bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benefits of population‐level interventions for dementia risk factors: an economic modelling study
Authors: Mukadam Naaheed , Anderson Robert , Walsh Sebastian , Wittenberg Raphael D , Knapp Martin Richard John , Brayne Carol , Livingston Gill 
Published: January 2025

AbstractBackgroundSome individual‐level interventions for dementia risk factors could be cost saving. We aimed to estimate the cost effectiveness of population‐level interventions for tackling dementia risk factors. We found such interventions for tobacco smoking, excess alcohol use, diet modification to decrease hypertension and obesity, air pollution, and head injury.MethodWe used published intervention effect sizes and relative risks for each risk factor. We used a Markov model to estimate progression to dementia in populations with and without the intervention, looking at lifetime risk, using the population of England as an exemplar.ResultBased on the effects on dementia, we estimated that reductions in excess alcohol use through minimum unit pricing would be expected to produce cost savings of £280 million and 4767 QALY gains respectively. Reformulation of food products to reduce salt and sugar intake and therefore reduce obesity and hypertension would be expected to produce cost savings of £2.4 and £1.1 billion, and QALY gains of 39,433 and 17,985, respectively. Introducing low emission zones in the largest English cities without them, so decreasing pollution and dementia would be expected to lead to £260 million savings and 5119 QALYs gained. Raising cigarette prices by 10% to reduce smoking rates, would be expected to lead to 2277 QALY gains and savings of £157 million from its effect on dementia. Legislating for compulsory bicycle helmets for children reducing head injury and dementia would lead to 1554 QALY gains and £91 million savings.ConclusionWe advocate for these population‐level interventions to help tackle lifecourse dementia risk and be cost‐saving.
Asian Cohort for Alzheimer’s Disease (ACAD) Study on Genetic and Non‐Genetic Risk Factors for Alzheimer’s Disease among Asian Americans and Canadians
Authors: Wang Li‐San , Ho Pei‐Chuan , Tee Boon Lead , Li Clara , Gu Yian , Yokoyama Jennifer S. , Reyes‐Dumeyer Dolly , Faber Kelley M. , Lee Wan‐Ping , Song Yeunjoo E. , Tzuang Marian , Vardarajan Badri N. , Yang Hyun‐Sik , Choi Yun‐Beom , Feldman Howard H. , Grill Joshua D , Henderson Victor W. , Hsiung Ging‐Yuek Robin , Mayeux Richard , Rosen Howard J. , Varma Rohit , Foroud Tatiana M. , Kukull Walter A. , Peavy Guerry M. , Lee Haeok , Yu W. Haung , Chui Helena C , Jun Gyungah R , Park Van Ta , Chow Tiffany W ,   The Asian Cohort for Alzheimer’s Disease Study
Published: January 2025

AbstractBackgroundAsian Americans and Asian Canadians (ASACs) are the fastest growing minority group in the US and Canada. However, ASACs are under‐sampled in Alzheimer’s disease (AD) research. To address the need of culturally appropriate clinical protocols and community‐based recruitment approaches for ASACs, the Asian Cohort for Alzheimer’s Disease (ACAD), the first large dementia genetics cohort focusing on Chinese, Korean, and Vietnamese, launched in 2021 to examine genetic and non‐genetic risk factors for AD among ASACs. Our clinical and community‐based participatory research (CPBR) scientists have a long collaborative history and diverse cultural and scientific training backgrounds: both are critical in leading AD and CBPR research.MethodUpon receipt of an NIA U19 grant in 2023, ACAD has expanded to 9 recruiting sites (7 US and 2 Canadian), a coordinating site, and an analysis site with a centralized data management system. ACAD developed a comprehensive study protocol including community outreach and recruitment strategies, the data collection packet (DCP), pre‐screening and sample collection procedures, and in English, Chinese (Mandarin and Cantonese), Korean, and Vietnamese. To ensure consistency, ACAD implemented a training curriculum for data/sample collect and for culturally appropriate recruitment approaches in collaboration with community partners, clinics, and nursing homes serving Asian communities.ResultAs of December 2023, more than 2,400 people expressed interests in ACAD. A total of 683 of the 899 consented participants completed DCP data into the REDCap (604 Chinese, 54 Korean, and 25 Vietnamese), while 399 saliva samples and 285 blood samples were received. Participants aged 60 –103 years at enrollment, 67% were female, and 47% reported having a college or above education. Currently, ACAD is revising the study protocol in response to feedback received in its pilot phase, including the need to include additional neuropsychological tests and cultural tailored lifestyle questionnaires with an emphasis on immigration experiences.ConclusionThe ACAD team (including community partners) have learned valuable lessons and demonstrated the feasibility of recruiting ASACs in clinical research. With an expansion plan and in collaboration with other AD research focuses on racial minority populations, insights from ACAD may identify potential novel, population‐specific therapeutic pathways for AD.
Memory function decline among Nigerian type 2 diabetic patients: Preliminary results from an ongoing multi‐centre case control study
Authors: Olayinka Juliet Nnenda , Irek Emmanuel , Adeoluwa Olusegun Adebayo , Ezekpo Okechukwu , Omiyale Benjamin , Ogunniyi Oluwafemi , Adarabioyo Idowu , Aberejo Olakunle , Otomewo Lily , Akpor Oluwaseyi , Ozolua Raymond 
Published: January 2025

