bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatigue predicts 10‐year risk of incident dementia in a population representative cohort of United States Medicare beneficiaries
Authors: Moored Kyle D. , Glynn Nancy W. , Carlson Michelle C , Donahue Patrick T. , Schrack Jennifer A
Published: January 2025

Background

Fatigue is prevalent in later life and may increase dementia risk independent of health conditions. Yet, existing epidemiologic studies include samples that are not nationally representative of U.S. older adults. These studies have also not examined fatigue in combination with current physical activity level, which is important because higher fatigue ratings may also stem from a more active lifestyle that could lower dementia risk. We examined whether self‐reported fatigue, both independently and jointly with self‐reported physical activity, was associated with 10‐year risk of incident dementia in U.S. older adults.

Method

Participants were from the National Health and Aging Trends Study (2011‐2021, N = 5,167), a population representative cohort of U.S. Medicare beneficiaries. Fatigue was self‐reported as having low energy in the past month that interfered with activities (yes/no). Participants also reported past‐month engagement in any vigorous activity that increased their heart rate (e.g., working out; yes/no). Probable dementia cases were ascertained using cognitive testing and proxy reporting. Analyses included discrete‐time proportional hazards models with sample weighting to account for survey design and adjusted for baseline age, sex, race/ethnicity, education, BMI, number of health conditions, smoking status, social isolation, and depressive symptoms.

Result

Twenty‐nine percent of participants reported fatigue. Frequencies of combined fatigue and activity groups included: “active/no fatigue” (31%), “active/fatigued” (8%), “inactive/no fatigue” (40%), “inactive/fatigued” (21%). There were 1,089 incident cases of probable dementia for up to 10 years of follow‐up (M±SD = 5.4±3.6 years). Individuals reporting fatigue (vs. no fatigue) had a 16% greater risk of incident dementia after full covariate adjustment (HR = 1.16, 95% CI: 1.01, 1.34, p = .041). Compared to the “active/no fatigue” group, the “inactive/fatigued” group had a 40% greater risk of incident dementia after adjustment (HR = 1.40, 95% CI: 1.16, 1.69, p = .001), but risk did not significantly differ for “active/fatigued” and “inactive/no fatigue” groups (p’s>.05).

Conclusion

Fatigue may be a signal of increased risk of incident dementia in U.S. older adults, independent of depressive symptoms and other health characteristics. Individuals reporting both fatigue and inactivity had the highest risk of dementia, suggesting that fatigue may be a symptom of underlying pathological processes, especially among those with low activity levels.
Gender differences in the impact of illiteracy on dementia risk among community‐dwelling older adults
Authors: Oh Dae Jong , Han Ji Won , Kim Tae Hui , Kwak Kyung Phil , Kim Bong Jo , Kim Shin Gyeom , Kim Jeong Lan , Moon Seok Woo , Park Joon Hyuk , Ryu Seung‐Ho , Youn Jong Chul , Lee Dong Young , Lee Dong Woo , Lee Seok Bum , Lee Jung Jae , Jhoo Jin Hyeong , Kim Ki Woong
Published: January 2025

Background

Illiteracy is highly prevalent in older women than in men, but whether the impact of illiteracy on dementia risk is differed by gender remains unclear.

Method

We enrolled 5,217 non‐demented older adults aged ≥ 60 years from the Korean Longitudinal Study on Cognitive Aging and Dementia. Presence of illiteracy was assessed by research nurses and the diagnoses of incident dementia and Alzheimer’s disease (AD) were made by standardized diagnostic interview by geriatric psychiatrists. Neuropsychologists assessed the cognitive performance by using Korean version of Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet Neuropsychological Assessment Battery. Multivariate Cox proportional hazard regression and linear mixed model analyses were used to identify the impact of illiteracy on the risks of all‐cause dementia/AD and cognitive decline during the 8‐year follow‐up respectively.

Result

Totally, 283 (98 men [4.4%]; 185 women [6.2%]) cases of all‐cause dementia and 227 (71 men [3.2%]; 156 women [5.2%]) cases of AD were identified during the follow‐up period (5.8 ± 2.4 years). Among 901 illiterate participants, 9 (7.9%) men and 101 (12.8%) women developed all‐cause dementia whereas 5 (4.4%) men and 89 (11.3%) women developed AD. Illiteracy was found to pose 2.8‐fold (Hazard Ratio [HR] = 2.79, 95% Confidence Interval [CI] = 1.95 – 3.99) and 2.9‐fold (HR = 2.89, 95% CI = 1.97 – 4.25) increased risks of all‐cause dementia and AD respectively in women. The HRs for association of illiteracy with all‐cause dementia (HR = 2.48, 95% CI = 1.66 – 3.68) and AD (HR = 2.54, 95% CI = 1.66 – 3.90) risks remained significant even when we separately analyzed the less educated women (educational years ≤ 6 years, n = 1,830). However, there was no significant association in men. The impact of illiteracy on the progression of cognitive decline was more pronounced in women (β = ‐0.962, SE = 0.147) than in men (β = ‐0.618, SE = 0.338).

