bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between Cardiovascular‐Kidney‐Metabolic Health and the Risk of Cognitive Decline and Alzheimer’s Disease Mortality in a Multiethnic Cohort Study
Authors: Liu Longjian , Gliebus Gediminas Peter , Zhao Xiaopeng ,   for the CKM‐AD/ADRD Research Group
Published: January 2025

Background

Cardiovascular‐kidney‐metabolic (CKM) health, a term recently defined by the American Heart Association, encompasses the interplay among metabolic, chronic kidney, and cardiovascular risk factors. We aimed to investigate the predictive significance of CKM disorders with the risk of cognitive decline and Alzheimer’s disease (AD) and AD‐related dementia (ADRD) mortality in a multiethnic population.

Method

We analyzed a cohort of 6,440 adults aged 45‐84 who participated in the Multiethnic Study of Atherosclerosis, with a baseline survey conducted in 2000‐2002, and were followed through to December 2015. Fourteen baseline measurements of established and emerging CKM factors were examined, including waist circumference, blood pressure (BP), carotid intimal‐medial thickness, serum glucose, triglyceride, high‐density lipoprotein cholesterol, C‐reactive protein (CRP), fibrinogen, interleukin‐6 (IL‐6), factor VIII, D‐Dimer, homocysteine, cystatin C concentrations, and urine albumin to creatinine ratio (ACR). Cognitive function was assessed using the Cognitive Abilities Screening Instrument (CASI) in 2010‐2012. AD/ADRD mortality was classified by clinical diagnoses. Logistic regression models estimated adjusted odds ratios (AOR) for cognitive decline (CASI score<Q1), and Cox regression models estimated adjusted hazard ratios (AHR) for AD/ADRD mortality. A sum CKM index reflecting the presence of multiple CKM risk factors was calculated to estimate the combined predictive effect of CKM disorders on AD/ADRD mortality risk.

Result

Over a mean 13‐year follow‐up, AD/ARAD mortality rates (95%CI) were 3.6 (3.1‐ 4.3) in men (126 deaths) and 2.0 (1.6‐2.5) in women (84 deaths) per 1000‐person years. Cognitive decline was significantly associated with elevated homocysteine concentrations (AOR=1.2, 95%CI: 1.1‐1.4), and ACR (1.2, 1.03‐1.5). AD/ADRD mortality was significantly associated with high BP (AHR=1.7, 95%CI: 1.2‐2.4), and elevated glucose (1.4, 1.1‐1.9), CRP (1.4, 1.1‐1.9), IL‐6 (1.7, 1.3‐2.2), D‐Dimer (1.5, 1.2‐2.1), homocysteine (1.9, 1.4‐2.6), cystatin C (1.6, 1.2‐2.2), and ACR (2.1, 1.6‐2.8). An increased sum CKM index significantly predicted a higher risk of AD/ADRD mortality.

Conclusion

This study underscores the significant role of CKM disorders in contributing to cognitive decline, with a notable predictive effect on the risk of AD/ADRD mortality. This research contributes to a growing body of evidence emphasizing the interconnectedness of metabolic, renal, and cardiovascular health with cognitive outcomes, paving the way for integrative approaches in managing these complex interrelations.
Multimodal intervention for risk reduction of dementia in older adults with type 2 diabetes: Post‐hoc sub‐group analyses of the J‐MINT
Authors: Sugimoto Taiki , Uchida Kazuaki , Matsumoto Nanae , Fujita Kosuke , Yokoyama Yoko , Kuroda Yujiro , Omura Takuya , Nakamura Akinori , Crane Paul K. , Arai Hidenori , Sakurai Takashi ,   J‐MINT study group
Published: January 2025

Background

This post‐hoc sub‐group analysis of the Japan‐multimodal intervention trial for prevention of dementia (J‐MINT) aimed to examine the efficacy of the multi‐domain intervention in older adults with type 2 diabetes.

Method

J‐MINT was an 18‐month, randomized controlled trial. Participants aged 65‐85 years with mild cognitive deficits were recruited and randomized into multidomain intervention (management of vascular risk factors, physical exercise, nutritional counseling, and cognitive training) and control groups (written health‐related information every 2 months). The outcome was the change from baseline to 18‐month follow‐up in a composite score derived from several neuropsychological tests, including tests of global cognitive function, memory, attention, and executive function/processing speed. Among individuals with diabetes, stratified analyses based on age at enrollment (65‐74 years vs. 75‐85 years), presence of memory impairment (with vs. without memory impairment), HbA1c levels according to the Japan Diabetes Society/Japan Geriatric Society recommended target range (within vs. above/below the target range), and APOE phenotype (0 vs. ≥1 APOE ε4 alleles), were performed using mixed models for repeated measures.

Result

Out of 531 participants enrolled in J‐MINT, 76 participants with type 2 diabetes and 356 without had at least one post‐baseline assessment and were included in the analysis. In participants with and without diabetes, there were no significant effects of the intervention on changes in the composite score. Among people with diabetes, stratified analyses revealed that the intervention effect was significant in individuals aged 65‐74 years (mean difference between the intervention and control groups, 0.310 [95% CI 0.104–0.517], p = 0.003). Moreover, the intervention appeared to be effective in those with HbA1c levels above/below the target range (0.304 [0.007–0.601], p = 0.045), although it did not reach statistical significance after Bonferroni correction (p < 0.005). There was no significant effect of intervention in stratified analyses based on memory impairment and the APOE phenotype.

