bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Cumulative Anticholinergic Use and White Matter Hyperintensity Burden
Authors: Li Kevin H , Krakauer Chloe , Nelson Jennifer C , Crane Paul K. , Andre Jalal B , Curl Patti , Yuh Esther C. , Ralston James , Gray Shelly L , MacDonald Christine
Published: January 2025

Background

Anticholinergic medication use has been found to be associated with higher dementia risk and cognitive decline in older adults. The presence of a biologic pathway through changes to white matter hyperintensities (WMH) remains unclear.

Method

We used the first clinically indicated magnetic resonance imaging (MRI) scan from each participant in the Adult Changes in Thought (ACT) Study—a prospective cohort study within Kaiser Permanente Washington (KPWA)—collected between January 2003 and March 2020 from participants ≥65 years old and with ≥10 years of continuous KPWA enrollment prior to the scan. Our primary cumulative exposure was total standardized daily dose (TSDD) of anticholinergic medications in the 10 years prior to the scan, grouped as non‐use, 1‐90 TSDD, 91‐365 TSDD, 366‐1095 TSDD, and ≥1096 TSDD. Neuroimaging outcomes were common data elements (CDEs) for WMH on MRI scans (Fazekas, Scheltens, Age‐Related White Matter Changes [ARWMC]). We used separate linear regression models for each outcome to estimate adjusted mean values of CDEs in each exposure group and test for differences in mean values.

Result

Of the 1,043 individuals included in analyses, 28% had no use, 33% had 1‐90 TSDD, 15% had 91‐365 TSDD, 7% had 366‐1095 TSDD, and 17% had ≥1096 TSDD. The mean age at the time of the scan was 81 years among a group that was majority female (58%) and White (88%). While most individuals were exposed to antihistamines (38%) among all anticholinergic classes, 65% of TSDD were accrued from antidepressants. Compared to no use, the ≥1096 TSDD group had a higher (worse) adjusted mean Fazekas (4.0 vs. 3.4; p: <0.001), Scheltens (14.3 vs. 12.2; p: <0.001), and ARWMC (5.6 vs. 4.8; p = 0.001). A dose‐response relationship was not found, but adjusted mean outcomes values were observed to be higher (worse) in the 1‐90 TSDD group relative to the no use group.

Conclusion

The highest anticholinergic burden was associated with greater WMH burden among older individuals who received an MRI due to clinical indications. The lack of a demonstrated dose‐response relationship warrants further research into biological mechanisms underlying the link between anticholinergic use and WMH burden.
Survival Disparities among Alzheimer’s Patients in Hawaii: Exploring Racial/Ethnic Disparities and Machine Learning for Survival Prediction in the Hawaii Medicare Population
Authors: Siriwardhana Chathura
Published: January 2025

Background

The survival outcomes following an Alzheimer’s disease (AD) diagnosis hold significant importance for health management, caregivers, patients, and their families. Hawaii is known as the most diverse ethnic population in the United States and there exist significant racial health disparities. This study investigates racial/ethnic disparities in survival among AD patients in Hawaii and develops Machine Learning models for overall survival prediction, utilizing Hawaii Medicare data.

Method

We utilized nine years of Hawaii Medicare data to gather information on developing AD after age 65, and followed them for capturing the all‐cause survival or until censoring. We examined the effects of race/ethnicity coupled with socioeconomic status (SE) on the risk of mortality. SE status was accessed by the surrogate marker: Medicare/Medicaid dual eligibility. Cox regression analysis was conducted on the overall survival while accounting for age at AD onset, Gender, and multiple comorbidities. Subsequently, a Survival Random Forest (SRF) was employed to predict survival within a machine learning framework, incorporating K years of longitudinal subject health profiles, including demographics, chronic disease profiles, observed acute conditions, and hospitalization history. A penalty‐based variable selection was employed for SRF development.

Result

The study included n = 9,393 AD subjects. Our analysis revealed that American Asians (AA) had a later age at AD diagnosis (p<.001), with an average age of 85.9, compared to 82.7 and 83.3 years for Whites (WH) and Native Hawaiians and Pacific Islanders (NHPI), respectively. Low SE level exhibited an increment in mortality hazard (Hazard Ratio [HR] = 1.36, p<.001). In comparison to AA with high SE (AA + high SE), increased hazards were found for AA + low SE (1.29, p<.001), WH + high SE (1.19, p<.001), WH + low SE (1.52, p<.001), and NHPI + low SE (1.39, p<.001). The SRF model with K = 2 setting demonstrated a Concordance (C) Index of 0.806 via five‐fold cross‐validation, exhibiting robust survival predictability of AD subjects. A permutation‐based study identified a list of factors influencing subject survival.

Conclusion

The onset of AD development and survival are influenced by race/ethnicity and SE status. When combined with longitudinal health data, machine learning demonstrates reasonable predictability of survival.
Alzheimer’s Disease and Healthy Aging Indicators Cognitive Decline
Authors: Khuld Hamna
Published: January 2025

Background

In the United States and Puerto Rico, cognitive decline and resulting Alzheimer’s disease are major public health concerns for older adults. According to the Alzheimer’s Association (2021), by 2050, people ages 65 and above with Alzheimer’s are estimated to grow to 12.7 million—rising in prevalence and severity. The rise in Alzheimer’s prevalence is attributed to genetic, environmental, and lifestyle factors—leading to memory, judgment, language, and behavior problems. This research examines whether there is an association between race and cognitive decline as indicated by adults ages 50 and above in the United States and Puerto Rico.

