Reduced Risk Of Dementia Research Articles

The novel estrogen receptor beta agonist EGX358 and APOE genotype influence memory, vasomotor, and anxiety outcomes in an Alzheimer’s mouse model

IntroductionAlzheimer’s disease (AD) prevalence and severity are associated with increased age, female sex, and apolipoprotein E4 (APOE4) genotype. Although estrogen therapy (ET) effectively reduces symptoms of menopause including hot flashes and anxiety, and can reduce dementia risk, it is associated with increased risks of breast and uterine cancer due to estrogen receptor alpha (ERβ)-mediated increases in cancer cell proliferation. Because ERβ activation reduces this cell proliferation, selective targeting of ERβ may provide a safer method of improving memory and reducing hot flashes in menopausal women, including those with AD. APOE genotype influences the response to ET, although it is unknown whether effects of ERβ activation vary by genotype.MethodsHere, we tested the ability of long-term oral treatment with a novel highly selective ERβ agonist, EGX358, to enhance object recognition and spatial recognition memory, reduce drug-induced hot flashes, and influence anxiety-like behaviors in female mice expressing 5 familial AD mutations (5xFAD-Tg) and human APOE3 (E3FAD) or APOE3 and APOE4 (E3/4FAD). Mice were ovariectomized at 5 months of age and were then treated orally with vehicle (DMSO) or EGX358 (10 mg/kg/day) via hydrogel for 8 weeks. Spatial and object recognition memory were tested in object placement (OP) and object recognition (OR) tasks, respectively, and anxiety-like behaviors were tested in the open field (OF) and elevated plus maze (EPM). Hot flash-like symptoms (change in tail skin temperature) were measured following injection of the neurokinin receptor agonist senktide (0.5 mg/kg).ResultsEGX358 enhanced object recognition memory in E3FAD and E3/4FAD mice but did not affect spatial recognition memory. EGX358 also reduced senktide-induced tail temperature elevations in E3FAD, but not E3/4FAD, females. EGX358 did not influence anxiety-like behaviors or body weight.DiscussionThese data indicate that highly selective ERβ agonism can facilitate object recognition memory in both APOE3 homozygotes and APOE3/4 heterozygotes, but only reduce the magnitude of a drug-induced hot flash in APOE3 homozygotes, suggesting that APOE4 genotype may blunt the beneficial effects of ET on hot flashes. Collectively, these data suggest a potentially beneficial effect of selective ERβ agonism for memory and hot flashes in females with AD-like pathology, but that APOE genotype plays an important role in responsiveness.

Dementia risk reduction in the African context: Multi-national implementation of multimodal strategies to promote healthy brain aging in Africa (the Africa-FINGERS project).

Dementia prevention in Africa is critically underexplored, despite the continent's high prevalence of modifiable risk factors. With a predominantly young and middle-aged population, Africa presents a prime opportunity to implement evidence-based strategies that could significantly reduce future dementia cases and mitigate its economic impact. The multinational Africa-FINGERS program offers an innovative solution, pioneering culturally sensitive, multidomain interventions tailored to the unique challenges of the region. Leveraging insights from landmark global studies such as Worldwide-FINGERS and Alzheimer's Disease Neuroimaging Initiative, the program employs a multideterminant precision prevention framework, grounded in community based systems dynamics. Africa-FINGERS further integrates cutting-edge state-of-the-art multimodal biomarker evaluations tailored to regional contexts, with the goal of advancing brain health and establishing a global standard for dementia prevention. This groundbreaking initiative highlights the potential for scalableand sustainable interventions, thus is poised to transform dementia risk reduction efforts across the continent. HIGHLIGHTS: Dementia rates are escalating in Africa, largely due to longer life spans and increased prevalence of modifiable risk factors. Yet, few regional interventions have directly targeted lifestyle factors to reduce dementia risk. The multinational Africa-FINGERS study will address this gap by adapting the successful FINGERS lifestyle intervention to African populations. Africa-FINGERS will pioneer a culturally informed, multidomain dementia risk reduction intervention in the African region through feasibility dementia prevention trials in rural and urban sites across Kenya and Nigeria in the first instance, enrolling 600 at-risk adults (≥ 50 years). The program adoptsparticipatory research methods to develop culturally appropriate interventions and build infrastructure to evaluate dementia biomarkers from ante and post mortem samples. A cost-effectiveness analysis will be conducted to guide the strategic implementation of Africa-FINGERS into regional health systems. The Africa-FINGERS strategy aligns with the Worldwide-FINGERS framework and integrates the global Alzheimer's Disease Neuroimaging Initiative approach, emphasizing multimodal analysis.