Conclusion

These results suggest that multidomain interventions may be particularly valuable for people with diabetes who are in the younger age group or whose glucose values are not in the target range. However, this should be confirmed in other data sets.
Older predicted age using AI EKG‐based age prediction is associated with higher Alzheimer’s disease neuropathologic change
Authors: Bermudez Camilo , Syrjanen Jeremy A. , Attia Zachi I , Friedman Paul A , Lopez‐Jimenez Francisco , Hu Mingzhao , Petersen Ronald C. , Knopman David S. , Ramanan Vijay K. , Jack Clifford R. , Nguyen Aivi T. , Reichard Ross R. , Kouri Naomi , Moloney Christina M. , Algeciras‐Schimnich Alicia , Murray Melissa E. , Mielke Michelle M. , Vemuri Prashanthi , Noseworthy Peter A , Graff‐Radford Jonathan
Published: January 2025

Background

There is increasing need for noninvasive biomarkers of Alzheimer’s Disease (AD) neuropathologic change for early detection and intervention through risk‐factor modification and disease‐modifying therapies. One such biomarker is the prediction of chronological age from routine clinical tests such as an electrocardiogram (EKG) to discriminate between observed biological age from chronological age for healthy aging. Deviation of true age from predicted age has been associated with heart failure, hypertension, and coronary heart disease. However, the association between EKG‐based age and underlying neuropathology has not been studied.

Method

We used a cohort of 336 participants from the Mayo Clinic Study of Aging, a population‐based prospective study of residents in Olmsted County, Minnesota, with antemortem EKG and post‐mortem brain autopsy (Table 1 & 2). Age was predicted from EKG using a validated convolutional neural network algorithm. We used ordinal logistic regression to identify associations between lower neuropathologic scores of AD (Thal phase, neuritic plaque score, Braak stage, and overall AD neuropathologic change) and the Age‐Gap, defined as EKG‐predicted age minus chronological age. Results were controlled for true age, sex, and APOE e4 carrier status. Neuropathologic scales were grouped into none, low, intermediate, and high categories. Observations were weighted by the inverse of years between last EKG and time of death to account for the time difference between acquisition of EKG and autopsy.

Result

We found that an increasing Age‐Gap (i.e. older predicted age) was inversely associated with lower overall AD neuropathologic change (OR 0.93 [0.89, 0.97], p = 0.002). Investigation of the components of AD neuropathologic change showed that an increasing Age‐Gap was also inversely associated with lower amyloid metrics such as Thal phase (OR 0.85 [0.80, 0.89], p < 0.001) and neuritic plaque scores (OR 0.91 [0.87, 0.96], p < 0.001), but not tau metrics like Braak staging (OR 1.05 [1.00, 1.10], p = 0.05).

Conclusion

In this work, we show that older predicted age on EKG, a noninvasive biomarker associated with vascular and biological aging, is associated with higher amyloid burden and neuropathologic change of AD.
Resistance exercise and Alzheimer’s disease blood‐based biomarkers in European cognitively healthy older adults
Authors: Esteban‐Cornejo Irene
Published: January 2025

In the quest to combat Alzheimer’s disease (AD), physical exercise has emerged as one of the leading non‐pharmaceutical approaches to improve executive function and ameliorate cognitive decline. The limited understanding of the mechanisms by which exercise impacts cognition in late adulthood hinders the widespread use of exercise as a therapeutic or preventive approach for AD. This underscores the urgent need for research aimed at unraveling the mechanisms by which exercise improves cognition.

This study delves into the unexplored realm of AD blood‐based biomarkers as potential mediators of the cognitive benefits induced by exercise. Despite their potential significance, no previous trials have examined the impact of exercise on these novel AD BBMs and their cognitive implications. These effects may vary based on exercise type (e.g., aerobic, high intensity interval training or mind‐body exercises), necessitating a thorough exploration of optimal exercise types and doses before advancing to comprehensive interventions.

Using data from the AGUEDA trial, a single‐site, two‐arm, single‐blinded, randomized controlled trial (RCT) involving 90 cognitively normal older adults from Spain (Europe), aged 65‐80 years old, this study marks the first attempt to uncover the effects of a 24‐week resistance exercise intervention on AD BBMs and their cognitive implications. We will share promising findings on the impact of exercise on AD BBMs related to AD pathological hallmarks (i.e., amyloid‐β peptides and p‐tau isoforms), to neuronal loss (NfL); and to neuroinflammation (GFAP).

This research not only will unveil the potential of resistance exercise as a powerful tool in AD prevention but also will help to set the stage for a new era of precision interventions targeting specific AD BBMs.
Beyond Credentials: Understanding Educational Gradients in Cognitive Function at Midlife
Authors: Grodsky Eric , Warren John Robert , Muller Chandra , Manly Jennifer J. , Brickman Adam M. ,   HSB
Published: January 2025

Background

A substantial body of research points to the persistence of educational credential gradients in cognitive function across the life course, from early adulthood through old age. Fewer studies have considered the roles of educational opportunities and achievements early in the life course in shaping (1) educational credential gradients or (2) variation in cognitive function among those with the same credentials. As a result, researchers underestimate the contribution of education writ large to variation in cognitive performance later in life.

