bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in referral source across racial and ethnic groups at Alzheimer’s Disease Research Centers
Authors: Chan Carol , Lane Kathleen A. , Gao Sujuan , Adeoye‐Olatunde Omolola A , Biber Sarah A , Risacher Shannon L. , Saykin Andrew J. , Wang Sophia
Published: January 2025

Background

Despite recognition of the need to increase underrepresented groups (URG) engagement in Alzheimer’s disease and related dementias (ADRD) studies, enrollment remains low. As a first step in examining these disparities, these analyses aimed to compare referral sources for Alzheimer’s Disease Research Centers (ADRC) enrollment of URG participants.

Method

These analyses included data from 48,330 participants across 46 ADRCs, obtained through the National Alzheimer’s Coordinating Center Uniform Data Set. Generalized logistic regression models with generalized estimating equations were used to examine the association of racial/ethnic group and professional vs non‐professional referral source. The ‘professional’ category included referrals made by healthcare professionals or ADRC staff, while the ‘non‐professional’ category included referrals made by self, family or friends. This association was examined across the entire sample, and then individuals who had completed magnetic resonance imaging (MRI). The analyses were adjusted for age, gender, education, visit year, and categorical CDR with random site effect to adjust for study site.

Result

Descriptive statistics are shown in Table 1. Non‐Hispanic Black and Asian participants were less likely to have completed an MRI. Across the entire sample, Non‐Hispanic Black and Non‐Hispanic Asian participants were less likely to be referred by a professional contact than Non‐Hispanic White participants (Table 2). In those who had completed an MRI, there were no significant differences across the racial groups, although we note that the sample sizes for those with MRI were much smaller (Table 3). Results for both analyses were similar when only participants who had a diagnosis of MCI or dementia and a global CDR of 0.5 or 1 at baseline were included.

Conclusion

One major factor leading to lower rates of URG participation in ADRD research is disproportionately fewer healthcare professional referrals. To develop and optimize ADRC recruitment strategies, future studies are needed to explore reasons for differences in URG referrals by healthcare professionals and non‐professionals.
Temporal order of gait speed decline relative to changes in measures affected early in Alzheimer’s disease
Authors: Bilgel Murat , Tian Qu , Walker Keenan A. , Moghekar Abhay , Ashton Nicholas J. , Kac Przemyslaw Radoslaw , Karikari Thomas K , Blennow Kaj , Zetterberg Henrik , Thambisetty Madhav , Resnick Susan M.
Published: January 2025

Background

Individuals with dual decline in gait and cognition have a greater risk of developing dementia. Understanding when gait speed declines relative to measures affected early in Alzheimer’s disease can improve risk assessment.

Method

Using data for 761 participants (1,108 cognitively unimpaired visits) from the Baltimore Longitudinal Study of Aging, we estimated the trajectories of gait speed, memory (California Verbal Learning Test [CVLT] immediate recall score), hippocampal volume, and plasma Aβ42/Aβ40, glial fibrillary acidic protein (GFAP), and p‐tau181.

We fitted a progression score (PS) model that aligns individuals based on the similarity of their multivariate longitudinal observations to reveal long‐term biomarker trajectories, accounting for individual differences in baseline level and rate of progression. We included height as a covariate for gait speed, first administration versus not for CVLT (to control for practice effect), intracranial volume for hippocampal volume, and estimated glomerular filtration rate for each plasma biomarker.

74 participants converted to mild cognitive impairment (MCI) or dementia after the last visit used for fitting the PS model and were used to verify that the estimated PS reflects neurodegenerative disease progression using a Cox proportional hazards model. We then examined the temporal ordering of the estimated biomarker trajectories by comparing the timing of peak relative changes.

Result

Greater PS at last visit was associated with a higher risk of conversion to MCI/dementia (hazard ratio for interquartile range normalized PS = 6.1, P < 2×10‐16). The PS‐only model had a better concordance index compared to an age‐only model for predicting conversion (0.880 ± 0.016 vs. 0.852 ± 0.018). Estimated trajectories as a function of PS are shown in Figure 1. The peak relative change in hippocampal volume occurred prior to that of gait speed (difference in PS between peaks: ‐0.57 [95% confidence interval ‐1.32, ‐0.05]), whereas p‐tau181 changed later (difference in PS between peaks: 1.95 [1.19, 2.45]) (Figure 2).

Conclusion

Decline in gait speed occurs after hippocampal volume loss but alongside other biomarkers known to be affected early in Alzheimer’s disease and it can prove useful in individualized prediction. Alternative approaches for examining temporal ordering will help assess robustness of findings.
Effect of plant‐based diets on plasma biomarkers of Alzheimer's disease
Authors: Eslick Shaun , Austin Grace , Ferguson Jessica , Garg Manohar , Martins Ralph N
Published: January 2025

Background

Interest and consumption of plant‐based diets (PBD) in the 21st century continued to increase, particularly in western societies, with the perception that PBDs are associated with beneficial health outcomes and a reduced environmental footprint. Evidence suggests that PBDs may be protective against neurodegenerative diseases, such as Alzheimer’s disease (AD). Health effects of PBDs such as reduction of inflammation, shift in gut microbiota composition, reduced risk of type 2 diabetes and cardiovascular disease are all believed to attribute to reduced AD risk. Therefore, we hypothesise that plasma amyloid beta (Aβ), glial fibrillary acidic protein (GFAP), neurofilament light (NFL) and phosphorylated tau (pTau) will be lower in individuals habitually following a vegan dietary pattern compared to those following a regular meat‐eating diet.