AbstractBackgroundType 2 diabetes mellitus (T2DM) is among the modifiable risk factors for Alzheimer's disease (AD) and ranks among the leading chronic diseases globally. It is characterized by elevated blood glucose levels and insulin resistance, which over time may impair memory performance. More so, saliva appears to be a promising biomarker for the diagnosis of AD since conventional methods appear invasive and expensive in the country. Therefore, we investigated the impact of T2DM on memory function in diabetic patients at the Afe Babalola Multisystem Hospital, Nigeria and also determined if saliva may be a reliable diagnostic tool to detect the risk of AD in diabetic patients.MethodSixty (60) subjects, consisting of 20 diabetic patients and 40 healthy controls who consented to the study were recruited. A mini‐mental state examination (MMSE) was used to assess the participants’ memory performance. Blood samples were collected from the subjects to estimate biochemical parameters, which include: fasting blood glucose, insulin levels, glycated hemoglobin levels oxidative stress markers (malondialdehyde (MDA), sodium dismutase (SOD), and reduced glutathione (GSH)), as well as inflammatory markers (interleukin‐6 (IL‐6) and tumor necrosis factor‐alpha (TNF‐α)). Saliva was collected to estimate the level of amyloid beta‐42 (Aβ‐42). All these parameters were analyzed using enzyme‐linked immunosorbent assay.ResultThere were significant differences (p<0.05) between the values for glucose, insulin, Aβ‐42, SOD, GSH, MDA, TNF‐α, IL‐6 amongst diabetic and healthy controls. The MMSE result on severity of cognitive impairment showed that 14 (70%) diabetic patients between the scores of 24 and 30 suffer no cognitive impairment, 4 (20%) diabetic patients within the score of 18–23 have mild cognitive impairment, and 2 (10%) diabetic patients between the scores of 0 and 17 suffer severe cognitive impairment in comparison to the healthy control, who suffered no cognitive impairment.ConclusionOur results show that T2DM may impair memory performance later in life and that oxidative stress, insulin resistance, elevated levels of Aβ42, increased glycated hemoglobin and inflammation may be implicated in this decline. This ongoing study also strongly suggests that saliva may be an effective and alternative method for the diagnosis of AD in diabetes patients.
Virtual Reality‐based Cognitive and Exercise Intervention for People with Mild Cognitive Impairment. A systematic review and meta‐analysis
Authors: Chan Joyce YC , Tsoi Kelvin KF 
Published: January 2025

