[Dementia Prevention]. / Demenzprävention.

Dementia is common and will continue to grow in importance and numbers in the future. However, as causal treatment is not possible in most cases, prevention is particularly important. This is not only aimed at cognitively healthy people, but is also a central element in all phases of the disease.

La depresión como factor de riesgo de la demencia: fisiopatología y modelos preclínicos de estudio / Depression as a risk factor for dementia: Pathophysiology and preclinical study models

El aumento de la esperanza de vida ha llevado a un incremento en la incidencia de enfermedades crónicas como la demencia. Tratar los factores de riesgo de la demencia, como la depresión, podría reducir su incidencia. Sin embargo, el tratamiento con antidepresivos no ha sido eficaz en el manejo de este síntoma, lo que aumenta el riesgo de demencia en el futuro. Es fundamental investigar las causas y el tratamiento de la depresión, y el uso de modelos animales es importante en este sentido. Este estudio busca analizar la relación entre la depresión y el riesgo de desarrollar demencia, así como los modelos preclínicos más relevantes para estudiar la depresión en roedores. (AU)

The increase in life expectancy has led to a rise in the incidence of chronic diseases, such as dementia. Treating the risk factors of dementia, such as depression, could help reduce its occurrence. However, antidepressant treatment has not proven effective in managing this symptom, thereby increasing the risk of dementia in the future. It is essential to investigate the causes and treatment of depression, and in this regard, the use of animal models is of great significance. This study aims to analyze the evidence supporting the relationship between depression and the risk of developing dementia, while also providing an update on the most relevant preclinical models for studying depression in rodents. (AU)

Vaccines and Dementia: Part I. Non-Specific Immune Boosting with BCG: History, Ligands, and Receptors.

Vaccines such as Bacille Calmette-Guérin (BCG) can apparently defer dementia onset with an efficacy better than all drugs known to date, as initially reported by Gofrit et al. (PLoS One14, e0224433), now confirmed by other studies. Understanding how and why is of immense importance because it could represent a sea-change in how we manage patients with mild cognitive impairment through to dementia. Given that infection and/or inflammation are likely to contribute to the development of dementias such as Alzheimer's disease (Part II of this work), we provide a historical and molecular background to how vaccines, adjuvants, and their component molecules can elicit broad-spectrum protective effects against diverse agents. We review early studies in which poxvirus, herpes virus, and tuberculosis (TB) infections afford cross-protection against unrelated pathogens, a concept known as 'trained immunity'. We then focus on the attenuated TB vaccine, BCG, that was introduced to protect against the causative agent of TB, Mycobacterium tuberculosis. We trace the development of BCG in the 1920 s through to the discovery, by Freund and McDermott in the 1940 s, that extracts of mycobacteria can themselves exert potent immunostimulating (adjuvant) activity; Freund's complete adjuvant based on mycobacteria remains the most potent immunopotentiator reported to date. We then discuss whether the beneficial effects of BCG require long-term persistence of live bacteria, before focusing on the specific mycobacterial molecules, notably muramyl dipeptides, that mediate immunopotentiation, as well as the receptors involved. Part II addresses evidence that immunopotentiation by BCG and other vaccines can protect against dementia development.

The impact of sodium-glucose co-transporter-2 inhibitors on dementia and cardiovascular events in diabetic patients with atrial fibrillation.

AIMS: The effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i and the risk of incident dementia in diabetic patients with AF, and to explore the interactions with oral anticoagulants or dipeptidyl peptidase-4 inhibitors (DPP4i). MATERIALS AND METHODS: We conducted a cohort study using Taiwan's National Health Insurance Research Database. Patients with diabetes and AFwithout a prior history of established cardiovascular diseases, were identified. Using propensity score matching, 810 patients receiving SGLT2i were matched with 1620 patients not receiving SGLT2i. The primary outcome was incident dementia, and secondary outcomes included composite cardiovascular events and mortality. RESULTS: After up to 5 years of follow-up, SGLT2i use was associated with a significantly lower risk of incident dementia (hazard: 0.71, 95% confidence interval: 0.51-0.98), particularly vascular dementia (HR: 0.44, 95% CI: 0.24-0.82). SGLT2i was related to reduced risks of AF-related hospitalisation (HR: 0.72, 95% CI: 0.56-0.93), stroke (HR: 0.75, 95% CI: 0.60-0.94), and all-cause death (HR: 0.33, 95% CI: 0.24-0.44). The protective effects were consistent irrespective of the concurrent use of non-vitamin K antagonist oral anticoagulants (NOACs) or DPP4i. CONCLUSIONS: In diabetic patients with AF, SGLT2i was associated with reduced risks of incident dementia, AF-related hospitalisation, stroke, and all-cause death. The protective effects were independent of either concurrent use of NOACs or DPP4i.

