Several studies have shown that dietary factors, particularly the consumption of products containing docosahexaenoic acid (22:6n−3, DHA), influence the risks associated with Alzheimer’s disease (AD). Furthermore, DHA has also been shown to reduce the risk of various AD-related occurrences, such as brain glucose hypometabolism, aggregations of the amyloid-beta peptide into fibrils and oligomers, as well as neuroinflammation.
DHA is an omega-3 fatty acid that is crucial to the structure of the human nervous system, cerebral cortex, retina, and skin. DHA can either be synthesized from alpha-linolenic acid or obtained from the consumption of human breast milk, fatty fish, fish oil, or algae oil.
Study: Red Blood Cell DHA Is Inversely Associated with Risk of Incident Alzheimer’s Disease and All-Cause Dementia: Framingham Offspring Study. Image Credit: NOOMEANG / Shutterstock.com
Previous studies have revealed that increased intake of DHA reduces the likelihood of developing AD in carriers of the APOLIPOPROTEIN E (APOE)-ε4 allele. Under natural conditions, the de novo synthesis of DHA is marginal, as the detection of DHA in tissues or blood is primarily attributed to dietary intake.
The lifespan of red blood cells (RBCs) is approximately 120 days. As a result, researchers assessing the long-term intake of DHA is more effectively conducted in RBCs as compared to other blood lipid pools such as serum/plasma phospholipids and total serum/plasma.
A prior study conducted in Canada, in which the study cohort included individuals above 65 years of age, reported no association between RBC DHA and the incidence of dementia. This study also reported that a higher blood mercury level, which is a biomarker of fish intake, was associated with a reduced risk of dementia.
Although epidemiological data on RBC DHA status and cognition are widely available, evidence on the relationship between RBC DHA status and incidence of AD is limited. Additionally, the interaction between the APOE genotype and DHA remains unclear.
About the study
Scientists have recently hypothesized that higher RBC levels of DHA are strongly associated with a reduced likelihood of AD and all-cause dementia. They further hypothesized the existence of an interaction between APOE-ε4 and DHA. Taken together, these hypotheses were tested in a recent Nutrients study using the Framingham Offspring Cohort.
The Framingham Health Study is an ongoing population-based study that is based in Framingham, Massachusetts. This cohort was first established in 1948 for identifying factors associated with the development of cardiovascular disease.
The Offspring cohort was developed in 1971 and included the children of the participants of the original cohort. To date, the entire cohort has been studied for nine examination cycles at a frequency of approximately once every 4 years.
The current study was conducted during the eighth examination cycle and included 3,021 participants. The authors collected RBCs from the participants and determined the DHA content.
Participants were excluded from the study if they had missing RBC fatty acid measurements, suffered from dementia, were younger than 65 years of age, or had missing information on their APOE genotype. Finally, 1,531 participants were considered for the present study and were followed for a median of 7.2 years for a diagnosis of dementia.
The current study reported that an increase in the concentration of DHA in RBCs was associated with a reduced risk of AD and all-cause dementia. Participants who were in the top quintile of RBC DHA exhibited nearly half the risk of developing AD during follow-up as compared to those who were in the lower quintile.
The researchers also determined the possible interaction between RBC DHA and APOE-ε4 carriership. To this end, an inverse relationship between RBC DHA and the risk of AD in ε4 carriers was observed, with ε4 carriers associated with a greater genetic risk of late-onset AD as compared to non-carriers. Thus, the study findings strongly indicate that ε4 carriers would greatly benefit from higher DHA consumption as compared to non-carriers.
The current study supports the existence of a connection between diet and brain health. More specifically, an increase in DHA intake appears to elevate RBC DHA levels, which is beneficial for brain health. The authors estimate that by delaying the onset of AD by five years, an individual could have an additional 2.7 years of life to live.
Taken together, the study findings are consistent with those of a prior study that revealed cross-sectional associations between RBC DHA and an individual’s cognitive performance.
In the future, researchers should focus on identifying better markers such as eicosapentaenoic acid (EPA, 20:5n−3) and/or DHA that can be used to predict an individual’s risk of dementia. Additionally, an optimal sampling system must be established to analyze omega-3 content in dementia patients.
Strengths and limitations
One of the main strengths of the current study is the large cohort that consisted of older adults living in community settings and under continuous dementia surveillance. Additionally, due to the continual collection of varied health measurements of the participants over the years, scientists could include this data as potential confounders in statistical models.
Nevertheless, the current study had certain limitations. For example, due to its observational nature, the authors failed to address causality and establish the directionality of associations. Another shortcoming of this study is its low number of ε4 carriers.
An additional limitation is that the scientists failed to determine if the single measurement of RBC DHA is suitable for estimating the risk of AD over a long period of time as compared to more frequent measurements.
- Sala-Vila, A., Satizabal, C. L., Tintle, N., et al. (2022) Red Blood Cell DHA Is Inversely Associated with Risk of Incident Alzheimer’s Disease and All-Cause Dementia: Framingham Offspring Study. Nutrients, 14(12), 2408. doi:10.3390/nu14122408.