bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual‐task disparities in gait and functional mobility among older adults with a fall‐related mild traumatic brain injury and people living with dementia
Authors: Okrah Albert K , Parada Stephen A , Jirau‐Rosaly Wanda D , Bursey Max , Reynolds Bradford , Ohamadike Chijioke , Jehu Deborah A
Published: January 2025

Background

Mild traumatic brain injury (mTBI) increases dementia risk. Delays in diagnosis are common due to insensitive tools, prolonging symptoms and time to treatment. Dual‐task gait and functional mobility deficits are present post‐mTBI and in people living with dementia (PWD); however, it is unclear whether dual‐tasking can be used as a tool to differentiate between groups. This study aimed to 1) assess whether dual‐task mobility is more sensitive to detect differences between older adults with a mTBI relative to PWD than single‐task mobility; and 2) examine dual‐task cost between groups.

Method

n = 3 community‐dwelling older adults with a fall‐related mTBI (Age:68.6 years, Montreal Cognitive Assessment (MOCA) = 23 points, 67% Female) and n = 25 PWD in residential care facilities (Age:82.1 years, MOCA = 10.2 points, 36% Female) wore 6 APDM inertial sensors and completed two usual pace walking trials (single‐task) with or without naming words (dual‐task). Participants also completed two trials of the timed‐up‐and‐go, which involved getting up from a chair, walking 3 m, turning around, walking back, and sitting down (single‐task) with or without completing a category task (dual‐task). Separate repeated measures analyses of variance were conducted for gait and the TUG.

Result

There were no between‐group interactions (p>0.05). There was a Condition by Measure interaction for gait (F(1.13,29.49) = 35.25, p<0.001, ηp
2 = 0.58) and functional mobility (F(1.53,39.89) = 6.0, p<0.01, ηp
2 = 0.19). Dual‐tasking provoked slower gait speed (dual‐task:0.36 m/s; single‐task:0.54 m/s), greater double limb support (dual‐task:38.0%; single‐task:31.8%), lower midswing elevation (dual‐task:0.91cm; single‐task:1.28cm), and shorter stride length (dual‐task:0.55m; single‐task:0.71m;p<0.001) than single‐tasking. The dual‐task TUG provoked longer time to completion (dual‐task:33.2s; single‐task:22.2s), smaller turn angle (dual‐task:120.7°; single‐task:140.2°), and slower turn velocity (dual‐task:80.3m/s; single‐task:94.1m/s) than the single‐task TUG.

Conclusion

There were no between‐group differences in single‐ or dual‐task mobility; however, these findings should be interpreted with caution as we have only tested n = 3 participants in the mTBI group, and data collection is ongoing. Both groups experienced some level of cognitive impairment, highlighting that the deficits observed in dual‐ relative to single‐task mobility were likely a manifestation of increased attention demand. Further work is underway to determine whether dual‐tasking may be a sensitive measure to screen and monitor mobility impairments in these populations.
Real‐world effectiveness of anti‐amyloid therapies: the feasibility of obtaining historic controls from large‐scale disease registries
Authors: Jönsson Linus , Winblad Bengt , Wimo Anders , Herring William L
Published: January 2025

Background

Novel anti‐amyloid therapies (AAT) for Alzheimer’s Disease (AD) have recently been approved in the United States, Japan and China, and are under regulatory review in Europe. Questions remain regarding the long‐term effectiveness and value of these drugs when used in routine clinical practice. Data from follow‐up studies will be important to inform their optimal use, including criteria for treatment initiation, monitoring strategies, stopping rules, pricing and reimbursement considerations. Newly initiated treatment registries will only or mainly enroll patients receiving AAT with no control arm ‐ for comparisons with of health outcomes in untreated patients, external historic control data will be required.

Method

We reviewed the literature to identify disease registries with relevant design and inclusion criteria.Patient‐level data was obtained from two registries deemed to be promising as sources of historic control data: the Swedish Registry for Cognitive Disorders (SveDem) and the National Alzheimer’s Coordinating Centers (NACC). From these registries we selected patients fulfilling key criteria for treatment with AAT and analyzed longitudinal data on relevant endpoints (disease progression, functional status and mortality) using survival analysis methods. Sample size requirements for evaluating the effect of AAT on these endpoints were estimated using the Lachin & Foulkes method assuming a risk ratio of 0.7 with treatment.

Result

35 disease registries were identified from 15 countries. Many did not include the relevant patient populations, endpoints or had insufficient follow‐up. From SveDem and NACC, 1378 and 7392 patients respectively were included, respectively. The median time to disease progression was 1.9‐3.2 years, time to full‐time care 2.7‐5.3 years, and median overall survival 11.4‐13.6 years. Approximately 248 events would be required to detect a difference in time to event with 80% power. In SveDem, a total number of 2717 disease progression events, 3916 full‐time care events and 842 mortality events were observed.