An analysis of omega-3 clinical trials and a call for personalized supplementation for dementia prevention.

INTRODUCTION: Targeted interventions are needed to delay or prevent the onset of neurodegenerative diseases. Poor dietary habits are associated with cognitive decline, highlighting the benefits of a healthy diet with fish and polyunsaturated fatty acids (PUFAs). Intake of omega-3 PUFAs docosahexaenoic acid (DHA), α-linolenic acid (ALA) and eicosapentaenoic acid (EPA) is linked with healthy aging, cardiovascular benefits, and reduced risk of Alzheimer's disease. Although omega-3 has health benefits, its intake is often inadequate and insufficient in modern diets. Although fish oil supplements offer an alternative source, inconsistent results from clinical trials raise questions about the factors determining their success. AREAS COVERED: In this this review, the authors discuss the aforementioned determining factors and highlight strategies that could enhance the effectiveness of omega-3 PUFAs interventions for dementia and cognitive decline. Moreover, the authors provide suggestions for potential future research. EXPERT OPINION: Factors such as diet, lifestyle, and genetic predisposition can all influence the effectiveness of omega-3 supplementation. When implementing clinical trials, it is crucial to consider these factors and recognize their potential impact on the interpretation of results. It is important to study each variable independently and the interactions between them.

Establishing the feasibility and preliminary efficacy of a health belief model based educational training program on health belief perceptions and dementia-preventive behaviors in people with type 2 diabetes.

This quasi-experimental study evaluated feasibility and preliminary efficacy of dementia-preventive educational training intervention program based on the health belief model for improving perceived health beliefs and dementia-preventive behaviors among people with type 2 diabetes mellitus. Two community hospitals with 72 eligible participants were chosen from 12 local institutions using simple random sampling method. One hospital (22 patients) was allocated to dementia-preventive educational training intervention, and the other hospital (23 patients) was allocated to control intervention (using simple random sampling). Primary study outcome was feasibility, and secondary outcomes were changes in dementia prevention behaviors and health belief perceptions. Recruitment rate was 62.5% (45/72) and 22 patients in each group totally completed outcome measures and attended sessions, indicating feasibility of the intervention and study design. There were no significant differences between groups at baseline. After training, participants in the intervention group had significantly higher scores than control group in prevention behaviors and perceptions of health beliefs. The intervention group experienced significant with-group changes in outcomes. Results show that conducting a subsequent fully powered experimental study is feasible, and the intervention has promising efficacy.

Physical Exercise and Health, 6: Sedentary Time, Independent of Health-Related Physical Activity, as a Risk Factor for Dementia in Older Adults.

Sedentary behaviors are leisurely behaviors that occur during waking hours performed while lying down or seated; examples are relaxing, conversing, using a smartphone, watching television, traveling in private or public transport, and thinking or working at a desk. Sedentary behaviors are common in everyday life; the average person spends 9-10 h/d sedentary. Findings from meta-analyses show that higher levels of physical activity are associated with a reduced risk of dementia and that near-absence of moderate to vigorous physical activity is associated with an increased risk of dementia. Sedentariness is a clearly defined construct that is more than just low levels of physical activity. Sedentariness, therefore, merits independent study. In this context, a recent cohort study, conducted in elderly subjects (mean age, 67 years) who were followed for a mean of 6.7 years, found that sedentariness, independent of current levels of moderate to vigorous physical activity, was associated in a dose-dependent fashion with the risk of incident dementia; the finding held true when reverse causation was addressed through the exclusion of subjects who developed dementia within 4 years of follow-up. The adjusted 10-year risk of dementia rose from about 8% with sedentariness at 10 h/d to about 23% with sedentariness at 15 h/d; the difference is clinically meaningful. Limitations of studies in the field are that residual confounding cannot be excluded, and that no randomized controlled trials exist upon which guidance may be based. Nevertheless, it could be prudent to decrease sedentary behaviors if only because these have also been associated with other adverse physical and mental health outcomes. Additional subjects explained in this article include reverse causation and how it may be dealt with during research design and data analysis, individual participant data meta-analysis, and making sense of results that are reported in terms of "per 1,000 person-years."

