bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining plasma biomarkers for β‐amyloid diagnosis and cognitive prognosis across the clinical spectrum: normal, amnestic, and non‐amnestic
Authors: Cousins Katheryn A Q , Phillips Jeffrey S , Das Sandhitsu R. , O’Brien Kyra , Tropea Thomas F. , Chen‐Plotkin Alice , Shaw Leslie M. , Nasrallah Ilya M. , Mechanic‐Hamilton Dawn , McMillan Corey T , Irwin David J , Lee Eddie B , Wolk David A
Published: January 2025

Background

Alzheimer’s disease (AD) is clinically heterogeneous, and can manifest as amnestic or non‐amnestic dementia, or be pre‐manifest in persons with normal cognition (NormCog). Utility of plasma biomarkers to diagnose AD and prognose cognitive decline must be evaluated in a clinically heterogeneous population representative of the AD spectrum. We investigate pathological and cognitive correlates of plasma phosphorylated tau 181 (p‐tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) across AD and AD‐related dementias (ADRD). We test 1.) if combing biomarkers improves diagnostic accuracy for β‐amyloid (Aβ) in NormCog and impaired cognition (ImpCog), 2.) if Aβ diagnostic accuracy in ImpCog differs by clinical syndrome (amnestic dementia vs. non‐amnestic dementia vs. mild cognitive impairment [MCI]), and 3.) how biomarkers predict future cognitive decline in Aβ+ and Aβ‐.

Methods

Participants were NormCog (n=132) and ImpCog (n=461; 130 MCI/impairment without MCI; 61 amnestic; 270 non‐amnestic), with confirmed Aβ status (247 Aβ+; 346 Aβ‐; cerebrospinal fluid/positron emission tomography/autopsy) and single molecule array plasma measurements. Logistic regression and receiver operating characteristic (ROC) area under the curve (AUC) tested discrimination of Aβ+ from Aβ‐; K‐folds cross‐validation and exhaustive selection determined optimal biomarker combinations. Chi‐square tests compared correct classifications to errors of the multivariable model and plasma p‐tau181 across phenotype. Survival analyses tested time to global clinical dementia rating (CDR) progression.

Results

Multivariable models (p‐tau+GFAP+NfL) had the best performance to detect Aβ+ in NormCog (ROCAUC=0.87) and were significantly better in Impaired (ROCAUC=0.87) compared to single analytes (all p<0.018) (Table 1; Figure 1). In ImpCog, multivariable model classification differed by phenotype (χ2=7, p=0.032), with highest accuracy in amnestic dementia (Accuracy: 92%), followed by MCI/impaired not MCI (81%), and non‐amnestic dementia (76%). Likewise, plasma p‐tau181 performance significantly differed by phenotype (χ2=6.8, p=0.035) (Accuracy: amnestic=90%; MCI/impairment without MCI=80%; non‐amnestic=74%). Survival analyses demonstrated that higher NfL best predicted faster CDR progression for both Aβ+ (HR=2.94, p=8.1e‐06) and Aβ‐ individuals (HR=3.11, p=2.6e‐09) (Figure 2).

Conclusion

Combining plasma biomarkers can optimize detection of AD pathology across cognitively normal and clinically diverse neurodegenerative disease. Still, diagnostic accuracy may be lower for non‐amnestic AD. Plasma NfL showed the most accurate prognosis across neurodegenerative spectrum.
Transition to hospice: how it impacts the mental health of caregivers of persons with dementia
Authors: Oh Oonjee , Oliver Debra Parker , Washington Karla , Demiris George
Published: January 2025

Background

Within the dementia space, many caregivers lack understanding of hospice care and may not be well prepared for transition to hospice. Nonetheless, few studies have explored hospice transition specifically from the perspective of caregivers for persons with dementia and how it impacts their mental health. In this study, we aimed to examine caregivers’ mental health indicators and their correlation structure based on the timing of hospice transition.

