bluuebunny/crossref_metadata_2025 huggingface dataset:
NLRP3‐inflammasome inhibition by Leishmania‐derived factors in the neuropathogenesis of Alzheimer’s Disease (AD): assessing the molecular and therapeutic role
Authors: La Rosa Francesca , Varotto Ilaria , Epis Sara , Cattaneo Giulia , Saresella Marina , Marventano Ivana , Hernis Ambra , Bandi Claudio , Clerici Mario
Published: December 2023

Background

The hygiene hypothesis suggests that certain aspects of modern life are linked to lower rates of exposure to pathogens and lower immune‐system stimulation, being in turn positively related to Alzheimer’s‐disease (AD) risk. Amazonian tribes exhibit an exceptionally high prevalence of infections in individuals of all ages resulting in a better‐regulated degree of inflammation and improved cognitive functions after infection with the high parasite like Leishmanias (L). These findings suggest that a highly pathogenic environment and chronic infections might be favorable to shaping ever‐lasting immune responses, including against neurodegenerative conditions. Typical parasitic infections among indigenous included spp, protozoan parasites recognized by the same receptors that sense misfolded‐Aß in microglia; it is followed by subsequent regulation of the NLRP3, a cytosolic multiprotein complex mainly expressed in myeloid cells and composed of the Nod‐like receptor (NLR), the adaptor apoptosis‐associated speck‐like protein (ASC), and the pro‐caspase1, leading to the cleavage of bioactive IL1ß and IL18. Herein we investigated a possible connection between L tarantulae, nonpathogenic for humans, isolated from the lizards Tarentolae annularis and Tarentolae mauritanica to reduce IL1ß, IL18, Caspase1 release and ASC‐speck formation.

Method

in vitro model of THP1 wild‐type and ASC‐knockout derived‐Macrophage were cultured in unstimulated or Lypolisaccaride and Aß treatment post L tarantulae (Lt‐p10)(10 parasites/cell) infection. L phagocytosis were quantified by confocal mycroscopy, cytokines production by ELLA and ASC‐speck formation and NLRP3 by AMNIS FlowSight.

Result

ASC‐speck formation as well as IL18 and caspase1 were significant (p<0.05)downregulated in LPS+Aß macrophages wild‐type post L‐infection compare to unstimulated cells; no significant differences were found for: i)IL1ß production on supernatants of cells; and ii)NLRP3 florecent‐mean between cell wild‐type and ASC‐knockout.

Conclusion

L is able to modulate the immune response in vertebrates, suppressing the inflammatory response, and allowing the parasites to survive and replicate in phagocytic cells of our immune system, such as in macrophages. Given this ability, one can imagine exploiting this effect of damping immune response to ameliorate or cure those diseases in which inflammation plays a key role or it is one of the major drivers, such as AD.
Impact of Independent Review on Potential MMSE Score Inflation at Screening in AD trials
Authors: Echevarria Barbara , Welch Matthew , Negash Selam , Cunha Catarina , Veronika Cimermanova , Randolph Christopher
Published: December 2023

Background

The Mini‐Mental State Examination (MMSE) is widely used as a screening tool in Alzheimer’s Disease (AD) clinical trials. Screening score inflation is documented in clinical trials of depression and anxiety. We investigated whether score distributions on several multi‐site multinational AD trials showed truncated scores around MMSE inclusion criteria cut‐off, and whether Independent Review (IRev), where site assessments are reviewed by independent clinicians, is an effective methodology to mitigate inclusion bias.

Method

MMSE screening score distributions from several clinical trials of Early Symptomatic and Mild to Moderate AD were examined. To assess the impact of IRev on screening score distribution, we compared two studies with similar inclusion criteria (Early AD, MMSE ≥ 22; CDR GS = 0.5 or 1) one with no IRev and one with IRev via audio recording.

Result

MMSE screening frequency distributions showed a statistically significant difference between IRev and No‐IREV groups (p < 0.001). The distributions for the two groups were also compared using several score ranges around the threshold. Significant group differences were observed across the score ranges; 20‐24 (D = 0.099, p = 0.01), 19‐25 (D = 0.094, p = 0.002), and 18‐26 (D = 0.0987, p < 0001), suggesting a smaller inclusion bias around the threshold in the IRev group.

Conclusion

We observed that screening score inflation occurs in AD trials and Independent Review may be an effective strategy to reduce the number of subjects inappropriately enrolled in the study. IRev should be applied to assessments that fall around the required scored for study participation.
Associations among Drinking Water Quality, Dyslipidemia, and Cognitive Function for OlderAdults in China
Authors: Pan Xi
Published: December 2023

Background

Epidemiological evidence has shown that poor drinking water quality can lead to dyslipidemia, which might be associated with cognitive decline or lower domain‐specific cognitive function in older adults. Given the prevalence of water pollution, dyslipidemia, and dementia in China, it is important to examine the association between drinking water quality and cognitive function in older Chinese and to identify the direct and indirect effects of drinking water quality and dyslipidemia on their cognitive function.

Method

Primary data for the study were selected from China Health and Retirement Longitudinal Study (CHARLS, 2015) and 4,951 respondents aged 60 and above were included. Data on drinking water quality were selected from the 2015 prefectural water quality data from the Institute of Public and Environment Affairs in China. Mixed effects models were conducted to assess the associations of cognitive function with drinking water quality and dyslipidemia. The mediation effects of dyslipidemia were examined by path analyses.