Fish oil supplementation and risk of dementia among diabetic patients: a prospective study of 16,061 older patients.

BACKGROUND: Although n-3 Polyunsaturated fatty acids (PUFAs) may benefit cognitive performance, the association of n-3 PUFA intake with dementia risk under dysglycemia has not been examined. We aimed to evaluate the relationship between fish oil supplement use or fish consumption and dementia risk among older patients with diabetes. METHOD: A total of 16,061 diabetic patients aged over 60 years were followed up in the UK Biobank. Fish oil supplements use (yes or no) was collected by the touch screen questionnaire. The diagnosis of dementia was ascertained by the UK Biobank Outcome Adjudication Group. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. RESULTS: A total of 337 cases of dementia were confirmed after a mean duration of 7.7 years (123,486 person-years) of follow-up. Habitual use of fish oil supplements showed a 24% lower dementia risk among older diabetic patients [HRs (95% CIs): 0.76 (0.60-0.98) (P = 0.031)] compared with non-users. Such inverse association was not modified by the APOE ε4 genotype. However, the consumption of both oily fish (≥2 times/week) and non-oily fish (≥2 times/week) had no significant association with dementia risk (p-trend = 0.271 and p-trend = 0.065) compared with non-consumers. CONCLUSION: In summary, fish oil supplementation may play a protective role in cognitive function across all APOE genotypes, while non-oily fish and oily fish consumption have no protective association among older diabetic patients.

GOIZ ZAINDU study: a FINGER-like multidomain lifestyle intervention feasibility randomized trial to prevent dementia in Southern Europe.

BACKGROUND: GOIZ ZAINDU ("caring early" in Basque) is a pilot study to adapt the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) methodology to the Basque population and evaluate the feasibility and adherence to a FINGER-like multidomain intervention program. Additional aims included the assessment of efficacy on cognition and data collection to design a large efficacy trial. METHOD: GOIZ ZAINDU is a 1-year, randomized, controlled trial of a multidomain intervention in persons aged 60+ years, with Cardiovascular Risk Factors, Aging and Dementia (CAIDE) risk score ≥ 6, no diagnosis of dementia, and below-than-expected performance in at least one of three cognitive screening tests. Randomization to a multidomain intervention (MD-Int) or regular health advice (RHA) was stratified by sex, age (>/≤ 75), and cognitive status (mild cognitive impairment (MCI)/normal cognition). MD-Int included cardiovascular risk factor control, nutritional counseling, physical activity, and cognitive training. The primary outcomes were retention rate and adherence to the intervention program. Exploratory cognitive outcomes included changes in the Neuropsychological Test Battery z-scores. Analyses were performed according to the intention to treat. RESULTS: One hundred twenty-five participants were recruited (mean age: 75.64 (± 6.46); 58% women). The MD-Int (n = 61) and RHA (n = 64) groups were balanced in terms of their demographics and cognition. Fifty-two (85%) participants from the RHA group and 56 (88%) from the MD-Int group completed the study. More than 70% of the participants had high overall adherence to the intervention activities. The risk of cognitive decline was higher in the RHA group than in the MD-Int group in terms of executive function (p =.019) and processing speed scores (p =.026). CONCLUSIONS: The GOIZ-ZAINDU study proved that the FINGER methodology is adaptable and feasible in a different socio-cultural environment. The exploratory efficacy results showed a lower risk of decline in executive function and processing speed in the intervention group. These results support the design of a large-scale efficacy trial. TRIAL REGISTRATION: GOIZ ZAINDU feasibility trial was approved and registered by the Euskadi Drug Research Ethics Committee (ID: PI2017134) on 23 January 2018. Retrospectively registered in ClinicalTrials.gov (NCT06163716) on 8 December 2023.

The Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) Diet for the Aging Brain: A Systematic Review.

The Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet seems a promising approach to preserve brain function during aging. Previous systematic reviews have demonstrated benefits of the MIND diet for cognition and dementia, though an update is needed. Additionally, other outcomes relevant to brain aging have not been summarized. Therefore, this systematic review aims to give an up-to-date and complete overview on human studies that examined the MIND diet in relation to brain aging outcomes in adults aged ≥40 y. Ovid Medline, Web of Science core collection, and Scopus were searched up to July 25, 2023. Study quality was assessed using the Newcastle-Ottawa Scale and the Cochrane Risk-of-Bias tool. We included 40 articles, of which 32 were unique cohorts. Higher MIND diet adherence was protective of dementia in 7 of 10 cohorts. Additionally, positive associations were demonstrated in 3 of 4 cohorts for global cognition and 4 of 6 cohorts for episodic memory. The protective effects of the MIND diet on cognitive decline are less apparent, with only 2 of 7 longitudinal cohorts demonstrating positive associations for global decline and 1 of 6 for episodic memory decline. For other brain outcomes (domain-specific cognition, cognitive impairments, Parkinson's disease, brain volume, and pathology), results were mixed or only few studies had been performed. Many of the cohorts demonstrating protective associations were of North American origin, raising the question if the most favorable diet for healthy brain aging is population-dependent. In conclusion, this systematic review provides observational evidence for protective associations between the MIND diet and global cognition and dementia risk, but evidence for other brain outcomes remains mixed and/or limited. The MIND diet may be the preferred diet for healthy brain aging in North American populations, though evidence for other populations seems less conclusive. This review was registered at PROSPERO as CRD42022254625.

Multidomain interventions based on a life-course model to prevent dementia in at-risk Chinese older adults: A randomized controlled trial.

BACKGROUND: Due to the time-dependent effect of specific risk factors for dementia, multidomain interventions based on a life-course model might achieve optimal preventive effects against dementia. OBJECTIVE: The purpose of this study was to investigate the effectiveness of multidomain interventions based on a life-course model of modifiable risk factors for dementia in at-risk Chinese older adults. DESIGN: This was a two-arm, proof-of-concept, randomized controlled trial. SETTING AND PARTICIPANTS: We randomly assigned 96 community-dwelling at-risk adults aged 60 years or older in a 1:1 ratio to either the 6-month multidomain intervention group (dementia literacy, physical activity, cognitive training, social activity and optional modules) or the control group (health education). METHODS: The primary outcomes were the dementia risk score and cognitive composite Z score. The secondary outcomes included the individual components of the dementia risk score (protective and risk factors) and cognitive composite Z score (global cognition, memory, executive function and language), social isolation (loneliness, social contact, and social participation), dementia literacy and prevention belief. Linear mixed models with maximum likelihood estimation were used to calculate the outcomes between the groups over time. RESULTS: The primary analyses showed that the dementia risk score was significantly lower (p < 0.001) and that the cognitive composite Z score was significantly higher (p = 0.013) in the multidomain intervention group than in the control group. Baseline characteristics did not modify the effects of the multidomain interventions (p value for interaction > 0.05). For secondary outcomes, statistically significant group × time interactions were observed for the protective (p = 0.001) and risk factors (p = 0.049), as well as in executive function (p = 0.020), loneliness (p = 0.029), dementia literacy (p < 0.001) and prevention belief (p < 0.001). CONCLUSIONS: Multidomain interventions based on a life-course model are feasible and have the potential to reduce dementia risk and improve cognitive function in at-risk Chinese older adults. REGISTRATION: The trial was registered at the Chinese Clinical Trials Registry (ChiCTR2100053417).

Protective effect of bilingualism on aging, MCI, and dementia: A community-based study.

