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A Randomised Placebo-Controlled Study of Purified Anthocyanins on Cognition in Individuals at Increased Risk for Dementia.
Aarsland, D, Khalifa, K, Bergland, AK, Soennesyn, H, Oppedal, K, Holteng, LBA, Oesterhus, R, Nakling, A, Jarholm, JA, de Lucia, C, et al
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. 2023;31(2):141-151
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A growing body of evidence suggests that some modifiable factors, including cardiometabolic disorders such as hypertension, diabetes and hypercholesterolemia, as well as lifestyle factors such as physical exercise and diet, are associated with an increased risk of developing dementia. Anthocyanins, a flavonoid subclass found in dark berries and fruits, are among the dietary factors that may have positive effects on the pathogenesis of Alzheimer’s disease. The aim of this study was to assess whether anthocyanins can improve cognition and reduce the risk of dementia. This study is a 24-week randomised, double-blind, placebo-controlled Phase II study. Two-hundred and six participants were randomly assigned to one of the two groups: anthocyanins (n=106) or placebo (n=100). Results show that there wasn’t any significant group difference at the end of the study (24 weeks) in episodic memory (primary analysis) or for the secondary cognitive outcomes. However, there was a significant difference in slopes during weeks 8−24 where the anthocyanin group improved while the placebo group worsened. Furthermore, anthocyanin capsules were well-tolerated and safe to use. Authors conclude that future studies need to explore the potential mechanisms leading to cognitive improvement, how they relate to bioavailability of anthocyanins and metabolites, the optimal dosage, and the duration of treatment.
Abstract
IMPORTANCE Identifying nutritional compounds which can reduce cognitive decline in older people is a hugely important topic. OBJECTIVE To study the safety and effect of anthocyanins in maintaining cognitive functioning in people at increased risk for dementia. DESIGN, SETTING, AND PARTICIPANTS Participants (206 individuals, aged 60-80 years) diagnosed with either mild cognitive impairment (MCI) or two or more cardiometabolic disorders (i.e., diabetes, hypertension, obesity) were enrolled at three different centres in Norway. INTERVENTION Participants were randomly assigned to four capsules with a total of 320 mg/d of naturally purified anthocyanins or placebo 1:1 for 24 weeks. MAIN OUTCOMES AND MEASURES The primary outcome was the Quality of Episodic Memory composite measure (0-100) from an online cognitive test battery CogTrack, which was administered at baseline and monthly for the next 24 weeks. Secondary outcomes included other cognitive scores from the CogTrack battery. We applied mixed effects models with a baseline test score, group, time and their interaction as fixed effects, as well as other predefined baseline covariates. The primary comparison was the group difference at week 24 based on a modified intention-to-treat principle. RESULTS The primary analysis did not show a significant group difference at 24 weeks (78.2 versus 76.8; adjusted mean difference 1.4 (95% confidence interval -0.9-3.7); effect size 0.15; p = 0.23). However, there was a significant difference in slopes during weeks 8-24 (p = 0.007); the anthocyanin group improved while the placebo group worsened. No differences were found for the secondary cognitive outcomes. Anthocyanin capsules were well-tolerated and safe to use. CONCLUSION Anthocyanin supplementation for 24 weeks was safe and well tolerated in people with MCI or cardiometabolic disorders. We found no significant group difference in episodic memory at the end of the study but statistically significant differences in slopes. Further studies are warranted to explore whether anthocyanins supplementation can reduce cognitive decline in people at increased risk of dementia. TRIAL REGISTRATION ClinicalTrials.gov, (Identifier NCT03419039). http://www. CLINICALTRIALS gov/, NCT03419039.
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Can dementia risk be reduced by following the American Heart Association's Life's Simple 7? A systematic review and dose-response meta-analysis.
Wu, J, Xiong, Y, Xia, X, Orsini, N, Qiu, C, Kivipelto, M, Rizzuto, D, Wang, R
Ageing research reviews. 2023;83:101788
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The American Heart Association (AHA) has defined ideal levels of seven modifiable cardiovascular health (CVH) factors, known as Life's Simple 7, that consist of smoking, physical activity, diet, body mass index, fasting blood glucose, total cholesterol, and blood pressure. Maintaining ideal levels of these factors has been recommended as a prevention strategy against not only cardiovascular diseases but also neurodegenerative disorders, e.g., cognitive decline and dementia. However, studies exploring the beneficial effects of the AHA’s CVH metrics on cognitive outcomes, especially among older populations, have been uncertain, and solid evidence is lacking in this field. This systematic review and meta-analysis aimed to quantify the relationship between the AHA’s CVH metrics and cognitive outcomes. 14 longitudinal studies were included in the meta-analysis. The results showed a considerable effect of a favourable total CVH score on reduced risk of incident dementia in adults aged 70 years or older. When looking at the individual factors, dementia risk can be reduced significantly if older adults achieved the recommended level of physical activity, blood glucose, or total cholesterol. The association with smoking appeared to be borderline, and there was no association between diet, body mass index hazard ratio or blood pressure and dementia risk. The authors concluded that their findings provide evidence that maintaining a favourable level of CVH score, either in mid- or late- life, would substantially reduce the risk of dementia among older adults. Preserving cardiovascular health by quitting smoking, engaging in physical exercise, controlling blood glucose and total cholesterol might be especially effective for forestalling cognitive decline and dementia.