Conclusion

The impact of illiteracy on dementia risk may be more significant in women than in men, irrespective of the educational attainment of the study population. Illiterate older women should be considered the primary target population for dementia prevention strategies.
Estimating Potential Eligibility for Disease Modifying Therapies for Alzheimer’s Disease Using Population‐Based Data in Alberta, Canada
Authors: Chowdhury Mohammad Z I , Thomas Gavin , Smith Eric E. , Bronskill Susan E , Kirkham Julia G , Ismail Zahinoor , Goodarzi Zahra , Roach Pamela , Ewa Vivian , Vedel Isabelle , Gruneir Andrea , Seitz Dallas
Published: January 2025

Background

Disease modifying therapies (DMTs) for Alzheimer’s disease (AD) have been approved in some countries although these treatments will require substantial health resources for their implementation. Initial capacity planning to identify the resources required to support DMTs begins with estimating the number of people with dementia who may be eligible for DMTs. We estimated the potential number of individuals with dementia who are eligible for DMTs using population‐based data in Alberta, Canada.

Method

We used provincial administrative health databases in Alberta, Canada (population ∼4.5 million) to identify all people newly identified with dementia between April 1, 2013 and March 31, 2022 using a validated dementia case ascertainment algorithm. The characteristics of this population were then described at the time of diagnosis including demographics, conditions potentially contributing to the diagnosis of dementia (e.g. stroke, parkinsonism), and medical contraindications to treatment (e.g. cancer, seizures). The characteristics of individuals with dementia were then compared to the inclusion criteria used in AD DMT trials to estimate the proportion of individuals with dementia who may be eligible for DMTs. We then compared the characteristics of individuals who were determined to be eligible for DMTs compared to those who were not eligible.

Result

A total of 77,479 individuals were identified with incident dementia during the study period with a mean age of 80.6 years and 58% were female. In this group, 15,044/77,479 (19%) had conditions other than AD as a potential cause of their dementia. Medical contraindications to DMTs were present in 24,580/62,435 (39%) of all individuals who had AD as their probable cause of dementia. Overall, 37,855/77,479 (49%) of the entire dementia population could potentially go on to receive biomarker testing to determine DMT eligibility. Individuals who were younger and women were more likely to be potentially eligible for DMTs at the time of dementia diagnosis.

Conclusion

Approximately half of all people diagnosed with dementia in Alberta could be eligible for DMTs based on their health history. Additional information on cognitive test scores, neuroimaging, and biomarker results are required to further refine estimates of the number of individuals potentially eligible to receive DMTs in Canada.
Looking to the future: How can clinical trials be designed in partnership with our participants?
Authors: Schott Jonathan M
Published: January 2025

The recent positive phase 3 clinical trials of new treatments and their licensing and roll‐out in the US and other countries represents a major turning point in Alzheimer’s disease research. As has been the case with many other diseases, e.g. multiple sclerosis and stroke, it is hoped that these successes will act as a catalyst, spurring the development not only of the next generation of amyloid immunotherapies but a range of other therapeutic approaches targeting different aspects of Alzheimer pathology, and different forms of dementia. How future trials are designed will likely have major impacts on their chances of success but also how they are deployed when licensed in clinical practice. It is of course vital that trials are designed to prioritise patient safety and use robust methodologies to produce valid results while maximising the possibility of gaining insights into mechanisms and any side‐effects. However, it is also imperative that protocols are acceptable to participants, and designed wherever possible to maximise compliance, improve accessibility, reduce cost and increase representativeness. Factors that need to be considered include those which may be dependent on the drug’s mode of action and likely effect, e.g. the length of the trial, the method of trial drug delivery, and any requirements for safety monitoring. Factors where there may be scope for change include, but are not limited to, the required number of trial visits, the length of assessments (e.g. including shorter MRI protocols for safety monitoring), the possibility of remote or at home as opposed to in‐hospital visits where possible, and simplifying methods for determining molecular pathology both as entry and potentially stopping criteria (e.g. if plasma can be used instead of CSF or molecular imaging). If we are to maximise the reach of our trials, ensure they are truly representative of all the people who might benefit, and increase recruitment rates, it is vital that we engage with study participants in the design of future studies, engage them as advocates for our research, and promote and actively involve individuals from diverse and under‐represented backgrounds.
Applying the eHealth Literacy lens to evaluate a virtual assistant to support family carers of people with dementia
Authors: Nguyen Tuan Anh
Published: January 2025

Background

We have co‐produced with carers of people with dementia (hereafter carers) a culturally tailored iSupport Virtual Assistant (VA), namely e‐DiVA, to support English‐, Bahasa‐ and Vietnamese‐speaking carers in Australia, Indonesia, New Zealand and Vietnam. The presented research reports qualitative findings from the e‐DiVA user‐testing study.

Method

Family carers and healthcare professionals working in the field of dementia care were given the e‐DiVA to use on their smartphone or handheld device for 1‐2 weeks. They tested all functions and content of the VA and provided feedback in a ‘Think‐aloud’ session, either in person or online. Data was analysed thematically, guided by the eHealth Literacy Framework (eHLF).

