bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive nutrient biomarker assessment in older adults at risk for dementia: Pre‐analytical and intra‐individual stability over 2‐4 years in the Nutrition and Brain Aging Study
Authors: Bowman Gene L. , Duskin Jonathan A , Haber Juliana A , Mattek Nora , Shrestha Hira , Corthésy John , Dodge Hiroko H , Silbert Lisa C , Quinn Joseph F , Kaye Jeffrey A
Published: January 2025

Background

Nutrient biomarkers (NBs) may serve as more accurate and precise indicators of dietary intake, particularly in older adults who often have subtle episodic memory recall and digestive/microbiome issues that alter the nutritional substrate readily available to the brain. NBs also allow insight into modes of action and metabolic changes that are actionable targets for modification through nutritional means in hopes of disease prevention and treatment. Prior to broad investment and deployment, the pre‐analytical and intra‐individual temporal variation over time should be documented to design and interpret clinical and epidemiological studies properly. We quantified 155 NBs and calculated their intra‐individual stability over time as selection criterion for future research to establish nutritional requirements for brain health and dementia prevention.

Method

Blood samples from three time points, spanning a 2‐4 years, were obtained from older adults participating in the NIA‐Layton Oregon Alzheimer’s Disease Research Center’s Nutrition and Brain Aging Study (NBAS). Blood samples were batched randomly across time points for quantification of blood amino acids, minerals, hydro‐and‐liposoluble micronutrients, lipids, 1‐carbon, and kynurenine pathway metabolites using a variety of state‐of‐the‐art methods including, inductively coupled mass spectrometry. Pre‐analytical coefficients of variation (CV) and intraclass correlation coefficients (ICC) were calculated for each NB to evaluate the intra‐individual stability in a subset of NBAS cohort (n = 315).

Result

The mean analytic sample (n = 137) baseline age was 85.6 (±8.3, 57‐101 years), and mean MMSE was 28.3 (±1.78) with all having Clinical Dementia Rating of 0.5 or less. Seventy‐three percent were female and 19% carried the apoEe4 allele. The pre‐analytical CVs range from 0.9 to 55.0% and the ICC from 0 to 0.87 (25%‐tile/median/75%‐tile 0.41/0.54/0.66). Twenty four percent had ICC< 0.40, 66% had ICC 0.40‐0.75 and 10% had ICC>0.75.

Conclusion

The pre‐analytical and intraindividual variation of NBs ranges widely in older adults. Most can reasonably estimate average blood concentrations over a 4‐year period using a single measurement (ICC≥0.40). NBs with ICC above 0.40 can be used for measurement error correction and those with ICC< 0.40 require repeat sampling and further investigation into the methodological/biological source of variation over time in older adults at risk of dementia.
Posturographic findings and reports of falls in elderly people with mild cognitive impairment: a comparative study
Authors: Anselmo Michele da Rocha , Novaes Juliana de Sá , Engelmann Gabriela Tomé Oliveira , Viana Bernardo M , Bicalho Maria Aparecida Camargos , Labanca Ludimila , de Oliveira Ana Julia Delfim
Published: January 2025

Background

Changes in the connections between the cortical regions responsible for integrating balance are observed in individuals with MCI, however, studies that clarify the association of these changes and the risk of falling due to body imbalance are still rare. The present study aims to compare the posturography response of individuals diagnosed with MCI in relation to individuals in a control group without MCI.

Methods

This research project was approved by the local ethics committee. The sample was composed of 64 elderly people, of which 32 participants were from the MCI group and 32 from the control group. Participants underwent medical and neuropsychological evaluation where the characterization of general health and cognitive diagnosis designation was determined. Furthermore, an anamnesis composed of questions regarding the presence of complaints of dizziness, reports of fall episodes in the last year and the presence of other associated comorbidities was applied. The Timed‐Up and Go scale was used and static posturography was performed to determine the postural profile of the sample. To evaluate posturography, two tests were performed: stability limit test and sensory integration test. The data from the present study were tabulated in Microsoft Excel® version 10.0 and analyzed using SPPS® version 20 software.

Results

Participants were comparable in terms of age, body weight, gender and education. The CCL group showed increased TUG time compared to the control group (p = 0.001) indicating decreased mobility. The occurrence of 53% of reports of falls in the last year was observed in the CCL group, with this presentation being higher than that observed in the control group (p = 0.001). In the posturography results, impairment was found in the CCL group in relation to the control at the limit of stability (p≤0.001), general balance index (p≤0.001), visual index (0.002) and vestibular index (<0.001).

Conclusions

Elderly people diagnosed with MCI may be more susceptible to balance disorders, increasing their risk of falling compared to healthy elderly people.
Establishing a Remote Patient Monitoring Infrastructure with Starlink in Indonesia for the Aging Population to Improve Alzheimer’s and Dementia Care
Authors: Kresnasandi Ida Bagus , Johnson Brian B
Published: January 2025

Background

Modernizing the remote patient monitoring (RPM) infrastructure in Indonesia has historically been limited by the unmet need of access to internet connectivity. New advancements made possible by Starlink and the internet of things (IoT) for RPM present new opportunities to connect people separated by geography and diverse cultural variations which includes over 700 languages and dialects. Alzheimer’s disease has increased by 87% from 2019 to 2022 and similar challenges in the United States apply to Indonesia; the cost of care, nurse shortage, and large aging population. Clinicians, scientists, and engineers now have the potential to solve the unmet need of insufficient aging care by leapfrogging previous technologies with the latest in artificial intelligence (AI) and digital health (DH).

