bluuebunny/crossref_metadata_2025 huggingface dataset:
Triangulation to make decisions about what are modifiable risk factors and the new risk factors
Authors: Mukadam Naaheed , Livingston Gill , Huntley Jonathan D , Liu Kathy Y , Gonzalez Sergi Costafreda , Selbaek Geir , Alladi Suvarna , Ames David , Banerjee Sube , Burns Alistair , Brayne Carol , Fox Nick C , Ferri Cleusa P , Gitlin Laura N. , Howard Robert J , Kales Helen C , Kivimaki Mika , Larson Eric B , Nakasujja Noeline , Rockwood Kenneth , Samus Quincy M , Shirai Kokoro , Singh‐Manoux Archana , Schneider Lon S. S. , Walsh Sebastian , Yao Yao , Sommerlad Andrew
Published: January 2025

Background

The 2020 Lancet Commission on dementia prevention, intervention and care estimated that up to 40% of dementia cases could be prevented by tackling 12 potentially modifiable risk factors, namely less education, hearing loss, hypertension, physical inactivity, diabetes, social isolation, excessive alcohol consumption, air pollution, smoking, obesity, traumatic brain injury, depression. As more evidence on risk factors emerges, the Lancet standing commission on dementia met to update evidence on established dementia risk factors and to consider the evidence for other risk factors.

Method

We used a lifecourse approach to understand how to reduce risk or prevent dementia, as many risks operate at different timepoints in the lifespan. We considered evidence for when in the lifecourse a risk factor was relevant to development of dementia as well as the size of the effect and strength of the evidence. Our interdisciplinary, international, multicultural group of experts adopted a triangulation framework, prioritising systematic reviews and meta‐analyses, performing new meta‐analyses where needed and debated and agreed on the best available evidence and its consistency. We considered whether there was evidence of disparities in impact of risk factors based on demographic characteristics, particularly ethnicity and socioeconomic status.

Result

Evidence for two new risk factors was considered strong enough to include this in our lifecourse model. We will present evidence for incorporation of these risk factors, including strength of evidence and potential mechanisms. We will also discuss risk factors for which evidence was not strong enough.

Conclusion

As more evidence about risk factors emerges we can increase our understanding of how dementia develops and how to potentially prevent it. Understanding the landscape of dementia prevention research is also helpful to appreciate where further evidence is needed and what form of evidence would be most helpful in advancing our understanding.
Interventions for people living with dementia: updates from 2024 Lancet Commission
Authors: Sommerlad Andrew , Huntley Jonathan D , Liu Kathy Y , Gonzalez Sergi Costafreda , Selbaek Geir , Alladi Suvarna , Ames David , Banerjee Sube , Burns Alistair , Brayne Carol , Fox Nick C , Ferri Cleusa P , Gitlin Laura N. , Howard Robert J , Kales Helen C , Kivimaki Mika , Larson Eric B , Nakasujja Noeline , Rockwood Kenneth , Samus Quincy M , Shirai Kokoro , Singh‐Manoux Archana , Schneider Lon S. S. , Walsh Sebastian , Yao Yao , Mukadam Naaheed , Livingston Gill
Published: January 2025

Background

The progressive nature of dementia and the complex needs means that people living with dementia require tailored approaches to address their changing care needs over time. These include physical multimorbidity, psychological, behavioural, and cognitive symptoms and possible risks arising from these and helping family caregivers. However, provision of these interventions is highly variable between and within countries, partly due to uncertainty about their efficacy and scarce resources. In the 2024 update of the Lancet Commission we aimed to summarise published evidence about the effect of non‐pharmacological interventions for people with dementia and their carers on cognition, neuropsychiatric symptoms and other person‐centred outcomes.

Method

We reviewed and summarised evidence according to expert consensus opinion.

Result

There is moderate‐quality evidence from a Cochrane review of 25 studies for effect of cognitive stimulation therapy on cognition; 1.99 (1.24‐2.74) Mini‐Mental State Examination points higher compared to control groups, and clinically relevant improvements in communication and social interaction. Multicomponent interventions for family carers reduce family carer depression, burden, or stress and are cost‐effective but remote delivery of these interventions was not better than care as usual. A meta‐analysis of 7 studies of tailored activity programmes for people with dementia found a moderate effect on improving quality of life (standardised ES Cohen’s d 0.79, 0.39–1.18; 7 studies, n = 160), decreasing neuropsychiatric symptoms (0.62; 0.40–0.83) and decreasing carer burden (0.68, 0.29–1.07) but there is little evidence on cost‐effectiveness. Exercise interventions were not effective in improving neuropsychiatric symptoms, cognition or functioning. We discuss evidence for other treatments for specific neuropsychiatric symptoms.