Result

Eighteen family carers and nine staff of aged care providers were recruited. Participants discussed all seven domains of eHLF, which were evidenced in the e‐DiVA. They include: 1) ability to process information, i.e. the VA contains information in a format that can easily be understood, e.g. animations; 2) engagement in own health, i.e. providing tailored lessons through need assessments and ‘chatbot’; 3) ability to engage actively with digital services, i.e. providing user manuals; 4) feeling safe and in control; i.e. secure login; 5) motivation to engage with digital services, i.e. providing quick responses/solutions to carers’ queries; 6) having access to systems that work, i.e. ability to access to the VA anytime anywhere; and 7) digital services that suit individual needs, i.e. available in users’ preferred language. Participants highly ranked domains 1, 2 and 5. They suggested further improvements including making content into audiobooks and messages (domain 1), as well as pointed out some potential barriers to use, especially on domains that require interactions between individuals and the digital system (domains 3, 5 and 7).

Conclusion

Findings show the high acceptance of the VA by both the carers and aged care providers, as well as a need for enhancement to improve accessibility.
Effectiveness of an intervention program to improve the detection of cognitive impairment in LMIC setting
Authors: Llibre‐Rodriguez Juan J. , Rodriguez‐Velasco Arianne , Gutierrez‐Herrera Raul , Almirall‐Sanchez Arianna , Zayas‐Llerena Tania , Guerra‐Hernandez Milagros , Llibre‐Guerra Jorge J. ,   DAVOS Alzheimer Collaborative
Published: January 2025

Background

While two‐thirds of the 57 million people with dementia worldwide live in low‐ and middle‐income countries, research to inform dementia‐related policy in these regions remains scarce. We aimed to increase early dementia diagnosis and the use of standardized cognitive assessment by PCP in primary care settings in Cuba

Method

We selected 16 Primary care clinics, with an estimated 160‐200 providers. Clinics were carefully paired based on a number of providers, population demographics, and baseline rates of cognitive impairment diagnosis before being randomized into two groups: one to receive a targeted intervention and the other to continue with usual care practices. The target intervention included a dementia training program and methods for cognitive assessment. A questionnaire about attitudes and practices towards the use of technology‐screening tools, diagnosis, and management of cognitive impairment in primary care was applied to GP at the beginning of the study, 6 months and 12 after training course. The primary endpoint was change in dementia diagnosis rates 12 months after the target intervention.

Result

Compared with the usual care group, the intervention group showed significant statistical improvement in the level of confidence in their ability to engage in key aspects of the neurocognitive evaluation, perform memory screening in older people during annual health visits, and confidence during cognitive evaluation. In addition, the intervention group showed significant improvement in interpreting the diagnostic test (χ² = 8.022; p‐value = 0.004), selecting which test is appropriate (χ² = 10.756; p‐value = 0.001) and familiarity with diagnostic criteria for different forms of dementia. In the intervention group, the frequency of PCP cognitive diagnoses (primary outcome) and referrals to memory specialists increase by 141% relative to baseline, and the use of standardized cognitive assessment for annual cognitive evaluation increased by 83%. The overall prevalence of dementia at selected primary care clinics was 10.6% (95% CI, 9.3%‐12.8%).

Conclusion

This study confirms the feasibility of training primary care physicians (PCPs) for the early detection, treatment, and support of individuals with dementia and their families.
Dementia Research Priorities in Low‐ and Middle‐income Countries in Southeast Asia: A scoping review of the literature and nominal group technique outcome
Authors: Mattap Siti Maisarah , Mohan Devi , Xi Hoon Jia , Ramachandram Dinesh Sangarran , Turana Yuda , Tan Maw Pin , Nguyen Tuan Anh , Wong Gloria HY , Anlacan Veeda Michelle M. , Suharya DY , Moloney Susan , Robinson Louise
Published: January 2025

Background

Dementia is a global public health concern, that poses daily challenges to the individuals, families, and healthcare systems worldwide. Sixty percent of those affected reside in low‐ and middle‐income countries (LMICs), where 71% of new cases are anticipated by 2025. Most dementia studies focus on high‐income countries, emphasizing the need for region‐specific investigations in areas like Southeast Asia, where diverse cultural, economic, and healthcare settings present unique complexities. Addressing specific challenges and priorities in Southeast Asia will facilitate tailored interventions and effective strategies. We aim to map dementia research priorities in Southeast Asian LMICs and align them with stakeholder‐identified priorities through a consultation process using the nominal group technique.

Method

A scoping review was conducted utilizing the Joanna Briggs Institute guidance. Four databases (OvidMedline, Scopus, PsycINFO, and CINAHL) were searched for eligible studies reporting dementia research priorities in LMICs in Southeast Asian. Comparisons were made to a stakeholders’ consultation during a two‐day workshop from the 9th to 10th February 2023 in Kuala Lumpur, Malaysia. Participants included the Southeast Asia‐Dementia (SEA‐Dem) Research Network members key stakeholders from Malaysia, Indonesia, Vietnam, Philippines, Singapore, and Hong Kong (n = 20). Research priorities from each participating country were generated and ranked, harmonized with those from the nominal group technique into tiers of priorities.

Result

Only two studies from Malaysia and Vietnam were eligible, reporting unranked research priorities. Nominal group technique ranked outcomes from Malaysia, Vietnam, Indonesia, and the Philippines were included. Top dementia research priorities were (1) local research and data collection capacity, (2) community awareness and engagement, and (3) health policy. Second‐tier research priorities included harmonizing guidelines and tools standardization, health inequalities, and availability of carer support. The third tier comprised multisectoral collaboration, integration of care, telemedicine, digital approaches, dementia risk reduction, health economics, and sustainable interventions.

