bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of surgical vs medical treatment for cholecystitis among people living with dementia
Authors: Adler Rachel R , Xiang Lingwei , Shah Samir K , Clark Clancy J , Kim Dae , Hsu John , Lin Josh , Lipsitz Stuart , Mitchell Susan , Weissman Joel S , Finlayson Emily
Published: January 2025

Background

Cholecystectomy is considered the definitive treatment option for cholecystitis, and patients living with Alzheimer’s Disease and Related Dementias (PLWDs) are at risk for increased mortality, complications, and delirium. However, the effect of different treatment options for cholecystitis among PLWDs has not been elucidated; therefore, this study compares outcomes following cholecystectomy, cholecystostomy tube, and medical management of cholecystitis among this high‐risk group.

Method

We conducted a retrospective analysis of Medicare claims data from 1/1/2016‐12/31/2020. The cohort comprised Medicare PLWDs with continuous fee‐for‐service coverage who were age 66+ and were admitted to an acute care facility with a primary diagnosis of cholecystitis between January 1, 2017 and December 31, 2018 and who had no admissions for cholecystitis in the year prior. We used inverse propensity weighting regression to adjust for confounding by indication. We compared mortality, length of stay, intensive interventions (i.e., intubation), discharge to a higher level of care, and readmissions among patients treated with cholecystectomy, cholecystostomy tube, and medically managed.

Result

We identified 10,187 individuals who met inclusion criteria. Of these, 5,888 (58%) were treated with cholecystectomy, 1,373 (13%) with cholecystostomy tube, and 2,931 (29%) were managed medically. After propensity weighting, we found PLWDs undergoing cholecystectomy had lower mortality (HR 0.66, p<.001), greater risk of delirium (OR 1.26, p = .001), intensive interventions (OR 1.67, P<.001) and discharge to a higher level of care (OR 1.15, p = .007), but lower risk of readmission (HR 0.88, p<.001) compared with subjects managed medically. Likewise, subjects with cholecystostomy tube had greater risk of delirium (OR 1.75, p<.001) and discharge to a higher level of care (OR 1.80, p<.001), but no differences in mortality, intensive interventions or readmissions compared to those managed medically.

Conclusion

Over half of PLWDs experiencing acute cholecystitis received definitive surgical treatment during the index admission. Cholecystectomy in this population was associated with reduced mortality compared to non‐surgical management, but no improvement in other outcomes such as delirium and discharge to a higher level of care. These data can help inform decision‐making discussions for patients with ADRD and their care partners when considering treatment options for acute cholecystitis.
MRI Hippocampus Differential Response to Donepezil vs Placebo in Mild Cognitive Impairment and Alzheimer’s Disease: A Systematic Review of Four Randomized Clinical Trials
Authors: Ismail Youssef A. , Haitham Youssef , Walid Mohammad , Mohamed Hazim , El‐Satar Youssef M. Abd
Published: January 2025

Background

Donepezil, an acetylcholinesterase inhibitor (AChEI), is an FDA‐approved drug to treat these neurodegenerative diseases, e.g., Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI). AChEIs are able to stabilize or slow decline in cognition, function, and behavior. Our objective is to investigate whether Donepezil is able to significantly reduce the rate of hippocampal (Hip) atrophy in neurodegenerative diseases.

Methods

We followed the PRISMA statement guidelines during the preparation of this systematic review. We searched in MEDLINE (PubMed), CENTRAL (Cochrane Library, November 2023), SCOPUS, and Web of Science and included randomized clinical trials (RCTs) comparing 10 mg donepezil‐treated with donepezil‐untreated (placebo) and/without control in terms of magnetic resonance imaging (MRI) follow up visits’ results.

Results

A total of four studies out of 174 met our inclusion criteria (599 participants; donepezil = 281, placebo = 318), two of them were ADs and the others were MCIs. 323 participants were female (representing 53.92% of included study population). Follow up between baseline and endpoint results was 12 months. Available outcome data cover reduction of hippocampal atrophy rate in patients with neurodegenerative diseases, but data on several outcome dimensions were either unavailable or not consistently reported across all studies. Results concluded from studies been conducted on MCI patients were statistically insignificant (P > 0.05) annual percentage of change (APC) of Hip volume at 12 months compared to placebo, but studies on AD patients indicated statistically significant APC of Hip volume at 24 and 50 weeks (P < 0.001), but one of these studies also reported no significant difference in neuropsychological performance between treatment groups.

Conclusion

The findings of this review suggest that donepezil reducing hippocampal atrophy rate was statistically insignificant for MCI and statistically significant for AD, but its clinical significance is questionable until further investigations. It is also important to note that while the data provided insights into the impact of donepezil, there were limitations, such as incomplete reporting of outcome dimensions in some studies.
Epimedium flavonoids improve cerebral white matter lesions by inhibiting neuroinflammation and activating neurotrophic factor signal pathways in spontaneously hypertensive rats
Authors: Zhang Lan , Li Lin , Ma Denglei , Wei Weipeng
Published: January 2025

Background

Cerebral small vessel disease (CSVD) is one of the most common nervous system diseases. Hypertension and neuroinflammation are considered important risk factors for the development of CSVD and white matter (WM) lesions.