Method

We conducted a secondary data analysis using the pre‐intervention data from an ongoing randomized clinical trial of a problem‐solving therapy intervention for hospice caregivers labeled ENCODE (Empowering Caregivers of Patients with Dementia), focusing on a sample recruited between December 2021 and mid‐January 2024. Recent transition to hospice was defined as enrollment in hospice for less than 14 days at baseline. We conducted two‐sample T‐tests and χ² tests to compare the demographics, caregiving characteristics, hospice setting, and mental health indicators (i.e., depressive and anxiety symptoms, perceived change in wellbeing, the mental component of health‐related quality of life (HrQoL)) between caregivers who recently transitioned to hospice and those who had been in hospice longer. Additionally, we compared the Pearson correlation matrices across mental health indicators based on the caregivers’ hospice transition.

Result

Among 156 caregivers (mean age = 59.63, female 82.05%, spouse/partner 16.03%), 62 (39.74%) caregivers recently transitioned to hospice. Compared to other hospice caregivers, we found that caregivers who recently entered hospice had significantly higher levels of depressive symptoms (p value = 0.031), higher levels of anxiety symptoms (p value = 0.001), and worse trends in overall changes in wellbeing (p value = 0.012). There were no significant differences in the mental component of HrQoL. The association patterns between each pair of mental health indicators were consistent across different timings of hospice transition.

Conclusion

In the context of dementia care, our results highlight that caregivers who just entered hospice are undergoing a challenging transition that often finds them in a mentally vulnerable position. To develop and implement effective strategies for caregivers of persons with dementia, we need to understand the needs and vulnerabilities of caregivers during hospice transition and identify the best timing for the delivery of supportive tools.
Psychological Contributors to Purpose in Life among a Culturally Diverse Aging Cohort
Authors: Vu Uyen TM , Farias Sarah Tomaszewski , Weakley Alyssa , Harvey Danielle J. , Meyer Oanh L.
Published: January 2025

Background

Purpose in life (PIL) refers to individuals’ derivation of meaning from life experiences, possession of a sense of direction and intentionality, and striving towards goals. PIL is associated with many positive health outcomes and reduced risk of cognitive decline and dementia in older adults. Importantly, PIL is potentially modifiable through intervention to reduce risk of Alzheimer’s disease and related disorders. However, it is a complex construct likely influenced by psychological, lifestyle, and demographic factors. This study examines factors contributing to PIL, with the long‐range goal to inform the development of intervention approaches.

Methods

This was a cross‐sectional study of participants from the University of California Davis Alzheimer’s Disease Research Center Longitudinal Cohort with a PIL score (N = 191). The mean age was 76.3 (SD = 7.2). Most were female (65%) and cognitively normal (85.3%). A substantial percentage were from underrepresented groups (45%). Independent variables of interest were grit, positive affect, emotional support, self‐efficacy, loneliness, and participation in physical and recreational activities. Covariates included age, sex, race, and education. Individual and joint linear regression models were run to examine associations.

Results

All variables were significantly associated with PIL in bivariate models, but only positive affect was associated with higher PIL in the joint model including all independent variables and covariates (B = 0.478, 95% CI [0.362, 0.655], p < .001). Loneliness was associated with lower PIL (B = ‐0.18, 95% CI [‐0.384, ‐0.053], p = .01).

Conclusions

Psychological, lifestyle, and demographic factors are important to consider in their association with PIL. Our findings showed that positive affect was associated with higher PIL and loneliness with lower PIL. These results have implications for future prevention and interventions to increase PIL in older adults, which may improve cognition and health. There are currently limited interventions that explicitly target PIL, and they are mostly in the cancer population. Conversely there are several evidence‐based approaches to increase positive affect that may also increase sense of PIL. Additionally, the association between loneliness and PIL suggests that increasing social connection may also bolster PIL.
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

Background

Some 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.

Method

We 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.

Result

Based 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.

Conclusion

We 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

Background

Asian 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.