Conclusion

Our ranked and harmonized latest dementia research priorities list can serve as a more nuanced and contextually informed dementia research directional guide for countries with similar backgrounds. Collaborative efforts to increase high‐quality dementia research capacity in Southeast Asian LMICs should be intensified for better dementia care in the region.
Trajectory patterns of behavioral and psychological symptoms of dementia (BPSD) in long‐term care facility residents in Japan and the United States
Authors: Arai Asuna , Katsumata Yuriko
Published: January 2025

Background

Behavioral and psychological symptoms of people living with dementia (BPSD) are considered to reflect the person’s quality of life and are also risk factors for increased burden on caregivers. Although symptoms of BPSD are known to be diverse and variable, it is unclear whether they show similar longitudinal patterns in different countries. Therefore, this study aimed to clarify the trajectory patterns in BPSD and related factors using data from Japan and the US and compare the results of the two countries.

Method

Using cohort study dataset that were followed up approximately annually in Japan and the US, we extracted data for four waves since 2015. In the US data drawn from the study at National Alzheimer’s Coordinating Center (NACC), long‐term care facilities included two categories such as the assisted living, adult family home, or boarding home, and skilled nursing facility, nursing homes or hospitals. In the Japanese data, long‐term care facilities were categorized into three types including adult group home for people with dementia, long‐term care health facility, and intensive care home for the elderly. A group‐based multi‐trajectory modeling was used to identify the longitudinal patterns of 12 BPSD symptoms over time. We also examined the characteristics of the participants belonging to each trajectory group.

Result

The long‐term care facility residents used for analysis were 480 in Japan and 164 in the US. Three trajectory groups of BPSD were identified among the participants both in Japan and the US. When comparing between two countries, the trajectories of these groups showed similar patterns. Factors associated with the probability of group membership tended to differ by group and also by country.

Conclusion

We identified three similar trajectory groups of BPSD in Japan and US long‐term care facility residents. It is suggested that the different backgrounds between countries did not have a great impact on the longitudinal pattern of multiple BPSD symptoms. It would be possible for Japan and the US to consider the BPSD preventive measures for residents in the long‐term care facilities in a common framework.
The role of primary care: An engagement study to improve evaluation of possible Alzheimer’s disease and related disorders at the entry point for patients in a large health system
Authors: Gaster Barak , Raetz Jaqueline G. , McKiddy Sarah , Suchsland Monica Zigman , Hsu Amy P , Fitzpatrick Annette L. , Belza Basia , Liao Joshua M.
Published: January 2025

Background

The number of people with Alzheimer’s disease and related disorders (ADRD) is increasing. As a result, the role of primary care providers (PCPs) to detect ADRD is increasingly important. Early detection requires that PCPs are adequately trained to perform clinical evaluations, and health systems will require more knowledgeable PCPs to effectively collaborate with specialists to achieve the capacity needed to diagnose and manage ADRD.

Method

With support of the Davos Alzheimer’s Collaborative, we developed a web‐training curriculum which was paired with tools integrated into the electronic health record (EHR). This intervention was implemented across a network of 14 community‐based primary care clinics from October 2022 to March 2023. PCPs in the network are primarily clinical, spending <5% of their time teaching or doing research. Patients in the network come from diverse backgrounds (41% non‐white). Data was extracted from the EHR to assess PCPs’ use of the tools and the number of cognitive evaluations performed. PCPs also received surveys measuring their confidence subscale for dementia.

Result

All 153 PCPs in the network received access to the EHR tools. Their use of the tools gradually increased, rising to a frequency of 195 patient encounters in the final three‐months of the study period (Figure‐1). The number of cognitive tests entered into the EHR increased from 0.9 to 4.7 per 1000 patient visits >age 50 (p<0.01) (Figure‐2). Fifty PCPs completed the before and after training survey. Their mean reported ADRD‐related clinical confidence subscore increased from 2.54 to 3.74 (p<0.01).

Conclusion

This PCP engagement intervention was effective when implemented across a large health system and was associated with more diagnostic cognitive evaluations and increased confidence in ADRD‐related ability by PCPs. As health systems experience growing pressures to meet the needs of patients with ADRD, they will increasingly require programs like this to educate and engage PCPs. This program is designed to be easy to disseminate to other health systems, a process currently underway via recorded trainings and downloaded EHR tools, in order to train PCPs to be both the initial points to begin evaluations and the effective continuity‐collaborators which health systems need.
Activity Diversity and Its Association with Cognitive Function at Baseline in the U.S. POINTER Study
Authors: Leng Xiaoyan , Howard Marjorie , Halloway Shannon , Farias Sarah Tomaszewski , Lee Athene KW , Papp Kathryn V , Baker Laura D , Snyder Heather M , Espeland Mark A.
Published: January 2025

Background

Recent cross‐sectional and longitudinal studies have shown that higher activity diversity ‐ defined as richness and evenness of daily activities are beneficial to older adults’ cognitive performance. This benefit is independent of frequency or level of cognitive challenge or physical activity.