INTRODUCTION: Lifelong bilingualism is associated with a delayed age at onset of dementia, but evidence from community-based studies is limited. We investigated the relationship between bilingualism and the prevalence of cognitive impairment in a linguistically diverse community. METHODS: A door-to-door community study was conducted from January to December 2021 in urban Bengaluru, India. 1234 individuals aged ≥60 years participated in the study. Participants were diagnosed with no cognitive impairment (NCI), mild cognitive impairment (MCI), or dementia using established diagnostic criteria. RESULTS: Dementia prevalence was higher in monolinguals (4.9%) than bilinguals (0.4%) (P = .001). The prevalence of MCI was also higher in monolinguals (8.5%) than bilinguals (5.3%) (P = .001). The study also revealed better cognitive function in bilinguals than monolinguals with NCI, after controlling for confounding variables. DISCUSSION: The current study provides significant support for the protective effect of bilingualism on cognitive impairment in an urban community with extensive bilingual interactional contexts in everyday life. HIGHLIGHTS: Bilingualism has been demonstrated to protect against dementia and mild cognitive impairment in a linguistically diverse community with extensive code-switching contexts. Bilingual older individuals had superior baseline cognitive performance compared to monolingual older individuals. Bilingualism was found to have an independent effect on general cognition after adjusting for major social determinants of health in the group without cognitive impairment.

[Prevention of dementia]. / Prävention demenzieller Erkrankungen.

With increasing life expectancy, the prevalence of dementia is increasing worldwide. Dementia is among the greatest challenges for healthcare and social systems of the future. Approximately 40% of newly diagnosed cases of dementia are associated with risk factors that can potentially be influenced by preventive measures. Based on the evidence from longitudinal studies, systematic reviews and meta-analyses, the Lancet commission on dementia prevention, intervention and care has defined 12 risk factors that are associated with an increased risk for dementia: low level of education, hearing impairment, traumatic brain injury, arterial hypertension, diabetes mellitus, smoking, excessive alcohol consumption, depression, obesity, social isolation, and air pollution.

Effects of rhythm-control and rate-control strategies on cognitive function and dementia in atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Growing evidence suggests that atrial fibrillation (AF) is an independent risk factor for cognitive impairment and dementia, even in the absence of thromboembolic events and stroke. Whether rhythm-control therapy can protect cognitive function remains unclear. We aimed to evaluate the efficacy of rhythm-control strategies in patients with AF regarding cognitive function and dementia risk. METHODS: We systematically searched the PubMed, Embase and Cochrane Library databases for randomised clinical trials, cohort and case-control studies evaluating the associations between rhythm-control strategies and cognitive function outcomes up to May 2023. We assessed the risk of bias using the ROBINS-I and the Cochrane risk-of-bias tool. Both fixed- and random-effects models were used to create summary estimates of risk. RESULTS: We included a total of 14 studies involving 193,830 AF patients. In the pooled analysis, compared with rate-control, rhythm-control therapy was significantly associated with a lower risk of future dementia (hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.62-0.89; I2 = 62%). Among the rhythm-control strategies, AF ablation is a promising treatment that was related to significantly lower risks of overall dementia (HR 0.62; 95% CI 0.56-0.68; I2 = 42%), Alzheimer's disease (HR 0.78; 95% CI 0.66-0.92; I2 = 0%) and vascular dementia (HR 0.58; 95% CI 0.42-0.80; I2 = 31%). Pooled results also showed that compared with patients without ablation, those who underwent AF ablation had significantly greater improvement in cognitive score (standardized mean difference (SMD) 0.85; 95% CI 0.30-1.40; P = 0.005; I2 = 76%). CONCLUSIONS: Rhythm-control strategies, especially ablation, are effective in protecting cognitive function, reducing dementia risk and thus improving quality of life in AF patients.

Ethical Considerations at the Intersection of Social Media and Dementia Prevention Research.