Result

Exposure to high quality drinking water was significantly associated with higher scores in mental status, episodic memory, and global cognition (β = 0.34, p < 0.001 for mental status; β = 0.24, p < 0.05 for episodic memory; β = 0.58, p < 0.01 for global cognition). Respondents who reported dyslipidemia diagnosis had higher scores in the three composite measures of cognitive function (β = 0.39, p < 0.001 for mental status; β = 0.27 p < 0.05 for episodic memory; β = 0.66, p < 0.001 for global cognition). An elevated blood triglycerides was only associated with higher scores in mental status (β = 0.21, p < 0.05). Self‐reported dyslipidemia diagnosis was a suppressor, which increased the magnitude of the direct effect of drinking water quality on mental status, episodic memory, and global cognition.

Conclusion

Drinking water quality was associated with cognitive function in older Chinese and the relationship was independent of natural or socioeconomic variations in neighborhood environments. Improving drinking water quality could be a potential public health effort to delay the onset of cognitive impairment and prevent the dementia pandemic in older people.
NETS‐seq advances the understanding of neuronal vulnerability in AD progression facilitating the identification of novel therapeutic targets at the single cell type level
Authors: Bayraktar Gonca , Christie Louisa , Brice Nicola , Xu Xiao , Stirparo Giuliano , Lizio Marina , Powell Justin , Cadwalladr David , Cheung Toni , Sheardown Steven , Page Keith , Dawson Lee A , Carlton Mark
Published: December 2023

Background

Alzheimer’s Disease (AD) is a complex, heterogeneous, and multi‐factorial disease of predominantly the aging population. Throughout disease progression, different brain regions and cell types within each region show varying levels of resilience to ongoing disease pathology. A better understanding of the biological properties of different cell types and an integrated analysis approach that incorporates information about the interplay between cell type vulnerability, pathological deposits, and inflammatory signatures are required for the development of novel therapeutics that delay the onset or slow the progression of AD.

Method

Cerevance has developed a proprietary Nuclear Enriched Transcript Sort sequencing (NETS‐seq) method that provides deep molecular insight into the dynamics of the brains of early‐stage AD, late‐stage AD, and non‐neurodegenerative age‐matched control donors at the individual cell type level. Machine learning methodologies based on gene expression were employed to stratify donors across the disease continuum and to identify gene changes associated with disease progression.

Result

NETS‐seq enabled us to profile more than a dozen distinct cortical cell types. These data show that many known AD risk genes, as well as many lesser described genes, change in expression in disease. We have also used pseudotime trajectory analysis to rank donors across disease progression from control to early‐ and late‐stage AD. Comparisons made across different cell types within the same brain region and the same cell types from different brain regions, have identified genes that may be contributing to AD progression at different stages of disease. These genes may contribute to ongoing neuronal vulnerability.

Conclusion

We have produced highly reproducible molecular profiles from neuronal (and glial) cell types from the human brain and demonstrated that many genes are specifically expressed in cortical neuronal subtypes and change across the AD disease continuum. Identifying changes in the transcriptomic signatures of vulnerable neuronal populations at different stages of disease has enabled the identification and selection of novel targets for AD drug discovery.
Modulation of the Immunoproteasome Affects Pathological Tau Aggregation in Alzheimer’s Disease
Authors: Nashman Zarrar , Runyan Avery , Sydney Eric , Myeku Natura
Published: December 2023

Background

The Immunoproteasome is a dynamic system found in microglia that is induced under inflammatory conditions and previously hypothesized to be causative of neurodegenerative disorders like Alzheimer’s Disease.

Method

Mice with immunoproteasome deficiency (LMPPS) and mice with intact immunoproteasome (PS19) were analyzed for AD progression through total tau aggregation and microglia activity. Primary microglia were extracted from normal and LMPKO mouse strains and their total engulfment of tau‐aggregate containing cells were compared.

Result

LMPPS mice had significantly higher mean aggregation of tau compared to PS19 mice. LMPPS mice also showed a significantly increased activation of microglia and a slightly increased number of total microglia compared to PS19 mice. In‐vitro results showed increased total engulfment of tau‐aggregate containing cells for LMPKO microglia but statistically insignificant difference when comparing proportion of engulfing microglia.

Conclusion

To our knowledge, our results are the first to show that the immunoproteasome is neuroprotective against tauopathies like Alzheimer’s Disease in mice.
Pathways explaining racial/ethnic and socio‐economic disparities in dementia incidence: The UK Biobank Study
Authors: Beydoun May A , Beydoun Hind A. , Fanelli‐Kuczmarski Marie T. , Weiss Jordan , Georgescu Michael , Meirelles Osorio , Lyall Donald M , Evans Michele K , Zonderman Alan B
Published: December 2023

Background

Pathways explaining racial/ethnic disparities in dementia risk are under‐evaluated.

Method

We examine those disparities and their related pathways among UK biobank study respondents (50‐74y, N = 323,483; 3.6% non‐White minorities) using a series of Cox proportional hazards and generalized structural equations models (GSEM).