Method

Establishing internet connection across the 16,771 islands is the first step to creating a communication network that provides the aging population in Indonesia access to the benefits of modern healthcare. With consistent and reliable access to internet access through Starlink satellite broadband internet a constellation of devices can be utilized in urban and remote areas such as the 12,000 villages that have no 4G internet access. For example WhatsApp is currently being tested to connect patients to clinicians because this application does not need a cellular plan. A pilot study conducted by Udayana University, Bali, could test the feasibility of delivering a RPM system to rural areas such as Batur village and the island of Nusa Penida.

Result

Solving the problem of lack of access to internet connectivity in Indonesia creates tremendous opportunity to deliver state of the art AI and DH tools to clinicians for Alzheimer’s, dementia care and healthcare overall, reducing health disparities on a national level.

Conclusion

Exporting the latest innovations from the top biomedical research institutions in the US to Indonesia could benefit the aging population by increasing their quality of life. Starlink is a key component of establishing access to communication infrastructure by allowing Indonesia’s public health insurance system, BPJS, to reach people in remote places.
The associations between air pollution and hippocampal volume: The Betula Project
Authors: Sindi Shireen , Andersson Micael , Stiernstedt Mikael , Oudin Anna , Nyberg Lars
Published: January 2025

Background

Long‐term exposure to ambient air pollution has recently been highlighted as a modifiable risk factor for dementia. However, the mechanisms underlying these associations still remain unclear. The goal of this study was to investigate the associations between air pollution and neuroimaging correlates in a sample of middle‐aged and older adults.

Methods

This study used data from the Betula Project, which is a longitudinal study on aging, memory and dementia in Umeå, Northen Sweden. Participants were aged 50‐81 years old. For air pollution measures, data were available for local and total fine ambient particulate matter (PM2.5, PM10) and black carbon (BC) from vehicle exhaust and wood‐smoke. Participants were scanned in a 3T Discovery 750 (General Electric) MR‐scanner. All T1‐images were processed through a longitudinal pipeline in Freesurfer ver 7.11. MRI outcomes included total grey volume, cortex thickness, ventricle volume, and hippocampus volume. After removing participants due to incorrect hippocampus segmentation or missing values in air pollution or nuisance regressors 249 participants were included in the analyses. Partial correlations were performed, adjusting for age, sex and education. Additional analyses were conducted, stratifying by APOE4 status and sex.

Results

The analyses showed that smaller hippocampal volume was associated with higher levels of all three air pollution measures (PM2.5 (r = ‐0.159, p = 0.012), PM10 (r = ‐0.125, p = 0.048), and BC (r = ‐0.148, p = 0.019)). In the APOE4 non‐carrier group, smaller hippocampal volume was associated with higher PM2.5 (r = ‐159, p = 0.034), whereas this association was not significant among the APOE4 carriers (r = ‐0.161, p = 0.178). The association between smaller hippocampal volume and PM2.5 was more pronounced among women (r = ‐0.168, p = 0.052) compared to men (r = ‐0.150, p = 0.112)

Conclusion

This study shows that ambient air pollution is associated with smaller hippocampal volume, and this association appears to be more pronounced among APOE4 non‐carriers and women. These results shed light on the mechanism through which air pollution may increase the risk for cognitive decline and dementia, with important implications for risk reduction initiatives.
Mapping healthcare utilization of people with Alzheimer’s Disease and Related Dementias to identify priority areas in the State of South Carolina
Authors: Knox Sara , Dooley Mary , Johnson Jada , Simpson Kit
Published: January 2025

Background

Alzheimer’s Disease and related dementias (ADRD) are a critical healthcare crisis in the State of South Carolina (SC), with over 115,000 individuals diagnosed with ADRD accounting for 11% of South Carolinians aged 65 or over and 52% of South Carolinians aged 85 or over. Exorbitant resources are used to care for these individuals, including $650 million in Medicaid dollars and over 300 million hours of unpaid caregiver time. SC has enacted a statewide plan to address ADRD with the mission of promoting “a comprehensive approach to risk reduction, early detection and diagnosis, high‐quality dementia services, and a coordinated and equitable continuum of care across…” Yet, ADRD does not present uniformly across SC. Heat mapping healthcare utilization of individuals with ADRD across SC provides an opportunity to better understand where resources should be directed to support individuals and caregivers currently coping with ADRD as well as inform future research aimed at risk reduction and disease prevention.

Method

We used the South Carolina All‐Payer (Hospital and Emergency Department Admissions) Encounter data from the South Carolina Revenue and Fiscal Affairs Office to map the occurrence of Alzheimer’s disease and related dementias at the county level between 2018‐2020. Counties were grouped into five recognized regions of SC, 1) Upstate, 2) Midlands, 3) Coastal, 4) Pee Dee, and 5) Low Country. The Chronic Conditions Warehouse algorithm for ADRD was used to identify ICD‐10 codes for ADRD. Rates per 10,000 were reported.

