Effects of a Multicomponent Intervention With Cognitive Training and Lifestyle Guidance for Older Adults at Risk of Dementia: A Randomized Controlled Trial.

Objective: This study examined the effects of a multicomponent intervention program on cognitive function in community-dwelling older adults with mild cognitive impairment (MCI) and subjective cognitive decline (SCD).Methods: This was a 2-arm, randomized controlled trial in which a multicomponent intervention was applied. Participants were recruited from June 2020 to August 2020, randomization and intervention began in August 2020, and the entire program ended in January 2021. It included cognitive training (mnemonic strategy training) and lifestyle guidance (diet, sleep, and exercise guidance) for 7 weeks. A total of 123 Chinese community-dwelling older adults experiencing MCI or SCD were randomly divided into a multicomponent intervention group (n = 62) and a health education group (n = 61). The global cognitive function was measured using the Mini-Mental State Examination (MMSE). The cognitive domains outcomes included memory functions measured using the immediate and delayed tests of the Auditory Verbal Learning Test (AVLT) and Logical Memory Test (LMT), and executive function and attention measured using the Digital Symbol Substitution Test (DSST) and Digit Span Test (DST). Data were collected at baseline and postintervention.Results: For cognitive outcome, the results of linear mixed-effect model showed significant time × group effects in the MMSE (Cohen d =0.63 [95% CI, 0.27 to 1.00], F = 10.25, P = .002). This study found significant time × group effects in AVLT-immediate (Cohen d = 0.47 [95% CI, 0.11 to 0.83], F = 8.18, P = .005), AVLT delayed (Cohen d = 0.45 [95% CI, 0.10 to 0.81], F = 4.59, P = .034), LMT-delayed (Cohen d = 0.71 [95% CI, 0.34 to 1.07], F = 4.59, P = .034), DSST (Cohen d = 0.27 [95% CI, -0.08 to 0.63], F = 4.83, P = .030), and DST (Cohen d =0.69 [95% CI, 0.33 to 1.05], F = 8.58, P = .004).Conclusions and Implications: The results support the feasibility and effectiveness of the multicomponent intervention program in improving cognitive function in community dwelling older adults at risk of dementia. The high adherence of this program shows its potential for promotion in the community and supports a larger and longer trial.Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200061420).

Nonpharmacological intervention therapies for dementia: potential break-even intervention price and savings for selected risk factors in the European healthcare system.

BACKGROUND: New effective treatments for dementia are lacking, and early prevention focusing on risk factors of dementia is important. Non-pharmacological intervention therapies aimed at these factors may provide a valuable tool for reducing the incidence of dementia. This study focused on the development of a mathematical model to predict the number of individuals with neurodegenerative diseases, specifically Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis. Scenarios for non-pharmacological intervention therapies based on risk factor reduction were also assessed. The estimated total costs and potential cost savings from societal were included. METHODS: Based on demographic and financial data from the EU, a mathematical model was developed to predict the prevalence and resulting care costs of neurodegenerative diseases in the population. Each disease (Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis) used parameters that included prevalence, incidence, and death risk ratio, and the simulation is related to the age of the cohort and the disease stage. RESULTS: A replicable simulation for predicting the prevalence and resulting cost of care for neurodegenerative diseases in the population exhibited an increase in treatment costs from 267 billion EUR in 2021 to 528 billion EUR by 2050 in the EU alone. Scenarios related to the reduction of the prevalence of dementia by up to 20% per decade led to total discounted treatment cost savings of up to 558 billion EUR. CONCLUSION: The model indicates the magnitude of the financial burden placed on EU healthcare systems due to the growth in the population prevalence of neurodegenerative diseases in the coming decades. Lifestyle interventions based on reducing the most common risk factors could serve as a prevention strategy to reduce the incidence of dementia with substantial cost-savings potential. These findings could support the implementation of public health approaches throughout life to ultimately prevent premature mortality and promote a healthier and more active lifestyle in older individuals.

[Efficacy and safety of choline alfoscerate in the preventive therapy of dementia in elderly patients with Mild Cognitive Impairment: a three-year prospective comparative study]. / Effektivnost' i bezopasnost' kholina al'fostserata v preventivnoi terapii dementsii u pozhilykh patsientov s sindromom myagkogo kognitivnogo snizheniya: rezul'taty trekhletnego prospektivnogo sravnitel'nogo issledovaniya.

