bluuebunny/crossref_metadata_2025 huggingface dataset:
The inverse association between cancer and Alzheimer’s disease: evidence from neuropathological studies
Authors: Abner Erin L. , Karanth Shama D , Aung Khine Z , Nelson Peter T
Published: January 2025

Background

Some types of cancer have been associated with reduced risk of clinical dementia diagnosis. Whether cancer history may be associated with neuropathological features of neurodegeneration or cerebrovascular disease is not well understood. We investigated the relation between cancer diagnosis and brain pathology in a sample of community‐based research volunteers enrolled in an Alzheimer’s Disease Research Center (ADRC) cohort.

Method

Data from autopsied participants from the University of Kentucky ADRC were linked to the population‐based Kentucky Cancer Registery, which is a CDC Surveillance, Epidemiology, and End‐Results (SEER) program. We examined the relationship between cancer diagnosis, clinical dementia diagnosis, Mini‐Mental State Examination scores and neuropathological features using inverse probability weighting to address bias due to confounding and missing data. To address bias due to inclusion of participants with dementia at cohort baseline, we repeated all analyses restricted to the participants who were cognitively normal at baseline.

Result

Included participants (n = 785) had a mean ± standard deviation age of death of 83.8 ± 8.6 years; 60.1% were female. Cancer diagnosis was determined in 190 (24.2%) participants. Participants with cancer diagnosis had lower odds of mild cognitive impairment or dementia, and higher cognitive test scores (e.g. Mini‐Mental State Examination scores evaluated 6 and ≤2 years antemortem, P < 0.001 for both comparisons). Cancer diagnosis also associated with lower odds of higher Braak neurofibrillary tangle stages (III/IV) or (V/VI), moderate/frequent neuritic plaques, moderate/frequent diffuse plaques and moderate/severe cerebral amyloid angiopathy (all P < 0.05). By contrast, TDP‐43, α‐synuclein and cerebrovascular pathologies were not associated with cancer diagnosis. Cancer diagnosis was associated with a lower burden of Alzheimer’s disease pathology and less cognitive impairment.

Conclusion

This study provides evidence that the inverse association between cancer and Alzheimer’s disease may not be fully explained by selection and survival bias. Ongoing research by our team is investigating the association between genetic burden of cancer risk and neuropathological features.
Cognitive assessment tools for older adults in the Arabic language: a systematic review
Authors: Kabalan Mayssan , Bazzi Ola , Al‐Barathie Josleen , Zein Ola El , Chehabeddine Lara , Chaaya Monique , de Leon Carlos Mendes , Elbejjani Martine
Published: January 2025

Background

Across the Arab world, Alzheimer’s disease and related dementias (ADRD) are a growing public health concern with the increase in the proportion of older adults. Yet, our understanding of these conditions remains limited because of a lack of data. Robust assessments of cognitive function are crucial for screening, prevention, and risk factor identification. This systematic review aims to identify available cognitive assessments in Arabic and assess their validity and performance.

Method

We conducted a comprehensive search with a broad inclusion criterion using Medline OVID, EMBASE, and APA PsychInfo up to November 2023. Our search included both studies developing or validating cognitive assessment tools in Arabic for individuals aged 50 and above, and studies applying any such tool in the Arabic language. Study selection and data abstraction were carried out in duplicate and independently and using standardized and pilot‐tested forms. We analyzed and reported the availability, appropriateness, and use of the available cognitive assessment instruments.

Result

Our review yielded 154 studies, of which 27 studies involved developing or validating a tool and 127 studies used a cognitive assessment tool. Among the validation studies, measures of validity, reliability, or normative data were available for 22 cognitive assessment tools. 21 studies focused on criterion validity with 18 testing tools compared to clinical assessments and 3 compared to other scales. Cut‐off scores, sensitivity, and specificity were tested in 21 studies for a total of 15 tools. 35% of the validation studies had no reliability measures. Three studies developed a new assessment tool. The Mini Mental State Examination was the most frequently validated and used instrument across diverse settings. Studies validating domain‐specific tools were limited, with memory being the most frequently validated. Among studies using a cognitive tool in Arabic, over half used unvalidated versions.

Conclusion

Psychometric evaluations of cognitive assessments for older Arabic‐speaking adults remain scarce with limited data regarding domain‐specific assessments, reproducibility, and suitability in different settings (different countries or different samples: clinical, community, nursing home). Findings emphasize this important challenge that can hinder robust data on ADRD burden and risk trajectories in Arab populations.
The combined effect of cognitive impairment and pain on functional and mobilitydisability among older adults in India
Authors: Muhammad Thalil , Pai Manacy
Published: January 2025

Background

We examined the associations between cognitive impairment, experiences of pain, and functional and mobility disability among older adults in India. Moreover, we assessed the combined effects of cognitive impairment and pain on functional and mobility disability among older Indians.