Method

We used the spontaneously hypertensive rat (SHR) as a model of early‐onset CSVD and administered epimedium flavonoids (EF) for three months. The learning and memorization abilities were tested by new object recognition test. The pathological changes of WM were assessed using magnetic resonance imaging, transmission electron microscopy (TEM), Luxol fast blue and Black Gold staining. Oligodendrocytes (OLs) and myelin basic protein were detected by immunohistochemistry. The ultrastructure of the tight junctions was examined using TEM. Microglia and astrocytes were detected by immunofluorescence. RNA‐seq was performed on the corpus callosum of rats.

Result

The results revealed that EF could significantly improve the learning and memory impairments in SHR, alleviate the injury and demyelination of WM nerve fibers, promote the differentiation of oligodendrocyte precursor cells (OPCs) into mature OLs, inhibit the activation of microglia and astrocytes, inhibit the expression of p38 MAPK/NF‐κB p65/NLRP3 and inflammatory cytokines, and increase the expression of tight‐junction related proteins ZO‐1, occludin, and claudin‐5. RNA‐seq analysis showed that the neurotrophin signaling pathway played an important role in the disease. RT‐qPCR and WB results showed that EF could regulate the expression of nerve growth factor and brain‐derived neurotrophic factor and their downstream related proteins in the neurotrophin signaling pathway.

Conclusion

This study might explain the potential mechanism of EF’s effects on the cognitive impairment and WM damage caused by hypertension.
Digital version of Defense Automated Neurobehavioral Assessment in South Asian Setting: Preliminary evidence from the P‐CARRS study
Authors: Jagannathan Ram , Komal Rani , Mohan Deepa , Subramani Poongothai , Pai Rima , Alladi Suvarna , Mohan Sailesh , Ali Mohammed K , Tandon Nikhil , Prabhakaran Dorairaj , Mohan V , Levey Allan I. , KM Venkat Narayan , Goldstein Felicia
Published: January 2025

Background

The Defense Automated Neurobehavioral Assessment (DANA) encompasses a suite of standardized neurocognitive screening tools designed for detecting various neurodegenerative diseases and subtle cognitive deficits. This study presents a pilot investigation into digital cognitive screening, utilizing an Android version of the DANA tests, conducted among a diverse South Asian population residing in India.

Methods

The study involved individuals aged over 50 years, nested within the ongoing population‐based longitudinal Precision‐CARRS study, representative of socio‐demographically and linguistically diverse adults from Delhi and Chennai in India. Cognitive functioning was assessed using the Android‐based mobile platform DANA screening library: code substitution (set shifting), Go/No‐Go (response inhibition), memory search (working memory), spatial processing (visuospatial), and simple reaction time (processing speed), facilitated by a commercially available FDA‐approved Linus Health digital application. To classify participants as cognitively impaired or intact, performance on the traditionally administered paper/pencil version of the Mini‐Cog screening test, which includes clock drawing and three‐item recall, was considered.

Results

A total of 358 participants (age, median: 61.0 years; range: 50‐89 years; female: 56%; educational categories: up to primary schooling: 8.4%; high school to secondary: 65.9%; graduation and above: 25.7%) with the Mini‐Cog screening test and smartphone‐based DANA screening were included in the analysis. Sixteen percent (n=58) of the participants were cognitively impaired on the Mini‐Cog (0‐2 points/5 total points). On average, DANA tasks were administered in ∼20 minutes. Older age (p<0.0001) was associated with worse DANA cognitive efficiency scores, response time, and fewer cumulative correct responses. There were no sex differences in performance, and only two of the five DANA task performances (code substitution and memory search) differed based on education categories. Compared to those without impaired Mini‐Cog scores, the impaired group had decreased cognitive efficiency scores, slower average response times, and fewer correct responses for two (Go/No‐Go and memory search) of the five DANA tasks (Table).

Conclusion

Our pilot study strongly demonstrates the potential of using smartphone‐based standardized DANA assessments in cognitive screening and the scalability of digital assessments in a diverse population from a resource‐constrained LMIC setting.
Comparison of cognitive behavioral therapy to delay the onset of dementia in patients with Alzheimer’s disease. A systematic Review
Authors: Ortega Christan J Monge , Flores Marcos Arreola , Ortíz Arid Barragán , Rodríguez Sergio M Carrillo , Suárez Gilberto Mauricio , Castillo David A Chávez , Posadas Maria F Estrada , Lara Sofia Andrade , Ortega Thania F Estrada
Published: January 2025

Background

Following a diagnosis of dementia, the patient experiences changes that mainly affect his cognitive behavior. Various behavioral therapies are currently being explored to reduce these symptoms and improve the patient’s quality of life.

Method

Flow chart

Result

In the context of the emotional impact associated with the diagnosis of dementia, the search for interventions to mitigate emotional and social deterioration in patients has intensified.

Cognitive therapy (CT) and rTMSA altogether: 2 types of non‐pharmacological interventions rTMS and CT, in a research study one group together and in the other CT alone. Both groups improved their MMSE test scores, although people who received rTMS in conjunction with CT showed better test scores.

Cognitive Rehabilitation (CR): a clinical trial was conducted to evaluate the effectiveness of cognitive rehabilitation (CR), which consists of strategies to improve procedural learning of skills and to learn or relearn relevant information. Resulted in effective intervention for people with early Alzheimer’s disease.

