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.

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.

The associations of serum vitamin D status and vitamin D supplements use with all-cause dementia, Alzheimer's disease, and vascular dementia: a UK Biobank based prospective cohort study.

BACKGROUND: Prior studies on vitamin D and dementia outcomes yielded mixed results and had several important limitations. OBJECTIVES: We aimed to assess the associations of both serum vitamin D status and supplementation with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD) incidence. METHODS: With a prospective cohort study design, we comprehensively assessed the associations of vitamin D and multivitamin supplementation, as well as vitamin D deficiency {25-hydroxyvitamin D [25(OH)D] <30 nmol/L}, and insufficiency [25(OH)D 30 to <50 nmol/L], with the 14-year incidence of all-cause dementia, AD, and VD in 269,229 participants, aged 55 to 69, from the UK Biobank. RESULTS: Although 5.0% reported regular vitamin D use and 19.8% reported multivitamin use, the majority of participants exhibited either vitamin D deficiency (18.3%) or insufficiency (34.0%). However, vitamin D deficiency was less prevalent among users of vitamin D (6.9%) or multivitamin preparations (9.5%) than among nonusers (21.5%). Adjusted Cox regression models demonstrated 19% to 25% increased risk of all 3 dementia outcomes for those with vitamin D deficiency [hazard ratio (HR) 95% confidence interval (CI)]: 1.25 (1.16, 1.34) for all-cause dementia; 1.19 (1.07-1.31) for AD; 1.24 (1.08-1.43) for VD] and 10% to 15% increased risk of those with vitamin D insufficiency [HR (95% CI): 1.11 (1.05, 1.18) for all-cause dementia; 1.10 (1.02-1.19) for AD; 1.15 (1.03-1.29) for VD]. Regular users of vitamin D and multivitamins had 17% and 14% lower risk of AD [HR (95% CI): 0.83 (0.71, 0.98)] and VD [HR (95% CI): 0.86 (0.75, 0.98)] incidence, respectively. CONCLUSIONS: Although our findings indicate the potential benefits of vitamin D supplementation for dementia prevention, randomized controlled trials are essential for definitive evidence.

Associations of Folate/Folic Acid Supplementation Alone and in Combination With Other B Vitamins on Dementia Risk and Brain Structure: Evidence From 466 224 UK Biobank Participants.

Previous researchers have tried to explore the association between folate/folic acid intake and dementia incidence, but the results remain controversial. We evaluated the associations of folate/folic acid supplementation alone and in combination with other B vitamins on dementia risk and brain structure. A total of 466 224 UK Biobank participants were investigated. Cox proportional hazards models were used to assess the associations between folate/folic acid supplementation status and the risk of Alzheimer's disease (AD) and vascular dementia (VD). Multivariable linear regression models were employed to evaluate the association between folate/folic acid supplementation status and brain structure. In the final model, folate/folic acid supplementation alone was significantly associated with a higher risk of AD (hazard ratio [HR] = 1.34, 95% confidence interval [CI] = 1.06-1.69, p = .015) and VD (HR = 1.61, 95% CI = 1.21-2.13, p = .001). Folate/folic acid supplementation alone was associated with a reduction in the hippocampus (ß = -95.25 mm3, 95% CI = -165.31 to -25.19 mm3, p = .014) and amygdala (ß = -51.85 mm3, 95% CI = -88.02 to -15.68 mm3, p = .012). The risk of AD and VD, as well as brain structure, in the group with combined folate/folic acid supplementation and other B vitamins did not show a statistically significant difference compared to the reference group (all p > .05). Folate/folic acid supplementation alone is significantly associated with a higher risk of AD and VD, as well as adverse alterations in brain structure. However, when combined with other B vitamins, these detrimental effects can be counteracted.

Attitudes and Considerations for Multidomain Lifestyle Approaches to Dementia Prevention: A Qualitative Study.