Result

The prevalence of ADRD was concentrated in two regions of the state, the Pee Dee region and the Upstate region. The Pee Dee region had the highest rates, with 9 of it’s 11 counties having rates of greater than 500/10,000. The eleven counties in the Upstate region had rates greater than 400/10,000. In the other three regions, counties typically had rates between 170‐ 300/10,000.

Conclusion

The findings from this study provide clear evidence that there is a greater need for resources to support SC residents with ADRD and their caregivers in the Pee Dee and Upstate regions. Future studies should examine environmental, sociodemographic, and economic factors of these regions that may contribute to increased disease prevalence.
Mid‐life occupational hazardous exposures is associated with late‐life dementia risk in the Wisconsin Longitudinal Study
Authors: Williams Victoria J. , Sicinski Kamil , Trane Ralph , Herd Pamela , Asthana Sanjay
Published: January 2025

Background

Exposures to environmental toxicants and pollutants occur at various points along the life course, with mounting evidence that late‐life pollution exposure increases risk for neurological disease, including dementia. Although occupational hazards constitute a primary source of modifiable environmental exposure during the working years, there is little research examining the protracted effects of mid‐life occupational exposure on late‐life dementia risk.

Method

This study leveraged life course data from the Wisconsin Longitudinal Study (WLS) to evaluate the effects of mid‐life occupational hazardous exposures on late‐life dementia outcomes. The WLS is a randomly selected population‐based cohort of 1/3 of all 1957 Wisconsin high school graduates and a selected sibling. Occupational hazardous exposures (to solvents and chemicals, pesticides, or airborne particulate matter) was prospectively collected in mid‐life (age ∼54). Dementia status was determined by a clinician consensus‐based approach using comprehensive medical and cognitive date collected in late‐life (age ∼81). Binary logistic regression was used to determine whether midlife occupational exposure predicted late‐life dementia risk, covarying for the effects of age, sex, education, adolescent IQ, ApoE‐4 status, systemic disease burden (hypertension, diabetes, stroke, heart disease), comprehensive smoking history, and occupational education and earnings scores.

Result

3811 WLS participants were included in the analysis, with 523 (13.7%) reporting history of midlife occupational hazardous exposure, and 322 (8.4%) receiving a research diagnosis of dementia. The full binary logistic regression model was statistically significant (Chi2(13) = 177.55, p<0.001), accounting for 10.4% of the overall variance in dementia outcome. Midlife occupational exposure significantly predicted dementia risk, such that history of occupational exposure conferred 47.8% increased odds of dementia in late‐life (OR = 1.478 [95%CI: 1.082‐2.020]).

Conclusion

Reported history of mid‐life hazardous occupational exposures significantly increased the odds of all‐cause dementia in the WLS cohort, even after accounting for key confounders including job characteristics that may independently influence dementia risk. Because dementia pathologies often begin accumulating in the brain 20‐30 years prior to the onset of the clinical syndrome, midlife offers a key window for addressing modifiable risk factors to prevent disease. Public policy regulating occupational hazardous exposures in the workplace constitutes a promising strategy to reduce dementia in the general population.
Discovery of novel small molecule Asparaginyl endopeptidase inhibitors via dual approach‐based virtual screening and molecular simulation studies
Authors: SINGH MEENAKSHI , Xavier Joyal , Tamhankar Sampada P , Amin Raj
Published: January 2025

Background

Neurological disorders are at epidemic levels in the world today. Various proteins are being targeted for the development of novel molecular therapeutics; however, no small‐molecule inhibitors have been discovered. Recent studies suggest that there are few molecules in clinical trials for various secretase (α, β, and γ), caspase, and calpain inhibitors. However, recently an emerging target was highlighted i.e. asparaginyl endopeptidase (AEP). This lysosomal cysteine protease cleaves the glycine‐rich C‐terminal to form an asparagine residue. In addition, the highly conserved and spatially close catalytic triad (Oδ1ASN42‐Nε2HIS148 ̴ 3.0Å) active site residue is Asn 42, His 148‐spacer‐Cys 189, which is responsible for proteolytic activity are also impacted by the cleavage of the C‐terminal region of AEP. Therefore, the current study focuses on screening, available small molecule databases for potential interactions with the active binding sites within the AEP binding pocket for inhibiting its proteolytic activity and restoring neuronal damage.

Method

Various online available CNS‐focused databases were screened to find small molecule inhibitors using an in‐silico structure‐based virtual screening method and molecular dynamics simulation. Further selected small molecules were assayed on overexpressed AEP stable cell line (HMC‐3) with exiting peptide and compound 11

Result

There is no small molecule inhibitor for the AEP yet, and the screened small molecule could be a potential hit for drug discovery. In addition, we have observed that AEP is involved in various proteinopathies which leads to neuroinflammation and can be reversed. Moreover, we found that our in‐silico screened molecules are more potent than the compound 11 and peptide. Further assays on a stable AEP immortal HMC‐3 cell line also line up with the in‐silico results.