Electronic Memory and Management Aid (EMMA): these therapies focus on a current intervention for older adults with Subjective Cognitive Risk (SCR), who maintain normal cognition, making the most of skill building and healthy habit formation. The research showed improvements in patients with early‐stage AD at 9 months. However, in more advanced stages, it proved ineffective.

Computerised cognitive training: it has started to show interesting evidence, although at present the evidence in favour remains weak and more robust studies are needed. Interestingly, the improvement was maintained at 6‐month follow‐up, but tended to decline at 12‐month follow‐up as baseline performance was reached.

Conclusion

Concluding, extensive research is being carried out in the development of therapies aimed at mitigating cognitive disorders associated with Alzheimer’s disease. Among these, several are presented in this abstract, with applications that not only improve the quality of life but also the cognitive functioning of patients, proving to be effective, especially in the early stages of the disease.
Comparison of intracranial volume adjustment methods to evaluate brain atrophy severity in AD continuum
Authors: Jung Wooseok , Suh Chong Hyun , Lee Seung Hyun , Kim Jinyoung , Kim Dong‐Hee , Cho Hyeonwoo , Lee Yeha , Kim Sang Joon
Published: January 2025

Background

Normative percentile (NP) quantifies brain atrophy by comparing regional brain volumes of a subject against age and sex‐matched cognitively normal populations. Accurate intracranial volume (ICV) adjustment is vital in NP quantification to minimize the effect of an individual’s head size. However, which intracranial volume adjustment method yields reliable normative percentiles remains unclear. This study explores the differences between ICV adjustment methods to compute NPs and their accuracy in atrophy quantification.

Methods

We sampled MRIs of 1261 subjects consecutively visited the memory clinic (932 MCI; 329 AD dementia) for memory concern and 275 from ADNI (150 MCI; 125 AD). We utilized the AI‐based ICV segmentation tool implemented in VUNO‐Med DeepBrain to measure ICV. We compared three ICV adjustment methods for the NP computation: raw volume, proportion, and residual approaches (Figure 2). To evaluate the reliability of NP, we gauged the correlation between left and right hippocampal NPs and their medial temporal lobe atrophy (MTA) scores manually annotated by two neuroradiologists with consensus. The cut‐off of the MTA score of each hemisphere is set to 2 for subjects with age < 75 and 3 otherwise.

Results

All ICV adjustment methods effectively reduced correlation with ICV (correlations: raw volume = 0.32±0.10, proportion = ‐0.06±0.09, residual = ‐0.07±0.08), but there was no statistically significant difference between the correlations of the proportion and residual methods to ICV. Also, the proportion method retrieves larger hippocampal NP from patients with smaller ICV than the residual method in all disease stage groups. Plotting the mean normative percentiles against ICV volumes suggests that the raw volume method generates more reliable NPs to detect abnormalities in patients with smaller ICV, but using the proportion method was more effective in those with large ICV in both ADNI and ASAN datasets.

Conclusion

Different ICV adjustment methods generate distinct normative percentiles. Despite their effective head‐size correction, applying ICV adjustment was only more effective in subjects with larger ICV than average. Further research is required to confirm if this result applies to other brain regions.
Predicting the risk of cognitive decline and speech impairment in the preclinical stage of Alzheimer's disease using structural MRI
Authors: Li Qingyue , König Alexandra , Linz Nicklas , Levin Fedor , Dyrba Martin , Spottke Annika , Falkenburger Björn , Laske Christoph , Düzel Emrah , Jessen Frank , Zerr Inga , Wiltfang Jens , Priller Josef , Heneka Michael T. , Wagner Michael , Teipel Stefan , Köhler Stefanie
Published: January 2025

Background

Speech abnormalities are increasingly recognized as a manifestation of cognitive deficits in Alzheimer's disease (AD) and its preclinical and prodromal stages. Here, we investigated whether MRI measures of brain atrophy, specifically in the basal forebrain and cortical language areas, can predict cognitive decline and speech difficulties in older adults within the AD spectrum.

Method

The ongoing Prospect‐AD study aims to develop an algorithm to automatically identify speech biomarkers in individuals with early signs of AD. We recruited participants for the Prospect‐AD study from the German national cohort studies DELCODE and DESCRIBE. Within Prospect‐AD, we captured speech recordings via automated phone calls in healthy controls and people with preclinical and prodromal AD. Speech features were extracted from the semantic verbal fluency (SVF) task of automated telephone conversations, using artificial intelligence‐based analysis of the audio recordings. We combined the speech data from Prospect‐AD with the clinical and imaging data from DELCODE and DESCRIBE, including socio‐demographic information, baseline AD diagnosis, neuropsychology, CSF amyloid status, and MRI scans. We used mixed‐effects regression to estimate the association of rates of cognitive decline and traits of automatically obtained speech features with regional atrophy.

Result

To date, we enrolled 220 participants in the Prospect‐AD study, 103 of whom are included in this report. Our participants underwent baseline clinical examinations and MRI scans between 2014 and 2022 (mean age = 68.1, SD=5.7 years, 67% female, mean MMSE score = 29.2, SD=1.3, CDR global score ≤0.5) with annual follow‐up over 4.9 years (SD=2.5 years) and successfully completed the baseline phone assessment in 2022‐2023.

The results will be presented at the conference.