Method

Men and women, 30‐75yrs without current or diagnosed CVD who followed a vegan (nil animal flesh or animal derived products) or regular meat (≥daily consumption of animal flesh) dietary pattern for a minimum of six months. Fasting blood was collected and plasma separated by centrifugation and stored at ‐80°. Biomarkers of AD including Aβ1‐40, Aβ1‐42, GFAP, and NFL and pTau181 were measured using ultra‐sensitive Single Molecule Array (SIMOA) assay platform.

Result

A total of 94 plasma samples were analysed from the vegan (n=47) and the regular meat eaters (n=47) dietary pattern groups. In the vegan group, the mean plasma Aβ1‐42/Aβ1‐40 ratio (p=0.01), plasma GFAP (p=0.04) and plasma NFL (p<0.01) were significantly lower compared to the regular meat eaters’ group. However, plasma pTau181 was found to be similar between the two groups (p=0.29).

Conclusion

This study demonstrated that blood‐based biomarkers are lower in individuals following a vegan dietary pattern compared to those following a regular meat‐eating diet, suggesting that PBDs may be protective against Alzheimer’s disease pathology.
Novel Diagnostic Tool for Detecting Cognitive Impairment by Integrating Functional Near‐infrared Spectroscopy and Plasma Biomarkers in a Large Chinese Cohort
Authors: Jiao Bin , Ouyang Ziyu , Zhang Sizhe , Zhang Cong , Xiao Xuewen , Liu Yiliang , Bei Yuzhang , Zhu Yuan , Yang Qijie , Xu Tianyan , Hao Xiaoli , Yang Xuan , Wan Meidan , Luo Shilin , Tang Beisha , Shen Lu
Published: January 2025

Background

An objective and effective screening tool for cognitive impairment (CI) is needed in the Chinese population. However, whether the integration of brain resting‐state functional connectivity (rs‐FC) and neurodegenerative plasma biomarkers can distinguish CI from cognitively normal (CN) individuals remains unclear.

Method

A total of 1077 participants from a longitudinal Liuyang community cohort were enrolled. The rs‐FC was collected using functional near‐infrared spectroscopy (fNIRS). Plasma biomarkers, including p‐tau181, p‐tau217, p‐tau231, Aβ40, Aβ42, NfL, and GFAP were detected using single molecule assay method.

Result

The average FC of the CI group was significantly lower than that of the CN group (p < 0.0001). The CI detection model based on the combined altered FCs, achieved an area under the curve (AUC) of 0.785, which showed better diagnostic performance than that of single plasma biomarker with AUC of 0.592‐0.631. However, the integration of altered FC and plasma biomarker presented the best accuracy with AUC of 0.887‐0.933. Totally, 27 FCs were correlated with plasma biomarkers, and among them, the strength of right part of Brodmann's area 6 vs. right part of Brodmann's area 1+2 (BA6R.vs.BA1+2R) was negatively associated with p‐tau231, p‐tau217 and GFAP. Additionally, 13 FCs could mediate the effects of three plasma biomarkers on cognition, including p‐tau217 (n = 3), NfL (n = 10), and GFAP (n = 1).

Conclusion

Rs‐FC based on fNIRS combined with plasma biomarkers is feasible and effective for non‐invasive CI screening.
Blood biomarkers of amyloid and tau pathologies, brain degeneration, inflammation, and oxidative stress in early‐ and late‐onset Alzheimer's disease
Authors: Xia Xinyi , Qin Qi , Tang Yi
Published: January 2025

Background

Blood biomarkers provide a non‐invasive and accessible means of detection for Alzheimer's disease (AD). Specifically, biomarkers associated with early‐onset AD (EOAD) illuminate the underlying mechanisms and provide valuable guidance for potential therapies. We aim to present blood biomarker evidence in individuals with both EOAD and late‐onset AD (LOAD), as well as in age‐matched healthy controls.

Methods

A total of 95 participants were enrolled in the study. We assessed levels of 18 distinct blood biomarkers, and concurrently examined cerebrospinal fluid amyloid and tau markers, neuropsychological test scores, APOEε4 carrier status, and neuroimaging markers. Group disparities, correlations, and the diagnostic utility of these biomarkers were investigated.

Results

In patients with EOAD, levels of blood IL‐4, IL‐6, and TNF‐α were notably lower when compared to LOAD. AD patients exhibited higher blood levels of p‐tau181, NfL, GFAP, tAOC, and MDA, as well as lower levels of Aβ1‐42, SOD, and IL‐12p70. Intricate interactions were observed among these blood biomarkers, with inflammatory markers demonstrating correlations with neuroimaging markers within the AD cohort. Individuals carrying the APOEε4 allele displayed elevated levels of GFAP and IL‐4 in comparison to non‐carriers. Additionally, blood levels of Aβ1‐42, p‐tau181, NfL, and GFAP were found to correlate with neuropsychological scores and proved effective in distinguishing AD, with GFAP exhibiting particular relevance in early‐onset cases.

Conclusion

The study demonstrated that individuals with EOAD may experience less inflammatory responses than older patients. Peripheral inflammation was associated with amyloid and tau pathologies, astrogliosis, oxidative stress, and alterations in brain structure and function. Blood Aβ1‐42, p‐tau181, NfL, and GFAP showed promise in detecting cognitive decline and AD, with GFAP exhibiting relevance in early‐onset cases.
Changes in peripheral AD biomarkers in a randomized controlled trial of Yoga vs. memory training in older women at risk for Alzheimer’s disease
Authors: Lavretsky Helen
Published: January 2025

Background

Biomarkers such as amyloid beta (Aβ) peptides and tau protein can correlate with changes in cognition and mood symptoms associated with AD. We aimed to investigate the blood biomarker response to a Kundalini Yoga (KY) compared to Memory Enhancement Training (MET) intervention as well as determine the predictive value of blood biomarkers on outcomes in a randomized trial targeting women at risk for Alzheimer's disease.