Conclusion

Follow‐up studies will be of key importance for confirming the clinical effectiveness and economic value of DMT in routine care. Established registry infrastructures with available historic datasets will play an important role. International collaboration may be needed to achieve sufficient sample size for assessment effects on some endpoints, such as overall survival.
Early adverse experiences of abuse, ventral striatum, and later life cognitive functioning
Authors: Kuenzi Morgane , Gheorghe Delia A , Bauermeister Sarah
Published: January 2025

Background

According to the World Health Organization, dementia is one of the leading causes of death and at least 55 million people worldwide currently have dementia. Therefore, identifying the factors that increase the risk of developing dementia, but also those that protect against it, as well as the mechanisms underlying these effects, are essential for prevention and the development of interventions.

Method

Literature findings underline the detrimental effects of early adverse experiences on a variety of later‐life biopsychosocial outcomes, including brain and cognition. Adversity and its consequences may, directly and indirectly, impact cognitive functioning and lead to an increased risk of developing dementia. However, the underlying mechanisms of the association between early adversity and cognition are not yet understood.

Our research aimed to understand the direct and indirect associations between early adversity and later life cognitive impairment as well as the potential mechanisms underlying these associations. A particular focus was given to the ventral striatum given previous evidence of its association with early adversity and its involvement in reward processing.

Result

Using the UK Biobank dataset, structural equation modeling (SEM) was performed.

The preliminary results highlight that the experience of early abuse is associated with a higher number of addictions. Individuals having experienced sexual abuse and emotional abuse showed slower reaction times. Addiction was associated with a smaller volume of the left ventral striatum. Interestingly, a higher volume of the left ventral striatum was associated with a faster reaction time. Finally, a significant mediation between the experience of early sexual abuse and the volume of the left ventral striatum via addiction was found.

Conclusion

The preliminary results found are in line with the literature findings showing associations between adversity and addiction and between adversity and cognition. In addition, the results suggest a mediating link between sexual abuse and the left ventral striatum via addiction, highlighting the importance of addiction in this association. Although direct associations between early adversity and reaction time were found, these associations were not mediated by the volume of the left ventral striatum. These findings highlight a potential pathway by which early adversity may affect the brain.
Neuroprotective Effect of Urolithin A against Cerebellum Changes in Streptozotocin‐Induced Alzheimer’s Disease Rat Model
Authors: Salari Mona Taghizade , Khani Leila , Behnam‐Rassouli Morteza , Gholami Kianoush , Ahmadnia Hananeh , Hasanpour Maede , Iranshahy Milad , Iranshahi Mehrdad
Published: January 2025

Background

Microbiota of the distal part of the intestine produces Urolithin A (Uro A) as a derivative of ellagitannins hydrolysis. Recently, the mitophagy, anti‐inflammatory, and antioxidant properties of Uro A have focused more attention on its probable beneficial effects on neurodegenerative states. The purpose of this research was to study the impact of Uro A on the histopathology of the cerebellum in a rat model of streptozotocin‐induced Alzheimer’s disease.

Methods

Young male Wistar rats underwent stereotaxic surgery and infused streptozotocin (STZ; 3 mg/Kg body weight, dissolved in 10 µl vehicle of ascorbic acid‐saline 0.1%), intracerebroventricularly. After that, rats of experimental groups 1 and 2 were administered daily (i.p.) Uro A at two different doses; 10 and 20 mg/kg body weight, respectively. At the end of the experimental period (2 weeks), rats were deeply anesthetized, perfused (10% formalin solution), and decapitated, and their brains were removed and post‐fixed in the same fixator. Then, the cerebellums were separated and processed for histological preparation. Paraffin sections (5 µm thickness) were stained (H&E) and examined under a light microscope.

Result

The microscopic photos of cerebellum sections of control, negative control, and experimental rats are presented in Figure 1. The photos show that, in comparison with the control, the disruption in the continuity of the Purkinje cell layer, as well as the abnormal morphology and lower density of Purkinje cells are obvious in the negative control section.

Conclusion

It seems that Uro A treatment could somehow limit the destructive effects of STZ on the cerebellar Purkinje cell layer. Previously, decreased densities of Purkinje cells and notable morphological changes have been reported in the cerebellum of Alzheimer’s patients (Baloyannis et al., 2000).
Brain Health Interventions in Clinical Practice: A Framework for Implementation and Provisional Results from Ireland’s first Brain Health Clinic
Authors: Connolly Eimear , Dolphin Helena , Knight Graham , Fallon Aoife , Kennelly Sean P
Published: January 2025

Background

At a population level, it is acknowledged that around 40% of all causes of dementia are attributable to twelve potentially modifiable risk factors (MRFs) identified by The Lancet Commission on Dementia Prevention. Preventative measures that target these MRFs should be integrated into clinical practice, alongside biomarker‐supported diagnosis of Mild Cognitive Impairment (MCI) or Dementia. However, most memory services do not routinely provide a preventative Brain Health Clinic (BHC).

Methods

Tallaght University Hospital Institute of Memory and Cognition (TIMC) is a Regional Specialist Memory Clinic (RSMC) in an Irish tertiary hospital which provides patients with biomarker‐supported multidisciplinary consensus diagnosis. It has established Ireland’s first BHC to identify and address MRFs for dementia. Here we outline a framework for implementation of a BHC integrated within a clinical memory service. The assessment tools used to capture specific MRFs will be detailed. Data has been collected from the first 75 patients attending the service, and their demographic details, consensus diagnosis and MRF profiles will be described.

