initial recruitment reflects a starting point for the enrollment of Black SuperAgers and Controls. Future plans involve implementing additional study‐wide CER recruitment methods, utilizing online registries as a recruitment source, and establishing ambassador boards to boost SRI enrollment of older Black adults. Strategy success will be carefully quantified, and outcomes will be shared for future research use.
Associations between obesity, AD pathology, and neurovascular health in cognitively normal older adults in US POINTER
Authors: Brinkley Tina E , Garcia Katelyn R , Mitchell Gary F , Tegeler Charles H , Sarwal Aarti , Bennett John , Kitzman Dalane W. , Lockhart Samuel N. , Leng Xiaoyan , Baker Laura D , Snyder Heather M , Harrison Theresa M. , Landau Susan M. , Bailey Margie J , Shaltout Hossam A
Published: January 2025

Background

Obesity is associated with adverse changes in the structure and function of both the brain and the vasculature and may modify risk for Alzheimer’s disease (AD). However, the degree to which excess total and central adiposity contribute to overall disease burden in late‐life is unclear. We investigated baseline associations between obesity, AD‐related pathology, and neurovascular health in 255 participants enrolled in the U.S. POINTER trial (mean age: 68.2±5.4 years, 53% female, 29% people of color).

Method

Baseline assessments included anthropometry to determine body mass index (BMI) and waist circumference and neuroimaging (MRI and PET) to assess global amyloid burden, entorhinal and temporal metaROI tau burden, hippocampal volume, cortical thickness, and white matter hyperintensity volume (WMHV). Ultrasound, tonometry, and continuous heart rate and blood pressure monitoring were also performed to evaluate the aorta and carotid arteries and assess autonomic function. Linear regression was used to examine cross‐sectional associations between the outcomes of interest adjusting for age, sex, race/ethnicity, education, and site.

Result

The majority of participants were overweight or obese (n = 220, 86.3%, mean BMI: 30.5±5.6 kg/m2) or had abdominal obesity (n = 190, 74.5%, mean waist circumference: 104.4±14.4 cm2). Overweight and obese individuals were more likely to be Black or Hispanic (p = 0.0028), have less than a college degree (p = 0.0245), and have altered carotid artery properties, including lower characteristic impedance (p = 0.0117), higher pulsatility (p≤0.01), and a larger diameter (p<0.01). Both BMI and waist circumference were positively associated with carotid pulsatility, carotid transmission coefficient, carotid diameter, and aortic normalized impedance, whereas negative associations were found with aortic pulsatility and aorto‐carotid reflection coefficient (all p<0.02). BMI was also positively associated with hippocampal volume (p<0.01). In addition, several neurovascular outcomes were associated with AD‐related pathology, independent of obesity. Notably, higher carotid‐femoral pulse wave velocity, lower baroreflex sensitivity, and lower heart rate variability were associated with greater WMHV (p≤0.01), while higher aortic pulsatility was associated with greater entorhinal and metaROI tau (p = 0.0132).

Conclusion

In older adults at risk for AD, overweight/obesity is associated with altered aortic and carotid structure and function, which likely has important downstream effects on the brain and may impact the development of AD.
Sex/Gender Differences in the Cognitive‐Aging Effects of Head Injuries due to Interpersonal Violence
Authors: Hanes Douglas William
Published: January 2025

Background

Traumatic brain injury is a risk factor for worse later‐life brain health, including dementia. Yet the role of interpersonal violence and its gendered nature in the TBI–cognition relationship has yet to be fully studied. While men and women alike commit and experience violence, gender‐based violence (GBV)—which primarily targets women, transgender and gender‐nonconforming people, and from which they tend to suffer worse injuries than men—is understudied. Using population‐based survey data, we examine gender differences in cognitive effects of self‐reported head injuries due to interpersonal violence.