Conclusion

There is developing evidence for benefit of psychological and social interventions on key outcomes including cognition, neuropsychiatric symptoms and quality of life, with sufficient strength of evidence and cost‐effectiveness to justify these being implemented and offered routinely to people with dementia. Interventions generally should be tailored to specific symptoms and individualised to patient preferences and goals. Most interventions have been tested in majority ethnic populations in high income countries: future interventions should be co‐designed with local communities to ensure that they are appropriate for the context, culture, beliefs and practices.
Measuring What Matters Most to People Living with Alzheimer’s Disease and Care Partners: What Matters Most Quantitative Research Development
Authors: Romano Carla (DeMuro) , Bratlee‐Whitaker Emily , Hartry Ann , Mearns Elizabeth S , Taylor Jim , Taylor Geri , Callahan Leigh F , Monks Doreen , Kremer Ian , Lappin Debra , Frangiosa Theresa , Sangodkar Sanjyot , Herring William L , Gnanasakthy Kajan , Goss Diana , McLeod Lori , Edwards Teresa , Poulos Christie , DiBenedetti Dana , Paulsen Russ
Published: January 2025

Background

Previous What Matters Most (WMM) research identified and verified patient‐important concepts among a diverse population of people living with Alzheimer’s disease (PLWAD) and their care partners across all stages of Alzheimer’s disease (AD). Additionally, a conceptual model of disease was developed using hypothesized domains and was further refined using qualitative data (Figure 1). This next phase of WMM research aims to quantify the importance of concepts, impacts, and outcomes and to determine priorities among PLWAD and care partners within a diverse sample including underrepresented ethnic and racial groups at each level of disease severity.

Methods

A cross‐sectional, observational, web‐based survey will be administered to up to 600 adults ≥18 years living with or at risk for AD and care partners of individuals across the disease spectrum. We aim to sample an equal distribution of participants categorized in 1 of 5 AD groups (Table 1) maximizing representation of educational levels, socioeconomic status, and ages, and to include approximately 50% participants who self‐identify as Black, Asian, Hispanic, or a mixed ethnicity. The survey builds upon an initial rating study (Hauber et al., 2023. Neurol Ther;12:505‐527) to (1) determine ranked priorities among WMM concepts, (2) evaluate the impact of the lived experience of concepts, and (3) evaluate construct validity of specific hypothesized domains, alongside clinical outcome assessments to facilitate health economic assessment (Table 2). A draft survey will be refined following cognitive debriefing with small samples across groups 1‐5 before completion by our target sample. Data may be stratified by AD group or background factors (e.g., ethnicity, education) for subgroup analyses, sample sizes permitting.

Results

Anticipated survey and clinical outcome assessment findings will provide rankings of concepts, impacts, and outcomes among a diverse and inclusive population of PLWAD and care partners across the spectrum of disease.

Conclusions

This research expands upon prior identification and verification of WMM concepts to determine priorities and characterize the lived experience of PLWAD and care partners across diverse and inclusive populations. Data are intended to inform treatment‐related needs, selection of important patient‐centric outcome measures, and study endpoints to better guide the development of AD treatments and services.
How Illness Context Shapes Caregiving: Comparative Ethnography of Diverse Caregiving Experiences
Authors: De Jesus Alma V Hernandez , Ginn Brandi , Perez Ignacia Arteaga , Abramson Corey M , Dohan Daniel
Published: January 2025

Background

Prior research shows that caregiving for people living with dementia (PLWD) varies with cultural, institutional, and social structural context, but less is known about the role of context in dementias of different etiologies. We compared experiences of caregiving in frontal‐temporal dementia (FTD) versus non‐FTD dementias using community‐based comparative ethnography. We expected to find differences in caring for people living with FTD (PLWFTD) versus people living with other dementias (PLWOD). Our analytical intent was to show how cultural, institutional, and structural context shaped these experiences and to identify opportunities for intervention.

Method

Data were obtained from three years of community‐based ethnography in diverse communities in five cities via participant‐observation (n = 282 daily fieldnotes) and in‐depth semi‐structured interviews (n = 80 PLWD and caregivers). For data collection, a diverse research team trained in observation and interview methods and met weekly to review field experiences. For analysis, we used a qualitative computational approach that included large language models to identify data about illness trajectory and caregiving experiences. We read through the resulting data deductively to examine our expected findings about PLWFTD versus PLWOD, and we used inductive analysis to make sense of unexpected and counterfactual findings. Our results highlight linkages among caregiving experiences, disease‐etiology, and social context.

Result

As expected, we found differences in caregiving experiences of PLWFTD and PLWOD, and we also found many similarities. Among PLWFTD, earlier onset and more difficulty obtaining diagnosis created difficulties and delays in assuming a caregiving role. Following diagnosis, caregivers could find it challenging to recognize and manage their own response to the behavioral and personality changes associated with FTD. These compounded challenges experienced by all caregivers such as feelings of guilt, frustration over behavioral changes, structural barriers to care, and institutional challenges showed much‐needed respite.

Conclusion

Caregiving for PLWD is taxing on multiple levels with some additional challenges related to dementia diagnosis. These findings contribute an in‐depth account of similarities and differences in caregiving experiences and can inform evidence‐based recommendations to support caregiving initiatives and PLWD. Among modifiable factors, our results suggest a need for mechanisms to support differential diagnosis and for provision of respite care.
“Post Diagnostic Support for People with Dementia and Carers,”
Authors: Badalova Aygun
Published: January 2025

Background

Proper name anomia is a common experience that can become amplified in patients with a diagnosis of dementia (PWD). The Gotcha! app aims to provide practice‐based therapy for PWD to relearn the names of key people in their lives. It has been developed according to the principles of errorless learning, which have previously been shown to improve the remembering the familiar people’s names and benefit the relationship between the PWD and their loved ones. (Clare et al, 1999, 2000, 2003).