Method

A total of 1688 participants from the U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk with physical, mental and social activities and cognitive outcomes (global, episodic memory, executive function and processing speed composite scores) measured at the baseline were included in this analysis. The sample was characterized by a mean age of 68.4 (SD: 5.2), 66.9% female, 29.6% less than college education and 33.6% non‐white. A total of 41 activities (11 mental, 21 physical and 10 social activities) are included to evaluate total, mental, social and physical activity diversity based on Shannon’s entropy (0 as no diversity and 1 as full diversity). Walking to do errands (e.g., take children to school or to/from a store) is considered both physical and social. A sequential multiple linear regression models were used to examine associations between activity diversities and cognitive outcomes, adjusted for (model 1) age, sex, race/ethnicity, education, area deprivation index national rank (ADI), and (model 2) additionally self‐reported general health, Framingham cardiovascular disease 10‐year Risk Score, depression (Geriatric Depression Scale total score) and finally (model 3) adding cognitive activity frequency (times/week).

Result

Higher total activity diversity is associated with better executive function in models 1 and 2 (p <0.0344) and the association was attenuated when adding cognitive activity frequency as in model 3 (p = 0.0594). Total activity diversity is not associated with global cognition, or episodic memory or processing speed. Higher mental activity diversity is associated with higher global cognition (p<0.0001), episodic memory (p <0.0003) and executive function (p < 0.0001) in all three models, but not processing speed (p >0.2432).

Conclusion

These results indicate that cognitive activity diversity is associated with cognitive function in older adults at risk of cognitive decline, which is independent of other risk factors and frequency of cognitive activities.
Implementation of a standardized Video‐based Asynchronous Neurological Examination (VANE) in a multi‐center study of AD/ADRD: Findings from The Diabetes Prevention Program Outcomes Study (DPPOS) AD/ADRD Project
Authors: Noble James M. , Nadkarni Neelesh , Martinez Dianilka , Temprosa Marinella , Bowers Anna , Doherty Lindsay , Febres Gerardo J , Sanchez Danurys , Goldberg Terry E. , Sherif Hanna , Luchsinger Jose A. ,   Diabetes Prevention Program Research Group
Published: January 2025

Background

The Diabetes Prevention Program Outcomes Study (DPPOS) is an established cohort of aging persons (mean age 72 years) with prediabetes and diabetes with a mean of 23 (range 21‐25) years of follow‐up. DPPOS added neuropsychological testing using the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDSv3) forms. Using the NACC UDS required implementing a standardized neurological examination across 25 US clinical sites, administered by project coordinators (PC).

Methods

A video‐based asynchronous neurological examination (VANE) was developed by clinicians with experience in the NACC‐UDS to harmonize with UDSv3 to anticipate common neurological diagnoses aside from dementia including diabetic cranial neuropathy, stroke and Parkinsonism. VANE was designed to be contactless, reproducible, to be administered by non‐clinicians, such as PCs. Using standard iPad software connected to a secure repository, the video exam includes extraocular and facial movements, visual field, speech (“Cookie‐theft”), gross motor strength, pronator drift, praxis and Parkinsonism (i.e. the Unified Parkinson’s Disease Rating Scale modeled examination as in UDSv3, including assessment of tremors, bradykinesia, finger and foot tapping, hand movements, postural stability and gait). Rigidity and pull‐testing were not included. A 10‐minute training video was developed for study staff, which demonstrates the examination step‐by‐step with scripts and video instructions in English and Spanish. Site‐specific performance review, feedback, and staff certification preceded central reading of video recordings by three physicians.

Results

During calendar year 2023, 608 neurological examinations occurred at 25 sites, each lasting 10 to 15 minutes. Each site on average completed 24 examinations (SD = 13.0, range 3‐48). Of the initial 442 examinations reviewed, 406 (91%) were completed using the script provided, 421 (95%) were error‐free, and 3 (0.6%) were non‐interpretable. Abnormal findings were noted in 153 participants (2% Parkinsonism, 1% cerebrovascular disease and 31% other neurological abnormalities). Suboptimal exams occurred at 10 of 25 sites (range 1‐4 per site) early in implementation.

Conclusions

Engaging research staff across 25 sites, and three physician‐reviewers, this study is the first to implement VANE as an efficient neurological examination model. VANE presents a novel paradigm for large multisite epidemiological studies considering incorporating neurological examinations conducted by non‐clinicians.
Investigation of Brain Signatures Across Diverse Metabolic States in MCI
Authors: Anagnostakis Filippos , Govindarajan Sindhuja Tirumalai , Mamourian Elizabeth , Erus Guray , Melhem Randa , Cui Yuhan , Abdulkadir Ahmed , Tosun Duygu , Shou Haochang , Nasrallah Ilya M. , Davatzikos Christos
Published: January 2025

Background

Late‐life obesity has been reported to have a negative relationship with risk for dementia and has been associated with lower risk of incident Alzheimer’s disease (AD) in non‐demented individuals. However, associations of obesity and cognition solely in patients with mild cognitive impairment (MCI) is unknown. These associations may be confounded by vascular risk that contributes to metabolic syndrome (MetS). This study investigates the complex interplay between obesity, metabolic syndrome, and neurodegeneration in MCI. We analyze neuroimaging measures, AD biomarkers including amyloid‐beta (Aβ) and tau levels in the cerebrospinal fluid (CSF), and a machine‐learning based imaging signature of AD‐like brain atrophy (the SPARE‐AD index) in distinct metabolic subgroups.