OBJECTIVE: To study the efficacy and safety of the use of annual course therapy of choline alfoscerate (CA) as a drug potentially capable of slowing or preventing the transition of amnesic type mild cognitive impairment (aMCI) into clinically pronounced dementia in a three-year open comparative study, as well as to explore the possibility of predicting the preventive effect of such therapy based on a number of clinical and biological parameters. MATERIAL AND METHODS: The study included 100 patients with aMCI, randomly divided into 2 groups: the therapeutic group consisted of 50 patients who received CA course therapy once a year for 3 years (20 intravenous infusions of 1000 mg (4 ml) in 100 ml of saline solution for 4 weeks) and a comparison group of 50 patients who underwent an annual examination at the center and did not receive therapy. Clinical and psychopathological, psychometric, immunological, follow-up, and statistical methods were used. RESULTS: A comparative three-year prospective study conducted in a group of aMCI patients treated with annual course therapy of CA for 3 years and aMCI patients who did not receive therapy with similar initial demographic, diagnostic, psychometric and immunological characteristics showed a lower progression of cognitive deficits (12.2% and 39.1%, respectively) and a lower conversion rate (8.2% and 26.1%, respectively) to dementia in the therapeutic group compared with the comparison group. The differences between the initial and final (after 1, 2 and 3 years of follow-up) cognitive functioning indicators in the therapeutic group and the comparison group were significant (p<0.05) on all scales and tests in favor of the therapeutic group throughout the entire follow-up period. CONCLUSION: The results allow us to consider CA as a possible model of preventive dementia therapy aimed at preventing the progression of cognitive deficits and the development of dementia in people at high risk of developing AD - patients with aMCI.

Nutrition for dementia prevention: a state of the art update for clinicians.

BACKGROUND AND OBJECTIVES: Dementia prevalence continues to rise. It is therefore essential to provide feasible and effective recommendations to encourage healthy brain ageing and reduce dementia risk across the population. Appropriate nutrition represents a potential strategy to mitigate dementia risk and could be recommended by clinicians as part of mid-life health checks and other health initiatives to reduce dementia prevalence. The purpose of this review is to provide a clinician-focused update on the current state of the knowledge on nutrition and dementia prevention. METHODS: Narrative review. RESULTS: Strong evidence exists to support the consumption of healthy, plant-based dietary patterns (e.g. Mediterranean, MIND or Nordic diet) for maintaining cognitive function and reducing dementia risk in later life and is supported by dementia prevention guideline from leading public health bodies (e.g. World Health Organization). Emerging evidence suggests potential cognitive benefits of consuming specific nutrients/foods (e.g. n-3 fatty acids or fish, flavonols and B-vitamins) and multi-nutrient compounds (e.g. Fortasyn Connect). Challenges and opportunities for integrating nutritional/dietary interventions for dementia prevention into clinical practice are explored in this review. CONCLUSIONS: Appropriate nutrition represents an important factor to help facilitate healthy cognitive ageing and allay dementia risk. The information provided in this article can help clinicians provide informed opinions on appropriate nutritional strategies as part of mid-life Health Checks and other risk reduction initiatives.

Sustainable Participation in Community Health Programs to Promote a Healthy Lifestyle and Prevent and Protect against Dementia among Rural Taiwanese Middle-Aged and Older Adults.

BACKGROUND: Resource and economic constraints limit access to health care in rural populations, and consequently, rates of chronic illnesses are higher in this population. Further, little is known about how rural populations adopt active and healthy lifestyle behavior for dementia prevention. OBJECTIVES: This study aimed to explore the impact of modification in lifestyle behaviors on changes in cognitive function among middle-aged and older adults living in a rural area of Taiwan. DESIGN: In this prospective longitudinal study, changes in lifestyle and cognitive function were compared between the experimental and control groups. SETTING: Six rural community care stations were randomly cluster sampled in southern Taiwan. PARTICIPANTS: A total of 155 participants were enrolled and classified into two groups according to their community activity participation rate (CAPR). The control group (n=68) had a CAPR < 1x/month, and the experimental group (n=87) had a CAPR ≥ 1x/month. MEASUREMENTS: Cognitive function of the participants was measured using the MMSE scale. Lifestyle behaviors were measured using a self-designed questionnaire based on the Transtheoretical Model. RESULTS: From 2018-2020, the experimental group successfully maintained a healthy lifestyle. The MMSE score in the experimental group was significantly higher in the 3rd year than that in the control group (25.37 vs 22.56, p < 0.001). CONCLUSIONS: Sustainable community participation and adopting a healthy lifestyle could effectively maintain the cognitive function of the study participants. However, more needs to be done to support rural older adults to maintain a healthy diet and control their weight.