Method

Women aged 60 years old and older with subjective memory complaints and high cardiovascular risk score were randomized to a 12‐week RCT of Kundalini yoga or Memory enhancement training (MET). We obtained blood samples at baseline and week 24 (6 months) to measures AB40; AB42 and p‐Tau. Participants completed the Beck Depression Inventory (BDI) for depressive symptoms, and Memory Functioning Questionnaire (MFQ) for subjective memory reports. Regression models were used to examine whether baseline and changes in biomarker levels including Aβ40, Aβ42, Aβ42/40 ratio and tau were associated with changes in outcomes at 24 weeks.

Result

A total of 79 patients (KY=40; MET=39) were randomized, and 63 completed the 24‐week follow‐up. There were no group differences in AD biomarkers at baseline or at 24‐week follow‐up. Baseline levels of Aβ40 were significantly associated with an increase in subjective memory (MFQ Frequency of Forgetting; r = 0.27, p=0.04). An increase in Aβ40 levels was significantly associated with a decrease in BDI (r = ‐0.33, p=0.02). There was no significant association of changes in Aβ42, Aβ42/40 ratio and tau with any outcomes.

Conclusion

Our findings indicate that greater levels of Aβ40 at baseline are associated with an increase in subjective memory at follow‐up and an increase in Aβ40 levels is correlated to a decrease in depressive symptoms as expected. It has been established that a low ratio of Aβ42/Aβ40 may reflect selective depletion of Aβ42 due to deposition in the growing plaques and subsequent AD pathology, while Aβ40 may have opposing effects on amyloid deposition and be neuroprotective. Our findings support the evidence that yoga can reduce stress, depression, and anxiety and may have an impact on peripheral AD biomarkers.
AI‐derived endophenotypes are causally associated with Alzheimer's disease
Authors: Wen Junhao , Toga Arthur W. , Davatzikos Christos
Published: January 2025

Background

Brain morphology changes due to both natural aging and various pathological conditions. We used magnetic resonance imaging (MRI) and artificial intelligence (AI) to derive three brain age gaps (Wen et al., 2023b) [gray matter (GM), white matter (WM), and functional connectivity (FC)‐BAG] for brain aging and 9 dimensional neuroimaging endophenotypes (Wen et al., 2023a) [DNE: Alzheimer's disease (AD)1‐2, autism spectrum disorder (ASD)1‐3, schizophrenia (SCZ)1‐2, and late‐life depression (LLD)1‐2) for disease heterogeneity (a.k.a., subtypes). We applied genome‐wide association study (GWAS) summary statistics of the 3 BAGs, 9 DNEs, and two AD case‐control studies (Lambert et al., 2013; Wightman et al., 2021) to decipher the potential causality between these AI‐derived endophenotypes and AD (Figure 1).

Method

We investigated whether the 3 BAGs and 9 DNEs (AD1‐2, ASD1‐3) were causally linked to AD using a bi‐directional two‐sample Mendelian randomization implemented in the TwoSampleMR R package (Hemani et al., 2018) with five different estimators. No individual data were used. The GWAS summary statistics of the 3 BAGs and 9 DNEs were performed using the UK Biobank data publicly available at https://labs.loni.usc.edu/medicine. The AD summary statistics are obtained at https://pgc.unc.edu/for‐researchers/download‐results/ for Wightman et al. and at https://gwas.mrcieu.ac.uk/ for Lambert et al., excluding the UK Biobank participants.

Result

We identified potential causal relationships from AD2, characterized by medial temporal lobe atrophy, to AD [P‐value=1.74x10‐4, OR (95% CI) = 1.25 (1.11, 1.40), number of SNPs=7], and AD to WM‐BAG [P‐value=7.18x10‐5, OR (95% CI) = 1.04 (1.02, 1.05), number of SNPs=13] (Figure 1). Regarding the latter, our sensitivity check indicated the absence of apparent outlier SNPs or horizontal pleiotropy (Verbanck et al., 2018) (Egger estimator intercept: ‐2.22x10‐3±3.87810‐3, P‐value=0.57). All five estimators demonstrated consistent causal effects. The funnel plot displayed no noticeable asymmetry. Most IVs exhibited positive effects on AD, with three showing a negative association. Additionally, leave‐one‐out analyses indicated that no single IV dominated this causal relationship (Figure 2).

Conclusion

This investigation revealed a causal association between two AI‐derived endophenotypes and AD. These endophenotypes could be used to identify individuals at high risk of developing AD and select populations in future AD clinical trials.
Identification of high‐performance blood‐based biomarkers for early screening and staging of Alzheimer’s disease by large‐scale plasma proteomic profiling in mild cognitive impairments
Authors: JIANG Yuanbing , Uhm Hyebin , Ip Fanny C. F. , Lo Ronnie M.N. , Cao Xiaoyun , Tan Clara M.C. , Law Brian C.H. , Kwok Timothy CY , Mok Vincent Chung Tong , Zetterberg Henrik , Fu Amy K.Y. , Ip Nancy Y.
Published: January 2025

Background

Early detection of Alzheimer's disease (AD), particularly during the mild cognitive impairment (MCI) stage, is crucial for effective intervention and treatment. However, existing diagnostic methods, through cognitive assessments, brain imaging, or cerebrospinal fluid profiling, are subjective, expensive or invasive. We previously showed that the plasma proteome is altered in AD, suggesting the feasibility of utilizing blood biomarkers for AD detection. Therefore, to develop a blood test for early screening and staging of AD, it is important to identify blood biomarkers associated with MCI/early AD and the features of AD progression.