Method

Gotcha! is a digital confrontation naming therapy app which enables patients to train one face per day by using photos that the app represents. During the development phase we carried our qualitative research (thematic analysis) on why PWD get involved in research projects such as ours. Gotcha! therapy block lasts for six weeks and prior to the therapy patients complete a multiple baseline paradigm with eight weekly tests of free naming of the to‐be trained faces. During the therapy, a novel speech verifier is used to provide real‐time feedback (Barbera et al. 2020). Two analyses method is used to investigate the behavioural data: 1) within‐subject non‐parametric analysis using Tau‐U metric (Parker et al. 2011); 2) a parametric group analysis using an ANOVA

Result

In terms of the quantitative data, our results from the first 20 subjects showed:

Within‐subjects, non‐parametric results

1) Tau‐U. 80% showed a positive trend with better naming during the training phase with 8/20 reaching statistical significance.

Parametric group results

2) ANOVA demonstrated a significant effect at the group level of training>baseline phase, F (1,19) = 13.18, p = 0.01

Conclusion

App‐based proper name anomia retraining works for the majority of PWD in our trial thus far. Being able to freely recall and produce the name of a relative or loved one has a big impact on people’s lives.
Coadministering nanonaringenin and vitamin E enhances hippocampal memory function and synaptic transmission in diabetic mice
Authors: OLAYINKA JULIET NNENDA , Egede Gabriella , Madu Victoria , Alari Hilda , Ezenwobi Chiamaka , Ekeh Cherechi , Igochukwu Anita Dimm , Akawa Oluwole Abidemi , Obisesan Abiola Oluwatosin
Published: January 2025

Background

Diabetic conditions are associated with alterations in brain functions like memory deficits through processes like synaptic dysfunction in the hippocampus. Administering a combination of silver nanonaringenin and vitamin E appears promising since they are known to prevent diabetes and memory deficits in previous studies, and nanoformulation of naringenin may be one way to improve delivery and bioavailability of naringenin in the brain. This study investigated the effects of co‐administering silver nanonaringenin and vitamin E against memory deficits and synaptic dysfunction in the hippocampus of a mice model of high‐fat diet and streptozotocin (HS).

Method

Ninety male mice (n = 15) were divided into six groups and fed with high‐fat diet except the normal group for 28 days. Diabetes was induced by streptozotocin (50 mg/kg intraperitoneally) on day 22. Weight and blood glucose levels were taken every week. On day 15, mice in the pretreatment groups (PNg 12.5 + Vit E 200 mg/kg and PNg 25 + Vit E) started treatment while on day 29, mice in the posttreatment groups (PtNg 12.5 + Vit E and PtNg 25 + Vit E) commenced treatment till day 42. Memory function (Y‐maze and novel object recognition test (NORT)) were performed. The hippocampal cornus ammonus 1 (CA1) was harvested for biochemical assays using ELISA (acetylcholinesterase enzyme (AChE) and insulin test). Immunofluorescence was used in detecting the expression of synaptophysin in the brain.

Result

Nanonaringenin and vitamin E restored memory function, and significantly decreased weight, glucose, insulin, and AChE levels in the HS‐treated mice compared to the HS group. Synaptophysin was scarcely expressed in the pretreatment (12.5 mg/kg) but densely expressed in the Pretreatment 25 mg/kg and Posttreatment (12.5 and 25 mg/kg) groups compared to the HS‐group.

Conclusion

Co‐administering silver nanonaringenin and vitamin E restored hippocampal memory function through reversing insulin resistance, cholinergic mechanism and restoring synaptic function in the CA1 of the hippocampus of HS‐induced mice.
Perceived Discrimination Influences Cognition in a Race‐Independent Manner
Authors: Ramanathan Shreya , Wharton Whitney , Williams McKayla , Swieboda Dominika , Butts Brittany
Published: January 2025

Background

Black/African American adults (B/AAs) are 64% more likely to develop Alzheimer’s disease (AD) than non‐Hispanic White adults (NHWs), and risk factors, including non‐biological determinants, are not fully delineated. Social determinants of health, such as socioeconomic status and lifetime discrimination, are associated with cognitive decline and increased AD risk. The purpose of this study is to examine the relationships of a perceived discrimination measure with sociodemographic characteristics and cognitive function in a racially diverse cohort of middle‐aged adults with a parental history of AD.

Methods

Perceived discrimination was assessed utilizing a compilation of self‐reported Perceived Discrimination measures including Expanded Everyday Discrimination, Coping with Discrimination, and Major Experiences of Discrimination from which six discrimination factors were extracted. Cognitive testing consisted of standardized tests in executive function, working memory, and verbal and visuospatial ability. Linear regression models were used to examine associations of perceived discrimination factor scores to cognitive function and sociodemographic characteristics.