Method

Upon 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.

Result

As 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.

Conclusion

The 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

Background

Type 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.

Method

Sixty (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.

Result

There 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.

Conclusion

Our 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

Background

Cognitive 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.

Method

A 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.

Result

Sixteen 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.

Conclusion

The 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

Background

Previous 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.

Methods

Data 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.

Results

While 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.

Conclusions

Lifestyle 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

Background

Timely 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.

Method

This 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.

Result

Our 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).

Conclusion

Consistent 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

Background

Socioeconomic 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.

Method

We 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 (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.

Result

Higher 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.

Conclusion

This 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

Background

To 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.

Method

We 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.

Result

Fifteen 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).

Conclusion

The 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

Background

Oxidative 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.

Method

In 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.

Result

Mean (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).

Conclusion

Higher 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.
Neuroprotective effects of omega‐3 oil on aluminium‐induced oxidative stress in the hippocampus of female Wistar rats
Authors: Nyen Tangban Cynthia , Prescillia Ajibade Testimony
Published: January 2025

Background

Aluminium chloride, an environmental toxicant induces neurotoxicity by increasing anxiety, causing cognitive deficit and memory impairment due to its effects on the hippocampus. Omega‐3 oil has been shown to improve cognition in neurologic disorders.

Method

Forty adult female rats were divided into 4 groups (n = 10). Group A received distilled water, group B received 100mg/kg aluminium chloride, group C received 300mg/kg of omega‐3 oil and group D received 100mg/kg Alcl3 and 300mg/kg omega‐3 one hour interval. All treatment was done orally for 28 days. Neurobehavioural test was done and the rats sacrificed on day 29. The hippocampus was dissected out and some preserved in phosphate buffered saline at 4°C and pH, 7.2 for oxidative stress and antioxidant markers, while others fixed in 10% formol‐saline for histological and immunohistochemical studies. Data analyzed using one way analysis of variance at p<0.05.

Result

The Alcl3‐treated rats showed deficit in cognition and spatial memory, increased oxidative stress marker and decreased antioxidant system compared with the control and omega‐3 oil‐treated groups. The hippocampus showed Pyramidal cell degeneration, vacuolation, karyorrhexis and pyknosis, and increased reactive astrocyte and B‐Cell lymphoma‐associated X‐protein (BAX) in the Alcl3‐treated group compared with the control and omega‐3 oil‐treated groups. Aluminium chloride induced oxidative stress, negative cognitive behaviour, memory loss and decreased the antioxidant capacity in the hippocampus of Wistar rats

Conclusion

Omega‐3 oil attenuated these negative effects suggesting its neuroprotective capability possibly through upregulating the antioxidant system, reducing astrogliosis or by preventing the pro‐apoptotic cascade.
Decentralised clinical trials for medications to reduce the risk of dementia: consensus report and guidance
Authors: Howard Leanne , Abdelnour Carla , Abner Erin L. , Allegri Ricardo , Dodge Hiroko H , Gauthier Serge , Hoyos Camilla M , Jicha Gregory A , Kehoe Patrick Gavin , Mummery Catherine J. , Ogunniyi Adesola , Scarmeas Nikolaos , Chen Xiaoying , Titiner Jodi R. , Weber Christopher J. , Peters Ruth , Trial The Clinical , Group Methodology Professional Interest Area Remote Trial Working
Published: January 2025

Background

Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralised clinical trials in dementia. There are many potential benefits associated with decentralised medication trials, but the field is currently lacking specific recommendations for their delivery in the dementia field.

Method

A modified Delphi method engaged a panel with substantial expertise in dementia trial design and delivery and backgrounds that included neurology, psychiatry, pharmacology and psychology, to develop recommendations for the conduct of decentralised medication trials in dementia prevention. A working group of researchers and clinicians with expertise in dementia trials further refined the recommendations.