Results

The assessments carried out in our BHC are outlined in Figure 1. The BHC Pathway is shown in Figure 2. Patients are followed longitudinally with repeat cognitive testing at 18, 36 and 54 months. The demographic data for the first 75 patients attending this service, their consensus diagnosis and MRF profiles are outlined in Table 1. The most common diagnosis was MCI (n = 61) of which 48 had an amnestic phenotype. Cerebrospinal Fluid (CSF) biomarkers for Alzheimer’s Disease (AD) pathology were tested in 32 patients (52.45% of MCI patients). Hypertension was the most evident vascular risk factor, found in 60% of participants. Over half of patients had self‐reported poor sleep using the Pittsburgh Sleep Quality Index (PSQI). Hearing was assessed in 63 patients (84%), with 35% (n = 22) of tested patients requiring referral for formal audiology testing, highlighting the importance of screening for this risk factor.

Conclusions

TIMC have implemented a BHC and embedded it within a RSMC model. This enables patients to engage in targeted, personalised MRF assessment and modification. The risk factor profile of patients attending our BHC provides a valuable insight into MRF prevalence in patients attending memory clinics.
Efficacy of Transcranial Alternating Current Stimulation (tACS) in Cognition and Memory in Patients with Mild Cognitive Impairement or Alzheimer’s Disease. A Systematic Review and Meta‐analysis of Randomized Controlled Trials
Authors: Hendi Nada Ibrahim , El‐Samahy Mohamed , AboEl‐Azm Yosra Hussein , Arar Amina , Ramadan Shrouk I , Zedan Esraa M , Yasen Noha Samy
Published: January 2025

Background

Gamma desynchronization is an early pathophysiological event in Alzheimer’s disease with a disturbance in oscillation in the gamma frequency range 30‐80 Hz. This disruption was found to be directly related to the disease progression and severity. Thus, the use of transcranial alternating current stimulation (tACS) possessed greater interest. tACS can induce synchronization of neural networks leading to improvement in behavior and cognition. However, there’s still controversy regarding the beneficial effect of tACS in improving cognition and memory in Alzheimer’s disease patients. This systematic review and meta‐analysis aims to pool and synthesize evidence from randomized controlled trials to assess the efficacy of tACS on memory and cognition in patients with mild cognitive impairment or Alzheimer’s disease.

Method

We searched PubMed, Scopus, Web of Science up to Dec 17, 2023. We included a total of seven randomized controlled trials comprising 246 patients with Alzheimer’s disease or mild cognitive impairment. Our primary outcomes were Rey auditory verbal learning scale (RAVL), short latency afferent inhibition (SAI), and face‐name association task (FNAT).

Result

There was a significant difference between tACS and sham groups in favor of tACS in RAVL immediate recall (MD = 8.80, 95% CI = [5.22, 12.38], P < 0.00001), delayed recall (MD = 1.34, 95% CI = [0.78, 1.89], P < 0.00001), and total recall (MD = 10.62, 95% CI = [5.33, 15.92], P < 0.00001). Short latency afferent inhibition was significantly reduced in the tACS group compared to sham group (MD = ‐0.35, 95% CI = [‐0.41, ‐0.29], P < 0.00001). There was also a significant difference in FNAT in favor of tACS group (MD = 3.29, 95% CI = [2.50, 4.08], P < 0.00001)

Conclusion

Preliminary evidence suggests the potential efficacy of tACS for improving cognition in Alzheimer’s disease patients. However, due to the limited number of studies and the small sample size, there’s still insufficient evidence to conclude a decision regarding this matter. More standardized, large clinical trials are needed to establish better evidence.
Implementing Digital Cognitive Assessments to Detect Cognitive Impairment: Results from the Davos Alzheimer’s Collaborative Early Detection Program
Authors: MacLeod Tim , Murray James F. , dos Santos Filho Otelo Corrêa , de Sá Paiva Lima Marcilea Dias , Govia Ishtar , Robinson Janelle , Kowa Hisatomo , Morimoto Kohei , López‐Ortega Mariana , McKean Alison , Ritchie Craig , Baksh Magda R. , Smith Steven R. , Willis Deanna R , Brosch Jared R. , Small Seamus , Martin Tammy , Selzler Katherine J.
Published: January 2025

Background

Cognitive impairment is frequently undetected or undiagnosed in the early stages. To increase the rates of detecting cognitive impairment, the Early Detection program of the Davos Alzheimer’s Collaborative System Preparedness (DAC‐SP) implemented digital cognitive assessments (DCA) in primary care and other non‐specialty settings.

Methods

The DAC‐SP Early Detection program was initiated in 2021 in seven healthcare systems across six countries. Sites were able to choose from several DCAs, and clinicians were provided training, including recognizing signs and symptoms of cognitive decline, and provided with post‐diagnostic support. Patients were eligible for a DCA if they were over 60 years of age, able to hear and see well enough to complete the assessments, and had no prior diagnosis of dementia. The DCA tools included Linus Health’s Core Cognitive Evaluation, Cogstate Cognigram, and Cogstate Brief Battery.