Method

Data come from baseline wave (2017‐19) of the Longitudinal Aging Study in India, with a sample of 31,464 older adults aged 60+ years. Cognitive impairment was assessed using measures of memory, orientation, arithmetic function, and visuo‐spatial construction skills. Functional and mobility disability was evaluated using the scales of activities of daily living (ADLs, score 0‐6), instrumental activities of daily living (IADLs, score 0‐7), and mobility (score 0‐9). Pain and pain frequency was self‐reported. Multivariable linear regression models were employed to examine the association between variables, and the interaction terms were used to test the moderation effects.

Result

Older adults who were cognitively impaired were more likely to report ADL (beta: 0.295, CI: 0.238, 0.352), IADL (beta: 0.642, CI: 0.547, 0.737), and mobility disability (beta: 0.605, CI: 0.490, 0.719). Similarly, those reporting any pain were more likely to report ADL (beta: 0.258, CI: 0.224, 0.292), IADL (beta: 0.421, CI: 0.367, 0.475), and mobility disability (beta: 1.320, CI: 1.244, 1.396). Further, the interactions between cognitive impairment and pain were statistically consequential (p<0.001) for ADL, IADL, and mobility disability, and the associations between cognitive impairment and functional and mobility disability were more pronounced among older women and those experiencing frequent pain (5+ days/week).

Conclusion

Our findings underscore the need for integrated healthcare approaches that address cognitive health and pain management simultaneously to help older adults maintain functional abilities and mobility. That female gender and frequent pain magnify the association between cognitive impairment and functional and mobility disability is useful information for providers and practitioners offering individualized care plans to older patients.
Insights from Alzheimer’s Disease Multimodal Screening and Prevention Strategies in Egyptian Healthcare Institutions: A Systematic Literature Review
Authors: Haitham Youssef , Ismail Youssef A. , Walid Mohammad , Mohamed Hazim , El‐Satar Youssef M. Abd
Published: January 2025

Background

Alzheimer’s Disease (AD) is a progressive, incurable neurological condition that is the most common cause of dementia. Five percent of people aged 65 to 74, 13.1% of people aged 75 to 84, and 33.3% of people aged 85 or older have AD, according to 2023 statistics. Due to the lack of scientific data comparing the success and cost‐effectiveness of screening programs and trial recruiting strategies, the main goal of this paper is to determine the existence and quality of AD screening (if existed) in Egypt, including how often it’s done, how common it is and how much information is known about the importance of AD screening among both healthcare professionals and the general public.

Methods

We reviewed database searches through November 2023 in MEDLINE, PsycINFO, and the Cochrane Central Register of Controlled Trials; and additional searches for ongoing trials through ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and Current Controlled Trials (ISRCTN Register). We also investigated healthcare units in Port Said, Ismailia and some units in Cairo about typical AD screening programs that have been established or scheduled to be initiated in the future.

Results

Healthcare units investigations show that the AD screening program has not been established yet and isn’t scheduled for any future dates. There was no previous history of screening programs being held in Egypt in any digital database. AD screening programs are a crucial part of regular public health awareness, especially for elderly individuals that are particularly vulnerable to its effects and are affected by it at a disproportionately high level compared to other people.

Conclusion

We could not find any solid evidence on the previous existence of any AD screening programs in Egypt. Further investigations are required to drive conclusive decisions about the quality of screening programs in Egypt.
Dementia, Mild Cognitive Impairment and Ambulatory Care Utilization
Authors: Chen Yi , James Bryan D , Capuano Ana W. , Banerjee Mousumi , Springer Mellanie , Bynum Julie , Grodstein Francine
Published: January 2025

Background

Dementia is underdiagnosed by the healthcare system, and MCI is rarely identified. Thus, while interventions to reduce cognitive decline are becoming increasingly available, it is not clear how appropriate individuals will be evaluated for treatment opportunities. A first step to improving diagnosis is understanding how older individuals with dementia or MCI interact with the healthcare system, especially ambulatory evaluation and management (E&M) visits, the backbone of healthcare.

Method

We investigated 2,116 community‐dwelling participants in four cohorts at the Rush Alzheimer’s Disease Center, all with linked Medicare Fee‐for‐Service claims. Each year from 2011‐19, we classified participants as no cognitive impairment (NCI), MCI, or dementia, based on their annual cohort evaluation; we then compared number of ambulatory E&M visits in claims over the next year across groups, controlled for demographics and comorbidities, using repeated measures generalized Poisson mixed effect models. We also considered annual likelihood of visiting different provider specialties, using logistic mixed effect models.

Result

We included 8,672 person‐years (PY) of followup: 76% with NCI, 17% with MCI, and 7% with dementia. Average age over followup was 82 years, and 24% of PY was among Black participants; mean number of ambulatory E&M visits was 9.7/year (SD 6.9). Dementia was strongly associated with fewer E&M visits (23% fewer visits/year, p<0.001) but changes began even in MCI, which was associated with about 5% fewer visits (p = 0.02), compared to NCI. Participants with dementia and MCI were more likely to visit a dementia‐related specialist (odds ratio [OR] = 1.9, p<0.0001 for MCI; OR = 1.8, p = 0.009 for dementia) than those with NCI, although only a small minority (<30%) saw these specialists. Further, both dementia (OR = 0.2, p<0.0001) and MCI (OR = 0.6, p = 0.0001) were related to substantially lower likelihood of seeing any other medical specialist, indicating that even those with MCI were not receiving the full spectrum of healthcare.