Socio-Cognitive Determinants of Lifestyle Behavior in the Context of Dementia Risk Reduction: A Population-Based Study in the Netherlands.

Background: Unhealthy behavior increases the risk of dementia. Various socio-cognitive determinants influence whether individuals persist in or alter these unhealthy behaviors. Objective: This study identifies relevant determinants of behavior associated to dementia risk. Methods: 4,104 Dutch individuals (40-79 years) completed a screening questionnaire exploring lifestyle behaviors associated with dementia risk. Subsequently, 3,065 respondents who engaged in one or more unhealthy behaviors completed a follow-up questionnaire investigating socio-cognitive determinants of these behaviors. Cross-tables were used to assess the accuracy of participants' perceptions regarding their behavior compared to recommendations. Confidence Interval-Based Estimation of Relevance (CIBER) was used to identify the most relevant determinants of behavior based on visual inspection and interpretation. Results: Among the respondents, 91.3% reported at least one, while 65% reported two or more unhealthy lifestyle behaviors associated to dementia risk. Many of them were not aware they did not adhere to lifestyle recommendations. The most relevant determinants identified include attitudes (i.e., lacking a passion for cooking and finding pleasure in drinking alcohol or smoking), misperceptions on social comparisons (i.e., overestimating healthy diet intake and underestimating alcohol intake), and low perceived behavioral control (i.e., regarding changing physical inactivity, altering diet patterns, and smoking cessation). Conclusions: Individual-level interventions that encourage lifestyle change should focus on enhancing accurate perceptions of behaviors compared to recommendations, while strengthening perceived control towards behavior change. Given the high prevalence of dementia risk factors, combining interventions at both individual and environmental levels are likely to be the most effective strategy to reduce dementia on a population scale.

The Multi-domain Lifestyle Intervention for Cognitive Impairment in Community-Dwelling Older Adults in Hangzhou (The Heritage Study): Study Design and Protocol.

BACKGROUND: The globe has been working to promote a multi-domain lifestyle intervention for dementia prevention in older adults, referring to the Worldwide-FINGERS (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) initiative. In China, the multi-domain lifestyle intervention has been implemented in rural communities (MIND-China), yet the adaptability of such intervention based on the urban communities in China has not been verified. OBJECTIVE: To examine the effectiveness and feasibility of the multi-domain lifestyle intervention on dementia prevention in at-risk community-dwelling older adults in China. DESIGN, SETTING, PARTICIPANTS: The multi-domain lifestyle intervention study is a community-based 2-year cluster randomized controlled trial (RCT). A total of 1200 participants aged 60-80 years old will be recruited from twelve communities in Hangzhou, Zhejiang. Inclusion criteria were the Montreal Cognitive Assessment 5 minutes protocol (5 min MoCA) score of 6-9 or the Ascertain Dementia 8 (AD 8) score of ≥2, and having modifiable lifestyle factors. INTERVENTION, MEASUREMENTS, RESULTS: Participating communities will be randomized into either the structured multi-domain intervention (SMI) arm or the self-guided intervention (SGI, general health education) arm. The SMI consists of cognitive training, physical exercise, and nutritional and dietary instruction for the first 12 months; and vascular risks monitoring and control for 24 months. The primary outcome is the global cognitive performance, measured by the comprehensive Neuropsychological Test Battery (NTB). The secondary outcomes include domain-specific cognitive performances, physical function, mental health, physiological and biochemical indices, adherence to healthy lifestyles, and neuroimaging metrics. The feasibility of intervention will be evaluated around the five dimensions of the RE-AIM framework and in conjunction with quantitative data, operational data and results of focus group discussions. CONCLUSIONS: Following the Worldwide-FINGERS, this cluster RCT will verify the adaptability of the multi-domain lifestyle intervention in the urban community settings in China. This study will add evidence for global dementia prevention and management among older adults.