Result

After ≤15 years, 5,491 all‐cause dementia cases were diagnosed. Minority status increased dementia risk by 24% (HR = 1.24, 95% CI: 1.07‐1.45, P = 0.005), an association attenuated by socio‐economic status (SES), (HR = 1.12, 95% CI: 0.96‐1.31). Total race‐dementia effect was mediated through both SES and Life’s essential 8 lifestyle sub‐score (LE8LIFESTYLE), combining diet, smoking, physical activity, and sleep factors. SES was inversely related to dementia risk (HR = 0.69, 95% CI: 0.67, 0.72, P<0.001). Pathways explaining excess dementia risk among minorities included ‘RACE_ETHN(‐)→SES(‐)→◊ DEMENTIA’, ‘RACE_ETHN(‐)→ SES(‐)→ COGN(+)→ DEMENTIA’ and ‘RACE_ETHN(‐)→SES(+)→ LE8LIFESTYLE(‐)→`DEMENTIA’, with SES reflecting higher socio‐economic status, COGN reflecting poorer cognitive performance and LE8LIFESTYLE reflecting better cardiovascular health, specifically lifestyle factors, with higher scores. RACE_ETHN is the Non‐White minority vs. White contrast.

Conclusion

Pending future interventions, lifestyle factors including diet, smoking, physical activity and sleep are crucial for reducing racial and socio‐economic disparities in dementia.
Finance management and inequalities in care spending in dementia since the COVID‐19 pandemic
Authors: Giebel Clarissa , Halpin Kath , O'Connell Lena , Carton Joan
Published: December 2023

Background

The ability to manage finances is one of the first daily activities to deteriorate in dementia. With finance tasks having gone even more remotely and digitalised since the pandemic, the aim of this qualitative interview study was to explore how finance management and spending habits of people with dementia living in the community may have been affected by the pandemic.

Method

We remotely interviewed 30 unpaid carers and people with dementia across the UK from February to May 2022 about their experiences of managing finances and spending habit changes during the pandemic. The topic guide was co‐developed with two unpaid carers. Data were analysed using inductive thematic analysis.

Result

The pandemic fast‐tracked the digitalisation of finance management tasks for people with dementia, which caused inequalities for many who were unfamiliar with digital formats. This necessitated further involvement of unpaid family carers in all aspects of finance management on behalf of the person living with dementia, leading to increased caring duties on top of existing tasks. Navigating the legalities surrounding financing care for dementia was similarly found to be characterised by barriers for most, with those from more socio‐economically disadvantaged backgrounds receiving less help to source financial support.

Conclusion

Support needs to be in place for people with dementia to manage their finances digitally, whilst carers need to be provided with clear guidance and support in how to navigate this daily activity. Legal arrangements with banks and other organisations should be in place as soon as possible to enable equitable support with this key daily activity.
Exploring Social Engagement in a Virtual Participatory Culinary Nutrition Education Intervention for Dementia Prevention
Authors: Beitel JulieAnne E , O'Connell Megan E , Lieffers Jessica , Lawson Karen , Cammer Allison
Published: December 2023

Background

Providing nutrition education through participatory cooking programs is a strategy to support adoption of healthy eating practices for dementia risk reduction. Social engagement, a modifiable risk factor for dementia, is an important feature of in‐person culinary interventions; few recommendations exist for virtual delivery. We aimed to examine participant social engagement within ‘The Cognitive Kitchen: Virtual Culinary Intervention for Dementia Prevention’.

Method

A six‐week virtual nutrition education and applied cooking class was delivered to two groups of 10 older adult participants. Two Registered Dietitians led discussions and cooking demonstrations focused on dementia risk reduction. Participants were invited to cook during sessions or prepare the recipes at their convenience. The study was guided by Interpretive Description methodology. Data included facilitator session notes, participant weekly virtual journal entries, two virtual focus group discussions, and individual interviews with 15 participants. The Positive emotion, Engagement, Relationships, Meaning, and Accomplishments (PERMA) model of well‐being helped structure thematic analysis examining participants’ experiences in the program and the function of social interaction.

Result

Participants appreciated the flexibility of the virtual setting and very few technical issues were observed. Thematic analysis revealed commonalities among participants’ experiences, including enjoyment of learning about creative ingredient transformation, enhanced accountability for meal preparation, and an appreciation for cooking as a social activity. Many participants recorded notes about meal preparation practices shared by other group members, and some participated in virtual recipe‐sharing, suggesting peer learning was a valuable component. Though the virtual program could not include casual social contact that would normally occur in an in‐person program, participants appreciated discussion questions to encourage social interaction. However, some found that cooking along with the demonstration limited their ability to learn and socialize.

Conclusion

Benefits to virtual delivery of a participatory cooking program include ability to expand program reach and reduced barriers to participation (e.g., travel, inclement weather, time). These considerations may be even more relevant for older adult care partners of persons with dementia. However, some elements of in‐person participation that foster social engagement are challenging to replicate virtually; additional effort by facilitators is required to ensure this important program component is maintained.
Incorporating clinical trial outcomes in health economic evaluations of disease‐modifying therapies for AD
Authors: Jönsson Linus , Gustavsson Anders , Handels Ron
Published: December 2023

Background

Evidence on cost‐effectiveness of novel therapies for Alzheimer’s disease (AD) is of increasing importance for patient access. Challenges involved in implementing treatment effects in health economic (HE) models is an important source of uncertainty around the value of new AD therapies. HE models are developed from observational studies that often include different patient populations and different endpoints and scales from clinical trials.