Conclusion

Automated speech‐based cognitive testing may assist in low‐threshold identification of older adults at higher risk for clinical progression to AD which in turn may assist in allocation of clinical resources. In future analyses, we will further investigate associations of cognitive performance and speech features with structural or functional connectivity changes in the brain using DTI or functional MRI data.
A lifespan approach to understanding reserve and resilience
Authors: Walhovd Kristine B , Fjell Anders M , Vidal‐Piñeiro Didac , James Sarah‐Naomi , Demnitz Naiara , Harrison Tessa , Sørensen Øystein
Published: January 2025

Background

That some individuals fall below a functional threshold sooner than others, can be ascribed to differences in “brain maintenance”, slope of change, or variation in previous level, intercept. Intercept differences may be captured in the concept “brain reserve”. Searching for factors that modify outcomes, we need to distinguish how such factors associate with differences in level versus slope of brain and cognition. This necessitates longitudinal data from multiple cohorts since associations can be small and represent different conditions and covariates across samples. Unfortunately, data from longitudinal cohorts are often not readily sharable.

Method

The results of meta‐and mega‐analytic techniques for age‐relationships of neuroimaging and other measures can be compared using data from the Lifebrain consortium (Walhovd et al. Eur Psychiatry. 2018 Jan;47:76‐87). Meta‐GAM, a method for meta‐analysis of generalized additive models (Sørensen et al. NeuroImage 2021;224:117416), yields valid results for modeling non‐linear relationships characteristic of lifespan trajectories. Using meta‐GAM requires less harmonization of measures and enables well‐powered cross‐sample analysis by estimating the relationships of interest separately in each data location without sharing the raw data. Meta‐GAM will be used to test the associations of modifiable and non‐modifiable factors with intercepts and changes in brain and cognition across multiple cohorts. All cohorts will have brain MRI and measures of cognitive function, in addition to factors of interest depending on cohort, such as early life (e.g. birth weight, parental SES), genetics and adult SES and lifestyle variables (e.g. physical activity, dietary pattern).

Results

Preliminary results indicate that individual differences in the level of brain and cognition may appear more stable, larger, and more pervasive than differences in change across the lifespan (Walhovd et al. TICS,2023;27:10). New analyses will focus on the relative strength of associations between potentially modifiable factors, intercept and change of cortical volume and general cognitive ability.

Conclusion

This initiative will allow collaboration and synergies in large‐scale, multi‐sample analyses of cohorts that cannot be shared due to regulatory, privacy or work burden concerns. Investigating how potentially modifiable factors are associated with both level and change may reduce the risk of ascribing undue importance to factors operating in older age.
Unmet Healthcare Needs in People Living with Dementia: Exploring Associations with Sociodemographic and Clinical Characteristics ‐ Findings from the InDePendent Study’s Baseline Assessment
Authors: Scharf Annelie , Kleinke Fabian , Michalowsky Bernhard , Raedke Anika , Pfitzner Stefanie , Mühlichen Franka , Buchholz Maresa , van den Berg Neeltje , Hoffmann Wolfgang
Published: January 2025

Background

The healthcare needs of People living with Dementia (PlwD) (such as Alzheimer’s disease) are often unmet. Information about the needs of community‐dwelling PlwD and their association with sociodemographic and clinical characteristics is needed to fill the knowledge gap regarding factors influencing unmet needs among PlwD and to conduct a comprehensive needs assessment to develop tailored interventions.

Method

We analyzed baseline data of the multi‐centre cluster‐randomized controlled trial (InDePendent) using descriptive statistics to describe patients' sociodemographic and clinical characteristics and Poisson regression models to predict unmet needs, separated by sex. Data were collected personally via face‐to‐face interviews.

Result

Most of the n = 417 participating PlwD were mild to moderately cognitively impaired, were not depressed, had an average of 10.8 diagnoses, took 6.7 medications, and had, on average, 2.4 unmet needs (62% of PlwD had at least one unmet need) measured by the Camberwell Assessment of Need for the Elderly (CANE). Low social support, a high body‐mass index, a lower education, functional impairment, and worse health status were associated with more unmet needs, regardless of sex. More depressive symptoms, a poor financial situation, and living alone increased unmet needs in women, while being recently treated by a general practitioner decreased unmet needs. The number of medications increased unmet needs in male PlwD.

Conclusion

PlwD had a broad array of unmet healthcare needs, indicating primary healthcare provision improvement potentials. The results underscore the significance of early assessment of patient’s clinical characteristics and unmet needs as a basis for individualized gender‐sensible intervention strategies.
Exploring the impact of a caregiver education program within the Comprehensive Resilience‐Building Psychosocial Intervention (CREST) for people with dementia: informal caregivers' perspectives
Authors: Casey Dympna , Smyth Siobhán , Doyle Priscilla , Gallagher Niamh , Whelan Barbara
Published: January 2025

Background

As part of the pilot Comprehensive REsilience‐building psychoSocial intervenTion (CREST) for people with mild to moderate dementia living in the community, a carer education program was developed. The aim of the program was to develop carers’ knowledge and skills regarding dementia to enable them to respond more confidently to the needs of the person with dementia, provide them with ‘me time’, with an opportunity to focus on their own health needs, meet other carers, and share experiences. This study explores the carers’ experience of the program, which consisted of six weekly, 2‐hour sessions with each week covering a different topic.