Results

The DCA results across the seven sites are presented in Table 1. There was notable variability in the number of patients screened across sites, which could be attributed to multiple factors (i.e., number of clinics onboarded/trained, additional testing for language and culture appropriateness of DCA tool prior to deployment, reduction in the number of elderly people visiting clinics during the COVID‐19 pandemic, available time of clinicians, etc.). The rate of cognitive impairment (abnormal and borderline) was also numerically higher at sites outside the US, independent of the DCA tool used. However, this study was not designed to evaluate operating characteristics of DCA tools, so further research is needed. Approximately 60% of the patients in the DAC‐SP Early Detection program tested abnormal or borderline for cognitive issues, suggesting the need for additional clinical assessment and follow‐up.

Conclusion

Findings from the DAC‐SP Early Detection program demonstrated a DCA can be implemented in existing patient care workflows, including primary care settings, and across healthcare systems globally with different resource settings. Adoption of DCAs in clinical practice can help improve the ability to detect symptoms of cognitive impairment and provide much needed earlier screening and care for patients and their families.
Association of MIND diet adherence with micronutrients and executive function among middle‐aged Latinos
Authors: Guimarães Rafael , Soto Yuliana , DiFilippo Kristen , Schwingel Andiara , Aguiñaga Susan
Published: January 2025

Background

By 2060, an estimated 3.5 million Latinos may develop Alzheimer’s disease (AD). Lifestyle factors, such as adhering to the Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet, may improve cognition and reduce AD risk. This study aims to compare micronutrient intake in low and high MIND diet adherence and assess if higher micronutrient intake is associated with higher executive function (EF) scores in middle‐aged Latinos.

Method

A cross‐sectional study assessed MIND diet adherence and EF in middle‐aged Latinos. The Block 2005 Food Frequency Questionnaire measured diet adherence and micronutrient intake (iron, zinc, calcium, manganese, selenium, Vitamins C, B6, B12, and D). MIND diet scores (<8.5 or ≥8.5) were dichotomized between low‐adherers and high‐adherers. EF was measured using Trails A and B test. A t‐test compared micronutrient intake in low and high adherers. Pearson correlation explored the relationship between micronutrient intake and EF.

Result

Data from 61 participants (Mage = 58.6 ± 8.7, 67% female) show higher micronutrient intake in high adherers. Results indicate a negative correlation between micronutrient intake and Trails A and B test scores (P<.05), suggesting better cognitive performance with higher micronutrient intake for all except Vitamin D. There were significant differences in micronutrient intake between low and high MIND diet adherers for all except Calcium and Vitamin D.

Conclusion

Latinos adhering to the MIND diet show higher micronutrient intake and better EF performance. Future interventions should culturally tailor MIND diet to enhance adherence, potentially improving cognitive function and reducing the risk of AD in this population.
Neuroprotective role of Piceatannol in Chronic Unpredictable Stress induced memory dysfunction
Authors: Grewal Amarjot Kaur , Dhaliwal Parneet kaur , Silakari Pragati , kumar Amit , Khan Heena , Singh Thakur Gurjeet
Published: January 2025

Background

Various studies have evidenced the neuroprotective role of SIRT1 activator. However, whether SIRT1 activator, Piceatannol pharmacological treatment is protective in chronic unpredictable stress induced memory dysfunction remains unknown. Therefore, this study design included testing the hypothesis that Piceatannol administered in chronic unpredictable stress induced memory dysfunction mice shows protective effects, explores & probes underlying the activation of SIRT1 pathway.

Method

Swiss albino male mice were subjected to chronic unpredictable stress which further resulted in memory dysfunction. The levels of cortisol, biochemical parameters, inflammatory mediators, and AChE activity were examined. For memory assessment, mice were subjected to morris water maze (MWM) and passive avoidance test. Histological changes were assessed using HE staining.

Result

Piceatannol (10 & 20 mg/kg; oral) dose dependently reduced chronic unpredictable stress induced memory dysfunction’s deleterious effects on biochemical parameters of oxidative stress (SOD, GSH, Catalase, TBARS), inflammatory parameters (IL‐6, IL‐1β, NF‐κB, TNF‐α, MPO), TSTQ, Transfer latency time, cortisol levels, AChE activity and histopathological changes, according to the findings. These neuroprotective effects of Piceatannol were significantly abolished by pre‐treatment with Sirtinol (10 mg/kg; i.p), a SIRT1 inhibitor. Current study concluded that induced neuroprotective benefits of Piceatannol (10 & 20 mg/kg; oral) in all probability, maybe mediated through SIRT1 activation. Hence, its neuroprotective effects can be further explored in clinical settings.

Conclusion

From the evaluation of the results of numerous parameters, we draw the conclusion that the neuroprotective effects of Piceatannol in chronic unpredictable stress induced memory dysfunction may have been caused by SIRT1 pathway activation.
Geographic measures of early life‐course social exposome in the evaluation of structural neuroanatomy: A scoping review
Authors: Melcher Eleanna M , Duran Monica , Mamlouk Gabriella M , Christensen Leslie , Kind Amy J.H.
Published: January 2025

Background

Early life‐course exposome, including area‐based social disadvantage, may influence the development of cognitive reserve, thereby impacting later‐life incidence of Alzheimer’s Disease and Related Dementias (ADRD). The primary goal of this scoping review is to evaluate the extent of literature examining early‐life exposure to area‐based disadvantage and its association with structural neuroanatomical differences. A secondary goal is to examine the commonalities in brain regions impacted as well as the components of the exposure‐metrics utilized to study the social exposome.