Method

We use data from the Health and Retirement Study (HRS; n = ), a survey of Americans age 51+. It gathered self‐reported lifetime head‐injury data in 2014, allowing participants to specify injury causes; we restricted our analysis to participants injured in a physical altercation or shot in the head. Participants also indicated injury severity in several binary variables. We calculated summary statistics to compare injury prevalence between men and women. To assess cognitive effects, we used multilevel regressions with subsequent cognitive performance (27 points possible) as the outcome variable and interaction between injury severity and sex/gender as the primary predictor variable, adjusting for race/ethnicity, education, and wealth.

Result

While men were likelier to report head injuries due to fights (c2 = 12.884; p < 0.001), women were over twice as likely to report ongoing health problems due to head injury (c2 = 10.638; p = 0.001), likelier to have been hospitalized due to a fight or gunshot‐caused head injury (c2 = 5.533; p = 0.019), and nearly 5x likelier to report losing consciousness due to choking (c2 = 5.069; p = 0.024). Women hospitalized due to a fight or gunshot experienced worse cognitive effects (b = ‐2.428; p = 0.004) than hospitalized men relative to unhospitalized men (b = ‐2.600, p = 0.005 and b = ‐3.372, p < 0.001, respectively).

Conclusion

In keeping with existing literature, women suffer worse injuries than men from interpersonal violence; women also have worse cognitive harms due to head injuries than do men. The reasons for these outcomes, and their relationship to GBV, requires further investigation.
Integrating NACC UDS with RDW EHR data for MCI prediction and identification of MCI related features
Authors: Wang Gefei , Xu Baijia , Xu Wanwan , Dodge Hiroko H , Zhao Yize
Published: January 2025

Background

Mild Cognitive Impairment (MCI) is considered as a transitional state between age‐related cognitive decline and dementia. Accurate prediction of those at risk of MCI is important for timely intervention and treatment of Alzheimer’s disease. In this study, we show that incorporating the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) with rich resources from Electronic Health Records (EHR), including comorbidities and medication histories, can achieve higher prediction accuracy, compared to using only one resource.

Method

In this study, we used the Research Data Warehouse (RDW) EHR data from Oregon Health & Science University (OHSU) as auxiliary information. We first cleaned variables by rescaling and one‐hot encoding. Missing data were imputed by the average of observations. Only data recorded before MCI transition were included. To fairly compare different feature sets, the same random forest classification model with 100 estimators is used. Feature importance from the random forest identified key factors.

Result

143 patients with both NACC records and OHSU RDW EHR were used after data cleaning. Among them, 85 patients transitioned to MCI. 100 random splits of training and testing datasets were generated to assess the accuracy. An Area Under the Curve (AUC) 0.671±0.075 (mean±std), sensitivity 0.759±0.102 and specificity 0.477±0.107 were achieved using variables from both NACC UDS and OHSU RDW EHR. The AUC is significantly higher than the AUC obtained only using NACC UDS (0.629±0.071) or OHSU RDW EHR(0.556±0.089), with p‐values < 0.001 using the Wilcoxon singed‐rank test (Fig. 1). The sensitivity and specificity obtained only using NACC UDS (0.726±0.108/0.457±0.109) or OHSU RDW EHR(0.687±0.126/0.333±0.140) are also relatively low. Feature importance suggested that some factors may have higher impact on MCI progression (Fig. 2). Green and orange features are from NACC UDS and OSHU RDW EHR, respectively.

Conclusion

Our exploration on combining clinical variables in NACC USD with OHSU RDW EHR shows promising ability for early prediction of MCI risk. In addition to NACC UDS, hospital diagnosis histories, especially for diseases like other mental disorders, sleep disorders, pain and hypotension, provide useful information. Our study shows the potential of integrating data resources for improved prediction of MCI and identification of related factors.
Social determinants in early midlife and trajectories in cognition and brain integrity in midlife
Authors: Dintica Christina S. , Cheunkarndee Julia , Bryan R. Nick , Launer Lenore J. , Yaffe Kristine
Published: January 2025

Background

Social determinants of health (SDOH) are increasingly recognized as important drivers of inequities in cognitive outcomes. However, most existing evidence is based on individual SDOH components. We evaluated the relationship between a cumulative SDOH index in early midlife and change in cognition and brain volume.