BACKGROUND: Dementia, with the most common form being Alzheimer's disease, is a global health issue and lifestyle-based strategies may reduce risk. Individuals with a family history of dementia are an important target group, but little is known about their attitudes and perceptions of dementia risk reduction. OBJECTIVE: To elucidate the attitudes to and key considerations for multidomain lifestyle-based dementia prevention strategies in middle-aged Australians with a family history of dementia. METHODS: Twenty participants (80% female; age range 47-65 years), undertook semi-structured phone-based interviews. Inductive thematic analysis of interview transcripts was conducted. Hierarchical coding frames and illustrative quotes were compiled and critically challenged until a final set of themes was produced. RESULTS: Some participants expressed a positive attitude toward lifestyle-based dementia prevention. Reasons related to wanting to future proof, believing that risk reduction is relevant at all life stages and/or that there is always room for improvement. Other participants had a negative attitude, expressing that they were already following a healthy lifestyle, did not feel it was relevant to them yet, and/or held a deterministic view that dementia is random. Important considerations congregated on the themes of being tailored/personalized, taking a holistic approach, and involving small, achievable steps. CONCLUSIONS: In individuals with a family history of dementia, a positive attitude to dementia prevention holds promise for intervention efforts, but in individuals expressing negative attitudes, further education and individual-level counselling may be warranted. Multidomain lifestyle-based preventive strategies also need to be tailored to the needs of key target groups to optimize appeal and effectiveness.

Plasma Omega-3 Fatty Acids and Risk for Incident Dementia in the UK Biobank Study: A Closer Look.

Dietary omega-3 fatty acids are promising nutrients in dementia. Several prospective cohort studies have examined the relationships between circulating omega-3 (an objective biomarker of dietary intake) and incident dementia, the largest to date being a report from the UK Biobank (n = 102,722). Given the recent release of new metabolomics data from baseline samples from the UK Biobank, we re-examined the association in a much larger sample (n = 267,312) and also focused on associations with total omega-3, docosahexaenoic acid (DHA), and non-DHA omega-3. Using Cox regression models, we observed that the total omega-3 status was inversely related to the risk of Alzheimer's (Q5 vs. Q1, hazard ratio [95% confidence interval] = 0.87 [0.76; 1.00]) and all-cause dementia (Q5 vs. Q1, 0.79 [0.72; 0.87]). The strongest associations were observed for total omega-3 (and non-DHA omega-3) and all-cause dementia. In prespecified strata, we found stronger associations in men, and in those aged ≥60 years at baseline (vs. those aged 50-59). Thus, in the largest study to date on this topic, we confirmed the favorable relationships between DHA and risk for dementia, and we also found evidence that non-DHA omega-3 may be beneficial. Finally, we have better defined the populations most likely to benefit from omega-3-based interventions.

A novel, multidomain, primary care nurse-led and mHealth-assisted intervention for dementia risk reduction in middle-aged adults (HAPPI MIND): study protocol for a cluster randomised controlled trial.

INTRODUCTION: Middle-aged multidomain risk reduction interventions targeting modifiable risk factors for dementia may delay or prevent a third of dementia cases in later life. We describe the protocol of a cluster randomised controlled trial (cRCT), HAPPI MIND (Holistic Approach in Primary care for PreventIng Memory Impairment aNd Dementia). HAPPI MIND will evaluate the efficacy of a multidomain, nurse-led, mHealth supported intervention for assessing dementia risk and reducing associated risk factors in middle-aged adults in the Australian primary care setting. METHODS AND ANALYSIS: General practice clinics (n≥26) across Victoria and New South Wales, Australia, will be recruited and randomised. Practice nurses will be trained to implement the HAPPI MIND intervention or a brief intervention. Patients of participating practices aged 45-65 years with ≥2 potential dementia risk factors will be identified and recruited (approximately 15 patients/clinic). Brief intervention participants receive a personalised report outlining their risk factors for dementia based on Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) scores, education booklet and referral to their general practitioner as appropriate. HAPPI MIND participants receive the brief intervention as well as six individualised dementia risk reduction sessions with a nurse trained in motivational interviewing and principles of behaviour change, a personalised risk reduction action plan and access to the purpose-built HAPPI MIND smartphone app for risk factor self-management. Follow-up data collection will occur at 12, 24 and 36 months. Primary outcome is ANU-ADRI score change at 12 months from baseline. Secondary outcomes include change in cognition, quality of life and individual risk factors of dementia. ETHICS AND DISSEMINATION: Project approved by Monash University Human Research Ethics Committee (ID: 28273). Results will be disseminated in peer-reviewed journals and at healthcare conferences. If effective in reducing dementia risk, the HAPPI MIND intervention could be integrated into primary care, scaled up nationally and sustained over time. TRIAL REGISTRATION NUMBER: ACTRN12621001168842.