Method

A systematic search for studies was conducted in PubMed, Scopus (Elsevier), Web of Science Core Collection (Clarivate), PsycINFO (EBSCO), and Google Scholar. Unique records were uploaded into Covidence for title/abstract screening and full‐text review by the study team. All articles were assessed for adherence to the following inclusion criteria: 1) English language, 2) participants 24 years of age or younger, 3) include structural neuroimaging as an outcome, 4) a geographically small area‐based metric of social disadvantage is treated as an exposure variable. Articles were excluded if they were non‐human subjects research, post‐mortem studies, reviews or meta‐analyses, or included participants who had underlying cognitive differences.

Result

After deduplication, the search retrieved 4,965 unique records. All titles and abstracts were independently screened by two team members, with a Cohen’s kappa greater than 0.8. After title and abstract screening, we identified studies that fulfilled inclusion criteria. These articles will undergo full‐text review to assess the study populations, the components of the area‐based metrics used, the time‐course of exposures in question, and the structural neuroanatomical differences found. Relevant themes in each area will be summarized.

Conclusion

Continued evaluation of the relationship between early‐life exposure to area‐based disadvantage and structural neuroanatomical differences may underscore opportunities to intervene on modifiable, fundamental causes of ADRD, namely development of cognitive reserve. With this review, we plan to establish what is known regarding the association between exposure to area‐based disadvantage in early life and neuroanatomical differences. This will enable further development of a theoretical model linking exposure to disadvantage with late‐life neurodegeneration and ADRD pathology.
Impaired baroreflex sensitivity and long‐term risk of dementia in community‐based older adults
Authors: Ma Yuan , Zhang Yiwen , Hamaya Rikuta , Westerhof Berend E , Shaltout Hossam A , Kavousi Maryam , Raso Francesco U S Mattace , Hofman Albert , Wolters Frank J. , Lipsitz Lewis A , Ikram M. Arfan
Published: January 2025

Background

Hypertension is an important modifiable risk factor for dementia, but the role of blood pressure (BP) in the development of dementia is not fully understood. Emerging data links increased BP variability and abnormal BP dynamics to dementia risk, but the relationship between baroreflex sensitivity (BRS), a fundamental physiological mechanism for maintaining stable BP, and dementia risk is unknown.

Methods

We investigated the association of BRS with the risk of dementia in community‐based older adults from the Rotterdam Study in the Netherlands. We determined cardiac BRS using a 5‐minute continuous beat‐to‐beat recording of BP and heart rate measured in a supine position between 1997 and 1999 and ascertained incident dementia cases using a standardized protocol from baseline through January 1, 2020. We quantified the association of cardiac BRS with dementia risk using adjusted cause‐specific hazard ratios.

Results

Of 1,819 participants (63% women; mean [SD] age, 71.0 [6.3] years), 421 developed dementia during a median follow‐up of 14.8 years. The association of cardiac BRS with dementia risk differed by antihypertensive medication use (P for interaction = 0.03) and was only observed in participants not taking antihypertensive medication. Specifically, reduced BRS was associated with a higher risk of dementia (cause‐specific hazard ratio [HR] comparing bottom versus top quintiles: 1.62; 95% confidence interval [CI]: 1.08‐2.42, P for trend = 0.02) and all‐cause mortality (corresponding HR: 1.77; 95%CI: 1.33‐2.37, P for trend<0.001) after adjusting for age, sex, APOE genotype, and traditional vascular risk factors. The association remained after additional adjustment for sitting BP level and beat‐to‐beat BP variability.

Conclusions

Among older adults not taking antihypertensive medication, reduced cardiac BRS was associated with a higher long‐term risk of dementia and all‐cause death over 23 years. Impaired BRS may be a novel biomarker of significant clinical relevance for early detection and prevention of dementia in older adults.
Classic biomarkers in exercise research for brain health promotion: From cells to communities
Authors: Barha Cindy K
Published: January 2025

There is growing recognition that exercise is a potent stimulus for improving cognitive and brain function in both humans and rodents. While the mechanisms underlying the effect of exercise on cognition are very likely multifactorial, it is clear that the secretion and function of several classical factors are involved. Work done in rodents implicates several growth factors, including BDNF, IGF‐1, and VEGF, in the ability of exercise to induce neuroplastic changes within key brain regions associated with learning and memory. However, confirming these growth factors as mediators of exercise efficacy in human trials has been less successful. This is likely related to several things, including a disconnect between human and rodent exercise studies in terms of design and analysis. We suggest that biological sex alone and in interaction with important genetic polymorphisms implicated in cognitive decline as vital moderating factors that must be considered in the search for exercise biomarkers.