Method

The Alzheimer’s Disease and Healthy Aging Indicators Cognitive Decline study is an ecological study that documents cognitive decline or memory loss among adults ages 50 and above. The data was collected from 2015 to 2019 by the Center for Disease Control, under the Behavior Risk Factor Surveillance System (BRFSS). The surveys documented cognitive decline or memory loss experienced by 16,799 older adults by age, race, sex, and state of residency.

Result

The main findings examine the association of cognitive decline by comparing races, using White, non‐Hispanic as the reference group. This analysis shows that Hispanic vs White has the highest OR of 10.35 and 95% CI of 3.128 to 34.256. Black, non‐Hispanic vs White, non‐Hispanic have the second‐highest OR at 3.130 with 95% CI at 1.277 to 7.674.

Association between cognitive decline and race showed a negative inverse relationship–cognitive decline (BRFSSPRCTG) decreases depending on the race. Races such as Native Am/Alaskan Native, Hispanic, and Black, White are statistically significant. However, Asian/Pacific Islanders had on average 0.67 standard error, which is not statistically significant (alpha = 0.05).

Age and its association with participants' state of residency shows that Maryland had the highest percentage of cognitive decline by either age group–ages 50‐64 years are 4.76%, and ages 65 and older are 4.50% likely to experience cognitive decline.

Conclusions

In conclusion, race is associated with cognitive decline depending on age and state of residency. Further research is needed because there was missing information on participants' education, income, zip code, socioeconomic status, etc., which may contribute to cognitive decline.
Financial toxicity of family dementia caregiving in South Korea
Authors: Yang Hyejeong , Seo Hyun‐Ju , Choi YuMi , Kim Jeong Lan , Kim Seong Min
Published: January 2025

Background

One out of every ten individuals aged 65 or above in Korea experiences dementia, with a total dementia care cost of KRW 18.7198 trillion, or approximately KRW 21.24 million per person. It was discovered that the cost of treating dementia increases annually as the severity of each patient’s condition worsens. The rise in dementia cases leads to an increased economic and social burden for care and reduced quality of life for patients and families. Therefore, we aimed to identify the prevalence of financial toxicity in dementia caregiving, its sociodemographic, and its recipients’ caregiving correlates in family caregivers in the context of South Korea.

Method

We utilized the Korean version of the Comprehensive Score for Financial Toxicity (COST) of a 12‐item questionnaire to quantify subjective financial toxicity in at least 300 primary family caregivers who are spouses, children, or siblings. The data will be collected using online platforms and paper printouts from hospital outpatient and community‐based dementia relief centers. Additionally, we will gather family caregivers’ characteristics, including general characteristics, socioeconomic factors (such as employment status and monthly income), presence of chronic diseases, and their recipient’s characteristics, including general characteristics of the recipient, treatment characteristics, resident region (urban or rural), time to since diagnosis, and dependency scale.

Result

We will present the prevalence of financial toxicity and related factors that have a significant impact on the financial toxicity experienced by these caregivers. The study results will be presented in a poster presentation at an upcoming conference.

Conclusion

Although approximately 80% of people with dementia are eligible and likely to cover long‐term care insurance in South Korea, no survey has been conducted to examine the prevalence and factors affecting the financial burden of primary family caregivers. Caregivers' perceptions of financial toxicity will increase the long‐term distress of the caregiving role. The findings of this study will help develop policy strategies to improve the financial well‐being of family caregivers of people with dementia.
Association of cardiorespiratory fitness with dementia risk across different levels of genetic predisposition: a large community‐based longitudinal study
Authors: Wang Shuqi , Xu Liyao , Yang Wenzhe , Wang Jiao , Dove Abigail , Qi Xiuying , Xu Weili
Published: January 2025

Background

Cardiorespiratory fitness (CRF), a proxy for cardiovascular and respiratory function, has been linked to health outcomes, but its association with cognition and dementia risk remains unclear. We aimed to investigate the association of CRF with domain‐specific cognitive function and dementia risk, taking genetic predisposition for dementia into account.

Method

Within the UK Biobank, 61,214 dementia‐free participants aged 39‐70 (mean age: 56.33 ± 8.15, 51.96% were female) were followed for up to 16 years to detect incident dementia. CRF score (measured in metabolic equivalent of task [MET] units) was estimated using a 6‐min submaximal exercise test on a stationary bike and divided into tertiles (i.e., low, moderate, and high). Tests of global and domain‐specific cognitive functions (including prospective memory, visual memory, verbal/numeric memory, and processing speed) were administered at baseline. Dementia was identified based on medical history and medical records. Genetic predisposition for dementia was estimated using the polygenic risk score for Alzheimer’s disease (PRSAD), tertiled as low, moderate, or high level. Data were analyzed using linear regression, Poisson regression, and Laplace regression.

Result

The age‐ and sex‐specific CRF ranged from ‐2.74 to 6.61 MET at baseline. In multi‐adjusted linear regression, compared to low CRF, high CRF was related to better global cognitive function (β [95% confidence interval]: 0.05 [0.04, 0.06]), prospective memory (0.06 [0.04, 0.08]), verbal/numeric memory (0.11 [0.09, 0.13]), and processing speed (0.05 [0.03, 0.07]). Over the follow‐up (median [interquartile range]: 11.52 [11.62–11.87] years), 553 individuals developed dementia. Compared to low CRF, the incidence rate ratio (IRR [95% CI]) of dementia was 0.61 (0.48–0.77) for high CRF, and the onset of dementia was delayed by 1.47 (95% CI: 0.64–2.30) years among people with high vs. low CRF. Among people with moderate/high genetic risk for dementia, high CRF can attenuate dementia risk by 35% (IRR = 0.65, 95% CI: 0.51–0.82). There was a trend of CRF to alleviate the genetic risk for dementia, but the additive interaction was not significant.