Predicting mid- and late-life dementia risk in primary care: A prognostic study from a national health screening cohort

The objective of this study is to develop and validate dementia risk prediction models for mid- and late-life individuals that are based on accessible variables within a primary care setting. Using the Korean National Health Insurance Service database (2010–2019), we analyzed 6,696,073 individuals aged 40 and older who participated in a national health screening program over a mean follow-up of 8.95 years. Potential predictors were selected based on a literature review and the available data. Dementia cases were identified using claim-based codes and validated by corresponding prescription information. 5-year dementia risk prediction models for mid-life (40–59 years), and late-life (60+ years) stages were developed using the Cox proportional hazards model. Model performance was assessed through discrimination and calibration. Both models included age, sex, body mass index, smoking, alcohol consumption, physical activity, diabetes, hypertension, dyslipidemia, and chronic kidney disease. The models’ AUROCs were 0.764 for mid-life and 0.743 for late-life. The impact of predictors on dementia risk was consistently stronger in mid-life than in late-life stages. Our models showed good calibration with low-risk estimates in mid-life and overall in late-life. These findings underscore the crucial role of managing modifiable risk factors, particularly during mid-life to reduce dementia risk.

Prevention of dementia using mobile phone applications (PRODEMOS): a multinational randomised controlled effectiveness-implementation trial

Abstract Background The expected increase of dementia prevalence in the coming decades will mainly be within low-and middle-income countries and those with low socioeconomic status (SES) in high income countries. Forty percent of dementia is associated with modifiable, lifestyle-related cardiovascular risk factors. Mobile health interventions with remote coaching can help reach underserved high-risk populations globally. Methods This open label, blinded endpoint, hybrid effectiveness-implementation randomised controlled trial (RCT) investigated whether a coach-supported mHealth intervention can reduce dementia risk in persons aged 55-75 years of low SES in UK or from the general population in China with at least two dementia risk factors. The primary effectiveness outcome was change in CAIDE dementia risk score (including age, education, sex, systolic blood pressure, total cholesterol, BMI, physical exercise) after 12-18 months of intervention. Main implementation outcomes were coverage, acceptability, appropriateness, adoption, feasibility, sustainability, fidelity, and costs using a mixed methods approach. Findings Between 15th January 2021 and 18th April 2023, 1,488 persons were included and randomised (734 intervention, 754 control), with 1,229 (82·6%) available for analysis of the primary effectiveness outcome. After a mean follow-up of 16 months, the mean CAIDE score improved by 0·16 points in the intervention group vs. 0·01 in the control group (Mean Difference (MD) 0·16, 95% Confidence Interval (CI) 0·03-0·29). The effect was larger in those who adhered to the intervention (MD 0·27, 95%CI 0·12-0·44) and those planning to change lifestyle (MD 0·33, 95%CI 0·10-0·57). Ten percent of those invited participated; of these, 81% adopted the intervention and 50% continued active participation throughout the study. For the individual components of the CAIDE score, there were no statistically significant differences for systolic blood pressure, total cholesterol and BMI, but in the intervention group physical inactivity was reduced more than in the control group (MD 6·7%, 95%CI 2·1 to 11·2) and more participants quit smoking (MD -3·1%, 95%CI -4·8 to -1·5). Interpretation A coach-supported mHealth intervention to improve lifestyle is modestly effective in reducing dementia risk factors in those with low SES in the UK and any SES in China. Implementation is challenging in these populations, but those reached actively participated. Whether this will result in less cognitive decline and dementia requires a larger RCT with long follow-up.