Method

We conducted a comprehensive profiling of the plasma proteome of MCI by measuring 1,160 proteins in a Hong Kong Chinese cohort, to identify novel blood biomarkers for MCI/early AD. We further developed a biomarker panel based on the identified MCI/AD‐associated blood biomarkers and validated its performance in an independent amyloid‐PET‐defined cohort.

Result

We identified 496 proteins that were dysregulated in MCI plasma, and these proteins, involved in different biological processes, exhibited distinct dysregulating patterns with disease progression. We further categorized these proteins into different groups based on their dysregulating patterns. By performing co‐expression network analysis, we identified an 18‐protein panel that captures the profile changes of plasma proteome in MCI and AD. This panel accurately classified MCI (AUC = 0.913‐0.925) and AD (AUC = 0.970‐0.993) in two independent cohorts. Moreover, this panel correlates with cognitive decline and the development of Aβ pathology in the brain, which outperforms some of the existing plasma ATN biomarkers.

Conclusion

This study comprehensively profiled the MCI plasma proteome and demonstrates the feasibility of a blood‐based biomarker assay for early detection and staging of MCI and AD, potentially facilitating early screening, monitoring, and intervention in future clinical settings.
Development of a robust blood‐based multi‐pathway biomarker assay for early screening and classification of Alzheimer’s disease
Authors: Ouyang Li , JIANG Yuanbing , Uhm Hyebin , Ip Fanny C. F. , Lo Ronnie M.N. , Cheng Elaine Y.L. , Cao Xiaoyun , Tan Clara M.C. , Law Brian C.H. , Ortiz‐Romero Paula , Puig‐Pijoan Albert , Fernández‐Lebrero Aida , Contador José , Mok Kin Y , Hardy John A. , Kwok Timothy CY , Mok Vincent Chung Tong , Suárez‐Calvet Marc , Zetterberg Henrik , Fu Amy K.Y. , Ip Nancy Y.
Published: January 2025

Background

Alzheimer's disease (AD) is a devastating neurodegenerative disease with delayed diagnosis until the manifestation of symptoms. Although the emergence of blood‐based biomarkers offers hope for easy detection of AD, existing AD‐associated blood biomarkers, known as the “blood ATN biomarkers”, mainly capture the pathological hallmarks of AD, overlooking other AD‐associated biological processes such as inflammation and vascular dysfunctions. Therefore, developing a blood‐based biomarker assay that captures dysregulation beyond the ATN biomarkers may help advance early detection and staging of AD, enabling a comprehensive examination of the disease status

Method

We leveraged ultrasensitive proteomic technology to develop a blood‐based, multiplex biomarker assay for AD. This assay simultaneously measures the levels of 21 blood proteins associated with different biological pathways, including neurodegeneration, inflammation, innate immunity, vascular functions, and metabolic activities. Moreover, we developed an AD risk scoring system by integrating the level changes of these 21 proteins in a machine learning‐based model. The performance of this 21‐protein biomarker assay in AD classification and indication of AD‐related endophenotypes was evaluated in three independent cohorts

Result

We showed that this 21‐protein biomarker assay accurately classifies AD (AUC = 0.9407–0.9867) and mild cognitive impairment (MCI) (AUC = 0.8434–0.8945). It also indicates amyloid pathology in Chinese and European populations. Moreover, this assay simultaneously evaluates changes in five biological processes, providing comprehensive assessment of disease status and revealing heterogeneity of AD among individuals. Notably, dysregulations of biological processes upon AD progression are different between Chinese and European populations, particularly in biological pathways related to inflammation and vascular functions.

Conclusion

Our findings demonstrate the utility of a blood‐based multi‐pathway biomarker assay for early screening and staging of AD in clinical settings and provide insights for patient stratification and the development of precision medicine.
Association of Neuroticism Personality According to the Degree of Social Contact with Incident Dementia
Authors: Liu Yufei , Tang Yi , Chang Jie
Published: January 2025

Background

Personality traits, especially neuroticism, can influence susceptibility to dementia. Although social contact can mitigate stress and risk of dementia, the extent to which social contact can mitigate excess risk associated with neuroticism remains unclear. The objective of study was to investigate changes in neuroticism‐associated excess risk of dementia arising from different levels of social contact.

Method

This prospective cohort study examined 393939 UK Biobank participants assessed from 2006‐2010 and followed up until December 2022. Participants without dementia at baseline or the first 2‐year follow‐up, and with complete neuroticism and social contact data were included. Neuroticism was measured using the Revised Eysenck Personality Questionnaire, categorized into low and high neuroticism. Low, intermediate, or high social contact levels were assessed based on household size, contact with family or friends, and group participation. Dementia incidence (all‐cause dementia, Alzheimer’s disease [AD], and vascular dementia [VaD]) were determined using linked electronic health records. Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia risk, adjusted for multiple covariates.

Result

Among 393939 participants (mean [SD] age: 56.4 [8.1] years; 53.7% female), 6588 cases of all‐cause dementia were recorded over 13.7 years. High neuroticism was associated with increased all‐cause dementia risk (HR = 1.16, 95% CI = 1.10‐1.22) and cause‐specific dementia subtypes (AD: HR = 1.10, 95% CI = 1.02‐1.19; VaD: HR = 1.16, 95% CI = 1.05‐1.29). Among high neuroticism participants, excess risk of all‐cause dementia showed a stepwise decrease with increasing social contact (low contact: HR = 1.27, 95% CI = 1.15‐1.40; intermediate contact: HR = 1.20, 95% CI = 1.12‐1.28; high contact: HR = 1.07, 95% CI = 1.00‐1.15). High social contact similarly decreased excess risk of AD (HR = 1.06, 95% CI = 0.95‐1.17) and VaD (HR = 0.96, 95% CI = 0.82‐1.12), comparable to those with low neuroticism.