Method

We analyze data from the nationally representative High School and Beyond (HSB) cohort, which has followed ∼25,500 people from high school in 1980 through age ∼60 in 2021‐22. The 2021‐22 round of HSB gathered high quality measures of cognition across multiple domains; the 1980‐1992 rounds gathered extensive information about educational opportunities, achievements, and attainments.

Result

We demonstrate that high school educational opportunities, and especially academic achievements, account for most of the credential gradient in cognition on selected cognition measures among adults who attended high school in the U.S. in 1980 as they approach 60 years of age. High school educational opportunities and academic achievements also help account for some of the variation in cognition among those with the same educational credential.

Conclusion

Educational credentials commonly employed to understand the contribution of education to cognitive aging therefore risk both mischaracterizing and understating the contributions of education to cognitive function and change over the life course.
Assessing attitudes and beliefs of dementia risk and prevention in middle‐aged adults
Authors: Simone Stephanie M. , Kaplan Marina , Giovanetti Tania
Published: January 2025

Background

Healthy lifestyle behaviors (e.g., physical activity, cognitive activity) protect against cognitive decline and reduce dementia risk. Alzheimer’s disease (AD) neuropathology begins several years before the onset of clinical symptoms and disability; thus, midlife may be a critical time during which healthy lifestyle behaviors may be most effective. Motivation is essential to engage and maintain healthy lifestyle behaviors, particularly in midlife when benefits may not be observed for up to decades later. The factors that shape individuals’ motivation to engage in healthy lifestyle behaviors for dementia risk reduction remain poorly understood, but will be important for designing effective dementia prevention programs. This study identified groups of participants in midlife who possess similar beliefs and attitudes (e.g., motivation) about dementia risk and prevention using a person‐centered approach (i.e., latent profile analysis [LPA]).

Method

There were 347 middle‐aged participants (M age = 54.67±5.97; 53% women; 86.5% White; M education = 14.28±2.25) from the US general population who completed an online questionnaire using Qualtrics which assessed demographics and attitudes and beliefs about dementia and lifestyle behavior changes for dementia risk reduction. Latent profile analysis was conducted using z‐transformed scores to identify subgroups of middle‐aged adults with similar beliefs and attitudes about dementia and dementia prevention (Table 1).

Result

Results suggested that a four‐profile model was the best fit for the data (Table 2), yielding four distinct subgroups that differed in beliefs and attitudes about dementia and dementia prevention (Figure 1). For example, Profile 2 showed the highest level of motivation to engage in healthy behaviors and greatest concern of everyday cognition but the lowest level of AD knowledge and health literacy, whereas Profile 4 showed a variable motivation pattern but the highest levels of apathy.

Conclusion

Subgroups of middle‐aged adults with different patterns of attitudes and beliefs (e.g., motivation) about dementia and dementia prevention were identified. Future work will focus on differences in healthy lifestyle behaviors (e.g., physical activity, cognitive activity) between subgroups and replication of the profiles in other cohorts. Insights gained may be used to inform who to target and how to design effective dementia prevention programs and policies for people in midlife.
Unsupervised machine learning model to predict cognitive impairment in subcortical ischemic vascular disease
Authors: Qin Qi , Yin Yunsi , Qu Junda , Tang Yi
Published: January 2025

Background

It is challenging to predict which patients who meet criteria for subcor‐ tical ischemic vascular disease (SIVD) will ultimately progress to subcortical vascular cognitive impairment (SVCI).

Method

We collected clinical information, neuropsychological assessments, T1 imag‐ ing, diffusion tensor imaging, and resting‐state functional magnetic resonance imaging from 83 patients with SVCI and 53 age‐matched patients with SIVD without cogni‐ tive impairment. We built an unsupervised machine learning model to isolate patients with SVCI. The model was validated using multimodal data from an external cohort comprising 45 patients with SVCI and 32 patients with SIVD without cognitive impairment.

Result

The accuracy, sensitivity, and specificity of the unsupervised machine learning model were 86.03%, 79.52%, and 96.23% and 80.52%, 71.11%, and 93.75% for internal and external cohort, respectively.

Conclusion

We developed an accurate and accessible clinical tool which requires only data from routine imaging to predict patients at risk of progressing from SIVD to SVCI.
Exploring knowledge valorization and utilization strategies in academic health science centers in the Netherlands: multi‐case study of Alzheimer centers
Authors: Zhu Eden Meng , Buljac‐Samardžić Martina , Ahaus Kees , Huijsman Robbert
Published: January 2025

Background

‘Intellectual assets’ generated in traditional university settings, that may not fit the interests of the standard ‘valuation criteria’ (i.e. commercially profitable), such as non‐pharmacological dementia care research, often remain siloed within their respective research disciplines and originating institutions. Implementation science can be leveraged to navigate the complexity of research innovation systems and enhance the outcomes of research valorization and utilization activities. Five specialized Alzheimer Centers were established to facilitate the creation, translation, implementation, and dissemination process for dementia research in the Netherlands. This study aims to use an implementation science‐guided approach to explore the knowledge valorization, implementation and dissemination activities present within the Centers to understand the activities and strategies used at each stage of the ‘knowledge‐to‐action’ process.