A comparative analysis of national dementia plans: preventive strategies in five European countries

Abstract Background About 8.5% of people aged +65 live with dementia in Europe. Preventive measures can avert up to 40% of cases. The aim of the study is to analyse National Dementia Plans (NDP) in Europe, to elicit how much dementia prevention is considered a priority and whether policies are evidence-based. Methods A qualitative comparative analysis was performed between NDPs of countries with the best healthy life expectancy in the elderly in Europe. The NDPs of France, Ireland, Italy, Spain, and Sweden were included. The consensus on actions and elements of prevention policies was evaluated, according to the WHO recommendations and to Cheung’s framework designed for evaluating chronic diseases policies. Results All the NDPs prioritised early diagnosis, public awareness, and community engagement for dementia risk reduction. They fostered the development of information system for data collection and established committees for progress monitoring. However, not all NDPs defined timelines for policy implementation and most of them expired years ago. NDPs included prevention research agenda, but their preventive actions did not address alcohol consumption, traumatic brain injury, and air pollution, representing 3 well-known risk factors attributable for the 15% of preventable cases. Neither integration of dementia with other chronic disease preventive strategies was present and a clear allocation of funds for NDPs always missed. Conclusions NDPs partially address risk factors of preventable cases. All countries need to update their NDPs, integrating new scientific evidence and allocating clear financial funds. This can potentially prevent millions of new cases, decreasing the burden of disease and improving the sustainability of health systems. Key messages • NDPs do not target adequately dementia in Europe. • New evidence-based preventive policies, including most recent identified risk factors, would have a clear impact on burden of disease and health systems’ sustainability.

Validation of the Updated "LIfestyle for BRAin health" (LIBRA) Index in the English Longitudinal Study of Ageing and Maastricht Aging Study.

The "LIfestyle for BRAin health" (LIBRA) index was recently updated with three new modifiable factors: hearing impairment, social contact, and sleep (LIBRA2), but has not yet been validated. Comparison of the performance of both LIBRA versions in predicting dementia risk. Longitudinal data from the English Longitudinal Study of Ageing (ELSA) and the Maastricht Aging Study (MAAS) were used. The weighted LIBRA (11/12 factors available) and LIBRA2 (14/15 factors available) scores were calculated, with higher scores representing an unhealthier lifestyle. Dementia diagnoses were based on self- or informant reported physician diagnosis, an informant-based cognitive screening tool, registry data or test data. Cox-proportional hazards regression was used to investigate the association between LIBRA(2) scores and dementia risk. Model fit and predictive accuracy were determined using the Akaike information criterion and Harrell's C index. Over an average follow-up of 8.3 years in ELSA and 17.9 years in MAAS, 346 (4.6%) and 120 (8.5%) individuals developed dementia, respectively. In ELSA, a one-point increase in LIBRA2 was associated with an 8% (1.06-1.11) higher dementia risk (LIBRA: 13%, 1.09-1.16). In MAAS, a one-point increase in LIBRA2 was associated with a 6% (1.01-1.12) higher dementia risk (LIBRA: 8%, 0.99-1.16). In ELSA, LIBRA (Harrell's C = 0.68) and LIBRA2 (Harrell's C = 0.67) performed similarly. In MAAS, LIBRA2 (Harrell's C = 0.62) performed better compared to LIBRA (Harrell's C = 0.52). LIBRA2 is a better model for identifying individuals at increased dementia risk and for public health initiatives aimed at dementia risk reduction.

LEAP! Rx: A randomized trial of a pragmatic approach to lifestyle medicine.

Clinicians lack the tools to incorporate physical activity into clinical care for Alzheimer's disease prevention. We tested a 52-week exercise and health education program (Lifestyle Empowerment for Alzheimer's Prevention [LEAP! Rx]) that integrates clinician referrals and community-based fitness resources. We randomized 219 participants to the LEAP! Rx (ie, exercise and monthly brain health education) or a standard-of-care control group and tested the effects on cardiorespiratory fitness, insulin resistance, body composition, lipids, and cognitive performance. Physicians were able to connect their patients to a community lifestyle intervention. The intervention group increased in cardiorespiratory fitness at 12 and 52 weeks (p=0.005). We observed no effects on secondary measures. Participants meeting 80% of weekly goals (150 min, moderate to vigorous activity) saw greater fitness improvements than those with less than 80% (p<0.001). These results hold promise for broad implementation of exercise interventions into larger healthcare systems and have implications for improved research recruitment strategies. NCT No. NCT03253341. Our community-based exercise program increased cardiorespiratory fitness. Our digital physician referral method increased the diversity of the participant sample. Our findings have implications for personalized dementia risk reduction strategies.