Conclusion

Impaired cognition was associated with fewer ambulatory E&M visits, and less complexity in healthcare; while these results were strongest for dementia, alterations appeared even with MCI. Finding ways to improve ambulatory care utilization for those with cognitive impairment is critical to identifying and supporting individuals who can benefit from treatment interventions.
The Effect of Upward Educational Mobility on Cognitive Performance Among Older Adults: A Comparison Between Mexico and South Africa
Authors: Meza Erika
Published: January 2025

Background

Upward socioeconomic trajectories across the life course have been protectively associated with late‐life cognitive outcomes. However, few studies have explored this association in low‐ and middle‐income countries (LMICs). Our study examines how upward educational mobility affects cognitive performance in nationally representative samples of older adults in Mexico and South Africa, two LMICs with a history of social and economic disadvantages and different educational transformations.

Method

Data were from two nationally representative samples of adults 50 years and older, the Mexican Health and Aging Study (MHAS), the Health and Aging in Africa Longitudinal Study in South Africa (HAALSI), and their harmonized cognitive aging ancillary studies, Mex‐Cog and HAALSI‐Dementia. We used linear regression models to evaluate the relationship between upward educational mobility in adjacent generations (i.e., first‐generation to receive a formal education) and cognitive performance (i.e., orientation, executive function, language, memory, and global cognitive domains).

Result

Our study included 1,031 participants whose parents did not receive any formal education; most were female (58%), and on average Mex‐Cog participants (n = 584) were slightly younger (mean: 69; sd: 9.3) than HAALSI‐dementia participants (n = 447; mean: 72; sd: 11.3). Among individuals whose parents did not receive a formal education, participants who received some education (i.e., upwardly mobile) had higher cognitive performance scores at baseline. Adjusting for age and sex, upwardly mobile individuals had 0.52 (95% CI: 0.42, 0.63) higher orientation, 0.39 (95% CI: 0.29, 0.48) higher language, and 0.37 (95% CI: 0.29, 0.46) higher memory performance in both cohorts. Greater benefits of upward educational mobility on executive function and global cognitive performance were observed for Mex‐Cog participants (B: 0.79; 95% CI: 0.67, 0.92 and B: 0.66; 95% CI: 0.54, 0.78, respectively) compared to their HAALSI‐dementia counterparts (B: 0.44; 95% CI: 0.33, 0.56 and B: 0.51; 95% CI: 0.39, 0.62).

Conclusion

Our findings emphasize the impact of greater access to educational opportunities on late‐life cognitive performance and the importance of contextualizing educational transformational benefits in different settings.
Recruitment Strategies and Preliminary Results from the IPAT Study
Authors: Zaenglein Jordan , Hall Tristyn , McGregor Margaret , Tomlinson Anna , Reagin Christopher , Mathison Stephen , Rivera‐Torres Solymar , Zhang Rong
Published: January 2025

Background

The Impact of Intensive Treatment of Systolic Blood Pressure on Brain Perfusion, Amyloid and Tau in Older Adults (IPAT) is an ongoing randomized control trial (RCT) for prevention of Alzheimer’s disease (AD) (NCT05331144). The primary outcome of the trial is to assess the impact of intensive lowering of high systolic blood pressure (SBP) on the accumulation of brain amyloid in older adults for a study duration of 2 years. Study recruitment started on October 25th of 2022 and will end in September of 2025. The goal is to enroll 180 participants. Inclusionary criteria include participants who are between the ages of 60 and 85 and have a systolic blood pressure (SPB) of 130mmHg or greater. Exclusionary criteria include those who have a history of major cerebrovascular disease, a diagnosis of Alzheimer’s disease and related dementias (ADRD), other major neurologic diseases, or cannot perform MRI.

Methods

A multimodal recruitment approach was implemented which includes hospital databases, virtual sources, referrals, and community outreach activities (Table 1). The recruitment response yield, scheduled consent visit yield, and randomization yield from October 2022 to December 2023 were analyzed across the recruitment source subgroups.

Results

The total recruitment response was 718 potential participants. Out of 718 potential participants, 77 individuals had an informed consent appointment scheduled (10.7%) and 23 of the 718 individuals were randomized (3.2%). The source subset that produced the highest yield for total recruitment response was hospital databases (67%). The source subset that produced the highest yield for consent visits scheduled was hospital databases (68%). The source subset that produced the highest yield for randomizations was hospital databases (56%) (Figure 1).