BACKGROUND: Ethical social media use underpins effective online engagement for dementia prevention research. Existing social media guidelines are broad and lack empirical justification reflecting the values and priorities of the dementia community and the challenges specific to prevention research. OBJECTIVES: By engaging professional and community experts, we sought to identify the ethical issues, motivators, and barriers pertaining to social media engagement for dementia prevention research. DESIGN: Semi-structured, qualitative interviews conducted online. SETTING: We recruited participants using a combination of accessible online databases, advertisements/posters through organizational newsletters and websites, social media, registries, and from our network of colleagues. PARTICIPANTS: Professional experts working in dementia research (n=15; e.g., researchers, coordinators) and experts with lived experience (n=14). Experts were from Canada, the USA, the UK, and Chile. MEASUREMENTS: Discussions were analyzed using thematic qualitative analysis methods. RESULTS: Professional experts revealed a dearth of social media guidelines for prevention research, relying on informal sources to supplement ethics board approval. They sought methods of strategic communication for public dialogue (e.g., misinformation, criticism). Experts by experience appreciated the educational benefits of social media but raised risks such as diminished online privacy, dementia-related stigma, being targeted for predatory practices, and misinformation. Various digital inequities (e.g., age, socioeconomic status) dampen social media's reach to diverse publics. Participants acknowledged that younger aging populations have more digital fluency and may benefit more from social media research engagement. CONCLUSIONS: Research professionals and community members identified ethical and contextual factors surrounding the use of social media for dementia prevention, and a need for more guidance. The next project phase will use these data to inform the co-creation of ethical guidelines for brain health research.

Cost-Effectiveness of Prevention for People at Risk for Dementia: A Scoping Review and Qualitative Synthesis.

Dementia is from an economic perspective a main challenge for economies worldwide because of increasing costs. Since there is no cure in sight, prevention seems the most promising approach for reducing health care cost due to Dementia. On the contrary, approximately 40% of dementias is attributable to modifiable risk factors and first studies showed that multidomain interventions may be effective for preventing dementia. Considering the increasing economic burden, for many health administrations worldwide, cost-effectiveness plays a mayor role. This scoping review wants to bring evidence to the question if prevention for people at risk may be cost-effective. Therefore, the four databases Medline (via Pubmed), CINHAL (via EBSCO), Business Source Complete (via EBSCO), and the Health Economic Evaluation database (HEED) were used to conduct a scoping review using PICO and a systematic search string. 3,629 studies were identified and seven met all inclusion criteria. The included studies showed clear cost-effectiveness for most multidomain interventions. The gained QALYs at mean were 0.08 (SD=0.08) and the intervention average costs 472.20 EUR per Person (SD=74.06 EUR). The Incremental Cost-Effectiveness Ratios varied between -80,427.97 and 104,189.82 EUR per QALY. The three core results are (i) prevention programs focusing on people at risk may be cost-effective and cost-efficient, (ii) multimodal prevention reveal cost saving potential, when the people at risk are defined well, (iii prevention in middle-aged cohorts may be also cost-effective if life-style related risk factors are addressed.

The Influence of Traffic Lights Presentation of Dementia Risk Screening Information on Older Adults' Motivations for Risk Reduction in Primary Care Settings.

OBJECTIVE: This study assessed older adults' preferences for how to communicate dementia risk information to maximize motivation for behavior change. METHOD: Eighty-nine community-dwelling older adults (aged 61 to 92 years, M=72.93, SD=6.36, 76% women) received dementia risk factor information in 2 formats: "traffic lights" (green=risk absent, amber=risk emerging, and red=risk present) or red/risk-only. Participants reported motivation to change risk-related behaviors, motivation to maintain good health behaviors, liking of the formats, categorical preference for traffic lights versus risk-only formats, reasons for preferences (open-ended), total applicable risks, and Motivation to Change Lifestyle and Health Behaviour for Dementia Risk Reduction. RESULTS: Traffic lights presentation was more motivating ( Z =4.16, P <0.001), more liked ( Z =4.80, P <0.001), and preferred, N Traffic =71, N Red =14, χ 2 (1)=38.22, P <0.001, over risk-only. Self-efficacy and motivation to maintain good health behaviors were significant unique predictors of motivation to change risk-related behaviors following traffic lights presentation over age, sex, education, total applicable risks, perceived susceptibility, cues to action, and liking of the traffic lights presentation format. Themes indicated (1) traffic light presentation is informative and clear, and (2) green-light information increases self-efficacy. CONCLUSIONS: Traffic light presentation increases patient motivation to reduce dementia risk. Green-light information increases self-efficacy. Maximizing motivation through information presentation can decrease dementia prevalence.