Methods

The International Pharmacoeconomic Collaboration on Alzheimer’s Disease (IPECAD) conducted a series of workshops with research groups developing HE models in AD, to systematically characterize methodological approaches to modelling and benchmark results from these models in standardized scenarios. We reviewed published models and contrasted the characteristics of these models with study design specifications of recent late‐stage clinical trials of AD DMT to highlight potential issues with incorporating efficacy data from clinical trials in existing HE models. Identified issues included: need for mapping between different scales used to assess cognition, function and other efficacy domains, incorporating effects on multiple domains, differences in trial populations and expected patient populations treated in routine care, and statistical methods for generating efficacy estimates for use in HE models.

Results

Three options were identified for translating trial efficacy estimates into HE models: 1) use actual trial data and model disease course post trial, 2) assume treatment reduces transition probabilities to more severe states, and 3) implement treatment effect as a proportional reduction of progression on the time scale.

Conclusions

The design of future clinical trials of DMT need to take into account the need to generate data to populate HE models. Pre‐specifying analyses of trial data for HE modeling purposes can reduce uncertainty and improve confidence in results.
Discriminant Validity and Time‐effectiveness of A Stepwise Dementia Case‐finding Approach in an Asian Elderly Community
Authors: Xu Xin , Chen Christopher , Yu Cheng Ching‐ , Venketasubramanian Narayanaswamy , Yuan Changzheng
Published: December 2023

Background

To investigate the discriminant validity and time‐effectiveness of a stepwise dementia case‐finding approach in a community‐based Singaporean older adult population.

Method

Participants who completed the Progressive Forgetfulness Question (PFQ) and the Abbreviated Mental Test (AMT) were invited to phase II and administered the Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and a formal neuropsychological battery. Participants were diagnosed by cognitive performance and DSM‐IV criteria into No Cognitive Impairment (NCI), Cognitive Impairment‐No Dementia (CIND) mild (≤2 cognitive domains impaired), CIND moderate (>2 domains impaired) and dementia. Receiver Operating Characteristic were conducted for different cognitive instruments (AMT, MoCA, MMSE) between PFQ = Yes and PFQ = No groups. All discriminant indices including sensitivity, specificity, positive (PPV), negative predictive values (NPV) and accuracy were calculated. Bayesian correction methods were used to adjust the verification bias. Screening time saving and number of subjects further evaluated was estimated in two scenarios with or without the PFQ.

Result

The PFQ showed an NPV of 94.2% for excluding dementia‐free cases after adjustment. After excluding PFQ = No participants, all cognitive tools achieved optimal NPV (>99%). Furthermore, the number of people requiring further evaluation decreased by 129 (42.7%), 58 (36.5%), 25 (14.3%) subjects, corresponding to 48.2%, 48.2%, and 47.8% of screening time being saved, when the PFQ was conducted prior to the MoCA, MMSE, and AMT, respectively.

Conclusion

Using a single‐question assessment as the first step of a case‐finding approach, followed up a cognitive test such as the MoCA, could minimize time and resources for further investigation in the community.
REMIND – a novel “Music‐Movement‐Mind” intervention for the prevention of dementia
Authors: Podolski Odile Sophie , Nicotra Angela , Köbe Theresa , Cardona Maria Isabel , Cornaro Clara , Koch Sabine , Wirth Miranka
Published: December 2023

Background

Lifestyle‐based motor, sensory and cognitive enrichment can target several health risk factors in the older populations by improving psychosocial, cognitive and physical (dys)function1,2. Based on these findings, we developed a novel intervention called REMIND (An Envi
r
onmental
E
nrich
m
ent
I
ntervention to Preve
n
t
D
ementia) for the promotion of healthy aging. REMIND uses dance movement therapy (DMT) and Tango Sistema Dinzel© to integrate enriching activities based on music, movement and mind into a multimodal program.

Objective

To present the REMIND program and feasibility check of the telehealth adaptation.

Methods

The intervention was developed and manualized in collaboration with neuropsychologists, neuroscientists and DMT specialists. Several modes of training are employed throughout the program, consisting of the three core components “Music, Movement, and Mind”. These core components are practiced simultaneously using facilitator‐guided exercises, each consisting of motor, sensory, cognitive, emotional, and social stimulations with increasing complexity. As such REMIND enables multimodal enrichment with the goal to improve cognitive and mental health of older adults by activating beneficial brain plasticity. The adaptation of the program into the telehealth setting was assessed qualitatively in four online expert sessions for feasibility.

Results

The REMIND program is published as an open access manual (doi.org/10.30819/5504) targeting the older population3. Through the simultaneous combination of motor (Movement), sensory (Music), and mental (Mind) stimulations, REMIND promotes enrichment of the body and mind. In the telehealth setting, the multimodal exercises are best practiced via an interactive video‐conference platform, adapted to the needs of older people, using small groups (n = 4‐8) and guidance of a trained facilitator. Break‐out groups, feedback rounds, and joined participation of family members are used to enhance and sustain inter‐personal contact and positive learning experiences in the digital environment. Supplementary on‐site sessions can facilitate social integration and participation.