Sensory impairments associated with cognitive impairment among older adults in China: A community-based, 10-year prospective cohort study.

To address an existing gap in knowledge due to limited and inconclusive evidence, we aimed to investigate the association between sensory impairments and cognitive decline among older Chinese individuals. We retrieved data on 6862 adults aged ≥65 years that were collected through the Chinese Longitudinal Healthy Longevity Study (CLHLS), a nationwide, prospective, community-based elderly cohort study. Visual or hearing impairment in the CLHLS were identified through self-reported questionnaire. Sensory impairments were categorised as no sensory impairment, hearing impairment only, visual impairment only, and dual sensory impairment according to hearing and vision function. Cognitive impairment was defined as having a score <18 on the Chinese version of the Mini Mental State Examination. We used a Cox proportional hazard model to evaluate the relationship between sensory and cognitive impairments. Among 6862 participants, 5.7% had dual sensory impairment, 7.4% had hearing impairment only, and had 17.2% visual impairment only. Compared with participants with no sensory impairment, those with hearing impairment only (adjusted hazard ratio (aHR) = 1.65; 95% confidence interval (CI) = 1.41, 1.92), visual impairment only (aHR = 1.25; 95% CI = 1.11, 1.41), and dual sensory impairment (aHR = 1.47; 95% CI = 1.25, 1.74) were significantly associated with higher risk of cognitive impairment in the fully adjusted model. Our results show that having hearing impairment only, visual impairment only, and dual sensory impairment was significantly associated with a higher risk of cognitive impairment among Chinese older adults aged ≥65 years. This suggest a need for the timely identification and management of sensory impairments for the elderly to reduce dementia risk.

Target trial emulation using cohort studies: estimating the effect of antihypertensive medication initiation on incident dementia.

Observational studies link high midlife systolic blood pressure to increased dementia risk. However, synthesis of evidence from randomized controlled trials has not definitively demonstrated that antihypertensive medication use reduces dementia risk. Here, we emulate target trials of antihypertensive medication initiation on incident dementia using three cohort studies, with attention to potential violations of necessary assumptions. We emulated trials of antihypertensive medication initiation on incident dementia using data from the Atherosclerosis Risk in Communities (ARIC) study, Cardiovascular Health Study (CHS), and Health and Retirement Study (HRS). We used data-driven methods to restrict participants to initiators and non-initiators with overlap in propensity scores and positive control outcomes to look for violations of positivity and exchangeability assumptions. Analyses were limited by the small number of cohort participants who met eligibility criteria. Associations between antihypertensive medication initiation and incident dementia were inconsistent and imprecise (ARIC: HR = 0.30 [0.05, 1.93]; CHS: HR = 0.66 [0.27, 1.64]; HRS: HR = 1.09 [0.75, 1.59]). More stringent propensity score restriction had little effect on findings. Sensitivity analyses using a positive control outcome unexpectedly suggested antihypertensive medication initiation increased risk of coronary heart disease in all three samples. Positive control outcome analyses suggested substantial residual confounding in effect estimates from our target trials, precluding conclusions about the impact of antihypertensive medication initiation on dementia risk through target trial emulation. Formalized processes for identifying violations of necessary assumptions will strengthen confidence in target trial emulation and avoid inappropriate confidence in emulated trial results.

Awareness of dementia risk factors among healthcare professionals at Hamad Medical Corporation, Qatar: a cross-sectional survey.

Dementia, a degenerative neurological disorder, is estimated to affect 82 million people worldwide by 2030 and 152 million by 2050, with a sharp increase in its incidence in the Middle East and Qatar. Lifestyle factors, such as smoking, physical inactivity, and obesity, may account for up to 40% of dementia cases. Healthcare practitioners who play an important role in health promotion must understand the modifiable risk and protective factors for dementia. This study investigated healthcare professionals' knowledge of dementia risk factors at Hamad Medical Corporation in Qatar. A sample of 737 healthcare professionals was recruited using simple random sampling from Hamad Medical Corporation. The target population included physicians, nurses, and allied healthcare workers from various departments. The participants completed an online survey between 1st January and December 31, 2023. The survey included questions on modifiable risk factors, preventive interventions, and dementia-related information sources. The study revealed that 76% of participants believed in dementia prevention and 87.4% were interested in learning about lifestyle choices and dementia risk. The majority of the participants were female and non-Qataris. Challenges to dementia risk reduction include lack of understanding, time restrictions, and motivational obstacles. Awareness of risk factors such as depression, alcohol use, and physical inactivity was identified. Digital platforms are the dominant source of information, highlighting the need for more dementia education and prevention programs. Given the gaps identified in knowledge, we recommend further training to improve the knowledge of healthcare professionals. In addition, further exploration of patients and caregiverss is warranted.