Methods

This study included N = 705 MCI patients (age = 75.3+‐7 years, 61% females) scanned with a median follow‐up interval of 30.3 months from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). N = 139 participants developed dementia. Participants were categorized as metabolic healthy (MH, N = 126) or unhealthy (MU, N = 579) based on MetS criteria, and further as normal weight (NW), overweight (OW), or obese (OB) based on their BMI. Risk of incident dementia among the metabolic states was evaluated using Cox regression. Volumetric brain changes, SPARE‐AD, and CSF total‐tau, p‐tau181, and Aβ1‐42 were analyzed separately using linear models with metabolic state as the predictor, corrected for APOE genotype, age, sex, education, and intracranial volume (volumetric data only). Results were corrected for multiple comparisons using the False Discovery Rate method.

Results

When compared to MH‐NW participants, only MU‐OB participants had a significantly lower risk for incident dementia (Hazard Ratio = 0.430, p<0.05), lower (more normal) SPARE‐AD (p = 0.029), total‐tau (p = 0.02) and p‐tau181 (p = 0.006). MU‐OB and MU‐OW participants had significantly higher volumes (p<0.05) of bilateral hippocampi, left temporal white matter, left posterior cingulate gyrus, and the right parahippocampal gyrus, and significantly lower volumes in the right anterior orbital gyrus. A similar pattern of was not observed in other subgroups.

Conclusion

Obese MCI patients with MetS had lower incident dementia, less AD‐like brain shrinkage and more favorable AD biomarkers. Our findings suggest that the cognitive impairment in MU‐high BMI groups might originate from causes unrelated to AD, and might be related to the vascular and metabolic changes.
MIND diet, Cerebrovascular Health, and Cognition among community‐dwelling Older Adults
Authors: Agarwal Puja , Lamar Melissa , Kapasi Alifiya , Evia Arnold M , Aggarwal Neelum T. , Cherian Laurel J , Bennett David A. , Leurgans Sue E. , Arfanakis Konstantions , Schneider Julie A.
Published: January 2025

Background

White matter hyperintensities (WMH) and cerebral arteriosclerosis involving thickening of the vessel wall and stenosis of brain arterioles are common in older adults and associated with poor cognition. The Mediterranean‐DASH Intervention for Neurodegenerative Disease (MIND) diet is associated with better cognition. Little is known about the association of the MIND diet with cerebrovascular outcomes and if this association mediates the link between diet and cognition. This study investigates the association of the MIND diet with WMH volume and arteriolosclerosis, and whether WMH and arteriosclerosis mediate the association between diet and cognition among community‐dwelling older adults.

Method

The study includes 561 participants from an ongoing longitudinal cohort study, the Rush Memory and Aging Project with dietary and neuroimaging data available no more than a year apart. MIND diet scores were obtained using a valid >142‐item food frequency questionnaire. In‐vivo magnetic resonance imaging (MRI) data were collected using a 3T MRI scanner. WMH were segmented using a deep learning model. Arteriolosclerosis was assessed employing a fully automated in‐vivo MRI‐based marker named ARTS (ARTerioloSclerois). An ARTS score was generated for each participant (higher scores indicate a higher likelihood of arteriolosclerosis). Global cognition was assessed using 19‐battery tests. Linear regression models controlled for age, sex, MRI scanner, and education. Mediation analysis was done using structural equation modeling.

Result

In our analytical sample (mean age (81 ± 7.5), 77% female, 16 ± 2.9 years of education a higher MIND diet score was associated with less WMH (β = ‐0.023, SE = 0.009, p = 0.015) and lower ARTS score (β = ‐0.013, SE = 0.004, p = 0.001). The effect estimates were stable when further controlled for BMI and physical activity. The MIND diet was associated with better global cognition (β = 0.0426, SE = 0.012, p = 0.0004), with an indirect association of 10.5% through ARTS score (β = 0.0045, SE = 0.0002, p = 0.038).

Conclusion

Among community‐dwelling older adults a higher MIND diet score is associated with less WMH and a lower likelihood of small vessel arteriosclerosis. The association of the MIND diet with cognition is partially mediated by arteriosclerosis. Lifestyle approaches such as adherence to a specific diet may improve cognition by maintaining the cerebrovascular health of older adults.

Fundings sources: R01AG054476; R01AG17917; R01AG076143
Higher MIND diet scores are associated with larger brain MRI hippocampal volume: the cross‐cohort collaboration
Authors: van Lent Debora Melo , Koijs Daniel , Bis Josh , Buelow Robin , de Crom Tosca O.E. , Decarli Charles , Dufouil Carole , Grabe Hans J. , Grasset Leslie , Ghosh Saptaparni , Goss Monica , Frenzel Stefan , Himali Jayandra J. , Ikram Arfan , Lopez Oscar L. , Mosley Thomas H. , Vasan Ramachandran S , Samieri Cécilia , Satizabal Claudia L , Simino Jeannette , Thomas Aline , Vernooij Meike W. , Voelzke Henry , Voortman Trudy , Wolters Frank J. , Yaqub Amber , Seshadri Sudha , Beiser Alexa S
Published: January 2025

Background

Higher Mediterranean‐ DASH for Neurodegenerative Delay (MIND) diet scores have previously been associated with larger total brain volume (TBV) in the Framingham Offspring Study (FOS) community‐based cohort. We investigated cross‐sectional relationships between the MIND diet and structural brain imaging volumes and white matter hyperintensity volume (WMHV) across six community‐based cohorts.