Method

Individual semi‐structured qualitative interviews from participants through purposive sampling of researchers employed across five Alzheimer Centers were conducted, and multiple case studies were produced. Interviews were conducted in‐person and virtually through Microsoft Teams, and all were audio‐recorded, transcribed verbatim, and analyzed using ATLAS.ti software. Leaders of each Alzheimer Center were involved in later stages of data analysis to help interpret and validate the results.

Result

Knowledge creation, and the translation of research findings into research products, was facilitated by the proximity between researchers and dementia patients, through ‘memory clinics’ and ‘client panels’ that provided researchers the opportunity to involve end‐users in research product development. Implementation of knowledge products was often facilitated through establishing early formal public‐private partnerships, involving well‐networked external intermediary organizations and university‐based technology transfer offices to determine implementation pathways. Dissemination was facilitated through strategically leveraging social media marketing tactics to expand reach and establishing partnerships to utilize existing dissemination channels.

Conclusion

Although similar knowledge valorization and utilization strategies were identified across the five Alzheimer Centers, the degree of success for the strategies found varied across each Center, which suggests a connection between the Alzheimer Center’s organizational maturity, the implementation teams’ overall readiness, and the selected strategies’ outcomes. Future studies may explore the relationship between organizational characteristics and implementation support readiness to develop a context‐appropriate implementation mapping approach, suitable for enhancing implementation support readiness in dementia research.
Gender differences in dementia risk factors and cognitive performance in the recruitment process of a FINGER‐like multidomain trial to prevent cognitive decline, the CITA GO‐ON trial
Authors: Tainta Mikel , Barandiaran Myriam , Ecay Mirian , Iriondo Ane , Estanga Ainara , Altuna Miren , Lopez Carolina , Saldias Jon , Garcia‐Sebastian Maite , Marta Cañada , de Arriba Maria , Reparaz‐Escudero Imanol , Ros Naia , Domper Jara , Mateo‐Abad Maider , Martinez‐Lage Pablo
Published: January 2025

Background

Sex and gender affect Alzheimer’s and Dementia differently. Some studies show that women are diagnosed at a later stage. This represents an essential challenge for healthcare and makes research challenging as gender biases may impact participant selection for clinical trials. We examined recruitment for the CITA GO‐ON trial, a lifestyle intervention trial to prevent cognitive decline.

Method

The CITA GO‐ON study (ClinicalTrials.gov, NCT04840030) is a population‐based randomized clinical trial that aims to evaluate the effectiveness of a multidomain lifestyle intervention in preventing cognitive decline. Participants are older adults (60‐85 years) at high risk of dementia (CAIDE dementia risk score ≥ 6) using the Cognitive Change Index and Fototest and Memory Alteration Test (T@M) screening tools. Interested individuals fill out a REDCap online form that allows pre‐selection (by estimated CAIDE) for an individualized face‐to‐face screening visit to confirm eligibility. The descriptive analysis of the recruited sample and the comparison of dementia risk factors and cognitive tool performance between genders are presented.

Result

Over 2500 subjects showed interest in the study by January 2022 through an online pre‐screening questionnaire. Of these, 60.4% were women (mean age, 67.52 years). After completing the online pre‐selection phase and the screening visit (n = 845), the representation of women dropped to 52.7% and 50.5%, respectively. Table 1 shows some preliminary data on the current recruitment process, which will be finished by Q2 2024. Preselected women have a lower mean CAIDE dementia risk score than men (p<0.001). Women also have fewer years of education and are less physically active. Blood pressure is higher in men. Although both sexes similarly report memory complaints, women perform better in cognition screening tools.

Conclusion

Women seem to be more interested in initiatives promoting healthy aging. We have observed differences in dementia risk factors between men and women that could be related to sociocultural gender differences in this range of age. As previous studies have shown, in our study women perform better on brief cognitive tests, making them less likely to be selected. This highlights the importance of considering sex and gender for future analysis, trial designs, and recruitment strategies.
Multilevel measures of socioeconomic disparities impact brain health and dementia across the Americas
Authors: Legaz Agustina , Gonzalez‐Gomez Raul , Migeot Joaquín , Escudero Stefanie Danielle Pina , Altschuler Florencia , Ibañez Agustin
Published: January 2025

Background

Socioeconomic disparities (SED) influence brain health and dementia. Latin America (LA) is characterized by high SED and a disproportionate prevalence of Alzheimer’s disease (AD) and frontotemporal lobe degeneration (FTLD) compared to high‐income populations like the United States (US). However, the impact of SED on brain reserve across neurocognitive pathways related to aging and dementia in LA remains unknown.

Method

We evaluated how SED impact brain volume and functional connectivity in participants with AD, FTLD, and controls from LA (Argentina, Chile, Colombia, Mexico, Peru) and US, triangulating three SED measures: (i) educational attainment (n = 1410), (ii) cross‐culturally harmonized social determinants of health (SDH; n = 2324), and (iii) structural inequality (GINI index; n = 2135). Data were obtained from the Multi‐Partner Consortium to Expand Dementia Research in Latin America [ReDLat], the Alzheimer’s Disease Neuroimaging Initiative [ADNI], and the Laboratory of Neuro Imaging [LONI]. We controlled for multiple potential confounders (e.g., scanner, TIV, age, sex).