Result

Overall, the recommendations support the delivery of decentralised remote trials in dementia prevention provided adequate safety checks and balances are included. A total of 40 recommendations will be presented, spanning aspects of decentralised clinical trials dementia prevention trials in phases 2b‐4, including safety, dispensing, outcome assessment, and data collection.

Conclusion

With these recommendations we provide an accessible, pragmatic guide for the design and conduct of remote medication trials for the prevention of dementia.
Identifying an EEG Biomarker for Memory Recall through EEG and EDA in the Presence of Music
Authors: Das Rupak Kumar , Khan Arshia A , Imtiaz Nabiha Zainab
Published: January 2025

Background

There is ample evidence that music can boost brain activity and jog deeply embedded memories. Literature indicates a significant improvement in autobiographical memory (ABM) recall for different individuals during background music sessions. Existing research is based solely on qualitative data, although music has a significant impact on physiological activity. Thus, it's important to explore the connection between memory recall and physiological activities.

Method

To better understand memory recall, the electroencephalogram (EEG) and electrodermal activity (EDA) data were gathered from healthy participants using wearable sensors. Physiological signals such as the electroencephalogram (EEG) and electrodermal activity (EDA) were recorded as quantitative data using various wearable sensors from 40 participants of different age groups while playing different background music sessions. The study involved listening to nine music sessions (three happy, three sad, and three neutral). Immediately after each piece of music, a post‐study survey was conducted to gauge if the participants recalled any autobiographical memories. A machine learning algorithm was developed to train a model using features collected from physiological data to determine if the memory recall was successful. The purpose of the study was to identify an EEG biomarker.

Result

The results of the EEG and EDA data analysis revealed that for all four EEG channels, there was a consistent increase in the alpha power (on average 16.2%) during the memory “recall” scenario (F3: p = 0.0066, F7: p = 0.0386, F4: p = 0.0023, and F8: p = 0.0288) compared to the “no‐recall” control. There was also a significant surge in the Beta power for two channels (F3: p = 0.0100 and F4: p = 0.0210) but not for the control (F7: p = 0.6792 and F8: p = 0.0814). Additionally, the EDA data analysis revealed significant differences in the phasic standard deviation (p = 0.0260), phasic max (p = 0.0011), phasic energy (p = 0.0478), tonic min (p = 0.0092), tonic standard deviation (p = 0.0171), and phasic energy (p = 0.0478). This implies that the memory recall biomarker is alpha power (8–12 Hz).

Conclusion

The results indicate that the biomarker for memory recall is alpha power (8‐12Hz).
Strategies and challenges for recruiting and retaining illiterate older adults with low socioeconomical levels in a non‐pharmacological trial: the PROAME study
Authors: Resende Elisa de Paula França , Friedlaender Clarisse Vasconcelos , Rocha João Victor de Faria , Zacarias Ana Paula , Assenção Joanna de Castro Magalhães , Ruppert Emma Patrice , Tomaz Kelle Luisa dos Santos , Grinberg Lea T. , Caramelli Paulo , Maciel Francisca Izabel Pereira
Published: January 2025

Background

Recruiting and retaining older adults for clinical trials is challenging, especially in low‐resource settings. Such challenges led to a systematic exclusion of such participants from clinical trials, compromising the generalizability of the results obtained in high income countries.

Objective

Here we describe the strategies we used in the PROAME study for recruiting and retaining illiterate older adults from low socioeconomical levels in a non‐pharmacological trial.

Methods

The PROAME study was conducted in Brazil (NCT04473235) to access whether late‐life education could improve episodic memory and functional connectivity in illiterate older adults. The sample size calculation to test the hypothesis was 120, 60 in each arm, with an 90% power to detect a significant difference between the groups.