Method

We analyzed data from 3130 dementia‐, stroke‐ and other neurological disease free adults (aged 65 to 74) who participated in the Atherosclerosis Risk in Communities (ARIC) cohort, Cardiovascular Health Study (CHS), Three City (3C) cohort, FOS cohort, Rotterdam Study (RS) or the Study of Health in Pomerania (SHIP) cohort. Individuals completed a brain magnetic resonance imaging (MRI) scan, and a validated food frequency questionnaire (FFQ) (ARIC, CHS, FOS, RS), 24h dietary recall (3C), or an extensive food list (SHIP). The MIND diet consists of ten healthy (e.g. green leafy vegetables, berries and fish) and five unhealthy (e.g. cheese, red meat and products and fast fried foods) components. Outcomes from brain MRI included TBV, total grey matter volume (TGMV), hippocampal volume (HPV), and WMHV. We used multivariable linear regression to relate MIND diet adherence to the outcomes. Results were combined in meta‐analysis using fixed effects and random effects models.

Result

Higher MIND diet scores (score range: 0‐15) were associated with larger HPV (beta = 0.015, 95% confidence interval = 0.004 to 0.026, cm³ per one unit MIND diet score increase) after adjustment for age, age squared, sex, time from clinical exam to brain MRI exam, total intracranial volume and energy intake, but not with TBV, TGMV and WMHV. Heterogeneity between studies was low (I2 = 0% TBV, TGMV, HPV) to moderate (I2 = 44% WMHV).

Conclusion

In cross‐sectional analyses, higher MIND diet scores were associated with larger HPV, but not with other brain volume measures. It might be that HPV was a more sensitive marker of brain health in the populations under study. Future studies are encouraged to examine the associations between the MIND diet and amyloid and tau positron emission tomography (PET) imaging to elucidate whether a relationship between the MIND diet and dementia pathologies exists.
NADPH oxidase 2 small molecule inhibitors as a therapeutic strategy in the treatment of Alzheimer’s disease
Authors: Peretin Jenna M , Dustin Christopher M , Cifuentes‐Pagano M. Eugenia , Pagano Patrick J. , Vazquez Alberto L
Published: January 2025

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with neuroinflammation and heightened production of reactive oxygen species (ROS) in the brain from overactive NADPH Oxidase 2 (NOX2). The current study examines whether administration of a novel, brain‐penetrant NOX2 inhibitor (CPP11G & CPP11H) reduces amyloid plaque load and improves AD‐associated vascular dysfunction in a male APP‐PS1 mouse model of AD.

Method

Intraperitoneal injections of CPP11G (n = 1) or CPP11H (n = 2) three times per week began at 9‐10 months of age in the treatment APP‐PS1 group (15 mg/kg). The control group of age‐matched APP‐PS1 mice received no treatment (n = 7). All mice were implanted with a 5mm cranial window for awake optical imaging at least 2 weeks prior to onset of treatment. Two‐photon microscopy was performed to assess longitudinal changes in amyloid plaque deposition after weekly Methoxy‐04 administration (1 mg/kg). Changes in plaque load were quantified weekly and averaged monthly. Additionally, wide‐field optical imaging at 620nm was performed with a 90s, 8% CO2 hypercapnic challenge. This imaging wavelength is sensitive to changes in blood oxygenation (OIS‐BOLD) to capture changes in vascular reactivity over time.

Result

Treatment with CPP11G/H shows a trend toward reduction in cortical plaque load when compared to an untreated cohort (Fig. 1). OIS‐BOLD results for vascular reactivity studies show a slight trend of improved vascular function over time with CPP11G/H treatment (Fig. 2).

Conclusion

Our preliminary findings show a strong trend in amyloid plaque reduction with ongoing CPP11G/H treatment in older‐aged AD mice and improved vascular function. Ongoing studies to increase the size of the treated cohort will reveal the reliability and statistical significance of CPP11G/H’s therapeutic benefits. We are also examining the impact of treatment on microglia activation and gliosis in APP‐PS1::CX3CR1‐GFP mice (Fig. 3).
A policy agenda to support care partners of people living with ADRD from historically underserved communities
Authors: Gelmon Sherril B , Dawson Walter D , Reed Jenn Hollandsworth
Published: January 2025

Background

Alzheimer’s disease and related dementias (ADRD) place enormous burdens on families, care partners, and the public programs that finance ADRD services. Caregiving is disproportionately provided by women, individuals of low socioeconomic status, and underserved minority populations, who also rely upon informal care and support. National dementia strategies rarely address the needs of care partners. This study was designed to identify policy opportunities that would emphasize and address care partner needs, with an emphasis on historically and currently underserved communities.

Method

Twenty‐four (n = 24) systematic interviews and five focus groups (n = 5) were conducted with care partners and organizations offering services that support people with ADRD. Data collection focused on historically underserved communities in the United States. Organizational leaders and care partners also participated in a modified Delphi process to identify priorities for supporting care partners. A comprehensive literature review provided additional information.