Supporting primary care practitioners to promote dementia risk reduction in Australian general practice: outcomes of a cross-sectional, non-randomised implementation pilot study.

Background Primary care practitioners worldwide are urged to promote dementia risk reduction as part of preventive care. To facilitate this in Australian primary care, we developed the Umbrella intervention, comprising a waiting room survey and patient information cards for use in consultations. Educational and relational strategies were employed to mitigate implementation barriers. Methods In this cross-sectional, non-randomised implementation study within the South East Melbourne Primary Health Network, we employed mixed-methods outcome evaluation. Antecedent outcomes (acceptability, appropriateness, and feasibility) and actual outcomes (adoption, penetration, and fidelity) were assessed from the perspective of primary care practitioners and patients. Results Five practices piloted the intervention and implementation strategies, including 16 primary care practitioners engaging with 159 patients. The Umbrella intervention was deemed acceptable, appropriate, and feasible, but penetration was limited. Approximately half of eligible primary care practitioners used the intervention, with moderate fidelity. Engagement with implementation strategies was similarly limited. While most strategies were well-received, improvements in online peer discussions and staff readiness were desired. Conclusions The Umbrella intervention is a viable approach to promoting dementia risk reduction in Australian general practice, supported by educational and relational strategies. Stakeholder-informed refinements to enhance uptake are recommended before advancing to a definitive trial.

Association between Multi-Domain Lifestyle and Objective Cognitive Impairment in Elderly People with SCD and MCI in Chinese Communities.

Controlling the lifestyle associated with dementia risk can delay the process of cognitive decline. Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are early states in the development of dementia and are also the window period for early intervention in dementia. The purpose of this study was to explore the association between multi-domain lifestyle and objective cognitive impairment in elderly people with SCD and MCI in Chinese communities and to provide reference for effective implementation of precise health management measures to reduce the risk of dementia. A total of 265 middle-aged and elderly volunteers recruited from the community were divided into SCD group (107 cases), MCI group (80 cases), and healthy control (HC) group (78 cases). All participants received clinical interview, examination, and cognitive assessments. The total Dementia Risk Reduction Lifestyle Scale (DRRLS) scores in the HC, SCD, and MCI groups [110.00 (11.25) vs. 101.00 (10.00) vs. 79.50 (20.75)] exhibited statistically significant differences among them. The total score of the DRRLS showed a significant negative correlation with the Trail-Making Test (TMT), and significant positive correlations with both the Verbal Fluency Test (VFT) and Auditory Verbal Learning Test (AVLT) scores (p < 0.05). After adjusting for confounding factors, such as age and years of education, multiple linear regression analysis revealed several points. In the SCD group, brain-strengthening exercise and interpersonal relationship scores were negatively correlated with TMT scores (β = -11.257, -15.077; all p < 0.05), while health responsibility, smoking control behavior, and interpersonal relationship scores were positively correlated with AVLT scores (β = 0.485, 0.344, and 0.406; all p < 0.05). In the MCI Group, brain-strengthening exercise, brain-healthy diet, and interpersonal relationship were negatively correlated with TMT (β = -22.011, -16.206, -11.696; all p < 0.01), whereas health responsibility, mental activity, smoking control behavior, interpersonal relationship, and stress management were positively correlated with AVLT (β = 0.450, 0.435, 0.308, 0.256, 0.607; all p < 0.05). In Chinese communities, the unhealthy lifestyle of elderly individuals with SCD and MCI is significantly associated with cognitive function impairment. The greater their unhealthy lifestyle habits, the more pronounced the scope and severity of cognitive function impairment becomes. Furthermore, different dimensions of lifestyle have varying impacts on cognitive domains.