AbstractBackgroundCognitive training and exercise intervention are suggested for enhancing cognitive functions in people with mild cognitive impairment (MCI). The use of virtual reality (VR) has been applied in cognitive training and exercise intervention in recent decades. However, it is still unclear whether VR‐based intervention is a useful means to enhance cognitive functions in people with MCI. Therefore, the objective of this meta‐analysis was to examine the effect of VR‐based cognitive training and exercise intervention on cognitive functions in people with MCI.MethodA systematic literature search was conducted via OVID databases, including Pubmed, Medline, Embase, and APA PsychoInfo. Randomized controlled trials (RCT) recruited people with MCI and examined the effect of VR‐based cognitive training and/or exercise intervention were included. The outcomes were global cognitive function and memory. All outcomes were measured by using standard cognitive assessment tools. The effects were pooled by meta‐analysis and standardized mean difference (SMD) was used to calculate the combined results. Subgroup analyses were conducted according to the type of VR‐based intervention.ResultSixteen RCTs involving 889 people with MCI were included. The mean age ranged from 67 to 87. The length of intervention ranged from 4 to 20 weeks. People with MCI who received VR‐based intervention showed better global cognitive function (SMD = 0.51, 95% CI = 0.20 to 0.83), verbal memory (SMD = 0.64, 95% CI = 0.26 to 1.01) and working memory (SMD = 3.00, 95% CI = 1.31 to 4.69) than the control group. In subgroup analysis, VR‐based combined cognitive training and exercise intervention showed a large and significant effect in enhancing global cognitive function and verbal memory, whereas VR‐based exercise intervention showed a large and significant effect in improving working memory.ConclusionThe present study demonstrated that VR‐based intervention can be able to enhance global cognitive function and memory in people with MCI. VR‐based combined cognitive training and exercise intervention appear to have a larger effect on cognitive functions. However, the number of studies in sub‐group analyses was small. Further research on the mode of VR‐based interventions is suggested.
Social Deprivation and Cognition in Older Adulthood: The Mediating Role of Lifestyle Activities
Authors: Hofbauer Lena M , Rodriguez Francisca S 
Published: January 2025

AbstractBackgroundPrevious research has shown that the experience of social deprivation is associated with impaired cognition in older adulthood. It has been proposed that this may be explained by social deprivation being associated with a less ‘brain‐healthy’ lifestyle. We thus investigate mediating effects of lifestyle in the association between social deprivation and cognition.MethodsData of 3,015 respondents (Mean Age: 74.68 years, SD: 6.49; Mean Follow‐Up 6.40 years, SD: 2.16) in the Health and Retirement Study (HRS) were included in the analysis. Social Deprivation Status was evaluated using scores on the Social Deprivation Index. Further, we constructed a Lifestyle Index to measure engagement in lifestyle activities. The final index reflects the frequency at with respondents attend educational/training courses, read, do writing, go to non‐religious organisations or clubs, volunteer, and spend time on a hobby/project. Growth curve modelling was used to model cognition over time. Path modelling was used to evaluate the mediation.ResultsWhile a higher Social Deprivation Status was associated with poorer cognition, a higher Lifestyle Index score was associated with better cognition (β = 1.56, [95% CI: 1.23, 1.89], p<.001). The association with change over time was significant but negligible (β = 0.00, [95% CI: 0.00, 0.00], p = .026). Mediation analysis showed that the Lifestyle Index score accounted for 14.8% and 23.5% of the effect of Social Deprivation Status on cognition at baseline and last follow up, respectively.ConclusionsLifestyle is a partial mediator in the association between social deprivation and cognition. Yet, the size of the mediation indicates that its contribution is limited and broader factors, such as structural disadvantage, are likely at play. Thus, prevention efforts should not be limited to individual lifestyle but rather consider broader factors associated with social deprivation.
Risk Factors for Mild Cognitive Impairment: Prediction Models Developed with Electronic Health Record Data
Authors: Li Gang , Devanarayan Viswanath , Halpern Rachel , Bell Joanne , Batrla Richard , DeSanti Susan , Frech Feride H , Vandercappellen Jo , Khachaturian Ara S , Crislip Richard , Meyerhoff Jeffrey , Perea Saul , Mattke Soeren , Hampel Harald 
Published: January 2025