Results

From 2021 to 2022, 130 illiterate older adults were approached at public adult schools. To help in the recruitment, we partnered with community adult schools and promoted educational lectures about brain health and the importance of participating in research. We provided groups sessions with participants and teachers to help the understanding of the informed consent. The main barrier for recruiting was afraid of undergoing the brain MRI scan, which accounted for 42% (9/21) of screening failure. After screening, 108 participants were recruited, 57% Blacks, 32% Mixed and 10% Whites. Most participants were women (71.3%), from low socioeconomic status (91%) with barely any formal education (mean of 1.9 ±2.1 years). Participants were allocated into 2 groups: the intervention received an intensive training in learning how to read and write, while the control received regular classes of math, geography, history, and sciences. The main barrier for retention was the need to work at the time the intervention was being performed, followed by severe diseases such as stroke. Seventy‐seven participants completed the follow up‐assessments after 6 months of intervention, an attrition rate of 28%.

Conclusions

Partnership with local communities outside the health care system helped in recruiting as we reached our sample size, but the low socioeconomical levels of participants forced them to abandon the intervention as they had to work.
Physical frailty, genetic predisposition, and incident dementia: a prospective cohort study of 274,194 participants
Authors: Gao Pei‐Yang , Tan Lan , Yu Jin‐Tai
Published: January 2025

Background

Frailty, a condition characterized by functional decline, is recognized as a potential modifiable risk factor for dementia prevention. Genetic risk is also considered an unregulated risk for dementia. However, their joint effect remains unclear. Therefore, this study aims to investigate the long‐term associations of physical frailty, genetic predisposition, and their combined effect on dementia risk.

Method

Participants without baseline dementia from the UK Biobank were included in this prospective longitudinal cohort study. Physical frailty was measured by the frailty phenotype, which comprises five components: slow walking speed, low physical activity, exhaustion, low grip strength, and weight loss; and a polygenic risk score (PRS) for dementia with low, intermediate, and high risk categories. Cox proportional hazards regression models were used to determine the association between physical frailty and genetic and dementia risks.

Result

Of the 274,194 participants (females, 146,574 [53.45%]; mean age, 57.24), 3,353 new‐onset dementia events were documented. Compared to non‐frailty, the hazard ratio (HR) for dementia incidence in pre‐frailty and frailty was 1.396 (95% confidence interval [CI], 1.294–1.506, P < 0.001) and 2.304 (95% CI, 2.030‐2.616, P < 0.001), respectively. Compared to non‐frailty and low PRS, the HR for dementia risk was 3.908 (95% CI, 3.051‐5.006, P < 0.001) for frailty and high PRS, which was monotonically increasing risk of incident dementia across the frailty status and PRS categories. Furthermore, slow walking speed (HR, 1.817; 95% CI, 1.640‐2.014, P < 0.001), low physical activity (HR, 1.719; 95% CI, 1.545–1.912, P < 0.001), exhaustion (HR, 1.670; 95% CI, 1.502–1.856, P < 0.001), low grip strength (HR, 1.606; 95% CI, 1.479–1.744, P < 0.001), and weight loss (HR, 1.464; 95% CI, 1.328–1.615, P < 0.001) were independently associated with dementia risk compared to non‐frailty. Additionally, precise differences among different dementia genetic risk populations were also identified due to differences in dementia risk resulting from the constitutive patterns of frailty.

Conclusion

Both physical frailty and high genetic risk are significantly associated with an increased risk of dementia. Early intervention to modify frailty is beneficial for achieving primary and precise prevention of dementia, particularly in those with a high genetic risk.
The Lived Experience of Participants in Preclinical Alzheimer’s Intervention Research
Authors: Meserve Nancy F
Published: January 2025

Preclinical Alzheimer’s prevention trials require a multi‐year commitment from diverse, cognitively unimpaired individuals willing to receive biomarker results of confirmed Alzheimer’s pathology and possible ApoE4 status. Participants learn new terms such as ARIA, edema and microhemorrhage and undergo numerous MRI scans for safety monitoring. They take quarterly composite Alzheimer’s assessments that are anxiety‐provoking and highlight weaknesses which may have been unrecognized in daily life. Infusions are often described as an hour in length, yet study visits may require several hours biweekly for record‐updating, infusion preparation and delivery, monitoring, and travel. Such a commitment has few, if any, corollaries in prevention of asymptomatic disease. Researchers and clinical site staff can benefit from the lived experience of preclinical trial participants. Their individual priorities, risk/benefit calculations, preferences for information and disclosure, engagement with their communities and hope for themselves and others may differ significantly from those with confirmed diagnoses in trials of disease‐modifying treatments.