Method

Qualitative data were collected from group/individual interviews with the carers during the education programme and at the end of the CREST intervention. Attendance rates were recorded and evaluation forms completed by carers at the end of each session. Qualitative data were analysed using thematic analysis and descriptive statistics were used for quantitative data.

Result

Nine carers completed the intervention with an average of 91% attendance (range: 67‐100%). Evaluations were very positive with all carers agreeing that the content of each session was helpful, relevant to their needs, and met their expectations. A key motivator to participate was to gain more knowledge and understanding about dementia and learning communication strategies were particularly useful. The support and learning that carers got from other group members, the social interaction and the emphasis on self‐care were important elements of the programme.

Conclusion

Carers of people with dementia need good support to enable them to manage the challenges of caregiving. The CREST intervention’s carer education program played a crucial role in assisting the carers in managing stress through better communication strategies. It also facilitated the creation of a supportive network among the carers and encouraged them to prioritise their own needs, ultimately enhancing their ability to fulfil their caregiving role.
Use of human iPSC lines to model Alzheimer’s genetic risk and understand disease mechanism
Authors: Goate Alison M. , Münch Alexandra , Molina Carmen Romero , Podlesny‐Drabiniok Anna , Peppler Grace , Garretti Francesca , Patel Tulsi , Lee Hyo , Marcora Edoardo
Published: January 2025

Background

Genome‐wide association studies (GWAS) have identified close to one hundred loci associated with Alzheimer’s disease (AD) risk. However, for most of these loci we do not understand the underlying mechanism leading to disease. Crispr genome editing in human induced pluripotent stem cells (hiPSCs) provides a model system to study the effects of these genetic variants in a disease relevant cell type.

Method

We used integrative genomics to identify the cell types and genes that are most likely to explain the disease risk identified in GWAS and the direction of effect associated with elevated or reduced risk. We used crispr genome editing to modify expression of these candidate genes and tested the impact of modulating gene expression on myeloid cell function and AD associated phenotypes in vitro and in vivo.

Result

AD risk alleles are enriched in myeloid cell enhancers but also in certain gene families. We have focused our functional studies on two such gene families: MS4A4A/MS4A6A and LACTB/B2. MS4A4A/MS4A6A are implicated in TREM2 signaling, and are major regulators of sTREM2 levels in cerebrospinal fluid (CSF) whereas LACTB/B2 are lactamases expressed in mitochondria. LACTB is the major modulator of succinyl carnitine levels, a metabolite in CSF associated with AD.

Conclusion

iPSC provide powerful models for understanding the molecular mechanisms underlying genetic risk for AD
The genetic epidemiology of dementia in under‐represented ethnic communities using studies of the COSMIC Consortium
Authors: Mather Karen A , Thalamuthu Anbupalam , Lipnicki Darren M. , Sachdev Perminder S. ,   COSMIC Consortium
Published: January 2025

Background

Most human genetic association studies have been undertaken in populations of European ancestry, despite >75% of the world’s population being of Asian or African ancestry. In addition, many of the non‐white genetic studies have had small sample sizes and lack replication. To date, >80 different genetic variants have been identified for late‐onset Alzheimer’s disease (AD) using populations mainly of European ancestry and from high income countries, despite more than ∼60% of dementia cases living in low and middle‐income countries. There is a need to evaluate genetic risk of dementia and related phenotypes in under‐represented populations, such as the multi‐ethnic cohorts of the Cohort Studies of Memory in an International Consortium (COSMIC). Polygenic risk scores (PRS) summarise the known genetic risk for a particular disorder or trait, such as dementia. But the applicability and generalisability of dementia PRSs based on genetic studies of European ancestry is unclear. This study aims to examine the utility and performance of dementia polygenic risk scores (PRSs) derived from European, non‐European, and trans‐ethnic samples for dementia diagnosis and its associations with cognitive impairment in COSMIC studies.

Method

COSMIC participants (middle‐aged to older adults) with genome‐wide genotyping, cognitive and dementia data will be included. Genotypes will be imputed to the appropriate reference panel/s. PRSs will be derived using the appropriate GWAS summary statistics based on European and non‐European based cohorts and trans‐ethnic analyses for the two most common types of dementia (Alzheimer’s disease [AD], vascular dementia [VaD]). Association analyses for the phenotypes of AD, VaD, and cognitive performance will be undertaken using regression adjusting for age, sex, and any other specific covariates.

Result

There are at least 14 COSMIC cohorts with genotyping and dementia/cognitive data available who have recruited participants of European and non‐European ancestry (n>15K), including studies from Japan, South America, Africa, India, and China. Performance of PRSes computed under various models for predicting dementia and cognitive impairment will be presented.

Conclusion

This work will elucidate the utility of specific and multi‐ethnic dementia PRSs predicting the risk of dementia and its endophenotype, cognitive impairment.
Caregivers of people with Alzheimer’s Disease in Puerto Rico 2021 ‐ 2022: A panoramic view of their epidemiological profile, health status and quality of life
Authors: Cabrera Alex , Felici Marcos E. , Cartagena Marianne
Published: January 2025

Background

Alzheimer’s Disease (AD) is the fourth leading cause of death in Puerto Rico (PR), with an estimated prevalence of 14%. Caregivers are an essential part in the management and care of people with AD. Providing care for a person with Alzheimer can change over time and can become a challenge for the caregivers. For this reason, self‐care is one of the most important things that a caregiver must do. The main objective of this research is to perform an epidemiological profile of caregivers for people with Alzheimer in PR and analyze the health status and quality of life variables collected by the PR Behavioral Risk Factor Surveillance System (PRBRFSS).