Conclusion

High CRF is associated with better cognitive performance at baseline, and lower dementia risk over follow‐up. High CRF could mitigate the impact of genetic predisposition on dementia risk by almost 40%.
Projected differences in wait times for diagnosis of Alzheimer’s disease for individuals dually eligible for Medicare and Medicaid in the U.S due to higher disease burden and obstacles to access
Authors: Mattke Soeren , Chu Samantha , Jun Hankyung , Hanson Mark
Published: January 2025

Background

As disease‐modifying treatments for Alzheimer’s disease (AD) are becoming available in the US, concerns have been raised that an unprepared healthcare system will be unable to cope with the expected influx of patients. Individuals dually eligible for Medicare and Medicaid might be disproportionately affected by wait times for three reasons. They have higher burden of disease; many practices do not accept Medicaid at all and those who do might limit the number of Medicaid patients because of lower payment rates under the so‐called lesser‐of policy. States with that policy may elect to pay only up to the Medicaid rate when covering Medicare cost‐sharing requirements for their indigent members. We estimate the effect of the three types of obstacles on wait times.

Method

We used a Markov model to predict wait times for dually eligible and regular Medicare beneficiaries in all 50 states and the District of Columbia from 2023 to 2050. Counts of both groups by age, sex and states were derived from Census data and Medicare enrollment records. We obtained Medicaid rates, estimates for price elasticity of supply of specialty services, willingness of practices to accept Medicaid and burden of disease from published data.

Result

Higher disease burden in duals is projected to lead to wait times of 59.8 months compared to 20.7 months for non‐duals even without considering Medicaid‐specific obstacles to access. Assuming 25% of specialists would not accept Medicaid at all would add around 21.9 months on average. As Medicaid payment rates differ by state, their effect on wait times is projected to vary substantially from adding 2.2 months on average in Virginia to adding at least 99 months in 14 states, such as West Virginia, Oregon and Pennsylvania. Figure 1 illustrates the interaction of disease burden and policy effect by state.

Conclusion

The socio‐economically disadvantaged group of duals might face disproportionate wait times for an AD diagnosis, which could be long enough to deprive them of access to treatment entirely and translate into avoidable disease progression and mortality, raising concerns about health equity.
A systematic review and meta‐analysis of the association between mood disorders and Alzheimer’s dementia
Authors: Ma Liwei , Goudey Benjamin , Masters Colin L. , Jin Liang , Pan Yijun
Published: January 2025

Background

Anxiety and depression are mood disorders that can manifest decades before the onset of dementia, including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). A systematic review with meta‐analysis was conducted to investigate whether anxiety/depression modifies the risk of MCI/AD.

Method

Embase, Global Health, MEDLINE, APA PsycInfo (from inception to July 2023) were systematically searched for well‐structured cohort studies examining the association between anxiety/depression and dementia. Meta‐analyses were performed, and summary relative risks (RRs with 95% confidence intervals [95% CI]) were calculated using a random effects model. The quality of the evidence was assessed using the GRADE tool.

Result

Thirty‐nine studies met the inclusion criteria. Anxiety was significantly associated with MCI (six studies, RR 1.50 [1.11‐2.03], p = 0.018) but not with AD (ten studies, RR 1.31 [0.94‐1.81], p = 0.099). Depression was significantly associated with both MCI (fourteen studies, RR 1.35 [1.08‐1.68], p = 0.012) and AD (nineteen studies, RR 1.57 [1.26‐1.96], p < 0.001).

Conclusion

The meta‐analysis has demonstrated that anxiety is associated with increased incidence of MCI, and depression is associated with increased incidence of both AD and MCI. The current study provides epidemiological evidence that anxiety and depression have potential additive effects to the clinical evolution of MCI/AD.
Gender‐ and age‐specific association of known type 2 diabetes mellitus on incident mild cognitive impairment five years later: Results from the population‐based Heinz Nixdorf Recall Study
Authors: Jokisch Martha , Platzbecker Anna Lena , Gronewold Janine , Jöckel Karl‐Heinz , Moebus Susanne , Erbel Raimund , Schramm Sara ,   the Heinz Nixdorf Recall Study Investigative Group
Published: January 2025

Background

Type 2 diabetes mellitus (T2DM) is considered a risk factor for dementia. The association of T2DM and mild cognitive impairment (MCI) is reported inconsistently and appears to be gender‐ and age‐specific. The aim of the present study was to investigate the (gender‐ and age‐specific) risk of incident MCI five years later in initially cognitively healthy participants with vs. without known T2DM.