Result

Across the three studies, SED was associated with impaired neurocognitive outcomes, especially in LA compared to the US. (i) Lower educational attainment was associated with reduced fronto‐temporo‐posterior brain volume and connectivity across all LA groups (Fig 1; multiple regressions and kruskall‐wallis comparisons, P<0.05 TFCE correction). (ii) Adverse SDH including childhood SDH, discriminated between controls, AD, and FTLD in LA, affecting patients’ cognition, severity, and functionality (Fig 2A‐B; XGBoost binary logistic regression). Also, adverse SDH induced reduced volume and connectivity (VBM and whole‐brain analysis, both P‐FDR<0.05) across LA groups (Fig 2C). Finally, (iii) Higher structural income inequality at both the state/country levels was associated with reduced volume and connectivity in the temporo‐parietal, cingulum‐limbic, and cerebellar regions, with more pronounced effects in LA groups (Fig 3; multiple regressions with grey matter volume [w‐maps, P‐FWE<0.05] and connectivity [wSDM coefficients, P‐Bonf<0.05]).

Conclusion

Findings suggest that exacerbated SED, observed in more diverse samples from LA, differentially and negatively impact neurocognitive factors in aging and dementia. This aligns with the notion that SED diminish brain and cognitive reserve, amplifying dementia burden. Tailored, local‐sensitive models are required to leverage the impact of SED in brain health and dementia, particularly in underrepresented populations like LA.
Circulating metabolomic profile of the MIND diet and its relation to cognition in middle‐aged and older adults
Authors: Chen Hui , Shen Jie , Tao Yang , Zhang Yaodan , Gao Mengyan , Ma Yuan , Zheng Yan , Zong Geng , Lin Qing , Tong Lusha , Yuan Changzheng
Published: January 2025

Background

Dietary factors are modifiable risk factors for dementia. In particular, the Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet has been associated with better cognitive function and lower risk of dementia. However, circulating metabolomic characteristics of the MIND diet and its associations with cognitive function remains unclear.

Method

In the current study, 45906 UK Biobank (UKB) participants (mean age: 56.4 years) were separated into a discovery cohort and an internal prospective validation cohort, and 6193 Whitehall II (WHII) study participants (mean age: 56.8 years) constituted an external validation cohort. We identified the metabolites associated with the alternate MIND diet score (aMIND) using linear regression models, and Benjamini‐Hochberg method was applied to control false discovery rate. We constructed a metabolomic signature score of the MIND diet using elastic net model and assessed the potential mediating role of the metabolomic signature in the associations of the aMIND with cognitive outcomes in the two cohorts.

Result

The aMIND showed significant associations with 149 out of 168 (89%) metabolites in the UKB discovery cohort, and 47 of these associations were also replicated in both the internal validation cohort and the external validation cohort, including 38 lipoprotein subclass, 4 fatty acid, 1 cholesterol, 1 inflammation, 2 lipoprotein particle size, and 1 triglyceride measures. The metabolomic signature score based on the selected metabolites was significantly correlated with the aMIND (Pearson’s r = 0.36, 0.31, and 0.27 in the discovery, internal validation and external validation cohort). In the UKB (491 incident dementia cases during a median follow‐up of 11.8 years), but not WHII (169 in 17.8 years), the MIND metabolomic signature score significantly mediated the association of the aMIND and incident dementia by 45%. In the WHII, association between the aMIND and cognitive function was partially mediated by the metabolomic signature (proportion = 19%, P for mediation = 0.039).

Conclusion

MIND diet was favourably associated with a panel of metabolites, and a MIND diet metabolomic signature score partially mediated the observed associations between MIND diet adherence and incident dementia and cognitive function.
Association between leisure activities and quality of life in older adults with dementia who use day care rehabilitation services
Authors: Kasuya Masashi , Tanaka Naofumi , Wang Yin‐Jung , Ouchi Yoshitaka
Published: January 2025

Background

Day care services provide not only physical exercise to improve physical function, but also a variety of activities. These activities are expected to enhance leisure activities of users and improve their QOL. However, the relationship between QOL and the presence of leisure activities in day care service users with dementia has not been clarified.

Method

Participants were 76 older adults (47 women, mean age 82 ± 7 years) aged ≥65 receiving day care services with MMSE scores between 10 and 23. They were administered a series of questionnaires on leisure activities and their quality of life was assessed using the Quality of Life in Alzheimer’s Disease (QOL‐AD). Other assessments included the Geriatric Depression Scale‐15 (GDS‐15) and the Apathy Evaluation Scale (AES). The participants were divided into two groups based on whether or not they participated in leisure activities. Age, gender, nursing care level, MMSE score, GDS‐15 score, AES score, and QOL‐AD score were compared between the two groups. A covariance analysis was then conducted with leisure activity participation as the independent variable and QOL‐AD score as the dependent variable.

Result

Fifty‐seven participants (37 women, age 80 ± 8 years) participated in leisure activities and 19 participants (10 women, age 83 ± 7 years) did not participate in leisure activities. There were no significant differences in age and gender between the two groups. The level of care required was significantly lower in the group with leisure activities than in the group with no leisure activities (p < 0.01), the MMSE score was significantly larger (p < 0.01) and the GDS‐15 score and AES score were significantly smaller (p < 0.05 and p < 0.01 respectively). Analysis of covariance using age, gender and nursing care level as covariates showed that the QOL‐AD score of the group with leisure activities was significantly greater than that of the group with no leisure activities (p<0.05).