Results

There were no significant differences in Aβ42 between B/AAs and NHWs, but significantly lower levels of total tau (p = 0.004) and p‐tau (p = 0.004) in B/AAs were found. Race was negatively correlated with Disrespect (p = 0.02) and Professional (p = 0.001), and positively correlated with Avoidance (p = 0.04), such that B/AA participants reported more discrimination in these domains. There was a significant correlation between Housing and both MoCA (p = 0.03) and global cognition (p = 0.01). The impact of perceived Housing discrimination on MoCA score approached significant interaction with education (p = 0.051) in the limited participant data. This suggests that perceived housing discrimination is most influential on global cognition in individuals with postgraduate education. These results may reflect prior reports of housing discrimination in B/AAs and housing mobility, even in high SES individuals.

Conclusions

We found that perceived discrimination influences cognition in a race‐independent manner in this racially diverse middle‐aged cohort with a family history of AD. These results also might be stratified by educational attainment and resulting geographic mobility. This study highlights the importance and impact of social determinants of health on cognition, and overall AD risk.
A systematic review and meta‐analysis of mobile health application interventions for community‐dwelling older adults with mild cognitive impairment and dementia
Authors: Wee Natalie Jian‐Ting , Lun Penny , Guo Liang , Shi Luming , Chan Edwin Shih‐Yen , Low Yiew Hock James
Published: January 2025

Background

Mobile health applications have the potential to enhance dementia care and promote well‐being among older adults living independently. This systematic review aims to synthesise and evaluate the existing evidence on the effectiveness of mobile applications developed to improve or maintain cognitive function among older adults diagnosed with mild cognitive impairment (MCI) and dementia.

Method

A systematic search was conducted across major electronic databases, including PubMed, The Cochrane Library, Embase, and PsycInfo, to identify relevant studies published from 2012 to 2023. Inclusion criteria encompassed randomised controlled trials and observational studies that assessed the impact of mobile applications on cognitive function in individuals with MCI or dementia compared with standard clinical care. Meta‐analysis was conducted to quantify the effect of cognitive training using mobile applications on cognitive outcomes, with subgroup analysis to explore the potential difference between various types of interventions.

Result

A total of 22 studies with 1227 patients (mean age range from 65 to 84) were included out of 5774 articles initially identified from the search. The included studies reported mobile applications with diverse cognitive training interventions applications run on a variety of digital platforms, such as mobile phones, tablets and laptops. A meta‐analysis was conducted to quantify the overall effect of cognitive training using mobile applications on cognitive function, employing standardized mean differences and random‐effects models.

Preliminary findings suggest a positive effect of mobile health applications in improving cognitive function in cognitively‐impaired older adults. Subgroup analysis explored the impact of different types of cognitive interventions on the observed effects.

Conclusion

Mobile applications improve cognitive function compared to standard clinical care in community‐dwelling older adults with cognitive impairment. This systematic review contributes to the understanding of the efficacy of cognitive training delivered via mobile applications for individuals with dementia. The synthesis of available evidence provides insights into the potential benefits of specific interventions and highlights gaps in the current literature. The results of this review have implications for the development of mobile applications to target cognitive function, and the design of future research studies aimed at assessing the use of mobile applications in individuals with dementia.
Exploring the Impact of Self‐Efficacy on Depression and Anxiety Symptoms in Mild Cognitive Impairment Patients and Their Care Partners: A Dyadic Analysis
Authors: Ren Dianxu , Tamres Lisa K , Lingler Jennifer H
Published: January 2025

Background

Research on the relationship between self‐efficacy and symptoms of depression and anxiety among individuals with mild cognitive impairment (MCI) has been limited. Furthermore, few studies have explored this relationship within the context of dyadic couples (patient/care partners) rather than focusing solely on individuals. The purpose of this study was to examine the associations between self‐efficacy in patient/care partner couples dealing with mild cognitive impairment and their symptoms of depression and anxiety using a dyadic analysis approach.

Method

We utilized baseline data from a NIH‐funded study for this cross‐sectional analysis. Participants were interviewed regarding self‐efficacy using The Coping Self‐Efficacy Scale, depressive symptoms using the Center for Epidemiological Studies Depression scale, and state anxiety using the Spielberger State‐Trait Anxiety Inventory. We employed the Actor‐Partner Interdependence Model (APIM) to examine the relationships between outcomes (depressive symptoms and state anxiety) and the predictor (self‐efficacy scale) for patients with MCI and their care partners controlling for dyads' age, gender, education level and self‐efficacy respectively.

Result

The sample consisted of 82 dyads comprising patients with MCI (59.8% male, average age 72.6 years, average education 16.5 years) and their care partners (24.4% male, average age 66.8 years, average education 15.5 years). The average self‐efficacy, depression and anxiety were 203.6±28.7, 6.51±4.29 and 26.0±6.01 for patient and 202.4±36.9, 7.61±7.66 and 26.8±7.40 for care partner respectively. Regarding depression, there was a significant actor effect of self‐efficacy for both patients and care partners. Increased self‐efficacy was associated with decreased depression for both patients (β = ‐0.07, P<0.001) and care partners (β = ‐0.11, P<0.001). A marginally significant partner effect of care partner’s self‐efficacy on patient depression was observed (β = ‐0.05, P = 0.066), but no effect of patient’s self‐efficacy on caregiver’s depression was found. For anxiety, there was a significant actor effect of self‐efficacy for both patients and care partners. Increased self‐efficacy was associated with decreased anxiety for both patients (β = ‐0.11, P<0.001) and care partners (β = ‐0.11, P<0.001). However, no partner effects were observed.