Adherence to the Mediterranean Diet, Sodium and Potassium Intake in People at a High Risk of Dementia.

Adequate sodium and potassium intake, along with adherence to the Mediterranean diet (MedDiet), are key factors for preventing hypertension and cerebrovascular diseases. However, data on the consumption of these nutrients within the MedDiet are scarce. This cross-sectional study aims to assess the association between MedDiet adherence and sodium/potassium intake in the MIND-Matosinhos randomized controlled trial, targeting Portuguese adults at a high risk of dementia. Good adherence to the MedDiet was defined using the Portuguese Mediterranean Diet Adherence Screener questionnaire (≥10 points), and both sodium/potassium intakes were estimated from 24-hour urine collections. The association between MedDiet adherence and these nutrients' intake (dichotomized by the median) was quantified by calculating odds ratios (OR) and respective 95% confidence intervals (95% CI) using a logistic regression. A total of 169 individuals (60.9% female; median age: 70 years; range: 36-85 years) were included. Good adherence to the MedDiet was observed among 18.3% of the sample. After adjusting for sex, age, education and using antihypertensive drugs, good MedDiet adherence was associated with higher sodium (OR = 3.11; 95% CI: 1.27-7.65) and potassium intake (OR = 9.74; 95% CI: 3.14-30.26). Increased adherence to the MedDiet may contribute to a higher potassium intake but seems to have limited effects on the adequacy of sodium levels.

Enhancing Dementia Risk Mitigation: Standardized Digital Monitoring in Clinical Trials and Platform Design for At-Risk Elderly Individuals.

BACKGROUND: Dementia is becoming a significant public health concern, affecting approximately 130,000 individuals in Austria, whereby nearly 40% of the cases are attributed to modifiable risk factors. Multidomain lifestyle interventions have thereby demonstrated significant effects in reducing the risk of dementia. OBJECTIVES: The goal was to define an interoperability framework to conduct standardized monitoring in clinical trials for enhancing dementia risk mitigation. In addition, the identified standards should be integrated into the components of the project. METHODS: A step-by-step approach was used, where initially data collection, aggregation and harmonization was carried out with retrospective data from various clinical centers. Afterwards, the interoperability framework was defined including the prospective data that is gathered during a clinical trial. RESULTS: A guideline for integrating healthcare standards was developed and incorporated into the technical components for the clinical trial. CONCLUSION: The interoperability framework was designed in a scalable way and will be regularly updated for future needs.

Risks and benefits of hormone therapy after menopause for cognitive decline and dementia: A conceptual review.

OBJECTIVE: The effects on the brain of hormone therapy after the onset of menopause remain uncertain. The effects may be beneficial, neutral, or harmful. We provide a conceptual review of the evidence. METHODS: We 1) provide a brief history of the evidence, 2) discuss some of the interpretations of the evidence, 3) discuss the importance of age at menopause, type of menopause, and presence of vasomotor symptoms, and 4) provide some clinical recommendations. RESULTS: The evidence and the beliefs about hormone therapy and dementia have changed over the last 30 years or more. Five recent observation studies suggested that hormone therapy is associated with an increased risk of dementia, and the association appears not to change with the timing of initiation of therapy. These harmful associations may be explained by a causal effect of hormone therapy on the brain or by several confounding mechanisms. We suggest that the use of hormone therapy should be customized for different subgroups of women. It may be important to subgroup women based on age at onset of menopause, type of menopause, and presence or absence of vasomotor symptoms. In addition, the effects may vary by type, dose, route, and duration of administration of estrogens and by the concurrent use of progestogens. DISCUSSION: The relation of hormone therapy with the risk of dementia is complex. Hormone therapy may have beneficial, neutral, or harmful effects on the brain. Hormone therapy should be guided by the clinical characteristics of the women being treated.

Herpes zoster vaccination and the risk of dementia: A systematic review and meta-analysis.