Conclusion

The REMIND program provides a low‐threshold prevention and early intervention tool that is accessible to the target group and health care system. Adaptation to the telehealth setting is cost‐effective, adaptable to individual needs and can be integrated into everyday life. A proof‐of‐concept study will evaluate feasibility and effectiveness of the REMIND program to promote psychosocial, cognitive and physical wellbeing in older adults.
Association of baseline dementia stage with cognitive markers during follow‐up in patients with dementia of Alzheimer type with and without post‐mortem Alzheimer pathology
Authors: Rosen Jurij , Jessen Frank
Published: December 2023

Background

Prediction of the course of cognitive function is of central importance in the care of patients with dementia of Alzheimer type (DAT) for individual management, counseling and treatment. Baseline clinical examination and cognitive function testing are decisive in the classification of the dementia type and stage, but their predictive value to foresee the future course of the disease is critical. This project aims to examine the relationship of baseline dementia stage and Alzheimer’s disease neuropathological changes (ADNC) at autopsy with cognitive function during the course of the disease.

Method

This study is based on longitudinal data from The National Alzheimer‘s Coordinating Center (NACC)‐Uniform and Neuropathology Data Set. Participants were retrospectively included based on the following criteria: Clinical diagnosis of DAT, cognitive function testing by Mini‐Mental State Examination (MMSE), and report of ADNC at autopsy (ABC score). Baseline dementia stages were defined by the MMSE score (≥27/20‐26/10‐19/≤9). Neuropathological diagnosis of Alzheimer’s disease was defined by ABC score levels “High” or “Intermediate” (confirmed‐ADNC) as opposed to ABC score levels “Low” or “Not” (no‐ADNC).

Result

Of 44,359 participants, 1,469 met inclusion criteria with 5,649 cognitive data points (i. e., on average 4.6±1.9 MMSE scores/participant). At baseline, 33%/49%/16%/2% of participants were assigned MMSE ranges of ≥27/20‐26/10‐19/≤9 respectively. The proportion of confirmed‐ADNC within the respective groups increased as a function of the baseline MMSE range (76%/90%/95%/96% respectively). Cognitive function changes from baseline to last visit depended on the neuropathological diagnosis (‐7 vs. ‐4 MMSE score points for confirmed‐ADNC vs. no‐ADNC respectively), but not on MMSE score at baseline (all ‐7 score points). Participants with a baseline MMSE score ≤9 decreased even less (‐3 score points).

Conclusion

The present descriptive analysis does not provide evidence for a clear association of cognitive function decline during follow‐up and baseline MMSE scores, in contrast to ADNC which predicted faster decline, in patients with DAT. Modelling analyses including covariates will be presented.
Development of a triage algorithm for mild cognitive impairment using electronic health record data
Authors: Li Gang , Batrla Richard , Betts Keith A. , DeSanti Susan , Frech Feride H , Galvin James E , Halpern Rachel , Juday Timothy , Toschi Nicola , Vandercappellen Jo , Mattke Soeren , Hampel Harald
Published: December 2023

Background

Timely detection and diagnosis of early‐stage Alzheimer’s disease (AD) become increasingly relevant with the introduction of new therapies. Electronic health records (EHR) data present an opportunity to identify cases with elevated risk of undiagnosed cognitive impairment and triage them for further evaluation. Such triage tools are critically important because population‐based screening of asymptomatic individuals is currently not recommended, but spontaneous detection rates are low. We previously developed a risk prediction algorithm to identify likely cases aged ≥50 years based on claims data.

Method

We will build on this work and develop an algorithm based on three data sources: claims, EHR data and the National Alzheimer’s Coordinating Centers (NACC) data. The claims database study, already completed, included newly‐diagnosed mild cognitive impairment (MCI) individuals and non‐MCI individual matched on age, gender and geographic region. Using data 2 years prior to diagnosis, medical conditions associated with MCI were used to build a predictive model. The EHR study will aim to augment the model with clinical data such as body mass index, smoking status, vital signs and laboratory results. The NACC study, including ∼5,400 MCI and ∼15,800 cognitively normal (CN) individuals, will be used to validate the algorithm.

Result

The claims database study identified 25 medical conditions that predict MCI risk (area under the curve, AUC = 0.78). The top five predictors for MCI were depression, stroke/transient ischemic attack, obstructive sleep apnea, hyperlipidemia, and hypertension. The predictive performance was better in the 50‐64 year than in the older age groups. Analyses of the EHR and NACC data are ongoing.

Conclusion

Data routinely collected in claims and EHR may be accurate enough to triage individuals with potential MCI for cognitive assessment in primary care.
Deep Learning for EEG‐Based Alzheimer’s Disease Diagnosis
Authors: Zhang Xiang , Wang Yihe , Chandak Payal , He Zihuai
Published: December 2023

Background

Electroencephalography (EEG) could be a powerful tool to diagnose Alzheimer’s Disease (AD) because it is pervasive, non‐invasive, and cost‐effective [1]. However, EEG‐based AD detection has suffered from poor performance and low generalizability due to the noisy nature of the signal and high inter‐patient variability. Here, we show that emerging deep learning techniques can alleviate these challenges and pave the way for the clinical use of EEG in AD detection.