AbstractBackgroundTimely identification of mild cognitive impairment (MCI) is key to early intervention. While primary care providers are the most likely entry point to detect early signs of MCI, their detection rates are low. Building upon a published study, we used electronic health records (EHR) to develop a clinically enhanced MCI risk prediction algorithm.MethodThis retrospective analysis utilized the Optum EHR database, which includes records for more than 110M individuals across the United States. MCI and non‐MCI cohorts were identified from January 2016 – March 2021. Index date was first MCI diagnosis for MCI cohort and randomly selected diagnosis record for non‐MCI cohort. All individuals were observed 2 years before index date. Derived from EHR, potential predictors of MCI included health status (e.g., body mass index [BMI]), pre‐existing conditions identified with EHR diagnosis records and abstracted note records derived via natural language processing. Predictors of MCI will be identified using logistic regression, and an MCI risk prediction algorithm will be established using machine‐learning approaches based on those predictors.ResultOur sample included 21,059 and 631,770 individuals with and without MCI and mean age 71.1 and 59.1 years, respectively (p<0.001). Selected comorbidities in Table 1 are statistically significantly associated with MCI. Current work explores adjusting for age and adding health status indicators: nearly 90% of individuals had BMI data, with mean 28.8 and 30.5 in the MCI and non‐MCI cohorts, respectively (p<0.001); 80% of individuals had smoking status data, 37.6% and 46.9% of the MCI cohort were previous smokers and never smokers, respectively, versus 29.2% and 54.2% in the non‐MCI cohort (all p<0.001).ConclusionConsistent with a recent published study, this analysis finds higher unadjusted odds of hypertension, hyperlipidemia, stroke, atherosclerosis, diabetes, weight loss, depression, hearing loss insomnia, sleep apnea, chronic obstructive pulmonary disease, and kidney disease in the MCI cohort. We aim to use the prediction model from this study to improve the ability to discriminate between MCI and non‐MCI individuals and, ultimately, to develop a triage tool for PCPs to identify individuals at elevated MCI risk for further workup, based on routinely available data.
Life‐course socioeconomic position and changes in cognitive function in Hispanic/Latino adults. Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Filigrana Paola , Moon Jee‐Young , Lipton Richard B. , Tarraf Wassim , Aviles‐Santa Larissa , Daviglus Martha L , Gallo Linda C , Perreira Krista M , Stickel Ariana M , Testai Fernando Daniel , Thyagarajan Bharat , González Hector M , Isasi Carmen R 
Published: January 2025

AbstractBackgroundSocioeconomic disadvantage at different life‐course stages has been associated with later life cognitive impairment. However, its association with changes in cognitive function needs to be further elucidated. We assessed the association between socioeconomic position (SEP) throughout the life‐course and cognitive function change in middle‐aged and older Hispanic/Latino adults.MethodWe used data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a multicenter community‐based cohort of Latinos in the US (n = 6351; age range 45‐74) and a follow up visit conducted 7 years later by the SOL‐INCA ancillary study. Childhood SEP was determined using parental education (<high school [HS], HS, >HS). An index combining participants’ education, household income, occupation, and assets determined midlife SEP (low, middle, high SEP). Using dichotomized childhood and midlife SEP, we classified participants into socioeconomic mobility categories (stable low or high SEP, upward or downward mobility). Cognitive function changes (7‐years change) were ascertained as the difference in test scores between visits. Cognitive function assessments included the Six‐Item Screener, Brief‐Spanish English Verbal Learning Test Sum and Recall, Controlled Oral Word Association, and the Digit Symbol Substitution Test. Cognitive measures were z‐score standardized and a global cognition (GC) score was created using confirmatory factor analysis. Survey linear regression models were performed accounting for demographic, behavioral, and clinical covariates, baseline cognitive function, and years from baseline.ResultHigher midlife SEP was associated with a slower decline in cognitive function in later life (b for GC middle vs. low SEP: 0.12, 95% CI: 0.05, 0.19; and high vs. low SEP: 0.26, 95% CI: 0.15, 0.35). Upward socioeconomic mobility vs. stable low SEP (GC b: 0.29, 95% CI: 0.20, 0.39) and stable high SEP vs. stable low (GC b: 0.43, 95% CI: 0.32, 0.54) were also associated with slower cognitive decline. Results were similar for each individual cognitive test. We did not find associations between childhood SEP and changes in cognitive function.ConclusionThis study highlights the benefits on cognitive aging of advantageous SEP over the life‐course. Having a higher midlife SEP, upward socioeconomic mobility, or a stable high SEP over the life‐course showed protection for cognitive decline in adulthood.
The Alzheimer’s Disease‐Health Index (AD‐HI): a novel, disease‐specific, patient‐reported outcome measure for use in Alzheimer’s disease clinical trials and patient monitoring
Authors: Engebrecht Charlotte 
Published: January 2025