Conclusion

The selected small molecule presented a potential non‐covalent interaction (hydrogen bonds, ionic bonds, and pi‐pi interaction) within the catalytic binding sites with high binding energies and stable complex during simulation when compared to exiting compound 11 and peptide. The findings from the current study will help identify the critical subgroups needed for the development of our lead AEP inhibitory molecule.
County‐level indicators of education quality and brain imaging markers of neurodegeneration and vascular injury among racially and ethnically diverse middle‐aged and older adults
Authors: Roscoe Joseph , Whitmer Rachel A. , Gutierrez Sirena , Eng Chloe W. , Glymour M. Maria , Decarli Charles , Barnes Lisa L. , Gavett Brandon E , Gilsanz Paola
Published: January 2025

Background

Early‐life education quality has been associated with dementia risk and late‐life cognitive functioning. However, the association between education quality and neuroimaging outcomes remains unclear.

Methods

These analyses utilized data from 450 participants in two harmonized cohorts of racially and ethnically diverse adults aged 50 years and older (KHANDLE and STAR) who completed brain Magnetic Resonance Imaging and whose self‐reported school location at 9th grade could be linked to historical educational quality data from the National Center for Education Statistics. Three county‐level indicators of 9th grade education quality were categorized into tertiles based on the pooled dataset and treated as ordinal variables with the lowest tertile serving as the reference: percent attendance, teacher‐student ratio (number of teachers per 30 students), and term length. Measures of gray matter volume, hippocampal volume, white matter hyperintensity volume (log‐transformed), and ventricular volume (log‐transformed) were residualized on total cranial volume. Linear regression models with robust standard errors estimated associations between education quality measures and each imaging marker, adjusting for age at imaging, demographics, childhood socioeconomic status, study cohort, and history of racial segregation in state of 9th grade education. Sensitivity analyses examined each education quality measures separately, adjusting for covariates.

Results

Higher teacher‐student ratio was associated with greater gray matter volume (β = 6.25, 95% CI: 1.57, 10.92) but was not associated hippocampal volume (β = ‐0.01, 95% CI: ‐0.14, 0.11), ventricular volume (β = ‐0.04, 95% CI: ‐0.13, 0.04), or white matter hyperintensity (β = ‐0.02, 95% CI: ‐0.31, 0.26) (Table 2). Higher percent attendance was associated with greater ventricular volume (β = 0.10, 95% CI: 0.03, 0.18) but was not associated with gray matter volume (β = ‐3.12, 95% CI: ‐7.07, ‐0.82), hippocampal volume (β = ‐0.06, 95% CI: (‐0.17, 0.05), or white matter hyperintensity (β = ‐0.02, 95% CI: ‐0.26, 0.22). Term length was not associated with any marker of neurodegeneration or vascular brain injury. Results were similar when examining each education quality measure separately.

Conclusions

County‐level teacher‐student ratio and percent attendance, markers of education quality, had qualitatively different associations with imaging markers of neurodegeneration. Additional studies in larger samples are needed to confirm and better understand underlying reasons for these potential differences.
Frailty and risk of delirium among UK Biobank participants
Authors: Cai Ruixue , Gao Chenlu , Zheng Xi , Hu Kun , Gao Lei , Li Peng
Published: January 2025

Background

Delirium is a common neurological complication in older adults after a major illness or surgery and is characterized by acute dysfunction in cognition, attention, and awareness. Once diagnosed, it is associated with an increased risk for dementia. Frailty is an age‐related syndrome and is associated with poorer postoperative outcomes, and is an emerging risk factor for delirium. The current study aimed to examine the association between frailty and delirium risk in middle‐ to older‐aged adults.

Method

We examined frailty and incident delirium in 389,040 UK Biobank participants (38‐73 years old; 178,377 females) were hospitalized at least once during follow‐up. Frailty at baseline was assessed using two validated measures: (1) frailty phenotype (FP) that is identified when three or more of the following five criteria were fulfilled: self‐reported weight loss, exhaustion, low physical activity, slow walking pace, and low grip strength; (2) frailty index (FI: range 0‐1) that is calculated from 49 items covering health, presence of diseases and disabilities, and mental well‐being (FI score ≥0.24 indicating frailty). A new onset of delirium was obtained from hospitalization records using ICD‐10 F05 coding. Cox proportional hazards models assessed the association between frailty and delirium.

Result

At baseline, 4.3% (15,311/359,979) and 5.2% (20,061/389,040) were identified as frail cases using FP and FI, respectively. The participants had been followed for a median of 12 years, with 6,710 newly developed delirium cases. Compared with non‐frail participants based on FP, participants with frailty were at a higher risk for delirium after adjusting for age, sex, ethnicity, and education (Hazard ratio [HR] = 3.22, 95% CI = 2.97‐3.49, p<0.0001). Similar results were observed based on FI, i.e., frail participants had an adjusted HR of 2.79 (95% CI = 2.59‐3.00, p<0.0001) for delirium compared with non‐frail participants. These observations were consistent after further adjusting for social economic status, body mass index, sleep duration, smoking, and alcohol consumption (HR = 2.48, 95% CI = 2.28‐2.70 for FP; HR = 2.17, 95% CI = 2.01‐2.35 for FI, both p values <0.0001).