To be or not to be: Arts-based approaches in public health messaging for dementia awareness and prevention.

OBJECTIVES: Multiple modifiable risk factors exist across the lifespan to reduce dementia prevalence, and public understanding of these factors is increasing. Yet dementia is frequently misunderstood and stigmatised, and dementia prevention is not generally recognised as a health priority. Current limitations of public health campaigns for dementia prevention must be addressed and innovative alternatives developed to improve public comprehension and implementation of preventative action across all stages of life. METHODS: In searching various databases and public information on dementia prevention, restraints were found in current health messaging which did not reflect the complexity of this health issue and address diversity of its impact across cultures and ages. In consultation with researchers and public health organisations, we outline four case studies in Australia where innovative arts-based approaches have been adopted and discuss the potential for arts-based approaches to address these gaps. RESULTS: Arts-based approaches have the unique capacity to shift perceptions on ageing and dementia, overcome language and literacy barriers, represent health concerns across cultures, and actively involve individuals, communities and healthcare professionals in the process of dementia prevention. Future campaigns can engage a variety of communities and environments with art mediums suited to their preferences, capacities and efficacy. CONCLUSIONS: Recommendations include example mediums, environments and people to engage. Future research is required to understand the impact of, and to improve, the long-term adoption of innovative arts-based approaches in dementia prevention practices.

Tea intake or consumption and the risk of dementia: a meta-analysis of prospective cohort studies.

Purpose: Dementia affects as many as 130 million people, which presents a significant and growing medical burden globally. This meta-analysis aims to assess whether tea intake, tea consumption can reduce the risk of dementia, Alzheimer's disease (AD) and Vascular dementia (VD). Patients and methods: Cochrane Library, PubMed and Embase were searched for cohort studies from inception to November 1, 2022. The Newcastle Ottawa Quality Assessment Scale (NOS) was applied to evaluate the risk of bias of the included studies. We extracted the data as the relative risks (RRs) for the outcome of the interest, and conducted the meta-analysis utilizing the random effect model due to the certain heterogeneity. Sensitivity analysis were performed by moving one study at a time, Subgroup-analysis was carried out according to different ages and dementia types. And the funnel plots based on Egger's and Begger's regression tests were used to evaluate publication bias. All statistical analyses were performed using Stata statistical software version 14.0 and R studio version 4.2.0. Results: Seven prospective cohort studies covering 410,951 individuals, which were published from 2009 and 2022 were included in this meta-analysis. The methodological quality of these studies was relatively with five out of seven being of high quality and the remaining being of moderate. The pooling analysis shows that the relationship between tea intake or consumption is associated with a reduced risk of all-cause dementia (RR = 0.71, 95% CI [0.57-0.88], I2 = 79.0%, p < 0.01). Further, the subgroup-analysis revealed that tea intake or consumption is associated with a reduced risk of AD (RR = 0.88, 95% CI [0.79-0.99], I2 = 52.6%, p = 0.024) and VD (RR = 0.75, 95% CI [0.66-0.85], I = 0.00%, p < 0.001). Lastly, tea intake or consumption could reduce the risk of all-cause dementia to a greater degree among populations with less physical activity, older age, APOE carriers, and smokers. Conclusion: Our meta-analysis demonstrated that tea (green tea or black tea) intake or consumption is associated with a significant reduction in the risk of dementia, AD or VD. These findings provide evidence that tea intake or consumption should be recognized as an independent protective factor against the onset of dementia, AD or VD.

The Association between Coffee and Tea Consumption at Midlife and Risk of Dementia Later in Life: The HUNT Study.