Method

1467 subjects of the second (t1) and third (t2) follow‐up examination of the prospective, population‐based Heinz Nixdorf Recall Study (t1: 2005‐2009, Ø62.9 years; t2: 2010‐2015, Ø68.1 years) with complete data regarding T2DM (t1), complete cognitive assessments (t1&t2) and with a cognitive performance within the age‐ and education‐adjusted norm (cognitively healthy; t1) were included. MCI at t2 was defined present, if the cognitive performance was below the age‐ and education‐adjusted norm in at least one cognitive domain with or without reported subjective cognitive decline. Known T2DM (t1) was defined as self‐reported physician‐confirmed diagnosis or use of antidiabetic medication (n = 145 (9.8%)). Using log‐linear regression analyses with Poisson distribution, the relative risk (RR) for incident MCI with 95% confidence interval (CI) for T2DM vs. no T2DM was calculated (adjusted (adj.) for age, body mass index, smoking status according to directed acyclic graph; stratified by gender and age (50‐65 years, middle‐aged & 66‐80 years, old‐aged)).

Result

Overall, 57 (39.3%) participants with T2DM vs. 363 (27.5%) without T2DM met criteria for MCI at t2. There was an increased RR of incident MCI (adj.: RR 1.31, 95% CI 0.98‐1.74) in participants with T2DM at t1. After stratification, the association was primarily present in middle‐aged participants (adj.: RR 1.67, 95% CI 1.09‐2.56 vs. RR 1.09, 95% CI 0.74.‐1.60 in old‐aged participants), especially in middle‐aged men (adj.: RR 1.84, 95% CI 1.09‐3.11 vs. RR 1.29, 95% CI 0.59‐2.83 in middle‐aged women).

Conclusion

Our longitudinal data confirm T2DM as a risk factor for incident MCI, especially for men aged 50‐65 years. Prevention of T2DM therefore could help to preserve cognitive performance and delay the development of dementia.
Demedarts
Authors: Mateus‐Berr Ruth Gabriele , Scharler‐Plotnik Pia Moana , Kielmeier Lisa , Rusz Alexandra
Published: January 2025

This rollator/walker called THE GARDENER is a so‐called Critical Design. it is not intended for actual use but to attract attention, to encourage new interpretations for designs for those affected. in spring and summer you can go for a walk with a raised bed, so to speak, and talk to/interact with other passers‐by, thus overcoming the loneliness of old age. Hapitically and olfactorily you have a positive connotation.
How Does Social Interaction Impact Grey Matter Volume in Healthy Older Women?
Authors: Kwan Heather , Parker Ashleigh F. , Szoeke Cassandra , Gawryluk Jodie
Published: January 2025

Background

The global population of adults over the age of 65 is expected to surpass 2 billion by 2050. Alongside this rise in the aging population, the incidence of age‐related cognitive decline and dementia will continue to grow. Importantly, women are at an elevated risk of cognitive decline compared to men. Therefore, it is imperative to identify modifiable risk and protective factors for aging women. The Lancet Commission highlighted low social contact as a modifiable risk factor for dementia and the Scaffolding Theory of Aging and Cognition‐Revised suggests potential neural structural benefits of such sources of enrichment. Structural neuroimaging allows for the examination of grey matter volume directly, in vivo. It was hypothesized that women with greater social interaction would demonstrate greater grey matter volume.

Method

The current study used magnetic resonance imaging to examine the relationship between grey matter volume and social interaction in healthy older women. Participants were all biological females over the age 60 and obtained from the Women’s Healthy Ageing Project. The current study included 151 healthy older women (MAge = 70.30 ± 2.88) who had 3T structural magnetic resonance imaging data and had completed the social composite score on the Short Form‐36 (SF‐36). The correlation between the social composite score and grey matter volume was examined using voxel‐based morphometry.

Result

The results did not reveal significant correlations between grey matter volume and scores on the SF‐36, although there were sub‐threshold (p<0.2, corrected) positive correlations in the posterior areas of the brain. A post‐hoc region of interest analysis also revealed a significant correlation between SF‐36 and grey matter volume in the cerebellum (p<0.05, corrected).

Conclusion

Age‐related cognitive decline continues to represent a significant and ongoing issue for our global population, particularly for women who are at an increased risk. It is crucial to continue to investigate the unique variables, such as social interaction, to improve the quality of life for aging women.
Data harmonisation to foster collaboration between Alzheimer’s disease registries
Authors: Perneczky Robert , Hyde Robert , van Beek Johan , Jessen Frank
Published: January 2025

Numerous drugs (including disease‐modifying therapies, cognitive enhancers and neuropsychiatric treatments) are being developed for Alzheimer’s and related dementias (ADRD). Emerging neuroimaging modalities, and genetic and other biomarkers potentially enhance diagnostic and prognostic accuracy. These advances need to be assessed in real‐world studies (RWS).

Currently, there are several national and two emerging international ADRD registries that differ in their data requirements. For instance, most existing registries do not routinely capture safety data. Outcome harmonisation would facilitate collaboration between international and national registries and, in turn, support interoperability, and enhance the statistical power and external validity of RWS.

In response, the International Registry for Alzheimer’s Disease and other Dementias (InRAD) convened a Steering Committee of leaders and investigators from registries in Europe, Asia and Australia to define a harmonised minimum dataset (MDS) and extended dataset (EDS) that enables collaboration. A wider stakeholder group, including patient representatives, regulators, payors and industry, will validate the agreed MDS and EDS (Figure 1). The harmonised MDS and EDS will form the basis of data captured in InRAD, which can also form the foundation of collaboration in future RWS within and across registries (Figures 2 and 3).

The harmonised MDS and EDS reflect the needs of two user levels. Firstly, the MDS and EDS should inform differential diagnosis and clinical decision making by presenting longitudinal data in a graphical dashboard summarising important outcomes at the point of care. The harmonised MDS will encompass demographics, functional and cognitive instruments, and rating scales. The harmonised EDS can answer specific questions and/or include additional functional and cognitive instruments to, for example, reflect local clinical practice and patient‐reported outcomes.