A sex difference exists in exercise efficacy for cognition, with older females showing greater benefits for executive functions than older males. The ε4 variant of the apolipoprotein E (APOE) gene moderates the effect of exercise on cognition; although the direction of the relationship is unclear. Biological sex may interact with the APOE gene to further moderate exercise effects on cognition. Our work indicates that biological sex interacts with APOE4 status to moderate exercise effects on the brain in both humans and rodents. Additionally, the BDNFval66met polymorphism also influences exercise efficacy for promoting cognition and neuroplasticity in a sex‐dependent manner. How these polymorphisms impact classic exercise biomarkers in males and females are important avenues of research. Work in rodents indicates that systemic/central sex hormones are further involved in the effect of exercise; though which hormones and to what extent is still unclear. There is an overall paucity of studies in humans that have investigated the role of different sex hormones in mediating the cognitive‐response to exercise in the context of aging. A greater appreciation of tissue‐specific effects of exercise on sex hormone production and growth factors and the synergistic interaction between biological sex and genetics, will help move this field forward.
Aerobic exercise and Alzheimer’s disease blood‐based biomarkers
Authors: Erickson Kirk I.
Published: January 2025

A greater amount of physical activity is associated with a reduced risk of developing dementia, including Alzheimer’s disease. Engaging in physical activity affects several pathways that are associated with memory impairments including hippocampal integrity, resting state networks, and metabolic function. Further, exercise interventions are effective at improving various measures of brain health in late adulthood that overlap with the cognitive functions that these brain regions support. Yet, there remains a poor understanding of the mechanisms that link physical activity and exercise behaviors to improvements in brain health outcomes and reduced risk of developing dementia. There is also significant heterogeneity in this literature that could likely be explained by factors that moderate the impact of exercise on brain health. In this presentation we will discuss recent research on exercise and brain health in late adulthood and will discuss the evidence for several levels of mechanisms and moderators of these effects including examining the impact of exercise interventions on Alzheimer’s disease blood‐based biomarkers. Preliminary results will be described from a multi‐site, 12‐month, 3x per week supervised, moderate‐intensity, Phase III randomized clinical trial of aerobic exercise in 648 cognitively normal adults between 65‐80 years of age. Blood samples were taken before and after the completion of the intervention as well as a comprehensive cognitive battery and PET amyloid. The results from this aerobic exercise intervention will be discussed including the impact of the intervention on cognitive performance and the role that changes in Alzheimer’s disease blood‐based biomarkers play in relation to functional outcomes. Overall, physical activity and exercise behaviors are important modifiable lifestyles that carry significant consequences for learning, memory, and Alzheimer’s disease risk in late adulthood.
Preference Assessment in Dementia Care: Systematic Literature Reivew
Authors: Lim Hyejeen , Choe Young Min , Hwang Jaeuk , Choi Soo‐Hee , Kim Seong Jae , Lee Jung Hie , Woo Jong Inn , Seo Eun Hyun
Published: January 2025

Background

Boosting shared decision‐making (SDM) for individuals with dementia is a critical aspect of patient‐centered care. This collaborative approach respects the autonomy and dignity of patients, even when they face challenges in communication or decision‐making due to their medical condition. Understanding patients’ values and preferences may be central to a successful SDM process. The aim of this study is to review various preference evaluation methods used for individuals with dementia in clinical settings, and to suggest the most effective and feasible tools for accurately measuring values and preferences.

Methods

We strictly followed an updated guideline for the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) (Page et al., 2021). A systematic review was conducted through a search of three online databases (PubMed, Web of Science, Cochrane) and included studies about patient preferences published in English between 2000 and 2023. This review included studies that used a quantitative approach including surveys and structured interviews to gather data on the preferences of individuals with dementia and cognitive impairment. Specific inclusion and exclusion criteria are shown in Figure 1.

Results

After identification of 268 studies, twenty studies were finally eligible for review (Figure 1). Five categories of preference evaluations were generated from the review: (a) values and preferences in decision‐making (n = 6), (b) treatment goals (n = 2), (c) discrete choice experiments for preferences (n = 3), (d) diagnosis disclosure and communication (n = 5), (e) advanced care planning (n = 4). Most of the studies demonstrated substantial reliability and validity in their assessment methods for individuals with dementia.

Conclusions

Our findings suggested that individuals with dementia can reliably express their values and preferences about treatment that they currently receive or will need in the future. Moreover, our review highlighted the need for flexible and adaptable assessment to accommodate each patient’s unique circumstances. The utilization of tools with the autonomy preference index, clearly defined treatment goals, and transparent diagnosis disclosure, seem to be critical for fostering effective SDM process.
Effect of Occupational Toxin Exposure on the risk of dementia; Results of the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD)
Authors: Kim Hak Hyeon , van der Bent Yvonne , Kim Tae Hui , Kwak Kyung Phil , Kim Bong Jo , Kim Shin Gyeom , Kim Jeong Lan , Moon Seok Woo , Park Joon Hyuk , Ryu Seung‐Ho , Yoon Jong Chul , Lee Dong Young , Lee Dong Woo , Lee Seok Bum , Lee Jung Jae , Jhoo Jin Hyeong , Han Ji Won , Kim Ki Woong
Published: January 2025

Background

The global increase in the aging population has led to a corresponding rise in dementia cases. This study explores the potential link between occupational toxin exposure and the incidence of dementia, aiming to identify high‐risk populations.