Methods

We included 3,224 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study with information on SDOH in early midlife (mean age 40.0 ± SD 3.6) and cognitive assessments and brain MRI 10, 15, and 20 years later. A weighted SDOH score representing the cumulative number of unfavorable SDOHs, identified from 13 components across 4 domains (economic stability, community and social context, education, and health care system access) was calculated and divided into quartiles (quartile 1 being the least favorable). Cognition was assessed using the Digit Symbol Substitution Test (DSST), the Stroop Test, and the Rey Auditory Verbal Learning Test (RAVLT). 1,108 participants had MRIs measuring white matter hyperintesities (WMHs) and total gray matter (GM). Mixed linear regression was used to examine the association between the SDOH index quartiles and cognitive and MRI outcomes adjusting for age, sex, race, and intracranial volume (for MRI).

Results

Participants in the least favorable SDOH quartile had steeper decline in the Stroop test (b: ‐0.16, 95% CI: ‐0.31 to ‐0.02) and the RAVLT (b: ‐0.04, ‐0.08 to ‐0.01), but not the DSST (b: ‐0.08, ‐0.21 to 0.07), compared to the most favorable SDOH quartile (Figure 1, A‐C). Moreover, participants in the least favorable SDOH quartile had higher accumulation of WMHs over time (b: 196.31, 95% CI: 89.41 to 303.21) and a steeper decline in total GM (b: ‐565.10, 95% CI: ‐1021.52 to ‐108.69), compared to quartile 4 (Figure 1, D, E). Quartiles 2 and 3 were not significantly different in rates of change in any of the cognitive tests or MRI measures compared to quartile 4.

Conclusion

High social disadvantage in early midlife is associated with accelerated decline in cognition and worsening of brain integrity already at midlife. Further studies identifying underlying mechanisms linking SDOH with cognition are needed to establish prevention strategies.
Characterizing White Matter Hyperintensity (WMH) Patterns with Texture‐Based Analysis
Authors: Alshikho Mohamad J. , Morales Clarissa , Pyne Jeffrey D. , Amarante Erica , Lao Patrick J. , Turney Indira C. , Edwards Natalie C. , Gu Yian , Manly Jennifer J. , Mayeux Richard , Brickman Adam M.
Published: January 2025

Background

White matter hyperintensities (WMHs) are areas of increased signal on T2‐weighted MRI scans. They vary in size, location, and intensity, suggesting different underlying conditions like small vessel disease and inflammation. This variation potentially links WMH to outcomes ranging from normal aging to severe neurological disorders. We used a texture analytic approach, Gray‐Level Co‐occurrence Matrix (GLCM), to characterize the intensity heterogeneity of WMHs. This method classifies WMHs into distinct zones based on homogeneity scores that represent uniformity in signal intensity. We explored associations among white matter microstructure, cerebral blood flow, and WMH volume within these zones.

Method

One hundred sixty‐one participants from the Washington Heights‐Inwood Columbia Aging Project (WHICAP) were included. White matter hyperintensities were labeled using in‐house software, which also created normalized homogeneity maps through GLCM. These maps were used to define three WMH zones based on their degree of homogeneity (i.e., homogeneous, intermediate, and heterogeneous) (Figure 1). We examined the relationship among fractional anisotropy (FA), cerebral blood flow (CBF), and WMH volume within these WMH zones and compared CBF and FA values across the zones.

Result

In homogeneous and intermediate WMH zones, there was no association between FA and CBF (rhomo.=0.022, phomo.=0.787; rinter.=‐0.12, pinter.=0.132). However, both FA and CBF negatively correlated with WMH volume in these zones (rFA‐homo.=‐0.348, pFA‐homo.< 0.0001; rFA‐inter.=‐0.538, pFA‐inter.< 0.0001; rCBF‐homo.=‐0.36, pCBF‐homo.< 0.0001; rCBF‐inter.=‐0.40, pCBF‐inter.< 0.0001).