Method

A descriptive cross‐sectional study was carried out using the PRBRFSS data for 2021‐2022. Univariate analysis was performed to obtain an epidemiological profile of caregivers for people with Alzheimer in Puerto Rico, as well as to analyze health status and quality of life variables.

Result

For 2021‐2022, according to the PRBRFSS, a total of 318,924 people in Puerto Rico identified themselves as caregivers. Among these, 16.9% reported being a caregiver of a person with Alzheimer. Approximately 23.0% of the caregivers for people with AD were in the 55‐64 age group, 63.9% were women, 41.4% were married, 70.6% had education above high school, and 47.2% had an annual income of $25,000 or more. In terms of health and quality of life, 23.1% reported having bad or poor health, 23.6% reported having depression, and 60.7% reported at least one comorbidity. Likewise, 24.4% reported difficulty seeing, 23.1% walking or ascending stairs, 18.6% concentrating or remembering, 11.0% performing tasks alone, 8.0% hearing, and 6.5% dressing or taking a bath.

Conclusion

Caregiving for a person with Alzheimer becomes more challenging over time due to the evolution of symptoms and the level of care needed. For this reason, caregivers need to maintain good health and reduce the risk of burnout. This research demonstrates the importance of continuing to create programs and support groups for caregivers of people with Alzheimer to encourage self‐care and improve their health and quality of life.
Relation Between Markers of Systemic Inflammation, White Matter Lesions, and Cognitive Performance in Late Adulthood
Authors: Jain Shivangi , Lesnovskaya Alina , Wan Lu , Molina‐Hidalgo Cristina , Huang Haiqing , Marsland Anna , Grove George , Oberlin Lauren , Kang Chaeryon , Kramer Arthur , Hillman Charles , McAuley Edward , Burns Jeffrey M , Vidoni Eric D , Sutton Brad , Erickson Kirk I.
Published: January 2025

Background

Aging is associated with heightened systemic inflammation, decline in selective aspects of cognition, and an increase in white matter lesions (WMLs). Both WMLs and systemic inflammation have been related to cognition. However, it is not clear how they interdependently relate to cognitive aging. In this study we examined whether WMLs mediate the relation between markers of systemic inflammation and cognition in late adulthood.

Method

Baseline data from the randomized clinical trial “Investigating Gains in Neurocognition in an Intervention Trial of Exercise” (IGNITE) were used, which included 598 healthy older adults (mean age=69.9±3.75 years). Interleukin 6 (IL‐6) and Tumor Necrosis Factor Alpha (TNF‐α) were included as markers of systemic inflammation. A confirmatory factor analysis of cognitive performance resulted in factors measuring episodic memory (EM), processing speed (PS), working memory (WM), attentional control (AC), and visuospatial function (VF). WML volumes were computed from FLAIR and T1 scans using UBO detector. Mediation models were run with age, sex, years of education, and study site included as covariates.

Result

Higher levels of IL‐6 were associated with more WMLs (b = 0.12, p < 0.001) as well as lower scores on all cognitive factors (all p < 0.03). In contrast, higher levels of TNF‐ α were associated with more WMLs (b = 0.10, p < 0.05) but not with any of the cognitive measures (all p > 0.3). More WMLs were associated with poorer PS, WM, AC, and VF (all p < 0.03), but not EM (all p > 0.05). Further, associations between IL‐6 and measures of PS, WM, AC, and VF were statistically mediated by WMLs (all b = ‐0.01, all p < 0.05).

Conclusion

These findings suggest that markers of systemic inflammation might lead to poorer cognitive performance by impacting WMLs. The differences between IL‐6 and TNF‐α with cognition highlight the need for more research to understand how different cytokine pathways relate to cognition. Our results are important for building a mechanistic framework to understand the interplay between inflammation, WMLs, and cognition and could inform the development of targeted interventions focusing on regulating cytokines to support brain health and cognitive aging.
Performance of a new instrument designed to assess medication use in cognitive impairment and dementia: A cross‐sectional analysis
Authors: Sharma Rishabh , Lee Linda , Chang Feng , Patel Tejal
Published: January 2025

Background

The Medication Review in Cognitive Impairment and Dementia (MedRevCiD) checklist is a new tool designed to assist health care professionals in optimizing medication use in individuals with Mild Cognitive Impairment (MCI) or dementia. It consists of 6 domains, each of which addresses a specific medication use issue such as medication management and adherence. The primary objective of this study was to compare the mean number of drug‐related problems (DRPs) identified with MedRevCiD Checklist to the Medication Appropriateness Index (MAI) in older adults attending a primary care‐based memory clinic.

Methods

A cross‐sectional analysis was conducted at a Multi‐speciality Interprofessional Team‐based (MINT) memory clinic. A medication review was conducted by applying the MAI initially, followed by application of the MedRevCiD checklist to assess medication use and to identify DRPs for participants enrolled in the study. The Wilcoxon signed‐rank test was used to determine if a significant difference exists in the average number of DRPs per person as identified through MedRevCiD compared to MAI.