Method

We formulate the problem of EEG‐based AD detection as a binary classification task. We propose an end‐to‐end deep neural network that utilizes contrastive representation learning to automatically learn low‐dimensional features from EEG trials. These features are then fed into a non‐linear classifier that predicts the probability of AD.

Result

We evaluated the model on a public dataset comprising 23 subjects (12 AD; 11 control) that have 663 trials in total [2]. (1) Patient‐dependent setup. In line with existing work in EEG‐based AD detection, we randomly assigned 80% of trials for training and the remaining 20% for tests, where the same patient could have trials in both groups. Our model achieved an F1 score of 99.35% which is competitive with, if not superior to, the state‐of‐the‐art baselines. (2) Patient‐independent setup. We then investigate a more challenging setup, where trials from a particular patient were assigned either to training (19 subjects) or to testing (4 subjects). The deep learning system is evaluated on patients it has not encountered before. Our model attains an F1 score of 86.45%, outperforming baselines by a significant margin (>20%).

Conclusion

Our results demonstrate that our deep learning model significantly improves the accuracy of EEG‐based AD diagnosis. In particular, our model sets the state‐of‐the‐art performance in the patient‐independent evaluation. This suggests that our model can learn a distinctive pattern of AD from a small group of subjects and apply it to unseen individuals: which is indispensable for real‐world deployment.

[1] Tait, X. et al. Eeg Microstate Complexity for Aiding Early Diagnosis of Alzheimer’s Disease. Scientific Reports, 2020.

[2] K. Smith, et al. Accounting for the Complex Hierarchical Topology of Eeg Phase‐Based Functional Connectivity in Network Binarisation. PloS One, 2017.
Examining the Interactive Effect of Cardiovascular Risk Factors and APOE Genotype on Population Health Disparities in dementia risk
Authors: Andrews Shea J , Renton Alan E. , Fulton‐Howard Brian , Brenowitz Willa D , Van Hulle Carol A. , Li Clara , Yaffe Kristine
Published: December 2023

Background

There is a need to better understand the role of modifiable risk factors in the development of racial/ethnic health disparities in Alzheimer’s disease (AD). In particular, research is lacking on how clinical risk scores may interact with genetic liability for dementia in diverse populations. Here, we examined the influence of the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Score (CAIDE) and APOE genotype on MCI/Dementia risk in non‐Latinx White (NLW), Black, and Latinx populations.

Method

Participants were from the National Alzheimer’s Coordinating Center Uniform Dataset who self‐reported as NLW (n = 15,296), Black (n = 2,136), or Latinx (n = 955) who were either cognitively normal or had a clinical diagnosis of MCI/Dementia at baseline (Table 1). CAIDE is comprised of age, gender, years of education, hypertension, obesity, and hypercholesteremia with scores ranging from 0‐14. Logistic regression models stratified by race/ethnicity were used to examine the association between CAIDE, APOE genotype, or their combination (9 categories combining favorable, intermediate, and unfavorable CAIDE scores with APOE e3/e3, e2+, and e4+) on MCI/dementia (Fig. 1‐2). Population differences were determined using Fisher’s z‐score method.

Results

APOE e2+ was associated with reduced odds of MCI/dementia in NLW participants, while APOE e4+ was associated with increased risk in Latinx, Black, and NLW participants. Higher CAIDE scores were associated with increased risk of MCI/dementia in Latinx and NLW but were non‐significant in Black participants. The association of CAIDE on MCI/dementia in Black participants was significantly different from that in NLW and Latinx participants. Similarly, the effect of APOE e4+ on the risk of MCI/dementia was weaker in Latinx compared to NLW participants. In NLW, increasingly unfavorable modifiable risk profiles attenuated the protective effect of APOE e2+ and accentuated the deleterious impact of APOE e4+ on MCI/dementia. In Black participants, modifiable risk factors did not significantly affect the relationship between APOE genotype and MCI/dementia; in Latinx participants, there was only a moderate effect.

Conclusion

The risk associated with APOE on MCI/Dementia is moderated by modifiable risk factors with suggestive population‐specific effects. Addressing health disparities will require risk scores that combine clinical, genetic, and social determinants of health and are applicable across diverse populations.
Impact of Multivitamin‐Mineral and Cocoa Extract on Incidence of Mild Cognitive Impairment and Dementia: Results from the Cocoa Supplement and Multivitamin Outcomes Study for the Mind COSMOS‐Mind
Authors: Rapp Stephen R. , Sachs Bonnie C. , Williams Benjamin J. , Gaussoin Sarah A. , Baker Laura D , Manson JoAnn E. , Sesso Howard D. , Shumaker Sally A. , Espeland Mark A. ,   COSMOS‐Mind Research Group
Published: December 2023

Background

COSMOS‐Mind, a large, randomized placebo‐controlled pragmatic trial in older adults, recently reported that daily supplementation with multivitamin‐mineral, but not cocoa extract, benefited global cognition. We assessed effects of these supplements on prespecified secondary outcomes of mild cognitive impairment (MCI) and all‐cause dementia (DM). We also assessed treatment‐related cognitive trajectories leading to conversion to MCI or dementia.

Method

COSMOS‐Mind (N = 2262) administered a telephone‐based cognitive battery at baseline and annually for 3 years. Proxies of participants meeting criteria for suspected cognitive impairment based on a cognitive screener (TICSm) were interviewed. An expert panel adjudicated cognitive status. Incidence rates of MCI, and separately DM, were compared among arms with proportional hazards regression. Changes in cognitive trajectories leading to MCI and DM were assessed with linear models.