BACKGROUND: Studies exploring the possible protective effect of coffee and tea consumption on dementia have shown inconsistent results so far. We aimed to investigate whether consumption of tea and different types of coffee at midlife are associated with dementia later in life and whether sex or ApoE4 influence such association. METHODS: We included 7381 participants from the Norwegian HUNT Study. Self-reported questionnaires assessed daily consumption of coffee and tea at baseline. After 22 years, individuals 70 years or older were screened for cognitive impairment. RESULTS: General coffee consumption and tea consumption was not associated with dementia risk. Compared to daily consumption of 0-1 cups of coffee, daily consumption of ≥8 cups of boiled coffee was associated with increased dementia risk in women (OR: 1.83, 95% CI: 1.10-3.04, p-value for trend = 0.03) and daily consumption of 4-5 cups of other types of coffee was associated with a decrease in dementia risk in men (OR: 0.48, 95% CI: 0.32-0.72, p-value for trend = 0.05). Furthermore, the association between boiled coffee and increased dementia risk was only found in ApoE4 non-carriers. Differences by sex or ApoE4 carrier status were not supported by strong statistical evidence for interaction. Tea consumption was not associated with dementia risk. CONCLUSION: type of coffee may play a role in the direction of the association between coffee-drinking habits and dementia later in life.

Dietary Components and Nutritional Strategies for Dementia Prevention in the Elderly.

BACKGROUND: For decades, evidence from observational studies and randomized controlled trials has converged to suggest associations of dietary components, foods, and dietary patterns with dementia. With population aging and a projected exponential expansion of people living with dementia, formulating nutritional strategies for dementia prevention has become a research hotspot. OBJECTIVE: This review aimed to summarize available data on the roles of specific dietary components, food groups, and dietary patterns in dementia prevention among the elderly. METHODS: Database search was carried out using PubMed, the Cochrane Library, EMBASE, and Medline. RESULTS: Polyphenols, folate, vitamin D, omega-3 fatty acids, and ß-carotene might decrease the risk of dementia. Consumption of green leafy vegetables, green tea, fish, and fruits is recommended. However, saturated fat, a diet rich in both dietary copper and saturated fat, aluminum from drinking water, and heavy drinking might increase dementia risk. Healthy dietary patterns, especially the Mediterranean diet, were proven to bring more cognitive benefits than single dietary components. CONCLUSION: We discussed and summarized the evidence on the roles of dietary components and patterns in dementia prevention among the elderly and found that some factors were closely associated with dementia risk in elderly. This may pave the way for the identification of dietary components and patterns as new therapeutic targets for dementia prevention in the elderly population.

Impact of multivitamin-mineral and cocoa extract on incidence of mild cognitive impairment and dementia: Results from the COcoa Supplement and Multivitamin Outcomes Study for the Mind (COSMOS-Mind).

INTRODUCTION: We assessed the effects of multivitamin-mineral and cocoa extract supplementation on incident mild cognitive impairment (MCI) and all-cause probable dementia. METHODS: COSMOS-Mind (N = 2262), a 2 × 2 factorial, randomized-controlled clinical trial administered a telephone-based cognitive battery at baseline and annually for 3 years. Incidence rates of MCI, and separately dementia, were compared among treatment arms with proportional hazards regression. RESULTS: Over 3 years, 110 incident MCI and 14 incident dementia cases were adjudicated. Incidence rates did not vary by assignment to multivitamin-mineral or cocoa extract (all p's ≥ 0.05); however, statistical power was low. When participants assigned to multivitamin-mineral versus placebo converted to MCI, their scores for global cognition (p = 0.03) and executive function (p < 0.001) were higher and had declined less relative to the previous year (p = 0.03 for global cognition; p = 0.004 for executive function). DISCUSSION: Multivitamin-mineral therapy may provide cognitive resilience, countering conversion to MCI, but not significantly reduce its incidence over 3 years. HIGHLIGHTS: Multivitamin-mineral supplementation did not reduce risks for cognitive impairment. Cocoa extract supplementation did not reduce risks for cognitive impairment. Multivitamin-mineral supplementation slowed cognitive declines for incident mild cognitive impairment.

Adaptation and virtual feasibility pilot of a mindfulness-based lifestyle program targeting modifiable dementia risk factors in older adults.