Dementia risk reduction between DOACs and VKAs in AF: A systematic review and meta-analysis.

Direct oral anticoagulants (DOACs) become the recommended treatment over vitamin K antagonists (VKA) in patients with non-valvular atrial fibrillation (AF). However, their effectiveness in reducing cognitive impairment and dementia compared to VKA remains unclear. A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Database. Randomized controlled trials, cohort, or case-control study that assessed incident dementia between AF patients who received DOAC compared to VKA were selected. Relevant study characteristics and the number of incident dementia diagnosis or hazard ratios (HRs) for incident dementia and each dementia subtypes were extracted. Random-effects model was used to perform meta-analysis. Standardized mean differences (SMDs) were used to estimate effect sizes for continuous data. Twelve cohort studies comprising 1 451 069 individuals were included. The incidence of dementia was lower in AF patients prescribed DOACs compared to VKA (HR 0.88, 95% CI 0.83-0.93, I 2 = 61.2%). A lower incident dementia in DOACs group relative to VKA was significantly observed in those less than 75 years of age (< 65 years, HR 0.83 (95% CI 0.72-0.97, I 2 = 0%); 65-74 years, HR 0.86 (95% CI 0.81-0.92, I 2 = 55.4%); and ≥ 75 years, HR 1.07 (95% CI 0.74-1.55, I 2 = 92.5%)) and for the subgroup of patients with vascular dementia (HR 0.91, 95% CI 0.824-0.997, I 2 = 0%). This meta-analysis reveals a reduction in incidence of dementia in AF patients prescribed DOACs compared to VKA, particularly in those less than 75 years old and in the vascular dementia subtype.

Cardiovascular health, measured using Life's Essential 8, is associated with reduced dementia risk among older men and women.

Dementia poses considerable challenges to healthy aging. Prevention and management of dementia are essential given the lack of effective treatments for this condition. A secondary data analysis was conducted using data from 928 InCHIANTI study participants (55% female) aged 65 years and older without dementia at baseline. Cardiovascular health (CVH) was assessed by the "Life's Essential 8" (LE8) metric that included health behaviors (diet, physical activity, smoking status, sleep duration) and health factors (body mass index, blood lipid, blood glucose, blood pressure). This new LE8 metric scores from 0 to 100, with categorization including "low LE8" (0-49), indicating low CVH, "moderate LE8 (50-79)", indicating moderate CVH, and "high LE8 (80-100)", indicating high CVH. Dementia was ascertained by a combination of neuropsychological testing and clinical assessment at each follow-up visit. Cox proportional hazards models were used to examine associations between CVH at baseline and risk of incident dementia after a median follow-up of 14 years. Better CVH (moderate/high LE8 vs. low LE8) was inversely associated with the risk of incident dementia (hazard ratio [HR]: 0.61, 95% confidence interval [CI]: 0.46-0.83, p = 0.001). Compared with health factors, higher scores of the health behaviors (per 1 standard deviation [SD]), specifically weekly moderate-to-vigorous physical activity time (per 1 SD), were significantly associated with a lower risk of incident dementia (health behaviors: HR:0.84, CI:0.73-0.96, p = 0.01; physical activity: HR: 0.62, CI: 0.53-0.72, p < 0.001). While longitudinal studies with repeated measures of CVH are needed to confirm these findings, improving CVH, measured by the LE8 metric, may be a promising dementia prevention strategy.

Resting-state EEG correlates of sustained attention in healthy ageing: Cross-sectional findings from the LEISURE study

While structural and biochemical brain changes are well-documented in ageing, functional neuronal network differences, as indicated by electrophysiological markers, are less clear. Moreover, age-related changes in sustained attention and their associated electrophysiological correlates are still poorly understood. To address this, we analysed cross-sectional baseline electroencephalography (EEG) and cognitive data from the Lifestyle Intervention Study for Dementia Risk Reduction (LEISURE). Participants were 96 healthy older adults, aged 50–84. We examined resting-state EEG periodic (individual alpha frequency [IAF], aperiodic-adjusted individual alpha power [aIAP]) and aperiodic (exponent and offset) activity, and their associations with age and sustained attention. Results showed associations between older age and slower IAF, but not aIAP or global aperiodic exponent and offset. Additionally, hierarchical linear regression revealed that after controlling for demographic variables, faster IAF was associated with better Sustained Attention to Response Task performance, and mediation analysis confirmed IAF as a mediator between age and sustained attention performance. These findings indicate that IAF may be an important marker of ageing, and a slower IAF may signal diminished cognitive processing capacity for sustained attention in older adults.