Conclusion

This study suggests that providing opportunities for leisure activities in day care services to older adults with dementia who do not participate in leisure activities in their daily lives may be beneficial in improving their quality of life.
Evaluation of the Memory Enhancing Activity of Dichloromethane Fraction of the Methanol Extract of Pycnanthus angolensis Stem Bark on Experimental Models of Memory Impairment
Authors: Chinwuba Patrici Eziafa , Ganiyu Bakre Adewale
Published: January 2025

Background

Pycnanthus angolensis (Welw) Warb., Myristicaceae, is used extensively in ethnomedicine. Numerous health benefits have being ascribed to the use of different parts of P. angolensis including its role in cognition enhancement and inflammation. Hence, this study was undertaken to investigate the stem bark of the plant for memory enhancing activity in mice.

Method

The plant material was grinded into powder and extracted by maceration with 80% methanol at room temperature for 48h. This was subsequently fractionated using N‐hexane, Dchloromethane (DCM), and Ethyl acetate. The Dichloromethane (DCM) fraction‐the most potent fraction‐ (25, 50, and 100 mg/kg) was evaluated for memory enhancing activity using the Y maze, Morris Water Maze (MWM) and the Elevated plus maze (EPM), on the D‐galactose plus scopolamine and ketamine induced amnesia model. The antioxidant markers and acetylcholinesterase inhibiting effect of DCM were also evaluated

Result

The results obtained from the behavioural studies indicate that the DCM fraction significantly (p<0.05) increased the alternation behaviour of the mice in the Y maze, decreased the escape latency in the MWM paradigm and decreased the transfer latency (TL) in the EPM. Biochemically, DCM increased Glutathione (GSH), and superoxide dismutase (SOD), but decreased Malondialdehyde (MDA) and acetylcholinesterase (AChE) activity in the brain.

Conclusion

The study therefore suggested that the DCM may possess significant memory enhancing activity, which may be due to the reverser of the activity of scopolamine, thereby, enhancing cholinergic transmission. The attenuation of the effect of ketamine by the DCM may possibly result from an increase in NMDA receptor activity.
Prevalence of undiagnosed dementia among older hospitalized patients: variation by social and demographic factors
Authors: Aliberti Márlon Juliano Romero , Avelino‐Silva Thiago J , Covinsky Kenneth E , Suemoto Claudia Kimie ,   CHANGE Study Group
Published: January 2025

Background

The profound impact of dementia on acute care, compounded by frequent underdiagnosis, is a significant challenge, especially among certain ethnic and minority groups, and remains largely unexplored in hospital settings. We used data from a multicentric study comprising 43 public and private hospitals in five countries to estimate the prevalence of undiagnosed dementia across different sociodemographic measures.

Method

The CHANGE (Creating a Hospital Assessment Network in Geriatrics) Study, an ongoing cohort designed to identify age‐related conditions like dementia, included patients aged ≥65 years admitted to 43 acute hospitals throughout Brazil and four other countries: Angola, Chile, Colombia, and Portugal. Upon admission, participants underwent a comprehensive geriatric assessment. To determine a previous dementia diagnosis, we consulted close family members and reviewed medical records. Trained investigators also administered the Clinical Dementia Rating (CDR) to family informants, referencing the patients’ cognitive status three months before admission to avoid the influence of acute cognitive impairment. Undiagnosed dementia was defined for participants with no clinical history of dementia and a CDR score ≥1. We estimated the prevalence of undiagnosed dementia across different sociodemographic measures and hospital types.

Result

In a sample of 2,452 participants (mean age = 79±9 years; women = 57%; Black or admixed = 42%), 1,032 (42%) presented with preexisting dementia (CDR ≥1), and among these, 448 (43%) had undiagnosed dementia (Table 1). Although no significant difference was found based on sex, undiagnosed dementia was associated with younger age, Black or admixed race/ethnicity, lower education levels, and lower income (Table 2). Moreover, the rate of undiagnosed dementia was more than double in public hospitals (47%) compared to private hospitals (22%), with a p‐value<0.001. Notably, Black patients with less than 8 years of education in public hospitals were significantly more likely to have undiagnosed dementia compared to White patients with higher education admitted to private hospitals, with undiagnosed dementia rates of 53% versus 20%, respectively (p‐value<0.001) (Figure 1).

Conclusion

Four out of ten older patients with preexisting dementia had not been diagnosed prior to hospital admission, underscoring the urgent need for practical diagnostic approaches to improve care in acute settings, particularly for ethnic and socioeconomic minorities in public hospitals.
Mental and Physical Health Factors Linking Perceived Control to Brain Health
Authors: Palms Jordan D , Morris Emily P. , Sol Ketlyne , Nelson Monica E , Scambray Kiana A. , Zahodne Laura B.
Published: January 2025

Background

Perceived control is a psychosocial construct thought to reflect one’s beliefs about their ability to influence life outcomes and includes both internal (self‐efficacy, mastery) and external (structural barriers, constraints) subcomponents. While perceived control has been found to relate to numerous health outcomes such as cardiovascular and mental health, less is known about its impact on brain health. A prior study found that behavioral (i.e., physical activity) and biological (i.e., metabolic systems) health factors mediated the relationship between perceived control and memory (Infurna & Gerstorf, 2013). Furthermore, preliminary analyses indicated greater external control was associated with lower cortical thickness. The current study extends this work by evaluating associations between internal (mastery) versus external (constraints) control and brain health, as well as underlying mechanisms.