Secondly, harmonised MDS and EDS facilitate collaboration between registries to, for example, benchmark, assess efficacy and important safety outcomes, and to inform health technology assessments. The harmonised data sets will be as lean as practical, undergo comprehensive beta‐testing by InRAD and the results shared with stakeholders.

The presentation will explore the background to and need for data harmonisation across registries, the latest iteration of the harmonised MDS and EDS, and InRAD’s overall progress.
Association between reserve, white matter integrity and cognitive function in Taiwan community‐dwelling older adults
Authors: Ou Tzu‐Chi , Chuang Yi‐Fang
Published: January 2025

Background

The benefit of the reserve, including brain and cognitive reserve, on cognitive functions has been examined in several studies. However, there has been limited evidence about the underlying mechanism, particularly in relation to white matter (WM) integrity. This study aims to investigate the influence of brain and cognitive reserve on cognition and white matter tract integrity among community‐dwelling non‐demented older adults.

Method

We included 379 non‐demented community‐dwelling older adults (287 cognitively normal and 92 mild cognitive impairment [MCI]). The sum of weighted education years and occupational skill level (International Standard Classification of Occupations 2008, ISCO‐08) was used to construct cognitive reserve (CR). The intra‐cranial volume (ICV) was obtained from brain MRI images and used as a proxy of brain reserve (BR). Cognition was assessed across five domains: global cognition, memory, attention, executive function, and language. Fractional anisotropy (FA) values were derived from diffusion tension imaging (DTI), indicating WM integrity. The FA of the global tract was the average of eight major bilateral WM tracts (Fornix, Cingulum, Uncinate fasciculus [UF], Corona radiata, Superior longitudinal fasciculus, Inferior frontal occipital fasciculus, Corpus callosum, Posterior thalamic radiation). We also measured medial temporal lobe (MTL) tracts, the mean from three bilateral MTL WM tracts (Hippocampal cingulum, Fornix, and UF).

Result

The mean age of the study population is 67.7 (±7.2). CR had positive effects on all cognitive domains in the total sample; the effects were stronger on memory (partial r = 0.39, p <0.001) and attention (partial r = 0.53, p <0.001) in normal older adults and stronger on global cognition (partial r = 0.55, p <0.001) and attention (partial r = 0.56, p <0.001) in MCI; BR only had positive effects on attention (partial r = 0.17, p <0.001) in normal older adults. Regarding WM tract integrity, we found that BR had negative effects on Fornix in both normal (partial r = ‐0.16, p = 0.01) and MCI (partial r = ‐0.23, p = 0.04).

Conclusion

CR has significant positive effects on all cognitive domains but has differential cognitive impacts between normal and MCI older adults. On the other hand, BR has significant negative effects on Fornix in both normal or MCI older adults.
Dementia Strategies of England and Glasgow Declaration: What Requires to be Done?
Authors: Bulsari Smruti
Published: January 2025

Background

Considering the enormity and pace of spread of dementia in Europe, Alzheimer’s Society (Europe) launched the Glasgow Declaration in 2014, giving these fundamental rights to persons living with dementia: timely diagnosis and diagnostic support, person‐centred quality care, equitable access to treatment and being respected as an individual. The objective of this study is to identify the focus areas of the dementia strategies of England, and whether the focus has changed over time. This study also examines how well the focus areas of Prime Minister’s Challenges 2015 and 2020 to ensure the accordance of Glasgow declaration rights.

Method

National Dementia Strategy 2009, Prime Minister’s Challenge on Dementia 2015 and 2020 are downloaded from the repository of dementia strategies of Alzheimer’s Society. Text from these documents is cleaned to remove the headers, footers, page numbers, table of contents and references. The text is then preprocessed, which includes removal of special characters, numbers, words tokenisation, part‐of‐speech tagging and lemmatisation, and removal of stop words, extra spaces and punctuations. This preprocessed text is then used to find the word frequencies, separately for each document. Hierarchical Dirichlet Process (HDP), Bayesian approach, is applied to the text of dementia strategies to identify the key focus areas of each of these strategies.

Result

All the three strategies have one common focus area: care and support for people with dementia. Research is an additional focus area in the 2020 strategy. The results of HDP support the findings based on the word frequencies; for all the three documents, care, support and health of people with dementia has consistently retained the key focus of these strategies throughout.

Conclusion

Dementia strategies have a consistent focus on care and support for people with dementia since the first strategy in 2009. These align with two of the rights of Glasgow declaration, for persons living with dementia. Despite that Glasgow declaration was launched five years after the first dementia strategy of England, the later strategies (2015 and 2020) continue to lack focus on the rights to timely diagnosis, equitable access to treatment and the right to be respected as an individual.
Development and Evaluation of Simvastatin based Self nano emulsifying drug delivery system for treatment of Alzheimer’s Disease
Authors:   Hardeep , Pandey Narendra Kumar
Published: January 2025

Background

Alzheimer’s disease (AD) is one of the leading causes of mortality and morbidity across the globe. Its incidences are increasing at an immense rate due to inadequate patient compliance. Hence there is a requirement for a requisite treatment strategy. With the enormous efforts of researchers, they have repurposed the drugs for the management of AD. Simvastatin (SIM) could be one of them. Hence the present work was focused on the formulation development and optimization of self‐nano emulsifying drug delivery system of SIM against AlCl3‐induced AD in rats.

