Challenge: Assessing Brain Fatty Acid Changes During Cognitive Decline

There is a growing literature about the links between the consumption of fish and shellfish, tissue levels of long-chain omega-3 fatty acids (omega-3s) found in seafood and the odds of developing age-related dementia. The most well known example of advanced mental loss is Alzheimer’s disease, a condition prevalent in adults above the age of 65. About 13% of these adults have Alzheimer’s disease, but nearly half (45%) of those 85 years of age or more have the condition, according to the Alzheimer’s Association. Ultimately, the disease is fatal. Although much is known about the disease, little is understood about preventing or treating it. A promising area of research is understanding how DHA, one of the two major long-chain omega-3 fatty acids (omega-3s) found mainly in seafood and fish oil, might reduce the risk of developing Alzheimer’s disease. For example, we know that DHA counteracts the inflammation that develops in the brain cells of individuals with the disease. It leads to the production of a potent substance NPD1 that protects cells and reduces the production of the abnormal protein that promotes the toxic effects of the disease. Further, we have learned that people who consume fish regularly and have higher tissue levels of DHA are less likely to develop Alzheimer’s disease than people who do not eat fish. You might think that treating people who show the early symptoms of Alzheimer’s disease—memory loss, inability to speak coherently or understand language and other functional disabilities—with DHA might slow the course of the condition. To date, DHA supplementation studies have been disappointing as symptoms progressed in spite of the intervention. There is some uncertainty whether the brain loses DHA with aging and whether brain and blood fatty acids change with the onset of dementia. A few studies reported that the brains of individuals who died with Alzheimer’s disease had less DHA compared with similar individuals who did not have the disease. Certain regions of the brain may lose more DHA than others, which may affect brain function. Some researchers observed an increase in the omega-3 content of red blood cells with age, but we are unsure about what happens in the brain. Investigators in Quebec, Canada, tackled these questions in a study of older adults with different degrees of cognitive impairment who were studied until their deaths. Participants were 85 years old when they entered the study. Participants with normal mental and cognitive function, mildly impaired cognition or Alzheimer’s disease were randomly selected before they died and then had the fatty acids in three different regions of the brain analyzed. Blood fatty acids were determined approximately one year prior to death. The investigators found that brain linoleic acid (the major omega-6 fatty acid in the diet) and all omega-6 fatty acids were significantly and markedly reduced in the participants with mild cognitive impairment or Alzheimer’s disease compared with the levels in cognitively normal participants. However, DHA and total omega-3 fatty acids were not significantly reduced in the Alzheimer’s patients. In contrast, the blood levels of DHA were 30% to 50% lower in the Alzheimer’s patients, but the amount of alpha-linolenic acid, the plant-based omega-3, was 8 times higher compared with unimpaired individuals. Blood omega-6 levels did not differ among the groups of participants. When dietary fatty acid intakes were similar, what caused these changes? When the investigators looked at whether the levels of fatty acids in the blood were correlated with those in the three regions of the brain selected, blood and brain fatty acid levels were unrelated. This observation suggests that examining blood fatty acids does not reflect what happens to these fatty acids in the three brain regions examined. The researchers suggested that in Alzheimer’s disease, DHA transport from the blood to brain may be altered, perhaps to maintain the levels of DHA in the brain. It is also unclear what the high levels of alpha-linolenic acid in the blood of Alzheimer’s patients might signify. Further, we lack an effective way to assess the changes in fatty acid metabolism in the brain during cognitive decline. Unraveling the functions of DHA as cognition changes continues to be a daunting task.