Conclusion

Enhanced social contact is associated with a stepwise reduction in dementia risk and may mitigate or potentially eliminate excess risk of dementia in individuals with high neuroticism, supporting social contact as a preventive strategy to reduce excess risks of dementia from neuroticism personality trait.
Characterization and Evaluation of Alpha‐Synuclein Aggregates: Unveiling Their Potential as a Biomarker for Parkinson's Disease (PD)
Authors: Debarnot Cecile , Challagundla Malleswari , Kleinert Christoph , Schulz Michael , Henn Claudia , Boehm Nils , Richter Mario
Published: January 2025

Background

Parkinson's disease (PD) is a debilitating condition that affects millions of people worldwide, yet there are currently no reliable biomarkers for its diagnosis. Alpha‐synuclein aggregation is a well‐known hallmark of PD pathology, but the behavior and kinetics of these aggregates are poorly understood. To address this gap in knowledge, this study utilized several approaches to evaluate the potential of alpha‐synuclein aggregates as potential biomarker for PD.

Method

Firstly, the aggregation behavior of alpha‐synuclein (aSyn) oligomers and fibrils was evaluated using a Real‐time quaking induced conversion (RT‐QuIC) assay. This assay differentiated PD from healthy samples in human skin, brain homogenates, and cerebrospinal fluid (CSF) samples. Secondly, a symmetric ECL assay was used to quantify alpha‐synuclein oligomers and fibrils. Finally, direct stochastic optical reconstruction microscopy (dSTORM) was utilized to visualize the size and shape of recombinant alpha‐synuclein fibrils and RT‐QuIC end products (fibrils) at high resolution.

Result

The results demonstrated that fast‐aggregating samples had higher concentrations of aSyn oligomers in skin and other samples compared to slow‐aggregating samples. Interestingly, human skin as a biological matrix showed a better and significant differentiation of healthy and PD samples, compared to brain or CSF indicating skin as a promising specimen for detecting alpha‐synuclein aggregation. Preliminary analysis of the average length and width of alpha‐synuclein aggregates showed promise, and further experiments with a larger sample size are required to prove whether different species of alpha‐synuclein fibrils/oligomers exist in healthy and disease samples.

Conclusion

These results provide a foundation for the continued investigation of alpha‐synuclein aggregation as a potential biomarker for PD.
Integrated Primary Care Model Reduces High‐Risk Medications for People Living with Dementia
Authors: Clevenger Carolyn K , Khakharia Anjali , Medders Laura J , Moore Miranda
Published: January 2025

Background

Harmful care including the prescribing of high‐risk and potentially inappropriate medications for older people is widespread among older adults, including people living with dementia (PLWD). Integrated Memory Care (IMC) is a comprehensive dementia care model where patients and their family caregivers access dementia‐sensitive geriatric primary care.

Methods

We conducted a retrospective observational study of adult patients of IMC, Cognitive Neurology (CN), and Primary Care (PC) clinics aged 65 and older with a diagnosis of dementia in 2019‐2021. We matched patients by age, gender and race and measured the hospitalization, rate of deprescribing and inappropriate screening test referrals using logistic regressions controlling for clinic. Additionally, we conducted a regression adjusted for state of illness (proxied by activities of daily living (ADL)) for the IMC and CN clinics.

Results

Overall, 509 patients seen in IMC were matched with 490 CN patients and 509 PC patients. Most patients were female and white and aged 70‐85. IMC patients had higher overall ADL scores than CN indicating more functional dependence.

IMC patients had higher odds of deprescribing high dose Antipsychotics (OR: 4.383, CI:1.405,13.677), benzodiazepines (OR: 3.338, CI: 1.541,7.231) and Opiates (OR: 1.004, CI: 0.415, 2.431) when compared to CN patients. After adjusting for ADL scores, the odds ratios were 4.952 (1.509,16.25), 3.434 (1.573, 7.494) and 0.991 (0.408, 2.404) respectively.

IMC also had higher odds of deprescribing high dose Antipsychotics (OR 5.538 CI: 1.21,25.359), benzodiazepines (2.632, CI: 1.297, 5.341) and Opiates (1.424, CI: 0.571, 3.55) when compared to PC patients.

Conclusions

Patients managed in a dementia‐sensitive primary care practice were deprescribed high‐risk medications after one‐year of management, reducing avoidable adverse events.
Community screening for dementia in Kenya: Lessons learnt from the DEM‐SKY program
Authors: Musyimi Christine W. , Ndetei David , Muyela Levi A. , Mutunga Elizabeth Kasimu , Masila Joe , Farina Nicolas
Published: January 2025

Background

The Integration and Evaluation of a Community‐Level Dementia Screening Programme in rural KenYa (DEM‐SKY) program, supported by the Davos Alzheimer’s Collaborative, leverages existing community resources to promote early detection of dementia among older adults and strengthen health system policy and practice in Kenya.

Methods

The DEM‐SKY program consisted of two key components: a training component and dementia screening component using then brief Community Screening Instrument for Dementia (brief‐CSID). The training component was divided into two stakeholder groups: Community Health Workers (CHWs) and hospital staff. Each group had different training needs to ensure the successful implementation of DEM‐SKY. Over a six‐month period, ten CHWs approached 3,546 older adults in Makueni County aged 60+ years to offer dementia screening. We adopted a process evaluation framework and used qualitative interviews to help identify factors that hampered or facilitated the successful adoption of dementia screening within the rural Kenyan context.