Methods

The current study included a subsample of older adults aged 55+ from the Michigan Cognitive Aging Project who completed magnetic resonance imaging (N = 120; Agemean = 62.6; female = 53%; non‐Hispanic Black = 30%). Multiple linear regressions examined associations between Mastery and Constraints subscales from the Perceived Control Scale, and brain health outcomes (cortical thickness composite of nine Alzheimer’s disease signature regions, total gray matter volume, total white matter volume, and white matter hypointensity volume). A mediation analysis explored potential mechanisms of association between perceived control and brain health outcomes through physical (number of chronic illnesses) and mental (depressive symptoms) health factors. Covariates included sociodemographics and total intracranial volume.

Results

Mastery was not associated with brain health outcomes. Constraints were negatively associated with cortical thickness (total effect b = ‐.02, 95%CI [‐.03,‐.002]) only. Depressive symptoms fully mediated the relationship between constraints and cortical thickness (indirect effect b = ‐.02, 95%CI [‐.03,‐.01]) such that more constraints led to decreased cortical thickness through increased depressive symptoms. No indirect paths through chronic disease burden were found.

Conclusion

These findings suggest that environmental constraints may be an upstream determinant of depressive symptoms, which can lead to negative downstream effects on brain health. Treatment approaches to mental and brain health should address structural barriers in addition to individual factors. Future longitudinal and/or intervention work is needed to confirm the direction of effects, which were based on previous theoretical and empirical work.
Allostasis links white matter hyperintensities with age‐related human brain structure and function: evidence from EEG and structural MRI
Authors: O'Byrne Daniel Franco , Laguardia Ana Maria Castro , Delgado Carolina , Campo Cecilia Gonzalez , Ibáñez Agustín , Medel Vicente
Published: January 2025

Background

The human brain integrity relies on the synergistic interplay between neural activity and supporting vascular and metabolic processes throughout life. This relationship, ruled by allostatic mechanisms, regulates brain architecture and activity. White matter hyperintensities (WMH) serve as indicators of the vascular impact on brain structure. While the strong association between vascular/metabolic systems and brain structure/function is established, the precise mechanisms linking allostasis to WMH remain elusive. We hypothesized that allostasis influences white matter through neuroinflammatory mechanisms, and WMH mediate neuroinflammatory effects on EEG measures.

Method

To test this hypothesis we conducted a comprehensive analysis on MRI, EEG, and multisystemic data from 196 subjects (20 to 75 years, 69 females) sourced from the LEMON database in Leipzig, Germany. Using the lesion segmentation tool (LST) on SPM12, we automatically identified WMH in fluid‐attenuated inversion recovery (FLAIR) images. FastSurfer was employed to determine the volumes of the bilateral hippocampus (HV) and lateral ventricles (VV), representing proxies for neurodegenerative and neuroinflammatory processes, respectively. Volumetric corrections were applied using total intracranial volume. Furthermore, a regression analysis was conducted to discern and subtract the shared contributions of VH and VV on each other. EEG data underwent spectral analysis for oscillatory (alpha waves) and aperiodic (1/f) components using NeuroDSP and FOOOF, respectively. An allostatic load index (ALI), incorporating lipid profile, inflammation, metabolic factors, and blood pressure, was computed. All measures were age, sex, and education level‐corrected.

Result

We found age differences in every metric of interest, but importantly just ALI, VV and 1/f correlated with WMH number and those effects survived age correction (Figure 1 A and B). VV, but not HV mediates the relationship between ALI and WMH. Also, WMH completely mediate the effects of neuroinflammation over the 1/f (Figure 1 C).

Conclusion

Our findings reveal that allostasis affects white matter through neuroinflammatory pathways, with WMH serving as crucial mediators of neuroinflammatory impact on EEG measures. This research provides key insights into the intricate interplay of vascular and metabolic factors with brain structure. Identified relationships and mediators open avenues for targeted interventions and personalized treatments in neurodegenerative and neuroinflammatory conditions.
Expected challenges for memory clinics introducing disease modifying treatments in the Nordics
Authors: Gustavsson Anders , Palmqvist Sebastian , Kern Silke , Saarinen Jukka , Jelic Vesna , Ghadbhan Sohad F , Lennhed Björn Strindberg , Jarholm Jonas Alexander , Dun Alexander Rieem , Cooper Alexandra , Ekelund Mats , Ellgren Maria , Fladby Tormod , Nägga Katarina
Published: January 2025

Background

New disease modifying treatments (DMTs) offer a new treatment paradigm in mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease (AD). This likely requires significant changes in patient management and need for added capacity for diagnosis, treatment and monitoring.

Method

We surveyed eight selected memory clinics in the three largest and two smaller regions of Sweden, plus one in each of Denmark, Finland and Norway on their current practice, number of patients by diagnosis and available resources. Findings were compared to clinic assumptions on a future scenario where eligible patients with MCI or mild dementia due to AD are offered DMT.

Result

Up to 3, but most often less than 1, incident patients in 1000 inhabitants per year are seen at surveyed memory clinics, of which on average about 40% have MCI or mild dementia due to AD. This constitutes not more than a few percent of the 10‐30 persons in 1000 inhabitants expected to have AD at this stage in the Nordics today. Most patients get amyloid biomarker confirmation as part of their diagnosis, while there are long wait times for radiology, in particular magnetic resonance imaging.