Method

We analyzed data from 2,485 male participants aged 60 and over in the Korean Longitudinal Study on Cognitive Ageing and Dementia (KLOSCAD). Participants were categorized into no or very low, low and high toxin exposure risk groups based on their lifetime occupation according to the International Standard Classification of Occupations classification. Exposure to the specific hazard type, including carcinogens, skin sensitizers, airway sensitizers, mutagenic substances, reprotoxic agents and biological hazards were identified in relation to their lifetime occupation. We conducted multinomial logistic regression analysis, adjusting for occupation‐related factors, APOE genotype, age, education, health status and lifestyle behaviors, to investigate the relationship between the levels of toxin exposure risk, specific toxin types, and the incidence of mild cognitive impairment (MCI), Alzheimer’s disease (AD) dementia and other dementia.

Result

Compared to the no or very low toxin exposure risk group, participants in the low toxin risk exposure group (odds ratio (OR) 2.24, 95% CI 1.08 – 43.64) and high toxin risk exposure group (OR 2.97, 95% CI 1.31 – 6.74) showed a significantly increased risk of AD dementia. Exposure to carcinogens, skin sensitisers, reprotoxic agents and biological hazards showed a significant association with the risk of incident AD dementia. Among toxin types, skin sensitizers presented the highest OR of 5.48 (95% CI 1.29‐23.31) in multivariable model. No significant associations were found with MCI and other dementia.

Conclusion

Higher risk of lifetime occupational toxin exposure may be associated with an increased risk of AD dementia, showing consistent results across various toxin types, underscoring the need for heightened attention to toxin exposure in AD dementia prevention.
Contrast of Early Phase Amyloid PET
Authors: Kameyama Masashi , Sakata Muneyuki , Ishibashi Kenji , Tago Tetsuro , Kamitaka Yuto , Toyohara Jun , Ishii Kenji
Published: January 2025

Background

The method of obtaining pseudo‐cerebral blood flow images from the initial minutes of amyloid PET scans has been proposed. This technique proves to be highly valuable as it not only indicates the presence of amyloid accumulation but also reveals sites of neurodegeneration. However, the obtained early images represent the K1 image rather than cerebral blood flow. Consequently, the contrast in early images from amyloid PET tracers is thought to be compromised when compared to cerebral blood flow images.

Method

To enhance the contrast in early images obtained from amyloid PET tracers and thereby improve diagnostic accuracy, we developed a method for contrast recovery and established a methodology for determining the parameter involved in achieving this contrast recovery, drawing insights from a thorough literature review. Additionally, we conducted a comparative analysis involving PiB's early images and FDG, investigating their respective contributions.

Result

Our study demonstrated a strong correlation between FDG and early images of PiB, with relatively inconspicuous underestimations in high‐blood‐flow regions.

Conclusion

While we theoretically established a method to recover the contrast in early images, our findings suggest that amyloid PET tracers may exhibit a higher permeability‐surface area product than anticipated. This observation raises the possibility that, without correction, these tracers might inherently provide sufficient contrast.
From Plan To Impact – expediting progress towards targets of the WHO Global Action Plan on Dementia
Authors: Barbarino Paola , Aguilar Diego , Arthurton Lewis , Lynch Chris
Published: January 2025

Background

In 2017, all 194 Member States of the World Health Organization (WHO) unanimously adopted the Global Action Plan on the public health response to dementia 2017‐2025, the primary aim being for countries to implement National Dementia Plans (NDP). However, as outlined in Alzheimer’s Disease International’s (ADI) recent From Plan to Impact report, WHO Member States have been far too slow to act ‐ falling far short of the 146 countries target. In response, ADI launched the #WhatsYourPlan campaign, in collaboration with ADI Members, with the single‐minded aim of galvanising governments to act on their 2017 commitment.

Method

Strategizing and working with ADI Members, official communications were sent to relevant ministries to enquire as to the status of the NDP, and to request a formal meeting. For Ministries where a response was not obtained, subsequent letters were sent to elicit a response. ADI has also, in some instances, sought advice and utilised WHO regional and national offices, and other multilateral bodies and stakeholders, to help follow up with Ministries of Health for those that have been willing to engage.

Results

52 ADI members and thus 52 countries, joined the campaign. In total from the onset of the campaign, 205 official communications were shared with Member States, resulting in a total of 29 high‐level meetings. In total 20 Member States committed to developing an NDP, just over a third of all participating ADI Members and over half of the number of plans already in existence in WHO Member States

Conclusions

Though progress on the GAP has been slow, ADI’s successful #WhatsYourPlan campaign demonstrates that collaborative efforts between governments and stakeholders can make a tangible impact on policy development and implementation of NDPs. The fight for a better world for people living with dementia is ongoing, and it is crucial to utilise all available means to transform this vision into reality. As such, ADI is calling for an urgent extension of the Global Action Plan until 2029 with current progress putting people living with dementia and their caregivers are at a severe disadvantage.
Characterizing brain structures associated with subjective cognitive decline and mild cognitive impairment: a population‐based study
Authors: Chen Ziwei , Xie Qianqian , Wang Jiafeng , Zhang Huisi , Li Chunyan , Cong Lin , wang yongxiang , Song Lin , Du Yifeng , Qiu Chengxuan
Published: January 2025

Background

The structural brain alterations for subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are poorly defined. We sought to characterize grey matter volume (GMV) and cortical thickness associated with SCD and MCI among rural‐dwelling older adults in China.