Conclusions

The IPAT Study had a success with total recruitment yield from the hospital database sources, but less success with virtual resources, referrals, and community outreach activities. However, a multimodal recruitment approach is essential to meet the overall enrollment goal of the project.
Association of moderate and vigorous physical activity with cognitive performance: results from the ELSI‐Brasil Study
Authors: Martins‐Pais Ingryd Mayara Nascimento , Rabelo Wendell Lima , Vidal‐Ferreira Naomi , Ferri Cleusa P , Suemoto Claudia Kimie , Gonçalves Natalia G
Published: January 2025

Background

Moderate physical activity (PA) is considered one of the main protective factors for the risk of dementia. It is estimated that 1.6% of dementia cases worldwide could be prevented with increases in physical activity. However, there is little evidence of the association between vigorous physical activity and cognitive performance. Therefore, this study aimed to investigate the association between moderate and vigorous physical activity and cognitive performance in older adults from the Brazilian Longitudinal Study of Aging (ELSI‐Brasil).

Method

The sample included 9,412 adults 50 years or older from the Brazilian Longitudinal Study of Aging. Cognitive performance evaluated the memory, temporal orientation, and verbal fluency domains. A global composite z‐score was derived from the tests. PA was assessed using the International Physical Activity Questionnaire. We used linear regression models to verify the association of moderate and vigorous physical activity with cognitive performance.

Result

After exclusions, a total of 7,954 participants remained. Mean age was 61.8±9,2 years, 61.8% were women, 44.3% were mixed, 36.4% practiced at least 150 minutes of moderate physical activity, and 21.1% practiced at least 75 minutes of vigorous physical activity (Table 1). Compared to participants who did not meet the guideline for moderate PA (less than 150 minutes/week), those who met the guidelines (150 to 299 min/week) and those who performed more than 2x the recommended amount of moderate PA (300 minutes or more/week) had better global cognitive performance (β = 0.174, 95% CI = 0.097;0.250, p<0.001; β = 0.196, 95% CI = 0.124;0.268, p<0.001, respectively) (Figure 1). We found no association between vigorous PA and cognitive performance (Figure 1).

Conclusion

While performing 150 minutes/week or more of moderate PA was associated with better cognitive performance, there was no additional benefit of vigorous PA for cognitive performance.
Long‐term cost‐effectiveness of collaborative dementia care for persons living alone versus those living with a caregiver in Germany
Authors: Michalowsky Bernhard , Platen Moritz , Blotenberg Iris , Teipel Stefan , Thyrian Jochen René , Hoffmann Wolfgang
Published: January 2025

Background

Previous trials reported that collaborative Dementia Care Management (cDCM) could be cost‐effective in the short term, especially for those living alone. However, long‐term evidence is lacking. Therefore, the study’s objective was to determine the long‐term efficacy and cost‐effectiveness of cDCM in those living alone compared to those living with a caregiver. compared with usual care.

Method

A General Practitioner (GP)‐based, cluster‐randomized‐controlled intervention trial (DelpHi‐MV) was conducted. Participating GP practices were randomly allocated to one of two arms (care as usual or cDCM). Participants were included if they were 70 years or older, living at home, and screened positive for dementia. Participants of the intervention group received a comprehensive needs assessment and individualized interventions by nurses specifically qualified for dementia collaborating with GPs and healthcare stakeholders over six months. Controls received usual care. We conducted a subgroup analyses separating the sample into those living alone versus those living not alone. Health‐Related Quality of Life (SF‐6D), Quality‐adjusted life years, and resource used were assessed at baseline, 12, 24 and 36 months.

Result

428 (n = 303 cDCM, n = 125 usual care) participants were included in the analysis. Based on multivariate regression models adjusted for baseline scores, cDCM was more cost‐effective in PlwD living alone. Compared to controls, the gain in QALY (alone: +0.224 [95% CI 0.03 to 0.42], p = 0.027; not alone: 0.079 [95% CI ‐0.11 to 0.27], p<0.417), savings in costs (alone: ‐3,815 [‐12,573 to 5,982], p = 0.485; not alone: 3,283 [‐3,514 to 11,121], p = 0.307), and the probability of cost‐effectiveness at WTP 40.000€/QALY was significantly higher in PlwD living alone (92% vs 32%). Differences in costs were especially due to a trend for delayed institutionalization in the first and second year for those living alone.

Conclusion

cDCM is cost‐effective in the long term beyond the intervention or short‐term periods, improving patients HRQoL and reducing costs in those living alone. Therefore, should become a health policy priority and translated into routine care practice. Whether cDCM more likely leads to better‐prepared institutionalization should be investigated in future research to support the community‐dwelling living situation as long as possible and make institutionalizations as smooth as possible.
Living alone with dementia in Japan: challenges and policies
Authors: Awata Shuichi
Published: January 2025

Background

Due to declining birthrate and increasing longevity, the number of older people living alone with cognitive impairment is rapidly increasing in Japan. They have a lot of challenges in terms of health, housing, finance, daily life and protection of rights, all of which should be clarified to create inclusive, equitable, and sustainable super‐aged societies.

Methods

A series of factual investigation was conducted using existing statical materials, community‐based epidemiological studies, clinic‐based case studies, and literature reviews.