OBJECTIVES: We developed a group-based program (My Healthy Brain, MHB) to engage older adults at-risk for dementia in healthy lifestyles. We report on a two-part study to adapt MHB by incorporating mindfulness skills, using mobile health technology to monitor and reinforce behaviors, and delivering it via live video. METHODS: Participants were older adults (age ≥ 60) with subjective cognitive decline (SCD) and at least one lifestyle risk factor. In Aim 1 (n = 11, 2 groups), we conducted focus groups to obtain qualitative feedback on proposed adaptations. In Aim 2 (n = 10), we conducted a virtual open pilot with exit interviews to explore the feasibility and outcomes of the adapted MHB. RESULTS: Thematic analysis revealed: (1) barriers and facilitators to healthy lifestyles, (2) positive impressions of MHB, (3) interest in mindfulness skills, and (4) openness to study technologies. MHB met a-priori feasibility benchmarks and was associated with improvements in cognition, lifestyle (e.g. physical function), and proposed mechanisms (e.g. mindfulness). Exit interviews confirmed high feasibility and satisfaction. CONCLUSION: The integration of mindfulness, live video, and mobile health technologies was feasible and promising for improving healthier lifestyles. The results inform the next feasibility RCT of MHB to prepare for efficacy testing.Supplemental data for this article is available online at http://dx.doi.org/10.1080/13607863.2022.2032600.

Concepts of dementia prevention in the health promotion among older adults: A narrative review.

The number of older adults with dementia is predicted to markedly increase in the coming decades. A person suffers from dementia every 3 seconds globally, and one out of every 7 people suffers from dementia in Taiwan. The purpose of this narrative review is to integrate existing concepts of dementia prevention into health promotion and improve older adults' quality of life. This narrative review was performed using the PubMed database by searching for basic research and systematic reviews on dementia prevention and health promotion among older adults. We established a framework for dementia prevention and health promotion with regard to the physical, mental, spiritual, and social health aspects. We identified the following strategies related to older adults towards dementia prevention and health promotion in follows: Physical health promotion: cognitive activities, physical activities, body mass index, balanced diet, rainbow diet, Mediterranean diet, dietary approaches to stop hypertension diet, mind diet, no smoking and drinking, avoiding the "three highs" (i.e., hyperglycemia, hyperlipidemia, and hypertension), and head trauma; Mental health promotion: Positive thinking, Brief Symptom Rating Scale (BSRS-5), depression scale, and ascertained dementia 8 questionnaire (AD8) screening; Spiritual health promotion: religious beliefs, spiritual music, meditative activities, mindfulness, yoga, Qi-gong, Tai-chi, and Baduanjin; and Social health promotion: A supportive family system, socialization, social support, social networks, social interaction, and social participation. The conclusion of this narrative review was to integrate the concepts of dementia prevention and health promotion among older adults.

Potential Protective Mechanisms of S-equol, a Metabolite of Soy Isoflavone by the Gut Microbiome, on Cognitive Decline and Dementia.

S-equol, a metabolite of soy isoflavone daidzein transformed by the gut microbiome, is the most biologically potent among all soy isoflavones and their metabolites. Soy isoflavones are phytoestrogens and exert their actions through estrogen receptor-ß. Epidemiological studies in East Asia, where soy isoflavones are regularly consumed, show that dietary isoflavone intake is inversely associated with cognitive decline and dementia; however, randomized controlled trials of soy isoflavones in Western countries did not generally show their cognitive benefit. The discrepant results may be attributed to S-equol production capability; after consuming soy isoflavones, 40-70% of East Asians produce S-equol, whereas 20-30% of Westerners do. Recent observational and clinical studies in Japan show that S-equol but not soy isoflavones is inversely associated with multiple vascular pathologies, contributing to cognitive impairment and dementia, including arterial stiffness and white matter lesion volume. S-equol has better permeability to the blood-brain barrier than soy isoflavones, although their affinity to estrogen receptor-ß is similar. S-equol is also the most potent antioxidant among all known soy isoflavones. Although S-equol is available as a dietary supplement, no long-term trials in humans have examined the effect of S-equol supplementation on arterial stiffness, cerebrovascular disease, cognitive decline, or dementia.