Results

Care partners from all populations reported lacking supports to help manage caregiving, despite being generally satisfied with clinical care and research involvement. Specific needs and types of supports varied across populations, due to cultural traditions, multiple systemic inequities, and legacies of structural racism. The findings suggest multiple unmet care partner needs across all populations, including ADRD‐specific information; navigation and coordination within and across systems; access to clinicians, care teams, and health/personal records; legal and financial resources; psychological and physical health supports; and in‐home and respite care.

These findings suggest policy opportunities to address specific needs of ADRD care partners. While the findings are derived from the US context, they have relevance for other national dementia strategies. Policy recommendations were identified related to equity of access, expansion of public insurance, workforce development, creation of information hubs, and adoption of technologies. Policies should support care partners by incorporating incentives for care coordination and navigation.

Conclusion

Changes in health and social policies are needed to better support care partners of people living with ADRD. Policymakers must collaborate with care partners to develop and implement new national dementia strategies to improve care partner experiences. To ensure equitable service provision, culturally appropriate policies and supports for care partners from underserved communities require prioritization.
Strengthening responses to dementia: Building an evidence platform for the development of Vietnam’s National Dementia Plan
Authors: Nguyen Tuan Anh , Dang Thu Ha
Published: January 2025

Background

Prior to formulating an effective national dementia plan in Vietnam, reliable information on current situation of dementia care, treatment and support in Vietnam was needed. This study was conducted to describe Vietnam’s response to dementia at three levels: individual (consumers and providers); health and social care organisations; and national healthcare system to guide the plan development.

Method

Guided by the “Towards a dementia plan: a WHO guide”, a comprehensive situational analysis was conducted, focusing on Policy, Service Delivery and Epidemiological assessments.

Result

Vietnam had a high level institutional and policy framework on aging, NCD, mental health and disability including the 2009 Law on the Elderly, which provides the legal umbrella for policies on older people. However, no dementia‐specific policy existed and policies to promote healthy brain remained weak. Rapid aging significantly contributes to the explosion of NCD including dementia in Vietnam. There were 660000 Vietnamese people estimated to be living with dementia in 2015, with resultant dementia related costs of US$ 960 million. The healthcare system is not yet prepared for the shift to NCD from an acute, communicable disease burden in the past. Health service delivery is hospital‐centric, with over‐reliance on hospitals and under‐utilization of primary care system that in turn is fragmented and poorly prepared to address the rising challenge of dementia. Both the public and primary healthcare providers have poor knowledge and little confidence but more positive attitudes toward dementia care and management. Social care and support specific for dementia is lacking although there is an impressive grassroots organisation of older people with nearly 100,000 branches.

Conclusion

To allow for a more harmonized response across the health sector and more effective use of limited resources, an integrated national action plan for dementia is sensible. However, Vietnam should take into consideration the potential for fragmentation and lack of dedicated resources being allocated to dementia. A new, integrated model of care focusing on a stronger primary healthcare system, community‐based social care and a healthy aging approach is needed to improve dementia prevention, care, treatment and support in Vietnam.
The relationship between meaningful activity and apathy among assisted living residents with dementia
Authors: Klinedinst Jennifer
Published: January 2025

Background

Apathy, or reduction in goal directed behaviors, is common in assisted living (AL) residents with dementia. Meaningful activity, defined as participation in activities that are enjoyable, tailored to the individual’s interests and abilities, related to a personally relevant goal, engaging, and related to an aspect of an individual’s identity, may be a promising strategy for reducing apathy in AL residents with dementia. However, there is a dearth of evidence examining the relationship between engagement in meaningful activity and apathy among AL residents with dementia. The purpose of this study is to determine the relationship between engagement in meaningful activity and apathy among AL residents with dementia. We hypothesized that AL residents who have apathy would have lower levels of engagement in meaningful activity than those residents without apathy.

Method

This study was a secondary data analysis using baseline data from a randomized controlled trial, Meaningful Activity for Managing Behavioral Symptoms of Distress (MAC‐4‐BSD) of 71 residents from 5 AL communities in Maryland. Apathy was measured using the apathy subscale of the Neuropsychiatric Inventory Questionnaire (NPI‐Q). Meaningful activity was measured from the resident using the Engagement in Meaningful Activities Survey (EMAS). Descriptive statistics including means or frequencies were conducted to describe the sample. A one‐tailed independent samples t‐test was conducted to test the hypothesis.

Result

Participants were on average 85.39 (s.d. = 8.20) years old, with moderate to severe dementia (Saint Louis University Mental Status exam score average m = 6.76, s.d. = 6.06). The majority were female (n = 52) and White (n = 62). They had an average length of stay of 1.84 years (s.d. = 1.67) and 8.24 (s.d. = 2.62) comorbidities. Overall, 41% (n = 29) of the participants had apathy. The mean EMAS score was significantly lower (37.52, s.d. = 10.54) among those with apathy than among those without apathy (41.63, s.d. = 9.62) (t = 1.69, p<.05).

Conclusion

Individuals living with dementia in AL with apathy tend to spend less time engaged in meaningful activities. Interventions are needed to test if increasing engagement in activities that are considered meaningful by the resident can help reduce apathy in this population and thereby improve quality of life.