Results

According to the national prevalence rate of dementia and the future population estimate by household type, the percentage of older people living alone with dementia were estimated to increase with age, particularly in female; those in oldest‐old population aged 85 years and more were estimated to be 7% in male and 14% in female in 2025 and rapidly increase during the first half of 21th century. A series of factual investigations suggested that older people living alone with cognitive impairment were more likely to feel lonely, have poor nutritional status, become victims of fraud and natural disasters, die after missing, and experience disruption of continuous living in a community. “Community Space”, the places where older people are able to stay freely and comfortably in a community, may contribute to improve accessibility to health and social care services. In addition to public advocacy systems such as the adult gurdian system, every service provider, prticularly health and social care service providers, should learn the skill for decision support. Public‐private partnership should be promoted to prevail rational accommodation in social environment.

Conclusion

The national and local governments should formulate comprehensive policies to ensure human rights of older people living alone with cognitive impairment in a community. The first version of the guidance to create social environment to support the lives of older people living alone with cognitive impairment was published in Japan.
An intervention to support persons living alone with cognitive impairment in the United States
Authors: Gibson Allison
Published: January 2025

Background

Although most individuals experiencing cognitive impairment reside with another, as many as one third may live alone. Such individuals may have difficulty managing their health and wellbeing. Further, they may be more isolated from healthcare and social services. Developing strategies to circumvent premature institutional placement and reduce use of emergency services is vital to keeping healthcare expenditures lower, and also recognizes the needs of individual’s safety, autonomy, and quality‐of‐life.

Methods

This study utilized a single‐arm, non‐randomized trial design. This proof‐of‐concept study aimed to establish feasibility of Services To Age in Your Home (STAY Home) service utilization and care management intervention to improve utilization of healthcare and social support services for persons living alone with cognitive impairment. The intervention implemented one session weekly for twelve weeks through in‐person visits by a team of social workers and student interns of approximately one hour. Potential participants underwent cognitive screenings, the Adapted Informed Consent Questionnaire, and the informed consent process was repeated every 30 days to try to ensure that participants were appropriate to participate. The primary outcome was to increase healthcare and social service utilization. Exploratory outcomes examined social support and biopsychosocial needs.

Results

Of the 12 participants, individuals reported limited, non‐traditional forms of social support. Analyses of the data demonstrate a significant need for this population to link those living alone with cognitive impairment to healthcare and social services (pre‐intervention only 42% had been seen by a social serivce provider in the last year; only 33% had seen a healthcare provider in the last year). Analyses demonstrate the intervention is feasible with high adherence to weekly visits (75%). While the study was not powered to compare secondary outcomes, quality‐of‐life increased for participants from pre‐ to post‐intervention (pre‐intervention x̄ = 2.7; post‐intervention x̄ = 3.3; p‐value = 0.01).

Conclusion

While many participants were willing to engage in the pilot program, additional barriers contributed to utilizing health and social services. Future studies must continue to explore potential solutions for this difficult‐to‐support population. In addition to increasing access to healthcare and support services, participants may also benefit from a medication adherence component to the intervention.
Effect of intentional weight loss through dietary intervention on cognition: The MIND Trial Study
Authors: Dhana Klodian , Ventrelle Jennifer , Carey Vincent J , Aggarwal Neelum T. , Arfanakis Konstantions , Sacks Frank , Barnes Lisa L.
Published: January 2025

Background

With the increasing prevalence of obesity and its negative consequences on health, weight management has emerged as a priority for public health. We conducted a study to investigate the association of intentional weight loss through dietary intervention on cognition among older adults participating in the MIND trial.

Method

MIND trial enrolled overweight older adults aged 65‐85 years with a family history of dementia but without cognitive impairment and self‐reporting a suboptimal diet. Participants were randomized to the MIND diet or a control (usual) diet for 3 years; both diets promoted weight loss through mild caloric restriction. Of 604 individuals enrolled in the MIND trial, 520 had measured weight at the baseline and year 3 visit and were included in the analysis. We computed the percentage of weight loss based on baseline and last assessment and grouped individuals into 4 categories: weight gainers, <5% weight loss, 5‐10% weight loss, and >10% weight loss. Linear mixed‐effect models were used to estimate the 3‐year change in global cognitive scores. Models were adjusted by age, sex, race, apolipoprotein E (APOE) e4 allele, baseline BMI, and dietary assignment.

Result

The mean age was 70 years, 65% were women, and the mean BMI was 34 kg/m2. During 3 years of dietary intervention, 78.5% of participants lost weight. The average weight loss ranged from 2.3 kg to 15kg. Compared to people who gained weight, those with >10% weight loss significantly improved their cognitive scores by 0.103 SD/units (95%CI 0.008, 0.199) at year 3 visit. In addition, individuals who lost weight had improved plasma levels of inflammation, lipids, and glucose during the trial period. Among people in the MIND diet group, those with >10% weight loss significantly improved their cognitive scores by 0.171 SD/units (95%CI 0.028, 0.314) compared to people who gained weight; there was no significant association in the control diet group.