Conclusion

Most patients expected to be eligible for DMTs in AD are not referred to memory clinics today, but are managed in primary care or are not presenting with cognitive complaints to health care at all. Therefore, the main challenge is likely not to treat patients already seen at memory clinics, but to manage a potential increase in patients that would benefit from DMTs. New referral patterns and health care seeking behaviors are therefore expected to determine the need for investments in additional capacity to diagnose and treat eligible patients.
The prevalence of Alzheimer disease in Odesa region
Authors: Vorokhta Yurii , Khubetova Iryna
Published: January 2025

Background

The prevalence of dementia in people aged 65 and over in the world is approximately 6‐10%, two‐thirds of these cases are due to Alzheimer disease The frequency of deaths from Alzheimer disease in Ukraine is 0.3 per 100,000 population, while in Great Britain this indicator is 112 per 100,000 people, USA – 82, France – 76, Germany – 51 [1, 2].

The purpose of the study was to estimate the prevalence of Alzheimer’s disease in the Odesa region.

Method

Retrospective analysis of the medical records about the registered cases of Alzheimer disease were received from Odesa Regional Mental Health Center for the years 2016‐2022. These data were analysed by the frequency and variance for indices of prevalence, age and gender structure.

Result

According to the retrospective data of the Odesa Regional Mental Health Center for the years 2016‐2022, a constant increase in the number of detected patients with Alzheimer disease was noted ‐ from 4.9 cases per 100,000 population in 2016 to 6.3 cases in 2022. The gender balance throughout the analyzed period was stable, with a slight predominance (60%) of women in the structure of patients.

The average age of men was 72.8±0.3 years, women – 78.6±0.3 years. Statistically significant differences (p<0.05) could be explained by longer life expectancy in women.

Conclusion

The prevalence of neurodegenerative diseases in the Odesa region, according to medical records, is significantly lower than the European average, which indicates underdiagnosis.

References:

1. 2023 Alzheimer’s disease facts and figures. Alzheimers Dement. 2023 Apr;19(4):1598‐1695. https://doi.org/10.1002/alz.13016. Epub 2023 Mar 14. PMID: 36918389.

2. Федотова М. С., Панфілова Г. Л., Цурікова О. В., Блажієвська О.М. Дослідження епідеміології деменції та хвороби Альцгеймера в Україні. [Research on the epidemiology of dementia and Alzheimer’s disease in Ukraine] Вісник фармації. 2021. 2(102) 50‐58 [Ukr]
A machine learning approach to predict tau positivity using clinical features in amyloid‐positive individuals
Authors: Arnold Daniel , Borelli Wyllians Vendramini , Machado Luiza Santos , Rahmouni Nesrine , Therriault Joseph , Servaes Stijn , Stevenson Jenna , Macedo Arthur C. , Schumacher‐Schuh Artur Francisco , Mattjie Christian , Barros Rodrigo C. , de Bastiani Marco Antônio , Lussier Firoza Z , Chamoun Mira , Bezgin Gleb , Benedet Andrea L. , Pascoal Tharick , Rosa‐Neto Pedro , Zimmer Eduardo R. ,   Alzheimer's Disease Neuroimaging Initiative (ADNI)
Published: January 2025

Background

Anti‐amyloid therapy appears to have an increased effect on reducing cognitive decline in amyloid‐ and tau‐positive individuals. However, clinical trials inclusion criteria require solely amyloid positivity. Herein, we developed a machine‐learning prediction model to identify tau positivity in amyloid‐positive individuals using clinical variables.

Method

We selected 1191 amyloid‐positive participants and tau status from ADNI, TRIAD, PPMI databases. Commonly shared clinical features selected between datasets were age, total MOCA scores, clinical diagnosis, sex, education, BMI, heart disease, stroke, hyperlipidemia and diabetes. Amyloid positivity was defined by amyloid‐PET (PIB‐PET, FBB‐PET or AZD4694‐PET) or CSF AB42 and Tau positivity defined by Tau‐PET (MK6240‐PET or AV1451‐PET) or CSF p‐tau181. The dataset was split into training (49%), validation (21%), and testing datasets (30%). A XGBoost model was tuned, and then used to predict the tau status outcome in the testing dataset.

Result

A total of 647 men and 544 women were included with mean age 66.1 ± 10.4 (mean ± SD) years, MOCA 25.1 ± 4.1 scores and education 16.1 ± 3.2 years (Table). The population consisted of 794 controls, 271 MCI and 126 dementia individuals. Tau status was negative for 854 individuals and positive for 337. The receiver‐operator characteristic (ROC) analysis showed that the area under the curve (AUC) was 0.81 for discriminating tau‐negative vs. tau‐positive, with 0.76 as sensitivity, specificity as 0.86, and accuracy as 0.83. The top 3 most impactful features were found to be age, diagnosis‐CN and MOCA score through a SHAP value analysis (Figure).

Conclusion

Predicting tau positivity with clinical and cognitive variables may improve the selection of individuals for AD trials. A two‐step workflow using this approach may significantly reduce the need for tau‐PET exams in trials by screening individuals using clinical variables. The following steps should include adding more individuals and other clinical variables through different cohorts to optimize the model applicability and test their performance in outcomes of clinical trials.