Method

On the basis of pre‐formulation studies oils, surfactants, and cosurfactants were selected. SNEDDS was prepared by stirring technique in which initial trials were done in the ratio of 1:1, 1:2, and 2:1. Further optimized by Box Behnken design. The developed formulation was further characterized for particle size, zeta potential, PDI, TEM analysis, and drug loading (DL). MTT assay was done using SH‐SY5Y cell lines to evaluate toxicity of the developed formulation. In vivo, the evaluation of the developed formulation was tested on an AlCl3‐induced AD rats model.

Result

The optimized formulation exhibited P.S, Z.P, PDI, and DL of 57.46±2.65 nm, ‐13.6±1.18 mV, 0.2±0.11 and 88%, respectively. MTT assay confirmed that the prepared formulation was free of toxicity and safe to use for in vivo study. Most importantly, in vivo, administration of SIM‐SNEDDS resulted in significantly increased bioavailability of SIM in the brain compared to the standard drug donepezil (DPZ) and unprocessed SIM. The range of therapeutic efficacy was better in SIM‐SNEDDS high dose followed by SIM‐SNEDDS low dose, and then DPZ and further naïve SIM bioavailability of SIM in the brain compared to the standard drug DPZ and unprocessed SIM. The range of therapeutic efficacy was better in SIM‐SNEDDS high dose followed by SIM‐SNEDDS low dose, and then DPZ and naïve SIM.

Conclusion

The results of the study concluded that SIM SNEDDS was safe to use in rats. The developed formulation helped in managing AD by promoting antioxidant, anti‐inflammatory and anti‐hyperlipidemic activity. Further explorations with other models and clinical trials are required to better understand the effect of SNEDDS of SIM.
Dementia and the Social Determinants of Health in Colombia
Authors: Romero‐Vanegas Sara Julieta , Pardo Rodrigo , Moreno‐Angarita Marisol
Published: January 2025

Background

Dementia onset and progression may be related to the social determinants of health (SDH), but information regarding those is scarce. Currently, we still lack knowledge about the role of structural determinants of health in dementia and their relationship to recognition spheres (care, social valuation, needs, and rights). This has been reflected in health policies that do not fulfill the expectations of the patients, caregivers, and health professionals.

Method

We performed an exploratory sequential mixed methods design. We included patients with a mild dementia diagnosis (N:28), caregivers (N: 208), and health professionals (N:39). We used a structured interview, study of cases, and focus groups to gather our information. We performed a triangulation method to evaluate the burden of known and unknown needs and afterwards a theoretical analysis of SDH and recognition theory.

Result

Our results suggest that there are individual factors that become risk determinants for dementia. These factors could be the focus of designing preventive or palliative approaches. Psychosocial variables (place of residence, environmental milieu, mobility facilities, insurance regimen, income level among others) modify the quality of life and well‐being perception.

We found that structural determinants, such as the socioeconomic and political context and politics are related to training, legal‐occupational‐labor, property, care, and access to health and respite needs. Cultural norms and values are associated with sociocultural needs beliefs and values, and governance is linked to rights and regulations. When we associate multidimensional needs with the determinants, we observe that they affect the spheres of recognition generating a negative impact on the disease progress, well‐being, and dignified life.

Conclusion

We found a relationship between SDH and the ten dimensions that we explored through the needs assessment methodology. Unresolved needs and lack of recognition related to social determinants, threaten the way of living and feeling dementia, as well as its evolution and progression. Our result could lead to community empowerment, inclusion, visibility at the decision‐making level, and formulation of policies and healthcare services if we understand the interaction between needs, the social determinants of health and the recognition spheres.
Effects of combination mixture of Cannabis sativa with psychoactive drugs on adenosine deaminase, ectonucleosides enzymes, redox status, cognition and hemodynamic function in male rats
Authors: Ajeigbe Olufunke Florence , Ademosun Ayokunle Olubode , Oboh Ganiyu , Lawrence Bodun Oluwaseun
Published: January 2025

Background

The effect of high consumption of psychoactive substances of codeine (CDE), tramadol (TMD), and Cannabis sativa (CNB) as concoction has been associated with altered brain cognitive and neurochemical functions. However, the understanding of the complex mechanism behind the intake of Cannabis sativa co‐administration with tramadol and codeine on both cardiac and brain function, neurotransmitters, purinergic, and antioxidant enzymes activities in the brain and heart of rats remains unreported.

Method

The measure of cognition using morris water maze (MWM) and Y‐maze tests, hemodynamic parameters namely systolic blood pressure (SBP) and heart rate (HR), acetylcholinesterase (AChE), butyl‐cholinesterase (BCHE), adenosine deaminase (ADA), arginase, catalase (CAT), superoxide dismutase (SOD) enzymes’ activities, reduced glutathione (GSH) and malondialdehyde (MDA), nitric oxide (NO) levels, in the brain and heart of CNB, TMD, and CDE exposed rats was done. Forty‐eight male Wistar rats were divided into 8 groups, n = 10. Group 1 was the control group, groups 2, 3, and 4 received oral doses of CDE (2 mg/kg bw), TMD (10 mg/kg bw), and CNB (200 mg/kg bw), while groups 5, 6, 7, and 8 received oral doses of CDE+TMD, CNB+ TMD, CNB+CDE, and CNB+TMD+CDE for a 28‐day period.