Conclusion

Our findings emphasize the importance of considering patient/care partner dyads to better understand the complex interplay between psychological outcomes and predictors in the context of mild cognitive impairment.
Effects of chrysin loaded self‐nano emulsifying drug delivery system for the treatment of Alzheimer’s disease
Authors: Vishwas Sukriti , Singh Sachin Kumar , Gulati Monica , Dua Kamal , Kakoty Violina , Bashir Bushra
Published: January 2025

Background

Alzheimer’s disease (AD) is a type of degenerative disorder that affects the brain. There are various herbal drugs that have been tested for their effectiveness in treating AD, and chrysin is one of them. Chrysin is a polyphenolic flavonoid that has several neuroprotective effects, including reducing the levels of AChE enzyme, accumulated amyloid β, oxidative stress, and neuroinflammation. It is also inherently senolytic, which helps to lessen the impact of cellular aging. However, chrysin has a limited ability to dissolve and is not easily absorbed by the blood‐brain barrier, which can reduce its effectiveness.

Method

We have developed a self‐emulsifying drug delivery system (SNEDDS) for chrysin to address these issues using a Box‐Behnken design (BBD) approach. The pharmacokinetic studies showed that chrysin SNEDDS had significantly higher bioavailability than regular chrysin. The pharmacodynamic studies assessed cognitive and motor functions in rats.

Result

SNEDDS has many advantages, including increased drug loading, ease of preparation, high stability, and increased bioavailability and blood‐brain barrier permeability. The optimized formulation of chrysin‐loaded SNEDDS resulted in a small droplet size, high drug loading, and good stability. The formulation was evaluated for its bioavailability, availability in the brain, and pharmacodynamic efficacy.

Conclusion

The results showed that chrysin SNEDDS loaded significantly improved cognitive functions in AD‐induced rats at both low and high doses. The biochemical studies also demonstrated that chrysin SNEDDS loaded reduced the levels of AChE enzyme, amyloid β, oxidative stress, and neuroinflammation.
Identifying priorities for medication management resources for people living with dementia and their care givers through community action
Authors: Watson Karen , Cross Amanda , Jokanovic Natali , Wesson Jacqueline , Lo Joanne , Gnjidic Danijela , Sawan Mouna J
Published: January 2025

Background

People with dementia and their care givers are provided limited guidance in medication management, potentially contributing to medication‐related harm. Importantly, there are no resources that provide comprehensive medication management guidance across care settings. To ensure that resources are co‐designed, genuine involvement of people with dementia, their care givers and the community in identifying the priorities for medication management guidance resources is needed. We explored community‐centred priorities for medication management guidance resources for people with dementia and their care givers.

Methods

We established a 23‐member consortium partnership with people living with dementia, care givers, healthcare professionals, and national consumer and professional organisations using a community‐based participatory research approach. A qualitative descriptive design, using four focus groups and two interviews with key informants was conducted between September to December 2023 to explore partners’ priorities for medication management resources across care settings. Content analysis was performed to generate a list of priorities.

Results

The key priorities for inclusion in the medication resource were to: 1) empower the person with dementia and their care givers to make informed choices, by providing pragmatic and accessible information to meet their needs and promote key questions to engage health providers in shared decision‐making; 2) inclusion of strategies to address medication challenges, and 3) suggested format and setting for the availability of information.

Conclusion

This is the first time a community action approach has been adopted to co‐design resources to support people with dementia and care givers in medication management challenges. The community‐centred priorities will be used to generate an inventory of consumer‐tailored communication strategies for people with dementia and their care givers.
Everyday Life of People Living with Dementia and its Impact on Their Lifestyle
Authors: Ali Istikhar , Dey Aparajit Ballav
Published: January 2025

Background

This ethnographic inquiry offers a nuanced exploration into the lives of individuals contending with dementia in India, utilizing data from the Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI‐DAD). Recognizing dementia as a complex global health challenge, we delve into its unique manifestations within India’s diverse regional and cultural landscape. While LASI‐DAD provides valuable quantitative insights into prevalence and risk factors, our research complements these statistics by providing an in‐depth understanding of the daily lives and lifestyles of those affected.

Method

Employing purposive sampling, we meticulously captured diverse experiences across regions, languages, and socioeconomic backgrounds of individuals aged 60 and older. Through a blend of participant observation and in‐depth interviews, we systematically unraveled the multifaceted dimensions of living with dementia in India, exploring daily routines, coping strategies, and familial and societal dynamics.

Result

Thematic analysis illuminated the profound realities encapsulated in the “Everyday Life of People Living with Dementia and Its Impact on Their Lives,” revealing two interconnected sub‐themes: 1. Emotional Struggles, where participants vividly described challenges adapting to contemporary settings and the emotional toll of living with dementia. 2. Evolving Social Dynamics and Behavioral Changes, wherein participants shared experiences of feeling marginalized in social settings amid the changes in their behavior and cognition.