Conclusion

Among overweight and cognitively unimpaired individuals at the baseline with a family history of dementia, a weight loss of 10% (average 15 kg) or more during 3 years of dietary interventions was associated with improved cognitive scores when compared to people who gained weight.
Prediction of Incident Alzheimer's Disease in Older Community‐Dwelling Adults using Wrist Accelerometry and Deep Learning
Authors: Midroni Julie , Yu Lei , Rabin Jennifer S , Liu Xilin , Goubran Maged , Buchman Aron S , Bennett David A. , Lim Andrew
Published: January 2025

Background

Drugs targeting Alzheimer's disease (AD) pathology are likely to be most effective in the presymptomatic stage, where individuals harbor AD pathology but have not manifested symptoms. Neuroimaging approaches can help to identify such individuals, but are costly for population‐wide screening. Cost‐effective screening is needed to identify those who may benefit from neuroimaging, such as those at risk of developing clinical disease. We present a deep learning algorithm that uses accelerometry recordings to predict clinically diagnosed AD in dementia‐free patients.

Method

Participants were from The Memory and Aging Project (MAP), a longitudinal cohort study of older adults focused on aging and dementia. As part of this study, participants were asked to wear a wrist accelerometer for ten days. We designed a feedforward neural network that synthesizes clinical and accelerometric features to predict clinical AD. Clinical features were selected based on ease of collection, and included age, sex, education, social isolation and purpose in life. The dataset included participants without dementia at the time of recording, who survived for and had a known clinical AD outcome within five years of the recording.

Result

The training dataset consisted of 875 unique patients. The test dataset consisted of 395 unique patients (mean age 81.5, SD= 6.8). 14.4% of the test set developed clinical AD within five years. On the test set, the model achieved 89% sensitivity (SN), 70% specificity (SP), and an F1 score of 0.87 (Figure 1). This is superior to accelerometric‐only (SN 67%, SP 70%, F1 0.68) and clinical‐only (SN 76%, SP 80%, F1 0.78) models. Model accuracy was similar for patients both with and without mild cognitive impairment at baseline. When the binarized model output was used as a predictor for five‐year AD‐free survival via Cox proportional hazards (Figure 2), it achieved a C‐index of 0.729 [95% CI 0.69 b‐0.77], a hazard ratio of 6.90 [95% CI 4.15‐11.47], and a log‐likelihood ratio of 71.05. Further tuning and validation of the model are underway.

Conclusion

A deep learning model using wrist accelerometry and easily obtained clinical features shows promise in predicting 5‐year AD outcomes in adults without dementia at baseline.
Towards predicting individual cognitive trajectories in AD using Quantitative Systems Pharmacology
Authors: Schuttel Ivo , Short Shaina M , Geerts Hugo
Published: January 2025

Background

While a number of recent anti‐amyloid antibodies demonstrated a robust reduction of amyloid biomarkers in clinical trials, the impact on functional improvement is much more variable. We hypothesize that this larger variability is driven by comedications, common genotype variants and underlying tau pathology.

Method

In a previously calibrated computational neuroscience model of ADAS‐Cog, we implemented the effect of soluble amyloid monomers and oligomers on glutamate and nicotinic AChR neurotransmission and the effect of intracellular tau oligomers on voltage‐gated Na and K+ channels and synaptic density. The quantitative relationship between amyloid and tau biomarker was derived from a mechanistic QSP model. The effect of CNS active comedications and impact of COMTVal156Met and 5HTT‐rs23352 genotype on relevant neurotransmitter receptors were calculated using affinity data and clinical information.

Result

We used a virtual twin approach to simulate the cognitive trajectory of individual patients from the ADNI database based on their individual baseline comedications, genotypes, amyloid and tau load. Comparison to the actual observed trajectory revealed the importance of common dopaminergic and serotonergic genotypes. We also found that serotonergic pharmacology of comedications could substantially modulate differential cognitive trajectories for the same amount of amyloid increase.

Conclusion

Such a predictive platform, once validated can be useful to support clinical trial design, with regard to stratification and protocol amendments and reducing outcome variability by comparing the cognitive trajectory of subjects on active treatment with the same patients in a virtual placebo arm.
Exploring the impact of mindfulness training and a health promotion program on cognitive and mental health of older adults
Authors: Santos Ana Carolina Teixeira , Gomes Leandro , Pereira Diana R , Ribeiro Fabiana , Silva‐Fernandes Anabela , Godinho Catarina , Carvalheiro Joana , Federspiel Carine , Steinmetz Jean‐Paul , Leist Anja K.
Published: January 2025

Background

The positive effects of mindfulness‐based stress reduction (MBSR) on cognition, stress relief, and sleep have been well‐documented. However, there is limited research on its potential benefits for older adults, particularly within vulnerable populations such as migrants. This study aimed to compare the impacts of MBSR with a health promotion program in individuals aged ≥55.