Result

Coadministration of CNB, TMD, and CDE was seen to led to the significant decrease in cognitive function, acetyl‐cholinesterase (AChE), butyl‐cholinesterase (BChE), monoamine oxidase (MAO) enzyme activities, and antioxidant enzyme activities in rats' brains when compared against control rats (P< 0.05). Interestingly, CNB, TMD, and CDE co‐administration led to significant decrease in SBP and HR whereas, the activities of ectonucleosides (NTPdase), adenosine deaminase (ADA), and malondialdehyde levels produced in the brain and heart were significantly elevated (P< 0.05) in rats.

Conclusion

Therefore, coadministration of CNB, TMD, and CDE led to neurotransmitter poisoning and hypotensive potential in rats which are a notable mechanism of actions in the understanding of the drug development and synergistic neurotoxicity effects of CNB, TMD, and CDE on rats' hemodynamic and cognitive functions, as well as cholinergic, purinergic, and antioxidant systems.
The Alzheimer’s Tau Platform (ATP): a Phase 2, combination amyloid and tau therapy clinical trial for early AD
Authors: Boxer Adam L. , Sperling Reisa A , Aisen Paul S. S , Petersen Ronald C. , Donohue Michael C. , Raman Rema , Bateman Randall J. , Barragan Eden V. , Rentz Dorene M. , Grill Joshua D , Karlawish Jason , Rissman Robert A , Johnson Keith A ,   Alzheimer’s Clinical Trial Consortium (ACTC)
Published: January 2025

Background

Anti‐amyloid immunotherapies modestly slow disease progression in early symptomatic AD; addition of other therapeutic modalities may be necessary to achieve larger treatment effects. Therapies that directly target tau can potentially produce substantial clinical benefit because the accumulation of insoluble tau protein is strongly correlated with the progression of AD. Which tau therapies are likely to be efficacious, whether or not to combine them with anti‐amyloid therapies, and which individuals are most likely to benefit are important unresolved questions that would require multiple parallel design trials to answer. Platform (umbrella) trials test multiple therapies in the same trial, allowing for substantial savings in time, cost and participant burden.

Method

ATP is a new NIH‐funded Phase 2 clinical trial platform that will be conducted as part of the AD Clinical Trials Consortium (ACTC) in partnership with industry and philanthropic groups. The goal is to investigate the effects of tau therapies on the biological hallmarks of AD including insoluble and soluble tau species, amyloid and other biomarkers of neurodegeneration. ATP will initially evaluate two tau therapies alone or in combination with an anti‐amyloid therapy. 900 participants with late preclinical or early prodromal AD (CDR 0 or 0.5) will be randomized to six arms for two years of blinded treatment, followed by an optional open label extension (Figure 1). At least 20 percent of participants will be from underrepresented groups. The primary endpoint is 18F MK6240 tau PET, with key secondary endpoints including plasma P‐tau and MTBR243‐tau, amyloid PET and clinical assessments (CDR‐SB, PACC5). Inclusion criteria are based on plasma P‐tau217, clinical status and regional 18F MK6240 uptake.

Result

Two tau therapies and an anti‐amyloid therapy have been chosen for inclusion in ATP and startup is underway. The final design, choice of therapies and design as well as plans for inclusion of additional tau therapies after the trial begins and other details will be presented.

Conclusion

The ATP is a six arm factorial design platform trial that is planned to begin in late 2024 or early 2025 that will support efficient development of tau and combination therapies for early, sporadic AD.
Improving young adult knowledge and attitudes towards reducing dementia risk
Authors: Savage Sharon A , Trotter Eloise
Published: January 2025

Background

Dementia may not be imminent for most young adults, however, lifestyle choices in early and midlife can play a significant role in dementia risk. Improving knowledge around modifiable factors and encouraging protective behaviours across the lifespan provides one important approach to lowering dementia incidence. This study aimed to test whether a short educational video, developed specifically for young adults, could improve knowledge of dementia risk factors and shift perceptions around when behaviour change may be relevant.

Method

An online, randomised controlled study was conducted with 88 Australian, aged 18‐24 years. Participants were allocated to view one of two 5‐minute, age‐targeted health videos: “Let’s Talk Dementia” (n = 41) or “Let’s Talk Health” (n = 47). Videos discussed health facts and provided easy‐to‐implement actions young adults could take to protect their future health. Participants were assessed prior to and immediately after watching the video. Assessment involved answering true/false statements regarding modifiable dementia risk factors and indicating the age at which participants believed it was important to make lifestyle changes to reduce dementia risk.

Result

At baseline, no differences were present between the two groups. Knowledge of dementia risk factors was limited (overall mean accuracy of 42%). Only 27% of participants showed awareness regarding the risk of hearing loss in midlife. Approximately 40% were unaware of the risks of hypertension and hyperlipidaemia. Following the video presentations, both groups improved their knowledge, although the greatest change was observed in the dementia video group (up to 76% accuracy vs 58% accuracy for general health video, t(87) = 4.24, p <.001). Here, more than 90% of participants now showed awareness of the risks of smoking, hypertension, and hyperlipidaemia, with 63% responding correctly regarding hearing loss. Majority of participants (69%) already indicated positive attitudes towards implementation of risk‐reducing behaviours by age 30, but increased to 93% of participants at immediate post‐intervention.