Result

At baseline, adjudication for suspected cognitive impairment was triggered for 419 (20%) participants, yielding adjudications of 217 (10%) MCI and 4 (0.2%) DM cases. During follow‐up, triggers were less frequent in the MVM than placebo arms: hazard ratio = 0.73 (p = 0.04). Across 3 years, 110 incident MCI and 14 incident DM cases were adjudicated. Incidence rates of these outcomes did not vary by assignment to multivitamin‐mineral or cocoa extract (all p≥0.05), however statistical power was low. Incident MCI was associated with a marked decline in cognitive function from the previous year (p<0.001). When participants assigned to multivitamin‐mineral versus placebo converted to MCI, their scores for global cognition (p = 0.03) and executive function (p<0.001) were higher and had declined less relative to the previous year (p = 0.03 for global cognition; p = 0.004 for executive function). Daily cocoa extract use did not attenuate cognitive decline leading up to MCI.

Conclusion

COSMOS‐Mind does not provide evidence that cocoa extract or multivitamin‐mineral therapy lowers risk of incident MCI or DM. Multivitamin‐mineral therapy, but not cocoa extract, may provide cognitive resilience countering conversion to MCI.
Age in Place, Move in VR: Investigating the Feasibility and Usability of a Custom‐made Virtual Reality Exergame to Promote the Well‐being of Community‐Dwelling Older Adults
Authors: Mehrabi Samira , Basharat Aysha , Mazen Sarah , Cao Shi , Boger Jennifer , Barnett‐Cowan Michael , Muñoz John , Middleton Laura E
Published: December 2023

Background

Interactive virtual reality (VR) games combined with exercise (exergames) are a plausible strategy to encourage physical activity (PA) among older adults. However, there is little systematic evaluation of the feasibility, usability, and potential benefits of deploying at‐home VR exergames among this population.

Method

Fifteen community‐dwelling older adults (M = 67.33 ± 5.3, age range 60‐77) (Table1) were recruited to play 18 sessions (each 15‐20 min) of a custom‐made VR exergame at home over six weeks. Recruitment, retention, and adherence rates were calculated to determine feasibility. The usability of the exergame was assessed through i) a game user experience questionnaire, ii) a self‐reported physical/emotional discomfort questionnaire, and iii) a perceived enjoyment scale. The exploratory outcome measures included changes in i) PA, ii) exercise self‐efficacy, iii) affect, iv) various cognitive and perceptual tasks and were assessed i) before and after acute data, and ii) before and after the intervention.

Result

Thirteen participants completed the study (13% attrition rate) without missing any exergaming session (100% adherence rate). The completion rate of cognitive assessments, perceptual tasks, and self‐reported questionnaires was ≥ 97%. Low levels of cybersickness were reported (M = 0.9 ±1.0 out of 10). The average perceived enjoyment and perceived rate of exertion were 3.2. ±1.1 (out of 5) and 2.4±1.9 (out of 10), respectively. Most of the participants (92.3%) found the exergame’s instructions easy to follow and had an overall positive experience (84.6%). Whereas the exergame was perceived as useful for increasing PA levels (61.6%), mood enhancement was reported among less than half of participants (46.2%) and only 38% indicated that they would choose VR exergaming for at‐home PA. The likelihood of playing VR exergames in the future was also low (38.5%). The exploratory outcome measures are presented in Table 2.

Conclusion

Our study provides insights into the feasibility and usability of a custom‐made VR exergaming intervention to promote PA in community‐dwelling older adults which may potentially benefit their well‐being. Our findings inform the future adoption of VR at home. Our results can also be used to inform large‐scale trials and support the design and deployment of other remote exergames and assessments.
Patient‐Public Involvement (PPI) in Dementia Trials Ireland (DTI): A network to increase capacity and capability to deliver clinical trials for dementia in Ireland
Authors: Leroi Iracema , Miller Anne‐Marie
Published: December 2023

Background

Dementia Trials Ireland (DTI) is a newly developed national network to increase capacity and capability to deliver clinical trials for dementia in Ireland. DTI activities are informed by a panel of people with lived experience of dementia and their care partners, following principles of 'patient and public involvement and engagement (PPIE).

Method

People with lived experience of dementia joined the DTI panel to provide consultation on the design and conduct of industry‐sponsored and investigator‐led clinical trials, providing insight into the lived experience of dementia. Monthly meetings and consultation workshops enable panel members to provide feedback to the DTI trial teams.

Result

Thirteen PPI panel members represented lived and care partner experience of FTD, AD, LBD, VaD have informed the following DTI network activities: (1) Advising on appropriate language use for trial Participant Information Sheets; (2) Co‐developing the logo for DTI; (3) Advising on our website and video content; (4) Representing DTI at online conferences and workshops; and (5) Providing researchers and clinicians with feedback on the lay summaries of scientific papers.

Conclusion

The panel has made meaningful changes to various outputs and activities of the trials' network, ensuring that the perspectives of people with lived or caregiver experience of dementia are included.
Resource utilization for pre‐screening study patients with cognitive disorders.
Authors: Gervais Pierre
Published: December 2023

Background

Drug development is a complex, expensive, lengthy, and multifaceted process. Patient recruitment tends to be a considerable and underestimated variable when it comes to planning and implementing a study. More information about evaluating patient sources and resource allocation will allow sites and sponsors to use their resources more effectively and to complete clinical projects earlier.