Results

A total of 44 participants with a mean age of 80.2 ± 6.2 years enrolled in the study. Of the participants, 45.5% (20/44) were female, 36.4% (16/44) had mild cognitive impairment, 20.5% (9/44) had mixed dementia and 11.4% (5/44) had vascular dementia. Participants had an average of 6.7 ± 3.4 comorbidities, most commonly hypertension (63.6%, 28/44), hyperlipidemia (31.8%, 14/44), chronic kidney disease (27.2%, 12/44) and obstructive sleep apnea (25%, 11/44). Participants were taking a median of 7.5 medications (interquartile range 6) per person. A total of 134 DRPs were identified with the use of the MedRevCiD as compared with 81 with the use of the MAI (mean 3.05 ± 4.0 with MedRevCiD vs 1.84 ± 2.9 with MAI; p<0.001). Over 50% of the DRPs identified with the MedRevCiD fell within Domain 6 which focuses on optimizing medication use, while the majority of the DRPs identified from the MAI were focused on drug/disease interactions.

Conclusion

Findings provide insight into the frequency of DRPs among older adults with MCI or dementia. The MedRevCiD checklist proved to be a valuable tool with heightened ability in detecting DRPs in this population.
Characterising subpopulations of patients with Alzheimer’s disease dementia who have high healthcare utilisation and costs
Authors: Edwards Sophie , Trepel Dominic , Ritchie Craig W , Hahn‐Pedersen Julie Hviid , Chan Mei Sum , Bray Benjamin D , Clark Alice , Wichmann Christian Ahmad , Evans Marc
Published: January 2025

Background

How and why healthcare utilisation and costs vary between patients with Alzheimer’s disease dementia (ADD) is not well understood but is important in ensuring that efforts to improve the diagnosis and treatment of ADD are prioritised effectively. We aimed to investigate variation in healthcare resource utilisation (HCRU) among patients with ADD in England and identify the clinical and demographic factors which characterise subpopulations with the highest HCRU.

Method

This was a retrospective cohort study using Discover, a linked electronic health record database of 2.8 million residents in London, England. We identified individuals with ADD using diagnostic codes and estimated HCRU and total healthcare costs over up to 9 years of follow up (2010‐2019). Individuals included in the 2019 cross‐section were stratified into cost quintiles, and K‐medoids clustering was used to identify subpopulations with high costs.

Result

We identified 18,116 individuals with ADD between 2010 and 2019 (Table 1). Costs in the highest HCRU cost quintile in 2019 accounted for 56% of all healthcare costs in the ADD population, were approximately 20 times higher than the lowest cost quintile (£13,665 vs. £678 per patient per year [ppy]) and were largely attributed to hospital admissions (Figure 1). Individuals in the higher cost populations tended to be older, male, have a higher comorbidity burden and a lower median survival than those in the lower cost populations. The three groups with the highest costs identified by the cluster analysis had substantial comorbidity burden, with more than 65% of individuals having four or more comorbidities (Figure 2). The most common comorbidities were cardiometabolic diseases, chronic kidney disease, and frailty. The costs in the highest cost cluster were more than double the cluster with lowest costs (£6,355 vs. £3,160 ppy).

Conclusion

Healthcare utilisation and costs in individuals with ADD vary widely, with a large proportion of costs being attributable to a minority of patients with multiple comorbidities, particularly cardiometabolic diseases and frailty. Health systems should focus on patients with clinical profiles associated with high costs in efforts to improve the timely diagnosis and treatment of ADD and mitigate the financial costs of ADD on patients, health systems, and society.
Social Support, Isolation, and Cognitive Health among LGBTQ+ Older Adults in the United States
Authors: Lampe Nik M. , McKay Tara
Published: January 2025

Background

Lack of social support and social isolation are risk factors for poor cognitive health. Lesbian, gay, bisexual, transgender, and queer (LGBTQ) older adults consistently report higher levels of isolation and less social support in population studies. In this study, we test the effects of support for LGBTQ+ identity and feelings of social isolation on subjective cognitive health in a cohort of LGBTQ+ older Americans.

Method

We use Wave 1 data from the Vanderbilt University Social Networks, Aging, and Policy Study (VUSNAPS). VUSNAPS recruited 1,256 LGBTQ+ adults aged 50+ in four US states between 2020‐2021. Subjective cognitive problems were measured using a 15‐item scale capturing problems with memory, cognition, and functioning. Chi‐square tests and logistic and Poisson regressions were used to test associations between levels of support from family, coworkers, neighbors, and number of days feeling isolated in the last 7 days with the number of cognitive difficulties reported and reporting >4 cognitive difficulties. Analyses control for gender, race, education, employment status, personal income, age, and married/partnered status.

Result

About 11% of respondents reported having >4 cognitive difficulties. Compared to respondents reporting <4 cognitive difficulties, respondents reporting >4 cognitive problems were more likely to be bisexual (16.8 vs 10.6%, p<.05), report personal income lower than US median personal income (16.2% vs 7.5%, p<.001), and be working less than full time (13.6 vs 7.3%, p<.001). Respondents with LGBTQ+ supportive families and coworkers reported significantly fewer cognitive problems (IRR = 0.698, p<.001; IRR = 0.846, p<0.1), and those with supportive families were 43.2% less likely to report >4 cognitive problems (p<.01). Presence of unsupportive families, coworkers, neighbors, and friends were significantly correlated with feelings of social isolation (p<.01 for each). One third of respondents (35.0%) reported feeling isolated ≥4 of the last 7 days. Respondents who reported feeling isolated ≥4 days were two‐and‐a‐half times more likely to report ≥4 cognitive problems (OR = 2.67; p<.001).