Identifying Dementia research priority for Qatar national dementia research plan: A Cross-sectional Survey.

The World Health Organization (WHO) published the Global Action Plan 2017-2025 seven years ago to address the dementia burden for those impacted, including persons living with dementia, their families, and health-care providers. There were seven action areas in the global action plan; the least achieved was action area seven (dementia research and innovation). The primary objective of the study was to assess the top 10 dementia research priorities among healthcare professionals, patients, caregivers, the public, and stakeholders to develop the Qatar National Dementia Research Plan. Convenience sampling was used in this cross-sectional survey. The study was conducted online with the involvement of HMC staff (physicians, nurses, and allied health staff) from all HMC facilities, patients and caregivers from Rumailah Hospital's Geriatric Department, and the public who attended the 2022 Advanced Dementia Research Conference. The survey was conducted during 22nd of October 2022 till April 31, 2024. Overall, 2000 participants provided their responses, which included health care professionals under HMC, including physicians, nurses, allied health staff, patients, caregivers, the public, and stakeholders in Qatar. Dementia Risk Reduction (79%) was the top priority for the survey participants. The remaining nine priorities were the impact of early treatment (76%), health system capacity (73%), implementation of best practices for care (73), access to information and services post-diagnosis (71), caregiver support (70%), emotional well-being (67%), care provider education (65%), end-of-life care (65%), and non-drug approaches to managing symptoms (65%). The survey results clearly indicated that most participants ranked Dementia Risk Reduction as their top priority, indicating the essential focus on dementia prevention. These findings, together with goals such as early treatment, healthcare system capacity, and caregiver support, highlight the importance of an integrated, multidisciplinary approach to dementia management.

Abstract P134: Effects of Antihypertensive Medications on All-cause Dementia: Evidence from Target Trial Emulation of 3 Million US Veterans

Introduction: Hypertension is a modifiable risk factor for all-cause dementia. Mechanistic and observational evidence suggest angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) may differentially affect dementia risk. Objective and Methods: We used longitudinal electronic health records of over 3 million US Veterans to conduct a target trial emulation with a new-user, active comparator design. We compared the intention-to-treat effect of initiating ARBs vs ACEIs (1/1/2000-12/31/2022) on dementia risk. We controlled for &gt;60 baseline covariates using inverse probability (IP) of treatment and overlap weighting. Dementia was ascertained using diagnosis codes and medications. We nonparametrically estimated the cause-specific cumulative incidence for each treatment group under the competing risk of death then computed treatment effects as weighted risk ratios with bootstrapped 95% confidence intervals. We also evaluated all-cause death and a composite outcome of dementia or death (dementia/Death) using Cox regression. Results: Among the 3,190,356 included Veterans (mean age 63, 5% female, 64% White, and 15% Black), 13% initiated ARBs and 87% initiated ACEIs. Overall, 8% developed dementia and 35% died over a median follow-up of 8 years. The risk of dementia was lower among ARB vs ACEI initiators (10-year risk ratio: 0.95 (0.94, 0.96)). The risk of all-cause death and dementia/Death were also lower among ARB vs ACEI initiators with overlap weighting. Conclusions: Among US Veterans with hypertension, ARB vs ACEI initiation was associated with a moderately lower risk of dementia. Future work assessing sustained treatment with ARB vs ACEI is needed to inform their use to reduce dementia risk.