INTRODUCTION: Previous studies have reported a decreased risk of dementia with herpes zoster vaccination. Given this background, this systematic review and meta-analysis aimed to investigate the association between herpes zoster vaccination and the risk of dementia. METHODS: We searched five databases until November 2023 for case-control, cross-sectional, or cohort studies investigating the association of herpes zoster vaccination and dementia. Odds ratios and 95% confidence intervals (95% CIs) were pooled in the meta-analysis. Meta-regression, subgroup, and sensitivity analysis were also conducted. RESULTS: We evaluated a total of five studies (one cross-sectional, one case-control, and four cohort studies) that included a total number of 103,615 patients who were vaccinated with herpes zoster vaccine. All the studies were of high quality, ranging from 7 to 9. Due to the high heterogeneity (I2 = 100%, p < .00001) observed in our study, a random effect model was used for the analysis. The pooled odds ratio was 0.84 (95% CI: 0.50, 1.43), p (overall effect) = .53), indicating that herpes zoster vaccination reduces the risk of dementia. CONCLUSION: Herpes zoster vaccination is associated with a reduction of the risk of dementia. More epidemiological studies are needed to confirm the association.

Dose-Dependent Effect of Aspirin Use in Reducing Diabetes-Associated Dementia Risk Among Elderly Patients With Type 2 Diabetes Mellitus.

OBJECTIVE: This study investigated the association between aspirin use and diabetes-associated dementia in older patients with type 2 diabetes mellitus (T2DM), assessing aspirin's potential protective effects, intensity of use, and dose-dependency against dementia. DESIGN: A cohort study evaluating the dose-dependent protective impact of aspirin against dementia in a population-based sample. SETTING AND PARTICIPANTS: Older patients with T2DM (≥60 years), comparing aspirin users with nonusers. METHODS: Used a time-varying Cox hazards model to assess dementia incidence. RESULTS: Older aspirin users exhibited a significant reduction in dementia risk (adjusted hazard ratio [aHR], 0.44; 95% CI, 0.41-0.46). The lowest aHRs for dementia were observed at a daily intensity of 0.91 defined daily doses (DDDs), and higher daily dosages (>0.91 DDD) showed gradually increasing aHRs (although still <1). Analysis of cumulative DDD revealed a dose-response relationship, with progressively lower aHRs across quartiles (0.16, 0.42, 0.57, and 0.63 for quartiles 4, 3, 2, and 1, respectively) compared with never aspirin users (P for trend < .0001). CONCLUSIONS AND IMPLICATIONS: Aspirin use in older patients with T2DM significantly reduces dementia risk. The optimal daily intensity of aspirin use (0.91 DDD) is associated with the lowest aHR for dementia. These findings suggest a dose-dependent relationship, supporting the potential benefits of higher cumulative dosages of aspirin in reducing dementia risk in this population.

Psilocybin for dementia prevention? The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases.

Major depression is an established risk factor for subsequent dementia, and depression in late life may also represent a prodromal state of dementia. Considering current challenges in the clinical development of disease modifying therapies for dementia, the focus of research is shifting towards prevention and modification of risk factors to alter the neurodegenerative disease trajectory. Understanding mechanistic commonalities underlying affective symptoms and cognitive decline may reveal biomarkers to aid early identification of those at risk of progressing to dementia during the preclinical phase of disease, thus allowing for timely intervention. Adult hippocampal neurogenesis (AHN) is a phenomenon that describes the birth of new neurons in the dentate gyrus throughout life and it is associated with spatial learning, memory and mood regulation. Microglia are innate immune system macrophages in the central nervous system that carefully regulate AHN via multiple mechanisms. Disruption in AHN is associated with both dementia and major depression and microgliosis is a hallmark of several neurodegenerative diseases. Emerging evidence suggests that psychedelics promote neuroplasticity, including neurogenesis, and may also be immunomodulatory. In this context, psilocybin, a serotonergic agonist with rapid-acting antidepressant properties has the potential to ameliorate intersecting pathophysiological processes relevant for both major depression and neurodegenerative diseases. In this narrative review, we focus on the evidence base for the effects of psilocybin on adult hippocampal neurogenesis and microglial form and function; which may suggest that psilocybin has the potential to modulate multiple mechanisms of action, and may have implications in altering the progression from major depression to dementia in those at risk.

[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)