In this talk, a woman with two copies of ApoE4, in her third year of the AHEAD‐45 preclinical‐AD trial on lecanemab, will portray her experience of trial participation, She reports also on her conversations with other current and future participants in this or similar studies. The perspective of a participant on biomarker and genetic disclosure, risk discussion and safety monitoring, symptom reporting, unscheduled MRIs, disclosure of isolated ARIA‐H and resumption of infusions will extend the understanding of how to overcome barriers to participation by others. The acknowledgement of uncertainties and encouragement of dialogue and questions empowers participants to partner with researchers. Recognition of the views of family members more skeptical of prevention than treatment of diagnosed dementia or other life‐threatening diseases may only be possible by listening to participants' experiences. The importance of participation may be best received when shared personally, in community groups and online by participants whose lived experience perspectives speak to the hopes as well as the fears of those with high risk of Alzheimer’s dementia.
Impacts of an Exercise and Behavioral Intervention on Community‐Dwelling Older Adults with Dementia and Their Family Caregivers in Thailand
Authors: Chen Hongtu , Levkoff Sue E , Sihapark Siranee , Hinton Ladson , Thongsiri Sirinart , Wisetpholchai Bussabong , Teri Linda , Gallagher‐Thompson Dolores , Intaraphet Suthida , Wang Kaipeng , Chuengsatiansup Komatra
Published: January 2025

Background

This study uses the data collected from the “Partnership in Implementation Science for Geriatric Mental Health (PRISM)” project, a randomized trial designed to test implementation support strategies for the delivery of the Reducing Disability in Alzheimer’s Disease (RDAD) program, an evidence‐based multi‐component exercise and behavioral/psychosocial intervention for older adults with dementia and their family caregivers in Thailand.

Method

A total of 353 dyads of persons with dementia (PwD) and behavioral and psychological symptoms of dementia (BPSD) and their family caregivers received a 12‐week RDAD intervention and were assessed at baseline, and at 3‐ and 6‐months post‐treatment. Longitudinal analyses were conducted using paired‐sample t‐tests to estimate the changes in each of the outcomes by treatment groups.

Result

Paired t‐tests showed that between baseline and 3 months, there were significant decreases in caregiver clinical outcomes, including caregiver burden (p = 0.047), depressive symptoms (p = 0.02), and BPSD‐related caregiver distress (p < 0.001). Similarly, there were significant decreases between baseline and 3 months in PwD’s mental health indicators, including BPSD symptoms (p < 0.001), BPSD severity (p < 0.002), and depression (p < 0.001). PwDs also showed a significant increase in physical function assessed by ADLs (p < 0.031) and cognitive function, as assessed by the Thai MMSE (TMSE) (p < 0.001), and these trends persisted between the 3‐ and 6‐month follow‐up assessments, with significant increases in ADLs (p < 0.001) and TMSE (p < 0.001). We also conducted heterogeneity regression analysis to assess whether the time changes might be determined by baseline characteristics (e.g., sex, age, subgroups) and found no significant influences of these factors on changes in outcomes over time.

Conclusion

The results suggest that the RDAD intervention significantly reduces caregivers’ psychological burden, depressive symptoms, and BPSD‐related distress and also improves the PwD’s mental, physical, and cognitive function. These findings provide evidence that supports efforts to expand the reach of US‐developed evidence‐based non‐pharmacological interventions to improve dementia care for community dwellers in resource‐limited settings like Thailand.