Conclusion

Age‐targeted educational videos appear a promising method to increase knowledge of dementia risk factors and encourage positive attitudes towards healthy lifestyle choices in young adults. Further investigation is now needed to understand motivational and behaviour change mechanisms to ensure knowledge is put into action.
Distinctive pattern mapping between cardiometabolic multimorbidity and neuropsychiatric disturbance in multi‐regional‐ethnical older adults
Authors: Zhang Haoran , Wen Haoxuan , Zhao Xuhao , Chen Christopher , Xiao Shifu , Liu Zuyun , Xu Xin
Published: January 2025

Background

Presence of cardiometabolic multimorbidity (CMM) has been linked to depressive symptoms in adults. The present study aimed to investigate the distinctive mapping between CMM and differential neuropsychiatric subsyndromes among multi‐regional and ethnical older adults.

Method

The present study included discovery and validation datasets. The discovery dataset consisted of two longitudinal and two cross‐sectional studies from Asian older adults from both clinical and community settings. The longitudinal validation dataset was from the UK Biobank (UKB). CMM was defined as the coexistence of ≥2 conditions including hypertension, hyperlipidaemia, diabetes mellitus, stroke, and other cardiovascular diseases (CVD). Subsequently, two CMM patterns, including metabolic (≥2 of hypertension, hyperlipidaemia and diabetes mellitus) and cardio‐cerebrovascular multimorbidity (≥2 of hypertension, stroke and CVD) were identified respectively. The neuropsychiatric inventory (NPI) was applied to define four neuropsychiatric subsyndromes in the discovery dataset: psychosis, hyperactivity, affective and apathy. In the validation dataset, the four subsyndromes were defined using previously established methods. Short‐term incidence of subsyndromes was defined as the development of neuropsychiatric symptoms (NPS) in recent 1‐2 years. Two‐step individual participant data was used to establish the cross‐sectional association between CMM and NPS. Cox regression models explored baseline CMM patterns and NPS incidence in both discovery and validation datasets.

Result

The discovery dataset included 2950 Asian participants for cross‐sectional analysis and 967 participants (675 NPS‐free at baseline) for longitudinal analysis. The validation dataset included 885 participants (765 NPS‐free at baseline) for longitudinal analysis. People with CMM had a higher presence of NPS and a higher risk of 1‐year incidence of affective syndrome (hazard ratio [HR] = 3.95, 95%CI = 1.44‐10.82). Regarding CMM patterns, metabolic multimorbidity was associated with affective syndrome at baseline (odds ratio [OR] = 1.35, 95%CI = 1.01‐1.81), as well as its short‐term incidence (HR = 3.88, 95%CI = 1.53‐9.85). In the validation dataset, CMM, especially metabolic multimorbidity, was also associated with an increased risk of short‐term incidence of affective subsyndrome (HR = 8.04, 95%CI = 2.65‐24.40, and HR = 6.44, 95%CI = 2.11‐19.62, respectively). Cardio‐cerebrovascular multimorbidity was not associated with incidence of any NPS in both datasets.

Conclusion

CMM, especially metabolic multimorbidity was associated with affective disturbances in multi‐regional‐ethnical older adults. Our findings emphasized the importance of targeted management of metabolic multimorbidity.
Effects of a multi‐domain intervention against cognitive decline on dementia risk profiles – Results from the AgeWell.de‐trial
Authors: Zülke Andrea , Pabst Alexander , Luppa Melanie , Czock David , Wiese Birgitt , Hoffmann Wolfgang , Frese Thomas , Gensichen Jochen , König Hans‐Helmut , Kaduszkiewicz Hanna , Thyrian Jochen René , Riedel‐Heller Steffi G.
Published: January 2025

Background

Dementia risk scores have been suggested a promising surrogate outcome for lifestyle interventions targeting cognitive function and dementia risk. First evidence suggests beneficial effects of multidomain lifestyle interventions on dementia risk scores. We investigated effects of the multidomain AgeWell.de‐intervention on dementia risk, assessed using the LIfestyle for BRAin health (LIBRA)‐index.

Method

Secondary analyses of AgeWell.de, a multicomponent intervention (including optimization of nutrition, medication, physical, social and cognitive activity) in older adults at increased risk for dementia (trial registration: German Clinical Trials Register, DRKS; ID: DRKS00013555). We analyzed data from n = 461 participants (age: 60‐77 years) with available information on all n = 12 risk/protective factors comprised by the LIBRA (coronary heart disease, diabetes, hypercholesterolemia, hypertension, depression, obesity, smoking, physical inactivity, renal disease, low‐to‐moderate alcohol use, high cognitive activity, healthy diet) at baseline and 24 months‐follow‐up. Intervention effects on LIBRA‐scores and individual LIBRA‐components were assessed using generalized linear models.

Result

The intervention reduced total LIBRA‐scores, indicating a decreased risk for dementia at 24 months follow‐up (b = ‐0.63, 95% CI: ‐1.14, ‐0.12). Intervention effects on LIBRA‐scores were particularly due to favorable changes in diet (OR = 1.60, 95% CI: 1.16, 2.22) and hypertension (OR = 1.61, 95% CI: 1.19, 2.18). In younger participants (60‐69 years), the intervention increased the odds of high cognitive activity at follow‐up (OR = 2.00; 95% CI: 1.20, 3.34).

Conclusion

The AgeWell.de‐intervention successfully reduced dementia risk, assessed using the LIBRA‐score, underscoring the usefulness of the LIBRA as a surrogate outcome when interpreting success of multidomain lifestyle interventions. However, several risk factors for dementia captured in the LIBRA, e.g., physical inactivity, did not change due to the intervention, possibly requiring more intensive interventions and support of participants in conducting the intervention.