Abstract
This study aimed to quantify the relationships between the American Heart Association (AHA) Cardiovascular Health (CVH) metrics, namely AHA Life's Simple 7, and cognitive outcomes. We searched PubMed and Embase (January 1, 2010-August 24, 2022) and finally included 14 longitudinal studies (311654 participants with 8006 incident dementia cases). Random-effects meta-analysis and one-stage linear mixed-effects models were performed. Increased CVH score seemed to associate with decreased risk of incident dementia in a linear manner, but this relationship varied by the measurement age of CVH metrics. That is, midlife CVH tended to have a linear association with late-life dementia risk, whereas a J-shaped association was observed between the late-life CVH score and dementia. In addition, late-life dementia risk was reduced significantly if individuals maintained an ideal level of AHA's CVH guidelines of physical activity, fasting plasma glucose, total cholesterol, and smoking. However, our meta-analysis did not show a significant association between CVH score and global cognitive decline rate. Following AHA's CVH guidelines and maintaining CVH at an optimal level would substantially reduce the late-life dementia risk. More research is required to explore the link between a favorable CVH score and cognitive trajectories among cognitively asymptomatic older populations.
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Quantifying dementia prevention potential in the FINGER randomized controlled trial using the LIBRA prevention index.
Deckers, K, Köhler, S, Ngandu, T, Antikainen, R, Laatikainen, T, Soininen, H, Strandberg, T, Verhey, F, Kivipelto, M, Solomon, A
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2021;17(7):1205-1212
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Lifestyle interventions are being increasingly recognised to delay or prevent the onset of dementia. Scientific research targeting one lifestyle factor has continually failed to show any benefits and therefore interventions targeting several lifestyle factors, before disease onset may be more beneficial. The Lifestyle for BRAin Health (LIBRA) score is a tool which assesses peoples risk of dementia based on several lifestyle factors and this trial used this tool to determine the dementia risk of individuals who entered The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). This study was the first randomised control trial showing benefits to cognition following multi-domain lifestyle interventions. The results showed that higher LIBRA score at the start of the trial was associated with poorer brain function over time and that the multi-domain lifestyle intervention was effective at decreasing LIBRA score, regardless of the risk at the start of the trial. It was concluded that LIBRA may be a useful tool to determine risk of dementia and that the FINGER intervention was of benefit to individuals regardless of their risk of dementia.
Abstract
INTRODUCTION Individuals in early dementia prevention trials may differ in how much they benefit from interventions depending on their initial risk level. Additionally, modifiable dementia risk scores might be used as surrogate/intermediate outcomes. METHODS In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), we investigated in post hoc analyses (N = 1207) whether the cognitive benefits of the 2-year multi-domain lifestyle intervention differed by baseline dementia risk measured with the "LIfestyle for BRAin Health" (LIBRA) score. We also investigated intervention effects on change in LIBRA score over time. RESULTS Overall, higher baseline LIBRA was related to less cognitive improvement over time. This association did not differ between the intervention and control groups. The intervention was effective in decreasing LIBRA scores over time, regardless of baseline demographics or cognition. DISCUSSION The cognitive benefit of the FINGER intervention was similar across individuals with different LIBRA scores at baseline. Furthermore, LIBRA may be useful as a surrogate/intermediate endpoint and surveillance tool to monitor intervention success during trial execution.
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Effect of a Multidomain Lifestyle Intervention on Estimated Dementia Risk.
Solomon, A, Handels, R, Wimo, A, Antikainen, R, Laatikainen, T, Levälahti, E, Peltonen, M, Soininen, H, Strandberg, T, Tuomilehto, J, et al
Journal of Alzheimer's disease : JAD. 2021;82(4):1461-1466
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Early identification of individuals at-risk of dementia is essential for effective preventive strategies. The aim of this study was to investigate the effect of a multidomain lifestyle intervention on the risk of dementia. This study is a post-hoc analyses of intervention effects on change in the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) Dementia Risk Score. The CAIDE score was used to select at-risk participants to the FINGER trial. FINGER is a multicentre study conducted in 6 centres in Finland. Results show a significant beneficial intervention effect, especially in women, on reducing estimated dementia risk measured by the CAIDE score. Authors conclude that CAIDE risk score can be used as a tool to communicate dementia risk, and to select persons that may benefit from lifestyle interventions.