This ethnographic inquiry extends beyond academic realms, carrying profound implications for individuals living with dementia and their families in India and globally. As the global dementia burden intensifies, our study contributes insights that foster more compassionate, culturally sensitive, and effective approaches to dementia care and management.

Conclusion

This study serve as the foundation for a broad exploration of the multifaceted experiences of people living with dementia, these insights are crucial for developing empathetic and effective support systems. The integration of ethnographic methods with LASI‐DAD’s dataset in this study provides a regionally and culturally nuanced understanding of dementia in India. Our research also significantly informs local healthcare and support systems, enriching the global discourse on dementia and offering vital insights to enhance the quality of life for individuals living with dementia, their families, and caregivers, both in India and worldwide.
Combined use of plasma p‐tau 181 and neurofilament light chain in Subjective Cognitive Decline and Mild Cognitive Impairment: future perspective and clinical applicability
Authors: Giacomucci Giulia , Mazzeo Salvatore , Ingannato Assunta , Crucitti Chiara , Bagnoli Silvia , Padiglioni Sonia , Galdo Giulia , Emiliani Filippo , Frigerio Daniele , Moschini Valentina , Morinelli Carmen , Sorbi Sandro , Nacmias Benedetta , Bessi Valentina
Published: January 2025

Background

There is an urgent need to move the use of plasma biomarkers from research setting to clinical practice for the early detection of Alzheimer’s disease (AD). The aims of the study were to explore the combined use of plasma p‐tau181 and NfL in Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI) patients, evaluating diagnostic accuracy and concordance to propose a flow chart for the clinical applicability.

Method

We included 43 SCD, 41 MCI and 21 AD‐dementia (AD‐d) patients, who underwent plasma p‐tau181 and NfL analysis with SiMoA assay. Twenty‐eight SCD, 41 MCI and 21 AD‐d patients underwent CSF biomarkers analysis (Aβ1‐42, Aβ1‐42/1‐40, p‐tau, t‐tau) and were classified as carriers of AD pathology (AP+) it they were A+/T+ (regardless of N), or non‐carriers (AP‐) when they were A‐ (regardless of T and N), A+/T‐/N‐, or A+/T‐/N+ according to the A/T(N) system.

Result

Plasma p‐tau181 and NfL separately showed a good accuracy (AUC=0.88), while the combined model (NfL+p‐tau181) showed an excellent accuracy (AUC=0.092) in discriminating AP+ from AP‐ patients in SCD and MCI. Plasma p‐tau181 and NfL presented only a moderate concordance (Coehn’s k=0.50, p<0.001) in discriminating AP+ from AP‐ patients. Concordant negative cases showed 10.25% of false negativity, concordant positive cases presented 6.66% of false positivity. The only NfL+/p‐tau181‐ patient was AP+. In NfL‐/p‐tau181+, 57.14% of cases were AP‐. A logistic regression analysis showed that both p‐tau181 and NfL significantly influenced the risk of having AD pathology. Using the regression coefficients associated with the two covariates in the logistic model (p‐tau181 and NfL), we estimated the risk of AD pathology: 10.91% (95%C.I. 3.55‐18.27) if both p‐tau181 and NfL were negative; 41.10% (95%C.I. 29.49‐52.71) and 76.49% (95%C.I. 66.48‐86.50) if only one biomarker was positive (respectively p‐tau18 and NfL); 94.88% (95%C.I. 89.69‐100) if both p‐tau181 and NfL were positive.

Conclusion

Considering the moderate concordance and the risk of presenting an underlying AD pathology according to the positivity of plasma p‐tau181 and NfL, the combined use of plasma p‐tau181 and NfL may give added value for the correct interpretation and the detection of AD pathology.
Blood biomarkers for Alzheimer’s disease diagnosis in the context of disease‐modifying treatment: a cost‐utility analysis
Authors: Aye Sandar , Handels Ron , Winblad Bengt , Jönsson Linus
Published: January 2025

Background

Recent developments in blood biomarkers (BBM) have shown promising results in diagnosing amyloid pathology in Alzheimer’s Disease (AD). However, information on how these BBMs can best be used in clinical settings to optimise clinical decision‐making and long‐term health outcomes for individuals with AD is still lacking. We aim to assess the potential clinical and economic value of BBM in AD diagnosis within the context of disease‐modifying treatment (DMT).

Method

We developed a decision analytic model to evaluate the long‐term health outcomes of using BBM in AD diagnosis. We compared standard of care (SOC) diagnosis workflow to the integration of BBM as a (1) referral decision tool in primary health center (PHC) and (2) triaging tool for invasive CSF examination in specialist memory clinic (MC). The conceptual framework is illustrated in Figure 1. We combined a decision tree and a Markov model to simulate the patient’s diagnostic journey, treatment decisions following diagnosis and long‐term health outcomes. We applied a cost‐effective price of DMT identified from price threshold analysis. A cost‐utility analysis was conducted from the societal perspective using a one‐year cycle length and a 30‐year time horizon. The outcomes were reported in percentage of correct diagnosis, costs (in 2022 Euros), quality‐adjusted life year (QALY), and incremental cost‐effectiveness ratios (ICER).