“Why miss today worrying about tomorrow?” A qualitative investigation of ways middle-aged and older adults manage dementia-related anxiety

ABSTRACT Background and Objectives Dementia-related anxiety (DRA) is the fear or anxiety about a current or future diagnosis of Alzheimer’s disease or another type of dementia. The purpose of the present study was to examine management of DRA. Methods and Design In semi-structured qualitative interviews, 50 community-dwelling adults (58–89 years old, M = 70.80, SD = 6.02) without dementia diagnoses reflected on their thoughts and feelings about dementia. A reflexive inductive thematic approach was used to examine ways people managed DRA. Results We identified five themes related to managing DRA: monitoring cognitive status (e.g., self-monitoring or objective assessment); active coping strategies (e.g., using external reminders, normalizing age-related change); interpersonal relationships and support (e.g., anticipating benefit of support from others); planning and preparing for potential outcomes (e.g., securing power of attorney, saying goodbyes); and personal responsibility to manage risk or accept diagnosis (e.g., lifestyle factors to reduce dementia risk, thereby reducing risk for burdening others). Conclusions Findings suggest internal and external means for coping with DRA that are likely to vary in degrees of usefulness. We consider findings within the context of relevant, established theories, attending to potential clinical interventions for individuals experiencing DRA.

Health promotion for dementia risk reduction in Indigenous populations of Canada, Aotearoa New Zealand, United States of America, and Australia: Scoping review protocol.

Health promotion programs and strategies have the potential to support people to live healthier lives. Dementia, a collective name for brain disorders that impact thinking and memory, affects over 55 million people worldwide. Currently, there is no cure for dementia, so prevention is critical. Health promotion has the potential to reduce dementia by targeting the twelve potentially modifiable risk factors. A project currently being undertaken by the research team aims to strengthen the quality of clinical care and health services that specifically address dementia risk for Australian Aboriginal and Torres Strait Islander peoples. One of the intended strategies supporting the project's aim is the need for appropriate and safe health promotion programs and resources that support dementia risk reduction. Consequently, the aim of this scoping review is to identify and determine the quality and appropriateness of existing health promotion programs and resources aimed at dementia risk reduction developed or modified for Indigenous populations of Canada, the USA, Aotearoa New Zealand, and Australia that could be incorporated into the broader project. The Joanna Briggs Institute method for scoping reviews will be used to identify programs and resources focussed on dementia risk reduction for Indigenous peoples. Searches will be limited to the English language and literature published since January 2010. Databases to be searched include: CINAHL, Medline, PsychInfo, PubMed, Scopus and Google. Data that answers the research questions will be extracted from the literature and recorded on a data charting form. A combination of quantitative and qualitative methods will be used to analyse the findings of the scoping review. Dissemination of the findings through continuing community engagement, conference presentations and publications will be led by Aboriginal and Torres Strait Islander members of the research team.

Non-Linear Association of Dietary Polyamines with the Risk of Incident Dementia: Results from Population-Based Cohort of the UK Biobank.

Natural polyamines, including spermidine (SPD), spermine (SPM) and putrescine (PUT), are evolutionarily conserved endogenous molecules crucially involved in central cellular processes. Their physiological importance may extend to the maintenance of cognitive function during aging. However, limited population-based epidemiological studies have explored the link between dietary polyamines and dementia risk. This study was a prospective analysis of 77,092 UK Biobank participants aged ≥ 60 years without dementia at baseline. We used Cox proportional hazard regression models to explore the associations between dietary polyamines and the risk of dementia, and restricted cubic splines to test the non-linear relationships. During a median follow-up of 12 years, 1087 incidents of all-cause dementia cases occurred, including 450 Alzheimer's disease (AD) cases and 206 vascular dementia (VD) cases. The fully adjusted hazard ratios (HRs) for the upper fourth quintile of dietary SPD, in comparison with the lowest quintile of intake, were 0.68 (95% confidence interval [95% CI]: 0.66-0.83) for the risk of all-cause dementia, 0.62 (95% CI: 0.45-0.85) for AD and 0.56 (95% CI: 0.36-0.88) for VD, respectively. A 26% reduction in dementia risk [HR: 0.74, (95% CI: 0.61-0.89)] and a 47% reduction in AD [HR: 0.53, (95%CI: 0.39-0.72)] were observed comparing the third with the lowest quintiles of dietary SPM. Dietary PUT was only associated with a reduced risk of all-cause dementia in the fourth quintile [HR (95% CI): 0.82 (0.68-0.99)]. Reduced risk was not found to be significant across all quintiles. There were 'U'-shaped relationships found between dietary polyamines and all-cause dementia, AD and VD. Stratification by genetic predisposition showed no significant effect modification. Optimal intake of polyamines was linked to a decreased risk of dementia, with no modification by genetic risk. This potentially suggests cognitive benefits of dietary natural polyamines in humans.