Method

A monocentric, randomized, double‐blind controlled clinical trial was conducted with 89 participants (≥55 years old), all Portuguese‐speaking immigrants in Luxembourg. They were randomly assigned to a 2‐month group intervention, either MBSR (N = 44) or Health Education Program (HEP, n = 45). Data collection occurred at baseline, end of the intervention, and one to three months post‐intervention. Executive functioning was assessed using the Trail Making Test, Stroop color‐word task, and letter‐number sequencing. Secondary outcomes encompassed general cognitive functioning, cortisol level, heart rate variability, and self‐reported affective and mindfulness states.

Result

Of the 125 individuals screened, 89 (mean age: 62.58 years ± 6.08, 63 [70.8%] women) were enrolled, with 75% completing at least one post‐intervention assessment in MBSR and 53% in HEP, included in the modified intention‐to‐treat analysis. The overall dropout rate was 36% and no adverse effects were identified. Time effects were observed in the Letter‐Number Sequencing (β = 0.47, SE = 0.23, t = 2.09, p = 0.04), anxiety (β = ‐1.70, SE = 0.49, t = ‐3.46, p < 0.01), and perceived stress (β = ‐2.17, SE = 0.71, t = ‐3.05, p < 0.01). However, there were no significant group differences or group*time interactions (p > 0.05).

Conclusions

Both interventions demonstrated positive impacts on attention, anxiety, and perceived stress among older migrants, indicating that these group interventions have the potential to improve cognitive and affective indicators irrespective of the intervention content. Future studies could further investigate these findings by incorporating an additional control arm with no social contact to help validate the protective effects of group interventions in older vulnerable populations. Our work underscores the significance of positioning these interventions as potential strategies within the realm of dementia prevention.
Strategies for recruiting diverse young adults into aging research
Authors: Munoz Haydee Izurieta , Casas Antonio , Gaddy Myles , Sanchez Selena Hernandez , Johnson Leigh A.
Published: January 2025

Background

In aging research, there is an increasing focus on the decades leading up to changes in cognition. Biomarker studies have suggested that biochemical brain fluctuations can occur up to 20 years prior to clinical symptoms. Including populations of adults who are 20 years away from any cognitive symptomatology in aging research can shed a light on the longitudinal factors involved in brain aging. The aim of this study was to describe and evaluate the methods of recruiting ethnically diverse younger adults (30‐49 years old) into aging research.

Method

The Health & Aging Brain Study‐ Health Disparities (HABS‐HD) study is a community based longitudinal study of cognitive aging in a multiethnic cohort. Participants must undergo an interview, neuropsychological testing, a blood draw, an MRI scan and PET scan of the brain. The study began in 2017, with the goal of enrolling 3000 diverse participants 50 years or older. Thanks to a grant from the National Institute of Aging, the study began enrolling 1500 participants 30‐49 years old in September 2022. The previous outreach strategies focused on older adults had to be modified and updated to cater to the younger group. The outreach team developed, implemented and tracked a variety of strategies from people signing up from the study through enrollment.

Result

From September 2022 through November 2023, 541 people 30‐49 signed up to be part of the study. 69.7% were female and 30.3% were male, with a mean age of 40 (SD = 5.9). Of those 541 sign ups, 461 participants scheduled an appointment and 332 came in for their study visit (61.4% enrollment rate). The sample included 207 Black/African Americans, 234 Hispanics, 93 Non‐Hispanic Whites and 7 participants of another race. Enrollment data showed that the younger group were recruited mostly through personal referrals (40.1%) and outreach events (38.1%).

Conclusion

The study team had to modify approaches to recruitment in order to enroll a younger cohort into the HABS‐HD study, since approaches used previously for older adult were not sufficient. Personal referrals were the biggest drivers of successful enrollment, which suggests that personal trust is crucial in recruiting a novel cohort.
Economic Implications of Dementia in the United States: Assessing the Relationship Between Direct Medical Spending and Informal Care Costs
Authors: Lastuka Amy , Breshock Michael , Dieleman Joseph L
Published: January 2025

Background

There are 6.7 million people living with dementia in the United States, and this number is projected to increase as the population ages. The cost of informal care makes up a large proportion of the societal costs of dementia due to the significant care needs associated with the condition.

Method

We combined previously created estimates of direct medical spending attributable to dementia with estimates of informal care costs to arrive at a total societal cost for dementia. Informal care estimates are based on survey data from the Health and Retirement Study, the National Health and Aging Trends Study, and the Behavioral Risk Factor Surveillance System. Both replacement cost and forgone wage cost are estimated for informal care.

Result

We estimated that the annual societal cost attributable to dementia in 2019 was $60,311 (95% uncertainty interval [UI] $56,230–$64,507) per prevalent case when informal case is measured in terms of replacement cost, and $36,245 (95% UI $34,562–$37,960) per prevalent case when informal care cost is measured in terms forgone wages of caregivers. The contribution of informal care to total costs varied substantially by state, ranging from 58% (95% CI 55‐60%) in Connecticut to 84% (95% CI 83‐85%) in New Mexico when measured in terms of replacement cost. When measured in terms of forgone wages, the contribution of informal care ranged from 43% (95% CI 41‐45%) in Connecticut to 69% (95% CI 67‐70%) in Arizona.