AbstractBackgroundTo bolster clinical trial infrastructure, there is a need to develop novel, valid, and reliable patient‐reported outcome (PRO) measures capable of tracking clinically‐relevant changes in Alzheimer’s disease (AD), Mild Cognitive Impairment (MCI) and dementia over time. This research describes the development and validation of the Alzheimer’s Disease‐Health Index (AD‐HI) as a tool to measure how patients feel and function in response to therapeutic intervention.MethodWe previously conducted semi‐structured qualitative interviews and a national cross‐sectional study with individuals with AD, MCI and dementia to ascertain the most prevalent and impactful symptoms identified by the participants. This data was used to generate the first version of the AD‐HI. We then conducted beta testing of the AD‐HI with individuals with AD and MCI to determine the instrument’s comprehensibility, ease of use, and applicability to the AD and MCI populations. Following participant feedback, we further modified the instrument and conducted test‐retest reliability, known groups validity (Figure 1), area under the curve (AUC) analysis (Figure 2), and factor analysis to validate the AD‐HI.ResultFifteen individuals with AD and MCI participated in the qualitative interviews and 104 individuals participated in the cross‐sectional study. We conducted beta testing with an additional 15 individuals with AD and MCI who stated that the AD‐HI was easy to use, clear, and highly relevant. Twenty‐three individuals with AD, MCI and dementia participated in test‐retest analysis. Known groups analysis demonstrated that the AD‐HI was able to differentiate between subgroups with varying levels of disease burden (based on employment status, disability status and those experiencing seizures).ConclusionThe AD‐HI is a valid and reliable regulatory‐grade instrument capable of measuring multifaceted disease burden in AD, MCI and dementia. The development, optimization and validation of the AD‐HI provides researchers and clinicians with a disease‐specific PRO for use in therapeutic trials and to potentially support FDA drug‐labeling claims.
Association of Blood Redox Markers with Alzheimer Disease Biomarkers and Cognitive Performance
Authors: Charisis Sokratis , Ntanasi Eva , Mamalaki Eirini , Skaperda Zoi , de la Colina Adrian Noriega , Kouretas Demetrios , Scarmeas Nikolaos 
Published: January 2025

AbstractBackgroundOxidative stress has been implicated in the pathogenesis of Alzheimer’s disease (AD). Nevertheless, whether redox perturbations are associated with cognition and AD pathology in the preclinical AD stages, remains unclear. We examined associations of blood redox markers with AD biomarkers and cognitive performance in older adults without clinical dementia.MethodIn a sample of 141 participants without clinical dementia from a memory clinic‐based cohort, we measured total antioxidant capacity (TAC), reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), reducing power (RP), and hydroxyl radical scavenging activity (HRSA), using standard laboratory techniques and absorbance spectrophotometry (Hitachi U‐1500). Cerebrospinal fluid (CSF) AD biomarkers, including Aβ42, pTau, and tTau, were measured using automated assays (Elecsys, Roche Diagnostics). Global and domain‐specific (i.e., memory, executive function, language, attention, and visuospatial abilities) cognitive performance was assessed with a comprehensive neuropsychological test battery. Associations of blood redox markers with AD biomarkers and cognitive performance were examined with logistic and linear regression models, respectively. Models were adjusted for age, sex, education, and APOE ε4 carriership. The false discovery rate for each outcome was controlled at <5% using the Benjamini‐Hochberg procedure.ResultMean (SD) age was 64.2 (9.1) years and 95 (67%) of the participants were women (Table 1). Higher TAC and HRSA values were associated with lower odds for pathologically low CSF Aβ42, whereas higher TBARS values were associated with higher odds for pathologically low CSF Aβ42 (Table 2). Higher TAC values were associated with better memory cognitive domain scores, whereas higher TBARS values were associated with worse memory cognitive domain scores (Table 3).ConclusionHigher blood TAC and HRSA, indicating better blood reactive oxygen species‐buffering capacity, were associated with lower odds for pathological CSF Aβ42, whereas higher TBARS, indicating increased lipid peroxidation, was associated with higher odds for pathological CSF Aβ42. Overall, these findings strongly point towards a link between redox imbalance and subclinical AD‐related neuropathology, and highlight the potential role of blood redox markers in AD risk stratification.