Abstract
We investigated the effect of a multidomain lifestyle intervention on the risk of dementia estimated using the validated CAIDE risk score (post-hoc analysis). The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a 2-year randomized controlled trial among 1,260 at-risk older adults (60-77 years). Difference in the estimated mean change in CAIDE score at 2 years in the intervention compared to the control group was -0.16 (95 %CI -0.31 to 0.00) (p = 0.013), corresponding to a relative dementia risk reduction between 6.04-6.50%. This could be interpreted as a reflection of the prevention potential of the intervention.
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Effects of oral nutrition supplements in persons with dementia: A systematic review.
Tangvik, RJ, Bruvik, FK, Drageset, J, Kyte, K, Hunskår, I
Geriatric nursing (New York, N.Y.). 2021;42(1):117-123
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Dementia is a chronic condition characterised as a decline in cognitive functioning that leads to dependence in the performance of daily activities, including nutritional sufficiency. As the dis-ease progresses, eating and drinking may become more difficult. The aim of this study was to investigate the effects of oral nutrition supplements (ONS) on nutritional intake and clinical outcomes in older persons with dementia. This study is a systemic review which included ten studies of which 9 where experimental studies (n=6 RCTs; n=3 non RCTs) based on patients with dementia who were undernourished. Results indicate that ONS improved daily intake of energy and protein, compliance was high, and more persons met the recommended nutrition intake. In fact, intervention with ONS improved nutritional status; however, no effects on cognitive or functional outcomes were reported. Authors conclude that there is the need for a more comprehensive intervention plan for people with cognitive impairments that addresses the individual nutritional challenges in order to systematically meet nutritional needs.
Abstract
OBJECTIVE Persons with dementia are at risk of malnutrition, evidenced by low dietary intake, which has consequences for nutritional status, activity of daily living and disease progression. The effects of oral nutrition supplements (ONS) on nutritional intake, nutritional status, and cognitive and physical outcomes in older persons with dementia were evaluated. METHODS PubMed, Medline, Embase, CINAHL and the Cochrane Central Register of Controlled Trials were searched in December 2017, and this was repeated in May 2019. The Preferred Reporting Items for Systematic Reviews and Analysis (PRISMA) checklist was used. Papers were considered if they presented experimental clinical trials using oral nutritional supplements to persons diagnosed with dementia, including Alzheimer's disease and mild cognitive impairment, and conducted in hospitals, nursing homes or homes. RESULTS We included ten articles reporting nine clinical trials. A total of 407 persons with dementia were included, of whom 228 used ONS for 7 to 180 days. Nutritional intake improved by 201 to 600 kcal/day. Energy intake from ordinary foods was not affected, thus ONS improved the persons daily intake of energy and protein. Body weight, muscle mass, and nutritional biomarkers in blood improved in the intervention groups compared with the control groups. No effects on cognition or physical outcomes were observed. CONCLUSION ONS increases the intake of energy and protein and improves nutritional status in persons with dementia; however, RCTs with longer intervention periods are needed to investigate the impact on cognitive and functional outcomes.
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Green Tea Intake and Risks for Dementia, Alzheimer's Disease, Mild Cognitive Impairment, and Cognitive Impairment: A Systematic Review.
Kakutani, S, Watanabe, H, Murayama, N
Nutrients. 2019;11(5)
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Around 50 million people worldwide suffer from dementia, with 10 million new cases being diagnosed every year. Diet may play a role in the prevention of dementia. In this systematic review, the authors reviewed eight previous studies examining the effects of green tea on dementia. Six of the eight studies supported a preventative effect of green tea intake. The authors suggested that green tea might positively influence biological mechanisms such as oxidative stress, inflammation, accumulation of plaques in the brain and the maintenance of healthy blood vessels. The authors concluded that green tea intake might reduce the risk for dementia, Alzheimer's disease, mild cognitive impairment, or cognitive impairment, but further studies are needed.
Abstract
Dementia has become a major issue that requires urgent measures. The prevention of dementia may be influenced by dietary factors. We focused on green tea and performed a systematic review of observational studies that examined the association between green tea intake and dementia, Alzheimer's disease, mild cognitive impairment, or cognitive impairment. We searched for articles registered up to 23 August 2018, in the PubMed database and then for references of original articles or reviews that examined tea and cognition. Subsequently, the extracted articles were examined regarding whether they included original data assessing an association of green tea intake and dementia, Alzheimer's disease, mild cognitive impairment, or cognitive impairment. Finally, we included three cohort studies and five cross-sectional studies. One cohort study and three cross-sectional studies supported the positive effects of green tea intake. One cohort study and one cross-sectional study reported partial positive effects. The remaining one cohort study and one cross-sectional study showed no significant association of green tea intake. These results seem to support the hypothesis that green tea intake might reduce the risk for dementia, Alzheimer's disease, mild cognitive impairment, or cognitive impairment. Further results from well-designed and well-conducted cohort studies are required to derive robust evidence.