Conclusion

Frailty predicted delirium in middle‐ to older‐aged adults. Assessment and management of frailty may help with risk stratifications for delirium.
Cognitive functioning and markers of immune and neural dysfunction in Post‐acute sequelae of COVID‐19
Authors: Reynolds William Cody , Abril Isabel , Quiñones‐Alvarado Raymond , Arnold Steven E , García‐Beltrán Wilfredo F , Guzman‐Velez Edmarie
Published: January 2025

Background

Over 65 million COVID‐19 survivors grapple with lasting neurological and cognitive symptoms that persist for months or years after infection, known as neuro‐Post‐acute Sequelae of COVID‐19 (neuro‐PASC). These symptoms are amongst the most common and incapacitating and are hypothesized to represent a heighted risk for neurological disease. Yet, little is known about the pathophysiological mechanisms underlying neuro‐PASC. Here, we examined whether worse neuro‐cognitive functioning was associated with markers of immune and neural dysfunction.

Methods

We report data for 55 people with PASC (average age = 46.09) and 37 healthy controls (HC; average age = 42.84). PASC participants were never in the ICU, 68% female sex, and infected an average of 471.27 days pre‐enrollment. HCs were 57% female sex and 15 were infected an average of 647.73 days pre‐enrollment but fully recovered. We assessed subjective cognitive decline using the Measurement of Everyday Cognition (ECog), memory with the RBANS list learning, and executive functioning with the Trail‐Making Test B (TMT‐B). PASC participants completed a self‐report questionnaire of PASC symptom severity. We measured plasma levels of CX3CL1/Fractalkine, a marker of immune function, and Ubiquitin C‐terminal hydrolase‐L1 (UCH‐L1), a marker of neural function. We conducted t‐tests and linear regressions adjusting for age.

Results

Neurological symptoms were amongst the most severe. Headaches, insomnia, and brain fog were rated as the ones that interfered the most with daily activities. Compared to HCs, PASC participants reported worse subjective memory, language, planning, organization, and attention decline. There were no significant group differences on cognitive test scores. PASC participants exhibited significantly higher CX3CL1/Fractalkine and UCH‐L1, although the latter was not significant when controlling for age. Those with higher levels of CX3CL1 exhibited higher levels of UCH‐L1, indicating a relationship between immune and neural dysfunction. Elevated UCH‐L1 levels were associated with worse TMT‐B performance, but not CX3CL1.

Conclusions

Findings show that neurological symptoms, including subjective cognitive decline, are highly prevalent and severe in PASC. There was clear evidence of heightened inflammation potentially from endothelial cells, and of neural injury, which was associated with worse executive functioning. Therefore, immune dysregulation and neural injury may be underlying neuro‐PASC, and potentially contributing to greater risk for brain disease.
Ten Year Patterns of Change in HbA1C and Risk of Dementia in a Diverse Cohort of Adults with Type 2 Diabetes
Authors: Whitmer Rachel A. , Moran Chris , Costales Brianna , Tsai Ai‐Lin , Lacy Mary E , Karter Andrew , Gilsanz Paola
Published: January 2025

Background

Though high HbA1c (marker for glycemic control) is associated with increased dementia risk, the influence of longitudinal changes in HbA1c is unclear. We examined the association between 10‐year trajectories of HbA1c and dementia risk in a large, diverse sample of people in Northern California.

Method

In a cohort of 32, 914 patients with Type 2 diabetes aged ≥ 50 years, we obtained repeated measures of HbA1c, dementia diagnoses, and comorbidities from electronic medical records (EMR) from 1996‐20021. We identified 5 latent trajectories of yearly mean HbA1c over a 10‐year period (Figure 1): Group 1‐HbA1cconsistently <7; Group 2‐ HbA1c consistently close to 7; Group 3‐moderate HbA1c peaking late between 7‐9; Group 4‐moderate HbA1c peaking early between 7‐9; Group 5‐ HbA1c consistently between 9‐11. Cox proportional hazards models estimated the association between HbA1c trajectories and incident dementia ≥5 years after the end of the exposure period adjusting for age (as timescale) and prevalent health conditions (Table 1) at the beginning of the trajectory period. Stratified models examined possible effect modification by sex or race/ethnicity.

Result

Approximately half of the sample were women (Table 1). The most common trajectory was Group 2‐consistently close to 7 (47%), followed by Group 1‐consistently <7 (35%), Group 3‐moderate peaking late (9%), Group 4‐moderate peaking early (7%), and Group 5‐ consistently high (3%). Compared to Group 1, Groups 3‐5 had elevated risk of dementia (Figure 2); risk was comparable in Groups 3 and 4 (HRGroup3 = 1.30 (1.14, 1.48) and HRGroup4 = 1.28 (1.10, 1.49)) and was highest in Group 5 (HR = 1.78 (1.42, 2.26). Group 2 was not at elevated dementia risk compared to Group 1 (HR = 1.02 (0.94, 1.09). These associations did not vary by sex or race/ethnicity.