Effects of a mindfulness-based versus a health self-management intervention on objective cognitive performance in older adults with subjective cognitive decline (SCD): a secondary analysis of the SCD-Well randomized controlled trial.

BACKGROUND: Older individuals with subjective cognitive decline (SCD) perceive that their cognition has declined but do not show objective impairment on neuropsychological tests. Individuals with SCD are at elevated risk of objective cognitive decline and incident dementia. Non-pharmacological interventions (including mindfulness-based and health self-management approaches) are a potential strategy to maintain or improve cognition in SCD, which may ultimately reduce dementia risk. METHODS: This study utilized data from the SCD-Well randomized controlled trial. One hundred forty-seven older adults with SCD (MAge = 72.7 years; 64% female) were recruited from memory clinics in four European countries and randomized to one of two group-based, 8-week interventions: a Caring Mindfulness-based Approach for Seniors (CMBAS) or a health self-management program (HSMP). Participants were assessed at baseline, post-intervention (week 8), and at 6-month follow-up (week 24) using a range of cognitive tests. From these tests, three composites were derived-an "abridged" Preclinical Alzheimer's Cognitive Composite 5 (PACC5Abridged), an attention composite, and an executive function composite. Both per-protocol and intention-to-treat analyses were performed. Linear mixed models evaluated the change in outcomes between and within arms and adjusted for covariates and cognitive retest effects. Sensitivity models repeated the per-protocol analyses for participants who attended ≥ 4 intervention sessions. RESULTS: Across all cognitive composites, there were no significant time-by-trial arm interactions and no measurable cognitive retest effects; sensitivity analyses supported these results. Improvements, however, were observed within both trial arms on the PACC5Abridged from baseline to follow-up (Δ [95% confidence interval]: CMBAS = 0.34 [0.19, 0.48]; HSMP = 0.30 [0.15, 0.44]). There was weaker evidence of an improvement in attention but no effects on executive function. CONCLUSIONS: Two non-pharmacological interventions conferred small, non-differing improvements to a global cognitive composite sensitive to amyloid-beta-related decline. There was weaker evidence of an effect on attention, and no evidence of an effect on executive function. Importantly, observed improvements were maintained beyond the end of the interventions. Improving cognition is an important step toward dementia prevention, and future research is needed to delineate the mechanisms of action of these interventions and to utilize clinical endpoints (i.e., progression to mild cognitive impairment or dementia). TRIAL REGISTRATION: ClinicalTrials.gov, NCT03005652.

Blueberry Supplementation in Midlife for Dementia Risk Reduction.

Late-life dementia typically develops over a period of many years beginning in midlife. Prevalence of metabolic disturbance also accelerates in middle age and is a prominent risk factor for dementia. Preliminary studies indicate that blueberry supplementation can improve cognitive performance and influence metabolism and brain function and therefore may have a role in early intervention to prevent neurodegeneration. In a randomized controlled trial, we investigated the effects of daily blueberry supplementation in a middle-aged sample of insulin-resistant participants with elevated risk for future dementia. We enrolled overweight men and women, aged 50 to 65 years, with subjective cognitive decline (SCD) and performed pre- and post-intervention assessments of cognition and metabolism and exploratory measures of peripheral mitochondrial function. We observed improved performances for the blueberry group on measures of lexical access, p = 0.003, and memory interference, p = 0.04, and blueberry-treated participants reported reduced memory encoding difficulty in daily life activities, p = 0.03. The blueberry-treated group also exhibited correction of peripheral hyperinsulinemia, p = 0.04, and a modest trend for increased mitochondrial uncoupling, p = 0.11. The cognitive findings indicated improved executive ability in this middle-aged sample. In addition, the changes in metabolic and bioenergetic measures imply potential mechanistic factors associated with anthocyanin and proanthocyanidin actions. The demonstration of these benefits in middle-aged individuals with insulin resistance and SCD suggests that ongoing blueberry supplementation may contribute to protection against cognitive decline when implemented early in at-risk individuals.