Result

Compared to SOC, integrating BBM in PHC increased patient referrals by 8% and true positive AD diagnoses by 10.4%. The lifetime costs for individuals diagnosed with AD were € 249,685 and €250,287, and QALYs were 9.5 and 9.52 in SOC and PHC pathways, respectively. The cost increments were €603, and QALYs gained were 0.01, resulting in an ICER of €48,296. Using BBM in MC reduced the exposure to invasive CSF procedures and costs but also reduced true positive AD diagnoses and QALYs. Detailed results were presented in Tables 1 & 2.

Conclusion

Using BBM at PHC to make referral decisions might increase initial diagnostic costs but can prevent high costs associated with disease progression, providing a cost‐effective DMT is available, whereas using BBM in MC could reduce the initial evaluation cost but incur high costs associated with disease progression.
Long‐Term Wildfire Smoke Exposure and Incident Dementia in a Large California Cohort
Authors: Elser Holly C , Frankland Timothy B , Tartof Sara Y , Mayeda Elizabeth Rose , Manly Jennifer J. , Torres Jacqueline M , Northrop Alexander J , Benmarhnia Tarik , Chen Chen , Casey Joan A
Published: January 2025

Background

Long‐term exposure to ambient air pollution–including fine particulate matter <2.5µm in diameter (PM2.5)–has previously been associated with incident dementia. As climate change drives longer and more intense wildfire seasons, exposure to PM2.5 produced by wildfires may be a unique and increasingly important risk factor for dementia.

Method

In this retrospective open cohort study, we examined the association between long‐term exposure to wildfire PM2.5 and dementia among Kaiser Permanente Southern California patients aged ≥60 from 2009‐2019 in California. Study participants were dementia‐free at baseline. Incident dementia was identified within the electronic health record using International Classification of Diseases 9 and 10 codes. Estimates for rolling three‐year average concentrations of wildfire and non‐wildfire PM2.5 were assigned for each participant based on census tract of residence, which was updated quarterly. We used pooled logistic regression to estimate the odds of dementia diagnosis associated with a one µg/m3 increase in the three‐year average of wildfire and non‐wildfire PM2.5. All models included fixed effects for calendar year and adjusted for age, sex, race and ethnicity, marital status, smoking status, Charlson Comorbidity Index (minus dementia), and census tract poverty and population density.

Result

The study included 1,227,241 members. Approximately half were women (53%) and were married (54%). A majority self‐identified as non‐Hispanic White (49%) or Hispanic (26%). Over the study period, the mean wildfire PM2.5 concentration was 0.09 (IQR: 9.6‐12.4). After adjusting for covariates, the odds of dementia diagnosis was 10% higher for every 1 µg/m3 higher three‐year average wildfire PM2.5 concentration (OR = 1.10, 95%CI: 0.96,1.25). For non‐wildfire PM2.5 the odds of dementia diagnosis was 1% higher for every 1 µg/m3 higher three‐year average exposure (OR = 1.01, 95%CI: 1.00,1.01).

Conclusion

Long‐term exposure to PM2.5, both wildfire and non‐wildfire, may be an important risk factor for dementia.
Blood‐based gene and co‐expression network levels are associated with AD/MCI diagnosis and cognitive phenotypes
Authors: Chen Xuan , Reddy Joseph S. , Wang Xue , Quicksall Zachary , Nguyen Thuy , Reyes Denise A. , Graff‐Radford Jonathan , Jack Clifford R. , Lowe Val J. , Knopman David S. , Petersen Ronald C. , Kantarci Kejal , Nho Kwangsik , Allen Mariet , Carrasquillo Minerva M. , Saykin Andrew J. , Ertekin‐Taner Nilüfer
Published: January 2025

Background

Alzheimer’s disease (AD) patients have decline in cognitive domains including memory, language, visuospatial, and/or executive function and brain pathology including amyloid‐β and tau deposition, neurodegeneration, and frequent vascular co‐pathologies detectable by neuroimaging and/or cerebrospinal fluid biomarkers. However, molecular disease mechanisms are complex and heterogeneous. It is necessary to develop cost‐effective blood‐based biomarkers reflecting brain molecular perturbations in AD. We identified blood‐based gene and co‐expression network level changes associated with AD/mild cognitive impairment (MCI) diagnosis and AD‐related phenotypes.

Method

We performed differential gene expression and weighted gene co‐expression network analysis, followed by meta‐analysis, using blood transcriptome data of 391 participants from the Mayo Clinic Study of Aging and 654 participants from the Alzheimer's Disease Neuroimaging Initiative. The neuroimaging phenotypes include microhemorrhages, infarcts, amyloid burden, hippocampal volume, and white matter hyperintensities. The cognitive phenotypes include standardized cognitive subtest scores and composite scores for memory, language, visuospatial, and executive function.

Result

Five out of 18 modules(M) are significantly associated with diagnosis or cognition (FDR‐adjusted p<0.05). M1 and M15 both positively associates with memory, M1 positively associated with language and M15 with visuospatial function. M1 and M15 are enriched in differentially expressed genes (DEGs) associated with language and executive function, respectively. M2 negatively associates with logical memory delayed recall scores(LMDR), memory, executive, and language functions and is enriched in DEGs for these phenotypes. M8 negatively associates with memory, language and executive functions and is enriched in DEGs for memory and language. M12 positively associates with LMDR. M1 and M15 are down‐regulated while M2 and M8 are up‐regulated in AD/MCI patients. Cell‐type enrichment analysis showed M2 is enriched in monocytes and neutrophils; M8 in monocytes; M15 in B cells (FDR <0.05). Gene ontology terms enriched in these modules indicated broad consistency with their cell types.