Method

This paper reviews the sourcing of patients and resource utilisation in hours for 6 pivotal Cognitive Disorder studies by gathering all patients contacted in various phases of a project: pre‐screening, screening, and randomization.

Result

Sourcing of patients was tracked for pre‐screening, screening and randomisation and are compared in number of calls, resource utilisation (hours), and number of randomized patients

A total of 1 726 patients were pre‐screened, which represents 575 hours of resources, the largest proportion of pre‐screened calls, 43%, was generated from internal database of patients resulting in 46% of randomized patients.

The second largest proportion of pre‐screened patients originated from newspapers with 18% of contacts that required 13% of resources and resulted in 14% of randomized patients.

Additional sources of pre‐screened calls were conferences (8%), canvassing (7%), friends (4%), medical references (3%), memory day (9%), radio (2%) and web site (2%).

Conclusion

We report a pre‐screened/screened/randomized ratio of 23:5:1 indicating that pre‐screening is important to secure patient enrolment though largely underestimated and rarely if ever accounted for in budget assessments. Given the current decline in the use of paper media, alternate solutions must be developed to replace this otherwise successful communication tool. More information is required to better characterize each recruitment method and to determine to which extent the randomization ratio is favorable with each initial source of patients.
Lived‐experienced of people living with dementia in Mauritius
Authors: Dorkhy Geeta Devi
Published: December 2023

Background

Mauritius has an ageing population of about 20%. There is a rise in the number of dementia due to increased prevalence of risk factors in the population. The interest of the researcher is to explore the daily living experience of people with dementia. Therefore, the understanding of the lived‐experience as detailed by the person himself/ herself is a unique, highly valued and rich adventure.

Method

In order to capture the lived‐experience of people with dementia, an audio‐recorded smartphone was used. One‐to‐one interview was conducted for 30‐40 minutes. Short interview questions relating to the daily living activities was used. Raw data was obtained until theoretical saturation. Data was decoded and grouped into sub‐themes, themes and main themes using thematic analysis.

Result

Lived‐ experience of person with dementia (n = 20) is rich. New data emerges from the interview process, exploring new dimensions of unknown. Seven of the main themes were ‘dependency’, ’family support’, ‘memory recall’, ‘caring’, ‘music and singing’, ‘activity’ and ‘knowledge on Alzheimer’s disease’. High emotions and the facial expressions were equally important.

Conclusion

‘Quality is more important than quantity’ in examination of real‐ life experiences.
Proteomics identifies immunological drivers of post‐infection brain atrophy and cognitive decline
Authors: Duggan Michael R , Peng Zhongsheng , Sipilä Pyry , Lindbohm Joni V , Kivimaki Mika , Davatzikos Christos , Erus Guray , Candia Julian , Daya Gulzar , An Yang , Karikkineth Ajoy , Lewis Alexandria , Moghekar Abhay , Walker Keenan A.
Published: December 2023

Background

Prior infections can modify the risk for dementia and neurodegenerative disease, yet the mechanisms by which infections contribute to neurodegeneration remain unclear.

Method

We examined how infection diagnoses documented in the Baltimore Longitudinal Study of Aging (BLSA) are associated with rates of change in brain volumes over time, and how these same infections relate to dementia risk using hospital records from UK Biobank and a Finnish multicohort sample (the Finnish Public Sector study, the Health and Social Support study, and the Still Working study). After determining how infections differentially relate to an immunological plasma proteome (942 proteins) in BLSA participants, we then identified a subset of infection‐related proteins that also predict changes in brain regions vulnerable to infection‐specific atrophy (candidate proteins). In addition to evaluating their associations with longitudinal cognitive performance as well as Alzheimer’s disease and related dementias (ADRD) plasma biomarkers (Aβ42/40, GFAP, NfL, pTau‐181), we also investigated the causal link between candidate proteins and longitudinal brain volume loss using Mendelian randomization. Study design is illustrated in Figure 1.

Result

A total of 982 cognitively normal participants (age: 65.4 [SD 14.9]); 55.2% female; 66.9% white) were included in the primary MRI analysis. Of the 15 infections examined, we identified six diagnoses related to accelerated brain volume loss, including influenza, viral, respiratory, and skin/subcutaneous infections, with atrophy commonly observed in the temporal lobe. Each infection linked to brain volume loss in the BLSA was associated with increased risk of dementia in the UK Biobank (n = 495,896), with many also associated with increased risk in the Finnish multicohort sample (n = 273,132). From a set of 260 infection‐related proteins, we identified 35 candidate proteins that also predicted changes in brain regions vulnerable to infection‐specific atrophy (Figure 2A‐F). Many candidate proteins were related to cognitive decline, plasma ADRD biomarkers or mechanistically implicated in longitudinal brain volume loss in Mendelian randomization analyses (Figure 2G‐H; Figure 3A).

Conclusion

We demonstrate that infections are linked to accelerated regional brain atrophy and dementia risk. Additionally, we identify molecular mediators by which infections may contribute to neurodegeneration (Figure 3B).