Method

This population‐based cross‐sectional study included 1072 dementia‐free participants derived from the brain MRI substudy of MIND‐China in 2018‐2020. We defined MCI following the Petersen’s criteria, and SCD as the self‐reported AD8 questionnaire score ≥2. Data were analyzed using voxel‐based morphometry (VBM), surface‐based morphometry analysis (SBM), and logistic regression models.

Result

SCD was defined in 243 individuals and MCI in 246 individuals. VBM analyses revealed a significant reduction in GMV among people with MCI compared to normal controls (NC) in several brain regions, such as bilateral temporal lobes and bilateral precuneus (P<0.05). There were no significant differences in GMV between SCD and NC (P<0.05). The ROI‐wise SBM analyses revealed that SCD was significantly associated with cortical thinning in the right paracentral sulcus, left caudal middle frontal gyrus, and entorhinal cortex (P<0.05) and that MCI was significantly associated with cortical atrophy in the left caudal middle frontal gyrus, temporal lobe, frontal lobe, and parietal lobe (P<0.05).

Conclusion

The structural brain altercations are characterized by reduced GMV mainly in the bilateral temporal lobe and bilateral precuneus, and thinner cortical thickness in the temporal lobe, frontal lobe, and parietal lobe for MCI, and by cortical thinning in the right paracentral sulcus, left caudal middle frontal gyrus, and entorhinal cortex for SCD.
The Associations of Physical Activity from Midlife to Late Life with Incident Dementia: The Health and Retirement Study, 1996‐2020
Authors: Zhang Yanan , Yang Chih‐Hsiang , Merchant Anwar T , Wei Jingkai
Published: January 2025

Background

While physical activity is found to be associated with a lower risk of dementia in numerous studies, less is known whether this association varies over time. We aim to examine the potential time‐varying associations of physical activity with risk of dementia from midlife to late life.

Method

Participants aged 54 to 64 years of the Health Retirement Study (HRS) in 1996 were included. Physical activity was measured using self‐report questionnaires. Physically active was defined as having vigorous activity ≥3 times a week during 1996‐2002, and as having vigorous activity >1 time a week during 2004‐2020. Ascertainment of dementia was based on the Langa‐Weir Classification of Cognitive Function (range 0‐27), which included immediate and delayed recall items, the serial 7s, and backward counting. A score <6 was considered having dementia. Participants were followed up until the occurrence of dementia, death/lost to follow‐up, or the last interview in 2020, whichever came first.

A time‐varying effect logistic regression was fit to examine the trend of the association between physical activity and dementia across ages. Regression covariates includes time‐invariant variables (age at baseline, sex, race/ethnicity, and education) and time‐variant variables [BMI (Kg/m2), current smoking status (Yes/No), number of days/week drinks, hypertension (Yes/No), diabetes (Yes/No), cardiovascular diseases (Yes if reporting any of heart problems or stroke), and cancers (Yes/No)]. Missing values were imputed by the values from the previous interview. To check the impact of revised definitions of physical activity, a sensitivity analysis was also conducted.

Result

A total of 7,001 participants were included in the analysis. During an average follow‐up period of 15.1±7.8 years, 736 cases of dementia occurred. Being physically active in midlife was associated with a lower risk of dementia. The association was not static and became attenuated with aging, and no significant association was observed after the age of 75.

Conclusion

The association of physical activity with incident dementia attenuated throughout the progress of aging. While the possibility of reverse causality needs to be further explored, our results may suggest that physical activity may be initiated at an earlier stage of life for risk reduction of dementia.
Education and Midlife Cognitive Functioning: Evidence from the High School and Beyond Cohort
Authors: Warren John Robert , Grodsky Eric , Muller Chandra , Manly Jennifer J. , Brickman Adam M.
Published: January 2025

Background

Education is associated with cognitive functioning and risk of Alzheimer’s Disease and related dementias (ADRD). However, researchers rarely consider anything about education other than highest degree completion. Do schools’ social and academic contexts and students’ other (non‐attainment) schooling outcomes independently predict cognitive outcomes? If so, this opens the possibility of manipulating educational policies and practices to improve long term cognitive well‐being.

Method

This study included a nationally representative sample of 12,530 Americans followed prospectively from high school through age ∼60 as part of the High School and Beyond cohort study. OLS regression models estimated associations between various aspects of education ─ including schools’ social and academic contexts; students’ grades, test scores, and course taking; and degree attainment ─ and multiple dimensions of cognition, before and after adjustment for confounders.

Result

Educational attainment predicts cognitive functioning at age ∼60. However, the social and academic contexts of schools and other measures of students’ educational performance predict cognition at least as well—even after adjusting for attainment.

Conclusion

Education is more than just how far in school people go, and degree attainment is not the only ─ or perhaps even the primary ─ thing about education that has long run consequences for cognitive functioning and ADRD risk. Advancing our understanding of how and why education shapes cognitive functioning and ADRD risk requires analyses of data with nuanced information about schools, schooling, and student performance.