Results

Our findings revealed that 18% of older adults in rural Kenya have cognitive and functional impairment indicative of dementia, translating to over half a million older adults in Kenya. The DEM‐SKY program also illustrated the importance of collaborative partnerships with policy makers, health care providers and community members while encouraging a proactive approach in tackling challenges right from project conception. Through emerging themes and experiences, we also highlight opportunities that strengthened health care systems and promoted infrastructure readiness to address dementia care gaps during implementation of a novel dementia screening program in a low‐resource setting. These include use of existing community resources, community‐based participatory approaches and stigma‐reduction activities prior to program implementation.

Conclusion

The implementation of the DEM‐SKY program has been a landmark in early detection of dementia in Kenya. It forms the first community‐based dementia detection program implemented in rural Kenya with limited specialists and inadequate infrastructure, hence providing timely initiation of care cascade for individuals with cognitive and functional impairment. This program could be used to inform governments to drive innovations that promote early detection and healthy ageing; and invest in future development and implementation of treatment and support systems for older adults with dementia in low‐resource settings.
Accommodating cognitive screening: An implementation study protocol for occupational therapists supporting clients with vision and/or hearing impairments
Authors: Dumassais Shirley , Wittich Walter
Published: January 2025

Background

Occupational therapists (OTs) play a crucial role in rehabilitation, aiming to improve the lives of individuals with sensory impairment and an increased risk of cognitive decline. Despite being responsible for cognitive screenings on occasion, they have expressed limited confidence in performing these with their clients with visual and/or hearing impairments (VI/HI). To improve this situation, OTs should gain expertise in collaborative sensory rehabilitation. The primary aim of this multiphasic implementation study is to advance rehabilitation, particularly in occupational therapy, by enhancing the proficiency, knowledge, and skills of practicing clinicians when administering cognitive tests to individuals with sensory impairment(s).

Methods

This study employs a comprehensive five‐phase methodology, starting with (1) a scoping review to identify existing practices in the research context. Subsequently, (2) a clinical practice survey explores current approaches within the field of occupational therapy. (3) Interviews and focus groups with OTs provide further qualitative insights. Then, (4) educational training resources are developed, and (5) their efficacy is assessed in the final phase, ensuring their quality, application, and perpetuation.

Results

Presently, the first two phases of this project have been completed and the third phase is underway. In the scoping review, the identified common strategies s in the cognitive evaluation of older adults with dual sensory impairment (DSI) include expert team involvement, using visual‐free cognitive tests, modifying scoring procedures, and implementing communication and environmental strategies. In the survey, OTs indicated customizing accommodations for individuals with VI and/or HI. Strategies included encouraging the use of visual aids and adjusting lighting for VI, promoting hearing aids and controlling noise for HI, and employing diverse approaches for DSI, such as subjective screening and recommending assistive technology.

Conclusions

Building on evidence‐based research as well as current practices, the collaboration between specialists and clinicians will bridge the knowledge‐to‐practice gap in rehabilitation through accessible education. Empowering OTs with such knowledge in their practice has the potential to improve the process of cognitive screenings as well as healthcare outcomes.
Effect of early Alzheimer's disease plasma markers on Aβ deposition: Evidence from SILCODE
Authors: Yu Xianfeng , Zhou Xia , Shi Rong , Jiang Jiehui , Han Ying
Published: January 2025

Background

Previous studies have found that AD‐related plasma markers are associated with Aβ deposition, but the specific effects remain unclear.

Method

Data were obtained from the Longitudinal Study of Cognitive Decline in China (SILCODE). Comprehensive neuropsychological assessments, MRI, plasma samples, and amyloid positron‐emission tomography (Aβ‐PET) data were collected. Through the SUVR value calculation and Aβ stage classification, as well as the correlation analysis between plasma biomarkers and voxel /ROI SUVR values and clinical scale information, respectively, mediation analysis was used to study the possible pathways.

Result

This study involved 148 participants from Xuanwu Hospital in Beijing, including 66 cognitively normal (CN), 59 subjective cognitive decline (SCD), 12 MCI and 11 AD patients in this dataset. The proportion of CN and SCD in stage A0‐1 was the highest, while A2‐4 MCI and AD increased. Analysis of variance showed that except Aβ42/Aβ40, the other three (p‐tau181, GFAP and NfL) plasma biomarkers had differences between groups, and GFAP showed significant differences in each stage. Plasma p‐tau181 was significantly lower in stage A0 and A1 than in stage A2 and A3. Plasma GFAP at stage A0 was significantly lower than that at stages A1, A2, and A3, and at stage 1, it was significantly lower than that at stages A2 and A3. Plasma GFAP at stage A3 was significantly higher than that at stage A4. There were two pathways that showed significant fully mediated effects: in the PET SUVR‐ plasma p‐tau181‐MMSE score pathway, all four meta‐ROI SUVR showed fully mediated effects, while in the PET SUVR‐ plasma GFAP‐MMSE score pathway, with only 2 meta‐ROI SUVR values, stage A2 and stage A4 showed mediation effects.