Conclusion

We find associations between subjective cognitive health and LGBTQ‐specific social support in a large sample of older LGBTQ+ adults. Availability of social support and risk of social isolation should be assessed when administering cognitive screenings for LGBTQ+ older patients.
Multivariate genomic analyses of frailty reveal the unique importance of cognitive and multimorbidity pathways for aging‐related health outcomes
Authors: Foote Isabelle F , Flint Jonny P , Fisk John D , Karakach Tobias K , Rutenberg Andrew , Martin Nicholas G , Lupton Michelle K , Cox Simon R , Luciano Michelle , Rockwood Kenneth , Grotzinger Andrew D
Published: January 2025

Background

Frailty is a complex clinical state that is associated with poorer health outcomes and increased dementia risk in older adults. It is routinely measured using the Frailty Index, which is a proportional score based on the number of ‘deficits’ that an individual has. Whilst such measures are useful for risk assessment, the aggregation of highly heterogeneous deficit profiles in genetic studies may obscure important insights into the underlying biology of frailty.

Method

We used Genomic Structural Equation Modelling to model shared genetic signal between 30 deficits from the Frailty Index using summary data from genome‐wide association studies (GWAS). This involved conducting a multivariate GWAS to identify genomic risk loci associated with each of the latent frailty factors in our model. We used polygenic risk scores (PRS) to test the predictive accuracy of the latent factors for detecting frailty status in 3 external cohort studies. Finally, we tested the genetic correlation between our latent frailty factors and >50 aging‐related outcomes, including dementia.

Result

The genetic architecture of the frailty deficits was best captured by a general factor influencing all 30 deficits, plus 6 additional latent factors representing genetic overlap between distinct subsets of deficits that were uncorrelated with the general factor. These 6 factors can be broadly described as reflecting pathways linked to social isolation, unhealthy lifestyle, multimorbidity, metabolic/respiratory status, cognition, and disability. GWAS conducted to measure the effects of individual genetic variants on these frailty factors identified 408 genomic risk loci. Our PRS analyses demonstrated consistent evidence that shared genetic pathways between frailty deficits linked to multimorbidity and cognition, but unique of the general frailty factor, are particularly important for predicting frailty status. Genetic correlation analyses further highlighted a significant genetic association between frailty pathways linked to cognition and Alzheimer’s disease (rg = 0.32, SE = 0.07, p = 5.58×10−06).

Conclusion

Our findings provide novel insights into the characterization of general and specific pathways within the frailty state at the genetic level. We demonstrate how refining our knowledge of frailty, particularly in relation to multimorbidity and cognitive impairment, may help to stratify frail individuals at increased risk of developing dementia or other adverse health outcomes.
Risk factors for subjective and objective cognitive decline in sexual minority older adults
Authors: Manca Riccardo , Flatt Jason D. , Venneri Annalena
Published: January 2025

Background

Sexual minority older adults (SMOAs) report subjective cognitive decline (SCD) more than heterosexual older adults (HOAs). Inconsistent findings have emerged about the risk of cognitive decline in SMOAs. This study aimed to compare the impact of multiple psycho‐social risk factors on both objectively assessed and subjectively reported cognitive decline between HOAs and SMOAs.

Method

Two samples of self‐identified HOAs (n = 4180) and SMOAs (n = 92) who completed Waves 8 and 9 of the English Longitudinal Study of Ageing were selected. Reliable change indices for episodic and semantic memory were created to assess longitudinal cognitive changes. SCD was self‐assessed for both memory and general cognition. Mental and cardiovascular health, marital status, loneliness, and socio‐economic status (SES) were investigated as risk factors for cognitive decline. The effect of each risk factor and their interaction effects with sexual orientation on memory changes and SCD were tested, respectively, with general linear and logistic regression models. Age, education, and sex were included as covariates. A sensitivity analysis was carried out in a sub‐sample (n = 92, per group) matched for demographics.

Result

Cognitive changes and rates of SCD were similar between SMOAs and HOAs. All risk factors, apart from marital status, were associated SCD risk, while only SES was associated with decline in episodic memory (β = .01, p = .038). A SES×sexual orientation interaction was found for semantic memory (β = ‐.06, p = .042); among those in the lowest quintile, SMOAs had better semantic memory preservation over time than HOAs. A sensitivity analysis found among those in the highest quintile, SMOAs had worse semantic memory decline than HOAs.

Conclusion

SCD was associated with a multitude of risk factors, in line with previous evidence of SCD as a heterogeneous construct. This was similar between SMOAs and HOAs. Longitudinal changes in semantic memory were, instead, differentially impacted by SES in the groups. Sensitivity analysis confirmed a potential lack of protective effect in SMOAs, although the groups did not differ for SES. These findings may be interpreted within the framework of material deprivation, which is more likely among SMOAs and may contribute to their cognitive decline more severely than in HOAs.