Conclusion

Over a 10‐ year period, consistently elevated HbA1c levels ≥ 9 are associated with an 80% elevated risk of dementia compared to those with a trajectory of HbA1c 6‐7. Those whose trajectory included HbA1c levels of 8‐9 either early (Group 4) or late (Group 3) in the10‐year period had approximately 30% increased risk. These results suggest that there are long‐term consequences of elevated HbA1c even if levels subsequently decrease.
Bidirectional associations between blood pressure and memory decline over 25 years: a 1946 British Birth cohort population‐based study
Authors: James Sarah‐Naomi
Published: January 2025

Background

Midlife blood pressure is a risk factor for cognitive impairment. Yet, the directional relationship between blood pressure and memory may vary across adulthood, be confounded by earlier life factors, and vary by sex. Using a population‐based cohort of people born in the same week, we investigate the bidirectional associations between diastolic blood pressure (DBP) and memory, spanning over 25 years of adulthood.

Method

Data from participants (n = 1922, 52% female) in the British 1946 birth cohort were included. DBP and Word Learning Test (WLT) performance were assessed at four points across adulthood (ages 43, 53, 60 and 69) by nurse visits. WLT incorporated three 15‐item word recall (summed to give a maximum score of 45) with alternating lists across assessments. Autoregressive cross‐lagged models assessed the bidirectional associations between WLT and DBP. Models were tested for sex effect modification and adjusted for childhood cognition; childhood socioeconomic position; education; and hypertensive medication use.

Result

The autoregressive cross‐lagged models revealed an independent unidirectional relationship between higher DBP in midlife predicting lower subsequent cognition (i.e. higher DBP at age 43 predicting lower memory at age 53; higher DBP at age 53 predicting lower memory at age 60 and 69, additively) (Figure 1). In contrast, there was a unidirectional relationship between later‐life cognition (at age 60) predicting higher subsequent DBP (at age 69), with preliminary results demonstrating a stronger effect in women. In a sex‐adjusted model, a 1 SD higher memory score at age 60 was associated with 4mmMg increase in DBP at age 69. Adjusting for childhood cognition, childhood SEP and education largely attenuated these effects but results mainly remained significant at the 5% level.

Conclusion

We provide evidence that higher midlife blood pressure is associated with subsequent lower memory, in line with previous studies, and even after adjustment for strong predictors of cognition, such as childhood cognition, education and SEP. However, our results also demonstrate evidence of a reverse association later in life, whereby lower memory is associated with subsequent lower blood pressure suggesting that cognitive processing may play a role in diastolic ageing processes, particularly in women.
Trends in Diagnosis of Dementia Subtypes in Nationwide Medicare Claims, 2015‐2021, by Race/Ethnicity, Sex, and Neighborhood Socioeconomic Status
Authors: Lusk Jay B , Ford Cassie B , Blass Beau , Johnson Kim G , Clark Amy G , Soneji Samir , O'Brien Richard J , Hammill Bradley G , O'Brien Emily C
Published: January 2025

Background

It is not well understood how incidence patterns of subtypes of Alzheimer’s disease and related dementias (ADRD) have evolved in real‐world practice. While cohort and brain bank studies provide precise biological definition of ADRD subtypes, these populations may not be representative and may not reflect how dementia is coded and diagnosed in routine clinical practice. Therefore, we sought to perform a nationally representative study of medical claims data to understand trends in diagnosis of dementia by dementia subtypes in routine clinical practice.

Method

We studied 100% of nationwide Medicare claims from 2014‐2021 and evaluated dementia diagnoses by specified subtypes with associated international classification of diseases (ICD) codes (Alzheimer’s disease, vascular, Lewy body, frontotemporal, alcohol induced, and not otherwise specified). We stratified results by age, sex, race/ethnicity, and neighborhood socioeconomic deprivation measured by the area deprivation index, a well‐established score that describes neighborhood socioeconomic conditions. Incidences are presented as number of new cases per 10,000 person‐years. Race/ethnicity were grouped as White, non‐Hispanic; Black, non‐Hispanic; and other race/ethnicity, concordant with other Medicare claims data analyses.

Result

A total of 5,721,711 patients with incident dementia were included in the study. Dementia diagnoses were more frequently coded as vascular in 2021 than 2015 (1.85 cases per 10,000 person‐years in 2015 vs 2.21 cases per 10,000 person‐years in 2021) and less frequently coded as not otherwise specified (29.1 cases per 10,000 person‐years in 2015 vs 22.17 cases per 10,000 person‐years in 2021). Coding by dementia subtype varied by race (Table 1) and sex (Table 2). Dementia diagnoses were much more frequently coded as “not otherwise specified” among beneficiaries from socioeconomically deprived neighborhoods (34.48 per 10,000 person‐years in the most deprived decile vs 25.76 in the least‐deprived decile) (Table 3).

Conclusion

In a national database of Medicare claims, there were substantial secular trends and differences in coding of dementia subtypes by race/ethnicity, sex, and neighborhood socioeconomic status. Secular trends in coding could reflect variation in health system performance of accurate diagnosis of dementia subtypes. Future studies should correlate claims data classifications with confirmed neuropathological classifications.
Assessing Clinical Research Barriers to the Participation of Underrepresented Groups in the AHEAD Study
Authors: James Taryn T. , Gleason Carey E. , Gooding Diane Carol , Carter Fabu P. , Cardenas Cecilia A. , Deering Olivia , Cole Aleshia , Cronin Kate , Carlsson Cynthia M. , Bouges Shenikqua
Published: January 2025

Background

To increase participation of underrepresented groups (URG) into clinical research studies such as the AHEAD study, a study assessing lecanemab in participants with preclinical Alzheimer’s disease (AD), it is necessary to understand and address barriers in an effort to mitigate them. Toward this goal, methods assessing community needs and plans to meet those needs are imperative. Our ultimate goal is to aid URG in understanding the clinical research process and to empower them to participate in AD research so that approved therapies are applicable to them.