Conclusion

The present study demonstrated the role of plasma in the early stage of AD, especially SCD, from the clinical diagnosis and Aβ stage dimensions. Studies have found that P‐tau181 has a good hint role throughout the course of AD, while GFAP may have a ceiling effect in the middle stage of AD and a significant hint role in the early and late stages of AD.
Cortical neurodegeneration influences annual posterior white matter hyperintensity progression
Authors: Moyano Jose Bernal , Menze Inga , Yakupov Renat , Peters Oliver , Priller Josef , Schneider Anja , Fliessbach Klaus , Wiltfang Jens , Jessen Frank , Buerger Katharina , Perneczky Robert , Teipel Stefan , Laske Christoph , Spottke Annika , Heneka Michael T. , Schreiber Stefanie , Düzel Emrah , Ziegler Gabriel
Published: January 2025

Background

For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussion about their coupled temporal dynamics (Garnier‐Crussard et al. 2023). Longitudinal evidence supporting this hypothesis remains nonetheless scarce (Ter Telgte et al. 2018).

We integrated surface‐based morphometry and bivariate latent change score modelling (BLCSM) to examine interrelationships between individual WMH and cortical thickness changes over a one‐year period in cognitively unimpaired participants.

Method

We analysed baseline and 12‐month follow‐up data from cognitively unimpaired DELCODE participants (n=393; median age 70.31 [IQR 66.06‐74.87] years; 52% females). We used T2w FLAIR and T1w MPRAGE data to segment WMH (LST; Schmidt and Wink 2019) and estimate cortical thicknesses (CAT12; Gaser et al., n.d.).

Using BLCSM in a vertex‐wise fashion, we tested whether baseline WMH volumes predicted cortical thinning rates and whether baseline cortical thickness predicted WMH volumes increases (Figure 1). Due to the posterior dominance of WMH in AD (Bernal et al. 2023), we focussed on parietal and occipital WMH. All models included age, sex, years of education, and total cardiovascular risk factors as covariates on baseline and change scores. We log‐10 transformed WMH volumes and corrected WMH volumes and thicknesses measurements for TICV via residualisation. We finally tested for moderation effects of CSF‐derived Aβ42/40 and pTau181 on cross‐domain coupling.

Result

BLCSM generally provided good data fits (RMSEA≤0.05, CFI≥0.095, SRMR≤0.05) across all analyses.

The mean thickness across precuneal and superiorparietal cortices at baseline predicted the progression of WMH better than any other cortical region (Figure 2B; βThick→ΔWMH=‐0.051, SE=0.011, Z=‐4.535, p‐value<0.001). This was especially evident with lower CSF‐derived Aβ42/40 (βThick*Aβ42/40→ΔWMH=0.176, SE=0.053, Z=3.309, p‐value=0.001).

WMH volume at baseline explained, in part, the level of thinning of parts of the fusiform cortex (Figure 2D; βWMH→ΔThick=‐0.139, SE=0.028, Z=‐5.030, p‐value<0.001). This interrelationship was moderated by CSF‐derived pTau181 (βWMH*pTau181→ΔThick=‐0.144, SE=0.053, Z=‐2.711, p‐value=0.007).

Conclusion

Cortical thinning and WMH progression may be mutually reinforcing processes that become reciprocally coupled prior to any detectable cognitive deficits. Hallmark AD proteins appear to moderate their interrelationships.
Brain‐based predictions of cardiovascular risk factors in midlife populations at risk of dementia
Authors: Cao Bolin , Deng Feng , Qi Qing , Dounavi Maria‐Eleni , Muniz‐Terrera Graciela , Malhotra Paresh , Koychev Ivan , O'Brien John T , Ritchie Craig , Lawlor Brian , Naci Lorina
Published: January 2025

Background

Dementia, particularly Alzheimer's disease (AD), is a significant public health concern, with midlife emerging as a critical period for preventive intervention (Livingston, 2017). Dementia's heterogeneity renders single risk factor insufficient for accurate identification of individuals at risk (Stephen, 2021). Multifactorial risk scores, such as the cardiovascular risk factors, aging, and dementia (CAIDE) score (Kivipelto, 2006), which include both cardiovascular (blood pressure, cholesterol, BMI, physical inactivity) and non‐modifiable factors (age, sex, APOE ε4 genotype), are vital in assessing dementia risk. This study, using the network‐based statistic (NBS)‐Predict model (Serin, 2021), aimed to explore the functional brain architecture associated with these risk factors, aiding in personalized prevention and intervention strategies for dementia.

Method

Resting‐state fMRI data, CAIDE, cardiovascular and non‐modifiable risk scores, and lifetime of experiences questionnaire (LEQ) data were analyzed from 585 healthy participants (females/males=207/378, mean age=50.9) in the PREVENT‐Dementia study (Ritchie, 2023). Using the Dosenbach atlas, functional connectivity (FC) matrices were constructed post‐data preprocessing. The NBS‐Predict model, employing a linear support vector machine with 10‐fold cross‐validation, feature selection at p<0.05, and 1000 permutations, predicted CAIDE, cardiovascular, and non‐modifiable risk scores (Figure 1). A hierarchical regression model assessed the impact of midlife LEQ score on FC linked to cardiovascular risk factors, with LEQ scores, age, sex, education years, and mean framewise displacement as independent variables.

Result

NBS‐Predict models significantly predicted the CAIDE (r=0.214, p<0.001), cardiovascular (r=0.201, p<0.001), and non‐modifiable (r=0.237, p<0.001) risk factors scores. Similar FC patterns were observed between the CAIDE and cardiovascular risk scores, particularly involving the somatomotor and cingulo‐opercular networks (Figure 2a), contrasting with distinct patterns for non‐modifiable risk factors. The non‐specific LEQ score positively correlated with FC in regions affected by cardiovascular risk factors (β=0.001, p=0.017).

