A Randomised Placebo-Controlled Study of Purified Anthocyanins on Cognition in Individuals at Increased Risk for Dementia.

Dag Aarsland, Khadija Khalifa, Anne K Bergland, Hogne Soennesyn, Ketil Oppedal, Lise B A Holteng, Ragnhild Oesterhus, Arne Nakling, Jonas A Jarholm, Chiara de Lucia, Tormod Fladby, Helen Brooker, Ingvild Dalen, Clive Ballard

Journal: The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 2023;31(2):141-151

PMID: 36372613

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Plain Language Summary

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.

Address: Centre for Age-Related Medicine (DA, KK, AKB, HS, LBAH, RO, AN, CDL), Stavanger University Hospital, Stavanger, Norway; Department of Old Age Psychiatry (DA), King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK.; Centre for Age-Related Medicine (DA, KK, AKB, HS, LBAH, RO, AN, CDL), Stavanger University Hospital, Stavanger, Norway; Department of Old Age Psychiatry (DA), King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK; The Faculty of Health Sciences (KK), University of Stavanger, Stavanger, Norway. Electronic address: [email protected].; Centre for Age-Related Medicine (DA, KK, AKB, HS, LBAH, RO, AN, CDL), Stavanger University Hospital, Stavanger, Norway.; Department of Electrical Engineering and Computer Science (KO), University of Stavanger, Stavanger, Norway.; Centre for Age-Related Medicine (DA, KK, AKB, HS, LBAH, RO, AN, CDL), Stavanger University Hospital, Stavanger, Norway; Department of Clinical Medicine (LBAH, AN), University of Bergen, Bergen, Norway.; Centre for Age-Related Medicine (DA, KK, AKB, HS, LBAH, RO, AN, CDL), Stavanger University Hospital, Stavanger, Norway; The Hospital Pharmacy Enterprise of Western Norway (RO), Bergen, Norway.; Department of Neurology (AJ, TF), Akershus University Hospital, Lørenskog, Norway.; Centre for Age-Related Medicine (DA, KK, AKB, HS, LBAH, RO, AN, CDL), Stavanger University Hospital, Stavanger, Norway; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience (CDL), King's College London, London, UK.; Department of Neurology (AJ, TF), Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine (HB, TF), University of Oslo, Oslo, Norway.; Medical School (HB), University of Exeter, Exeter, UK; Ecog Pro Ltd. (HB, CB), Bristol, UK.; Section of Biostatistics, Department of Research (ID), Stavanger University Hospital, Stavanger, Norway.; Medical School (HB), University of Exeter, Exeter, UK.

DOI: 10.1016/j.jagp.2022.10.002