Method

This work was made possible by an AHEAD Diversity Recruitment Supplement grant funded to University of Wisconsin‐Madison (UW‐Madison) by the Alzheimer’s Clinical Trial Consortium (ACTC) to increase URG participation in the AHEAD study. Our approaches include using surveys to identify barriers in order to develop a strategic plan to overcome them. Surveys assessed whether potential participants had knowledge of 1) lecanemab, 2) the AHEAD study, and 3) if they would be comfortable in a study involving a medication, among others. Interested individuals were rewarded with a swag bag for completing the surveys

Result

The findings showed that URG were not likely to be aware of lecanemab or the AHEAD study. Additionally, while they wanted to know if they met the criteria for the study, they were less comfortable about a clinical study involving a medicine (Figures 1). Moreover, we identified other barriers to research participation, such as factors that were more likely to prevent URG from meeting study criteria. These included not knowing family history or their AD biomarker status, which was necessary inclusion criteria for individuals age 55‐64 (Figure 2).

Conclusion

Surveys at community events are useful in identifying barriers to the engagement of URG in AD clinical trials. To decrease barriers and push the pendulum towards increased participation of URG in biomedical research, increased educational efforts are needed on AD, the clinical trial process, and drug development. Moreover, researchers must make sure that URG are not ruled out from the study onset, meaning inclusion criteria must consider some unknown challenges such as not knowing medical or family history.
Investigating Individual and Familial Stress on Alzheimer’s Disease among a Global Cohort of Non‐Hispanic Blacks and Hispanic/Latinos
Authors: Moise Rhoda , Cai Dingtian , Rajabli Farid , Hamilton‐Nelson Kara L. , Adams Larry D. , Cuccaro Michael L. , Kunkle Brian W. , Vance Jeffery M. , Reitz Christiane , Tosto Giuseppe , Bush William S. , Haines Jonathan L. , Byrd Goldie S. , Akinyemi Rufus O. , Ogunniyi Adesola , Blanton Susan Halloran , Pericak‐Vance Margaret A , Seixas Azizi A , Consortium Africa Dementia
Published: January 2025

Background

Stress has emerged as a risk factor in the development and progression of Alzheimer’s Disease (AD). However, there is limited research on the impact cumulative individual and familial stress has on AD. This study aims to investigate the relationship between stress and AD within a global cohort of underrepresented populations including Black Americans (BAs), Hispanic/Latinos (H/Ls), and Africans (As).

Method

The total sample size was N = 328. Binomial regression in R examined the stress‐AD association, controlling for age, sex, race/ethnicity, and site. Stress was defined as “a situation in which a person feels tense, restless, nervous, or anxious, or is unable to sleep at night because his/her mind is troubled all the time.” Individuals were asked 1) Do you feel this kind of stress these days? and 2) While growing up did you and your family experience stress? Participants rated stress on a 0‐4 Likert scale. Binary recoding distinguished low (not at all) and high stress (all else). Ethnicity was coded as H/Ls and Non‐Hispanic Black Utilizing the binomial family, the analysis robustly explored the relationship between stress and AD diagnosis.

Results

A quarter of the sample (mean age = 73.53, SD = 8.63) had AD, while most had no cognitive impairment (mean age = 71.13, SD = 6.88). 73% were females (N = 240). Low‐stress individuals are 1.812 times more likely to be non‐cognitively impaired (p = 0.03767). Familial stress is not significant (p = 0.83255). Although there were significant results for ethnic group and age, their interpretation captures the distribution of cases and controls within those groups. Our experimentation was not designed to test them, but the inclusion of these variable in the model serve to adjust for the main variable of interest, stress.

Conclusion

This study reveals the stress‐AD link in a diverse population, emphasizing the necessity of targeted interventions considering individual stress in cognitive health research, urging further exploration of familial stress and ethnicity nuances. Understanding these relationships is crucial for tailored support systems and preventive strategies. Future research should delve deeper into stress as a modifiable AD risk factor, exploring underlying mechanisms for a comprehensive understanding. Additionally, future studies should design to further explore age and ethnicity in AD prediction.
Preclinical Alzheimer Disease pathology in studies of memory and aging
Authors: McKay Nicole S. , Millar Peter R , Barthélemy Nicolas R. , Benzinger Tammie L.S. , Morris John C. , Bateman Randall J. , Schindler Suzanne E. , Gordon Brian A.
Published: January 2025

Background

Preclinical Alzheimer disease (AD) describes a period prior to symptom onset during which pathology begins to accumulate. Recent development of neuroimaging‐ and biofluid‐ measures of AD pathology has allowed for in vivo quantification of preclinical pathological burden. Prior work estimated that by age 85, only one third of older adults remain free of amyloid and AD‐related atrophy.