In the heterogeneous zone (Figure 2), FA and CBF were negatively correlated (rhetero.=‐0.422, phetero.< 0.0001). CBF, but not FA, was associated with WMH volume (rCBF‐hetero.=‐0.471, pCBF‐hetero.< 0.0001; rFA‐hetero.=0.085, pFA‐hetero.=0.300)

In homogenous WMH regions, both [FARatio (0.776±0.009) and CBFRatio (0.96±0.014)] values were lower than in intermediate [FARatio (0.84±0.009) and CBFRatio (0.97±0.014)] and heterogeneous zones [FARatio: (1.029±0.009), CBFRatio: (1.002±0.014)].(Figure 3)

Conclusion

Distinct correlation patterns exist between CBF and FA in WMH clusters defined by intensity heterogeneity. Homogeneous zones, likely reflect older lesions, show low microstructural integrity and minimal relationship with CBF, suggesting high gliosis. Heterogeneous zones, possibly reflecting recent white matter damage, show associations between CBF and microstructure, potentially indicating active inflammatory processes contributing to vascular injury.
Evaluating Life Simple Seven’s Influence on Brain Health Outcomes: The Intersection of Lifestyle and Dementia
Authors: Denier‐Fields Diandra N. , Gagnon Ronald E. , Ryther Brenda , Canovi Ian A. , Wilkinson Diane , Sparks Lia J. , Rivera‐Rivera Leonardo A. , Betthauser Tobey J. , Bendlin Barbara B. , Johnson Sterling C. , Engelman Corinne D.
Published: January 2025

Background

Lifestyle factors have been studied for their role in dementia, but few have comprehensively assessed both Alzheimer’s disease (AD) and cerebrovascular disease (CBVD) pathologies. This study innovatively integrates AD, CBVD, and cognitive composite scores (CCS) within the same cohort to investigate the association of the Life Simple Seven (LS7) score with a broad spectrum of dementia‐related outcomes. Our research aims to unravel the intricate relationships between lifestyle and various dementia pathologies, challenging conventional research paradigms.

Method

Analyzing 1210 Wisconsin Registry for Alzheimer’s Prevention (WRAP) study participants, we focused on LS7 score calculations from questionnaire data and clinical vitals (Table 1). We assessed brain health indicators over intervals of 2‐4, 4‐6, and 6‐8 years post‐LS7 scoring. CBVD outcomes included white matter hyperintensities (WMH) and cerebral blood flow (CBF); CCS outcomes comprised delayed recall, executive function, immediate learning, and the Pre‐Clinical Alzheimer Cognitive Composite 3 (PACC3); AD outcomes involved PET amyloid (PiB) and tau (MK6240) imaging (Table 2). Our study controlled for age, sex, race/ethnicity, apolipoprotein E ε4 (APOE ε4) count, years of education, and practice effects as appropriate for each outcome.

Result

Higher LS7 scores were associated with 0.06 lower %WMH at 2‐4 years, per point increase in LS7 score (n = 275, p = 0.005), contrasted with 0.05 higher %WMH annually for participants over 65 (p<0.001; Figure 1). In relation to CBF, although there is a general decrease during aging that accelerates in disease states, higher LS7 scores were associated with relatively higher ASL perfusion in both gray and white matter at 2‐4 and 6‐8 years. For PACC3 scores, one point increase in LS7 score was associated with 0.04 higher scores (n = 872, p = 0.041) at the 2‐4 year interval, while an increase in age was associated with lower PACC3 scores by 0.05 (p≤0.001). No significant associations were found between LS7 scores and the remaining CCS or AD imaging.

Conclusion

This study highlights the impact of cardiovascular health, influenced by lifestyle choices, on cognition, likely through the cerebrovascular pathway. It underscores the importance of lifestyle interventions in vascular dementia prevention and management, offering critical insights for developing strategies to mitigate cognitive decline and dementia risk.