Conclusion

The study demonstrated a significant overlap in FC patterns between CAIDE and cardiovascular risk factors in midlife, distinct from patterns associated with non‐modifiable risk. This suggested different neurobiological pathways influencing dementia risk in midlife, emphasizing the importance of personalized dementia prevention strategies. The findings highlighted the positive impact of an active and engaged lifestyle on brain health, reinforcing the need for early intervention targeting cardiovascular health for dementia risk reduction.
Genetic predisposition to clinical AD and AD pathology is differentially associated with baseline and 3‐year period change for specific AD‐related markers
Authors: Genius Patricia , Rodríguez‐Fernández Blanca , Shekari Mahnaz , Sánchez‐Benavides Gonzalo , López‐Martos David , Minguillon Carolina , Esteller Manel , Navarro Arcadi , Gispert Juan Domingo , Vilor‐Tejedor Natalia ,   for the ALFA study
Published: January 2025

Background

Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by early changes in brain structure and cognitive function before the age of onset. This study investigated whether the genetic load for clinical AD and AD pathology predicts AD‐related brain and cognitive changes over a 3‐year period, targeting the preclinical phase in cognitively unimpaired (CU) middle‐aged individuals.

Method

The sample of the study was defined by 429 CU middle‐aged participants at risk of AD from the ALFA+ nested cohort with available information on genetics, brain imaging markers and cognitive data [Table 1]. A subset of them had information at two‐time points (N=367) [Figure 1]. Genetic predisposition for clinical AD (PRSAD and PRSADnoAPOE) and AD pathology (PRSAβ42‐CSF and PRSpTau‐CSF) were calculated. We used linear regression models to assess the association between each PRS and global amyloid PET deposition expressed in Centiloids, AD Dickerson MRI‐signature, hippocampal volume and cognitive outcomes, at baseline and rate of change over visits after controlling for confounders. PET and MRI outcomes were defined as the annual rate of change. Cognitive outcomes were z‐scores of the two‐time points difference. Models were adjusted for time between visits.

Result

At baseline, higher genetic predisposition to clinical AD was associated with increased amyloid‐PET levels and higher average thickness of AD‐affected regions. Additionally, higher PRSAD was associated with reduced AD‐related cognitive performance and worse language [Figure 2]. Over the three‐year period, AD‐genetic load predicted higher annual amyloid accumulation in the brain, independently of APOE. Conversely, genetic predisposition to higher CSF Aβ42 levels predicted lower annual rate of change for Centiloids. PRSAD was also associated with annual reduction of hippocampal volume. Finally, genetic predisposition to AD beyond the APOE region was associated with executive functioning rate of change [Figure 2].

Conclusion

The results of this study showed the role of genetic predisposition to AD, affecting amyloid PET deposition, brain structure changes, and cognitive decline. These findings emphasized the importance of considering a comprehensive range of genetic markers in risk assessments for AD, particularly in its early stages, and highlight the potential of personalized genetic approaches to enhance predictions and interventions in the management of AD.
Greater subjective cognitive decline is associated with higher plasma Alzheimer’s disease biomarkers in cognitively normal Hispanics living in Miami, FL
Authors: Barker Warren W , Pinero Yaimara Gonzalez , Velasquez Karen , Gonzalez Joanna , Velez‐Uribe Idaly , Herrera Mileidys , Duara Ranjan , Salmon David P. , Galasko Douglas R. , Marquine Maria J. , Zlatar Zvinka
Published: January 2025

Background

Subjective cognitive decline (SCD), or a person’s perception of changes in their cognitive abilities, has been identified as a possible early marker of preclinical Alzheimer’s disease (AD) in non‐Hispanic Whites; however, research is lacking about the clinical utility of SCD in diverse populations. This study investigated the associations of self and informant reports of SCD, plasma biomarker profiles of AD, and objective cognitive performance in Hispanic older adults living in Miami.

Method

Hispanic participants enrolled in the 1Florida Alzheimer’s Disease Research Center who completed neuropsychological testing and blood draws for biomarker analysis were eligible. Plasma biomarkers included phosphorylated tau (p‐tau217 and p‐tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). The Subjective Cognitive Decline Questionnaire self (MyCog) and informant (TheirCog) versions were used to assess SCD. Cognitive tests included the Montreal Cognitive Assessment (MoCA) and the Craft story 21 verbatim immediate (Craft‐Im) and delayed recall (Craft‐Del). Relationships between plasma biomarkers, cognitive performance, and SCD were explored using Spearman's rank correlation, with an uncorrected p‐value of 0.05.

Result

The cohort included 52 Hispanics (age 73.3±7.3 years; education 15.2±3.0 years; 63% female; 96% from Cuba or South America) with a consensus diagnosis of cognitively normal (CN, n=17) or mild cognitive impairment (MCI, n=35). Among CN participants (Tables 1 and 2), greater MyCog scores were significantly associated with higher p‐tau217 (rs=0.68), p‐tau181 (rs=0.58) and lower MoCA scores (rs=‐0.48). Greater TheirCog scores were significantly associated with higher p‐tau181 (rs=0.58) and lower MoCA scores (rs=‐0.52). Among MCI participants (Tables 1 and 2), greater MyCog scores were associated with lower p‐tau181 (rs=‐0.37). There were significant correlations between various cognitive test scores and p‐tau217 (MoCA, rs=‐0.50; CraftIm, rs=‐0.44) and NfL (CraftIm, rs=‐0.34; CraftDel, rs=‐0.33).

Conclusion

Greater self and informant reported SCD are related to higher AD plasma biomarker load and worse cognition in a small sample of CN Hispanics, suggesting potential clinical utility. Self‐reported SCD was inversely related to plasma biomarkers in those with MCI, suggesting loss of insight. Larger and more diverse longitudinal studies are needed to elucidate if CN Hispanics with elevated SCD and AD plasma biomarkers progress to MCI and AD.