Conclusion

We identified five modules significantly associated with AD/MCI or cognitive phenotypes using blood transcriptome data. These findings nominate blood transcriptome changes and their enriched biological processes as potential pathomechanisms in cognitive decline and AD/MCI development. We aim to investigate these blood transcripts as potential biomarkers for AD or AD‐related phenotypes and therapeutic targets through additional replication and experimental validation studies.
Effect of monthly training meetings about level of knowledge for dementia caregivers in Lima, Peru: preliminary results
Authors: Custodio Belen , Chambergo‐Michilot Diego , Montesinos Rosa , Agüero Katherine , Verástegui Graciet , Custodio Nilton
Published: January 2025

Background

Dementia is considered a public health problem due to the exponential increase in cases in recent years, as it not only has an impact on health services, but also affects the social and economic level, especially in low and middle income countries. Evidence has shown that a trained caregiver improves the patient’s quality of life, reduces behavioural symptoms and decreases the likelihood of the caregiver developing burnout. Currently scarce research has reported on the level of knowledge of dementia, specifically targeting caregivers in LMIC, that’s why we aimed to measure the level of knowledge of caregivers attending to monthly training compared to untrained caregivers.

Method

This is a cross‐sectional analysis, comparing the level of knowledge between trained and untrained dementia caregivers in Lima, Peru. The training program (Lonchecito para cuidadores) consists of 10 virtual meetings per year, led by a healthcare professional, where the main topics are: types of dementia, management of behavioural symptoms, application of non‐pharmacological measures and caregiver well being. The instrument used was the Dementia Knowledge Assessment Scale (DKAS‐Spanish version), a validated scale with 25 true or false statements. A Student’s T test was performed to compare the mean scores of DKAS‐S between the trained versus untrained caregivers.

Result

To date, 46 caregivers have participated in the study, representing 45% of the total sample. 80% of caregivers are women and 85% are informal caregivers. (Table 1) The preliminary results show a difference of two points on DKAS‐S between trained (mean score 16.22 ± 2.29) compared with untrained caregivers (mean score 18.21 ± 3.15). (Figure 1) A relevant finding is that 65% or more of the caregivers answered incorrectly questions 13, 15 and 19, which are related to onset symptoms of dementia, care in advanced stages and management of behavioural symptoms, respectively.

Conclusion

The training program (Lonchecito para cuidadores) provides an increase in dementia knowledge. Training makes a difference between the two groups of caregivers, a reinforcement or different approach should be considered for the topics where both groups had the highest number of incorrect answers.
The Impact of a 12‐Month Exercise Intervention on Cognitive Function in Adults with Down Syndrome
Authors: Ptomey Lauren , Helsel Brian , Danon Jessica , Szabo‐Reed Amanda , Washburn Richard , Donnelly Joseph
Published: January 2025

Background

Evidence in adults without Down syndrome (DS) suggests that exercise during mid‐life improves cognitive function and decreases risk of later life dementia. Studies supporting this relationship in adults with DS are limited. The purpose of this study was to examine changes in cognitive function after a 12‐mo exercise intervention in adults with DS without dementia.

Method

Adults with DS were randomized (2:2:1) to one of three exercise interventions: remotely delivered group exercise sessions conducted 1x/wk. (RL), remotely delivered group exercise sessions conducted 3x/wk. (RH), or a usual care control (UC) which did not receive the remotely delivered sessions. All groups received an activity tracker, access to resources for increasing exercise, and twice monthly 20‐min remotely delivered individual support/education sessions. Physical activity (accelerometry) was assessed across 12 mos. Cognitive function was assessed at baseline, 6, and 12 months, using the CANTAB® DS Battery, which included tests measuring multitasking, episodic memory, and reaction time. Linear mixed‐effects analyses were used to test the effect of the intervention on changes in cognitive function, controlling for age, sex, and level of intellectual disability

Result

Eighty‐one adults with DS (age ∼27yrs., ∼55% female, ∼24% minorities) were randomized to the RH (n = 34), RL (n = 32) or UC (n = 15) groups. Study retention was 100% and study adherence to the remote exercise sessions was 90% in the RH arm and 79% in the RL arm. MVPA increased by 10.6 min/day and 1.4 mins/day in the RH and UC arms, respectively, but decreased by ‐3.2 mins/day in the RL arm. Across all groups episodic memory (p = 0.018), 5‐choice movement time (p = 0.017), and 5‐choice reaction time (p = 0.022) improved across the intervention, however, there were no significant group or group x time effects.

Conclusion

In adults with DS, participation in a 12‐month exercise intervention led to improvements in episodic memory and reaction time regardless of intervention arm. Future adequately powered trials are warranted to examine the impact of long‐term exercise on cognition function outcomes compared to a non‐exercise control.