Method

Here, using complementary multimodal biomarkers of AD pathology, we aimed to reproduce and extend these estimates of preclinical AD prevalence in a cohort of cognitively unimpaired (Clinical Dementia Rating = 0) older adults (demographics in Figure 1). We included neuroimaging‐derived measures of amyloid and neurodegeneration (cortical amyloid, cortical thickness, summary tau), as well as biofluid‐derived measures of non‐specific AD pathology (amyloid42:40, phosphorylated‐tau217, neurofilament light). Gaussian mixture modelling defined the probability of biomarker positivity, which we examined as a function of age (Figure 1).

Result

Our results reproduce and extend prior estimates of AD pathology in cognitively unimpaired older adults, confirming in our independent sample that AD pathology is present in cognitively unimpaired individuals. Cerebrospinal fluid‐derived measures of amyloid peaked at a rate close to 60%, but all measures of amyloid and neurodegeneration were observed to rise to be present in at least 40% of cognitively unimpaired older adults. Unsurprisingly, tau was observed at the lowest rate, potentially reflecting its tight associated with cognitive impairment.

Conclusion

We have replicated and extended prior reports of large proportions of older adults being afflicted by silent, preclinical, AD pathology. Rates of preclinical Alzheimer Disease pathology is important to estimate in large older adult cohorts so that these silent pathologies do not bias estimates of healthy aging. However, it is important to note that cohorts examining sporadic AD recruit individuals with family histories of AD and therefore have higher rates than average populations of apolipoprotein‐variant carriers, which may influence the rates of AD pathology. Characterizing the prevalence of preclinical AD is critical for understanding the pathophysiology of AD, may inform the design of clinical trials or interventions, and may also provide important context for furthering our understanding of cognition across older adulthood.
The Good Life program for healthy brain aging is an active registry for clinical research recruitment
Authors: Johnson David K
Published: January 2025

Background

The Good Life program for healthy brain aging (TGL) is an online program for positive lifestyle change that is made up of exercise, diet and social support classes. Since 2020, The Good Life has served thousands of older Californians. Currently, we host 17 classes weekly for our 750 active members (in both English and Spanish). Our exercise and cooking classes are our most watched content. Exercise classes attendance is 20‐70 participants per show (x11 weekly). Our x3/week cooking classes attendance is 20‐50 participants per show. We provide The Good Life freely and, in the process, engender goodwill ‐ a proven pathway to rebuilding trust and fostering reciprocity. The Good Life enjoys funding support from the State of California as public health program to support Black and Latinx healthy aging. In 2023 it expanded broadly across 13 California counties participating in the CDC’s Healthy Bain Initiative, providing TGL to all California residents. Three of the 13 counties are now creating local content tailor made to their specific ethno‐geographies.

Method

TGL is implementing a 9‐step infrastructure building plan to (1) Extend this California program to scale nationally to serve large numbers of participants in NIA clinical research and training network centers; (2) Engage Black and Latinx American communities across the nation in a thoughtful, fun, and clinically meaningful health education campaign with messaging that will facilitate recruitment and enhance retention; (3) Evaluate the success of our precision engagement program using empirical metrics: (i) participant enrollment into clinical trials, (ii) time spent watching content per digital segment, (iii) number of clicks into subsequent public health messaging. These metrics will be correlated with participant data describing changes in attitudes re (a) Trust in Biomedical Research and (b) Stages of Research Volunteerism.

Result

Since May 2023, TGL has recruited 260 Black Americans into 3 academic clinical research programs.

Conclusion

TGL is a scalable internet‐based program with potential reach well beyond its large existing membership.
Synthesis and biological evaluation of some novel coumarin‐oxadiazole conjugates as potential candidates for the treatment of cognitive decline
Authors: Arora Geetakshi , Piplani Poonam
Published: January 2025

Background

The present study demonstrates the design, synthesis and pharmacological evaluation of coumarin‐oxadiazole hybrids as potential molecules of therapeutic significance for the treatment of cognitive dysfunction.

Method

Eight novel coumarin‐oxadiazole hybrids have been synthesized by employing suitable synthetic procedures and characterized by various spectral techniques i.e. FT‐IR, 1H NMR and 13C NMR. All synthesized compounds were evaluated for their in‐vitro acetylcholinesterase (AChE) inhibition at five different concentrations. After in vitro studies, the compounds have been evaluated against behavioural alterations using step down passive avoidance and escape learning protocol at a dose of 2.0 mg/kg with reference to standard drug, rivastigmine. These compounds were further evaluated for their ex vivo acetylcholinesterase inhibition using mice brain homogenate as a source of the enzyme. Biochemical estimation of markers of oxidative stress (lipid peroxidation, superoxide dismutase, glutathione, catalase) has been carried out to access the role of synthesized molecules on the oxidative damage induced by scopolamine.

Result

The compounds 114, 117 and 120 were found to be the most promising in amelioration of cognitive impairment due to scopolamine as evidenced in both the behavioural animal model and ex vivo acetylcholinesterase assay. The coumarin‐oxadiazole based analogues have been found to exhibit promising antioxidant effects as indicated by the assessment of various biochemical parameters.

Conclusion

Our results depicted that the anti‐amnesic effect of the synthesized conjugates on scopolamine‐induced memory impairment may be related to the mediation of the cholinergic nervous system and their effective antioxidant activity.