We found a negative relationship between direct and indirect costs of dementia. When disaggregating based on type of care, we found that this inverse relationship was driven by long‐term care and ambulatory care. The cost of informal care was not correlated with the cost of emergency department care or inpatient care.

Conclusion

The inverse relationship between direct and indirect costs of dementia provides suggestive evidence that they act as substitutes. While the substitution between informal care and long‐term care is unsurprising, more research is needed to understand potential mechanisms linking informal care and ambulatory care costs.
Characteristics of heart failure complicated by dementia
Authors: Kokubo Manabu , Shimizu Atsuya , Kamihara Takahiro , Hirashiki Akihiro , Takeda Akinori , Arai Hidenori
Published: January 2025

Background

With its rapidly aging population, Japan has been seeing an increase in the concurrent incidence of dementia during heart failure treatment, making disease management difficult. Nevertheless, not much has been uncovered about the actual state of the treatment status and prognosis of heart failure patients with dementia.

Method

At the National Center for Geriatrics and Gerontology, we retrospectively analyzed cases of patients who died of heart failure between 2018 and 2022, who were also complicated with dementia, and whose treatment progress from the initial onset of heart failure to death could be confirmed.

Result

Overall, 20 patients satisfied the above criteria. Their mean age at death was 89.4 ± 3.3 years (10 males: 89.3 ± 2.3 years; 10 females: 89.5 ± 3.7 years). The mean duration from the initial onset of heart failure (heart failure stage C) to death was 2.4 ± 3.3 years, with a maximum of approximately 11 years and a minimum of several days.

The mean number of hospitalizations during the course of the disease was 2.1 ± 1.4, with the highest number being 6, and 9 patients ending up dying during the first hospitalization. Four patients developed dementia after the onset of heart failure, and their treatment duration tended to be prolonged. Only four patients were institutionalized at the time of the onset of heart failure. The most common underlying disease was hypertension, which was observed in 19 patients. Additionally, atrial fibrillation, chronic kidney disease, valvular heart disease, and ischemic heart disease were noted in 9, 10, 6, and 6 patients, respectively. Regarding the classification of heart failure, 12 patients had HFpEF, and 8 had HFrEF

Conclusion

The 5‐year survival rate following the initial onset of heart failure is reported to be 75%. However, a poorer prognosis is likely expected if a heart failure patient is complicated with dementia. The possible factors behind this include the onset of the disease upon entering the older age, the status of oral medications, and difficulty in self‐management. A more detailed examination of the actual situation will be required.
The Southern Illinois University Longitudinal Cognitive Aging Study: A Cohort Analysis
Authors: Settelmyer Zachary , Overby Mark S. , Botchway Albert , Scaife Steven , Zec Ronald F. , Ala Thomas A. , Shah Raj C. , Ranjit Eukesh , Hascup Erin R. , Trivedi Mehul A.
Published: January 2025

Background

The Southern Illinois University Longitudinal Cognitive Aging Study (SIU LCAS) is a community‐based, longitudinal cohort study initiated in 1984. LCAS was initially designed to improve the sensitivity of neuropsychological testing to diagnose mild cognitive impairment (MCI) and dementia in individuals residing in central and southern Illinois.

Method

Participants are recruited from the community via newspaper advertisement, word‐of‐mouth, and community presentations. Individuals with a family history of Alzheimer’s dementia (AD) are strongly represented in this cohort. Participants must be cognitively normal at baseline and free from any neurological, uncontrolled medical, or psychiatric disease at their first visit. Recruitment is primarily focused on individuals over age 60. Participants complete a neuropsychological test battery assessing all major cognitive domains as well as questionnaires assessing personality, subjective cognitive ability, lifestyle factors, and detailed medical history.

Result

The study has enrolled over 1,600 normal control participants since study inception. 150 original participants continue their participation. The average age at first visit is 66.5 (age range: 20‐95). The majority of participants are female (68.4%) and White/Not Hispanic (97.8%). Most participants (93%) have at least 12 years of education. 95% of the participants remained in the state of Illinois throughout their study participation. 29% of participants come from small or rural towns based on NCES locale boundaries data. 39% of participants reside in disadvantaged communities based on Area Deprivation Index scores of 8‐10. 55.4% of participants completed at least two study visits. 22% participants have completed >10 study visits. 63% of study participants are deceased. Only 26 of the deceased participants were enrolled in the brain donation program (17 with autopsy‐confirmed Alzheimer’s disease). 103 individuals met the diagnostic criteria for MCI or AD at baseline. 87 participants enrolled as controls declined to MCI or AD during their participation. 15 participants developed another neurological condition. An additional 86 participants who discontinued participation were found to have been diagnosed with MCI or dementia after discontinuation based on available medical records.

Conclusion

Current directions involve the recruitment of participants from areas of central and southern Illinois who reside in some of the most disadvantages communities in the United States.