A reanalysis of data from a previous study identified a difference between people with low and high levels of inflammatory biomarkers. The cognitive performance of people with high levels of inflammation improved after they consumed anthocyanin supplements [1].
Inflammation and dementia
Dementia is a complex disorder that involves multiple biological processes, including neuroinflammation. Previous research has found that in some susceptible individuals, neurodegeneration and cognitive decline might be accelerated by exposure to persistent inflammation [2]. The researchers believe that understanding this interaction might offer some therapeutic options.
Anthocyanins are flavonoids present in many fruits and vegetables, such as red and purple berries, grapes, apples, plums, and cabbage [3], and are known for having antioxidant and anti-inflammatory properties [4]. The authors of this paper believe that these anthocyanins are a possible intervention to reduce inflammation, thus slowing down the progression of dementia.
Taking another look at its effects
The authors of the paper recently conducted a Phase 2 24-week placebo-controlled randomized study addressing “the impact of anthocyanins on cognitive function in older individuals at increased risk of dementia.” Their original study did not find statistically significant effects. However, they made some observations that could indicate benefits in subgroups of participants [5].
The study enrolled 100 men and 101 women aged 60 to 80 years, and 98.5% of participants completed the study. 65 participants had mild cognitive impairment (MCI), and 136 had cardiometabolic disorders (CMDs). None of the participants was diagnosed with dementia during the enrollment. 103 of the participants received the treatment, and 98 received placebo. The participants had three follow-ups at 4, 12, and 24 weeks.
The participants in the intervention group took capsules “containing 80 mg of naturally purified anthocyanins from blueberry (Vaccinium myrtillus) and black currant (Ribes nigrum).” Participants took four capsules daily, divided into two doses (320 mg of anthocyanins per day). Identical capsules were given to the placebo group but didn’t have active ingredients. Dosing was established based on a previous study [6].
The participants’ cognitive abilities were assessed monthly using ten tests, including cognitive domains such as attention, memory, and cognitive speed.
Two clusters with different effects
The authors analyzed the original study’s data, focusing on participants’ inflammatory profiles and finding that they could be grouped into two distinct clusters. In Cluster 1, participants had higher inflammatory biomarkers and “higher body mass index, the prevalence of diabetes, medication usage, and leukocyte counts.” In Cluster 2, inflammatory biomarkers were lower and HDL (“good”) cholesterol levels were higher.
When those clusters were analyzed separately, the researchers noted significant improvement in the cognitive performance of Cluster 1 participants compared to placebo. Cluster 2 didn’t show significant improvements.
The authors suggest that the anthocyanins’ anti-inflammatory properties helped improve cognition, but this is just speculation as they did not investigate the molecular mechanisms behind this observation.
Personalized approaches
Previous studies addressed different supplements as possible treatments for dementia prevention. Those studies looked at omega-3 supplements, Mediterranean diets, vitamin E, and anthocyanins [7, 8], but most did not see positive effects. The authors suggest that a personalized approach that considers inflammation alongside genetic, environmental, and lifestyle differences may be more effective. They believe that “anthocyanins can be a promising intervention for individuals at risk of dementia and with elevated inflammation.”
People with higher levels of inflammation demonstrated significantly better cognitive function after anthocyanin treatment compared to placebo at 24 weeks. Additionally, these individuals had higher BMI, a greater prevalence of diabetes, increased medication usage, and lower HDL cholesterol levels compared to those with lower inflammatory profiles. The anti-inflammatory and antioxidant properties of anthocyanins suggest they could be a promising intervention, warranting future prospective trials in individuals with elevated inflammation levels.
Strengths and limitations
This analysis was not planned in the original research. Thus, the small cohort size is not powered enough to calculate effect size and sub-group analysis. The researchers also do not have the data regarding participants’ dietary changes during the study that could impact anthocyanin absorption.
The cohort included a population from Norway with homogeneous habits and similar diets. This makes the study participants similar but limits the generalizability of results to different populations. The cohort also varied because it included people with MCI and CMD, which might make it more difficult to detect the impact of the treatment on one group, but it can also be viewed as a strength since it can broaden clinical applicability to different populations.
The authors believe that future studies should focus on populations with higher levels of inflammation and employ larger sample sizes.
Literature
[1] Borda, M. G., Barreto, G. E., Baldera, J. P., de Lucia, C., Khalifa, K., Bergland, A. K., Pola, I., Botero-Rodríguez, F., Siow, R. C., Kivipelto, M., Zetterberg, H., Ashton, N. J., Ballard, C., Aarsland, D., & NJ FINGER (2024). A randomized, placebo-controlled trial of purified anthocyanins on cognitive function in individuals at elevated risk for dementia: Analysis of inflammatory biomarkers toward personalized interventions. Experimental gerontology, 196, 112569.
[2] Langworth-Green, C., Patel, S., Jaunmuktane, Z., Jabbari, E., Morris, H., Thom, M., Lees, A., Hardy, J., Zandi, M., & Duff, K. (2023). Chronic effects of inflammation on tauopathies. The Lancet. Neurology, 22(5), 430–442.
[3] Mattioli, R., Francioso, A., Mosca, L., & Silva, P. (2020). Anthocyanins: A Comprehensive Review of Their Chemical Properties and Health Effects on Cardiovascular and Neurodegenerative Diseases. Molecules (Basel, Switzerland), 25(17), 3809.
[4] Reis, J. F., Monteiro, V. V., de Souza Gomes, R., do Carmo, M. M., da Costa, G. V., Ribera, P. C., & Monteiro, M. C. (2016). Action mechanism and cardiovascular effect of anthocyanins: a systematic review of animal and human studies. Journal of translational medicine, 14(1), 315.
[5] Aarsland, D., Khalifa, K., Bergland, A. K., Soennesyn, H., Oppedal, K., Holteng, L. B. A., Oesterhus, R., Nakling, A., Jarholm, J. A., de Lucia, C., Fladby, T., Brooker, H., Dalen, I., & Ballard, C. (2023). A Randomised Placebo-Controlled Study of Purified Anthocyanins on Cognition in Individuals at Increased Risk for Dementia. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 31(2), 141–151.
[6] Zhang, H., Xu, Z., Zhao, H., Wang, X., Pang, J., Li, Q., Yang, Y., & Ling, W. (2020). Anthocyanin supplementation improves anti-oxidative and anti-inflammatory capacity in a dose-response manner in subjects with dyslipidemia. Redox biology, 32, 101474.
[7] Castellanos-Perilla, N., Borda, M. G., Aarsland, D., & Barreto, G. E. (2024). An analysis of omega-3 clinical trials and a call for personalized supplementation for dementia prevention. Expert review of neurotherapeutics, 24(3), 313–324.
[8] Guerchet, M., Prince, M., Prina, M., 2014. Nutrition and dementia: a review of available research. Published online February 11. https://www.alzint.org/resource/nutrition-and-dementia/.
