|By Tré LaRosa
In this iteration of the Unseen Links to Alzheimer’s, we are investigating the potential connection between diet and Alzheimer’s. In previous blogs, we looked at the connections between gingivitis and air pollution and Alzheimer’s. The objective of these blogs is to not only recap and describe the available evidence for these potential links but to convey valuable insights about the research process and scientific theory.
Science can seem a bit frustrating since there can be a great deal of uncertainty. From an outside perspective, science can seem so uncertain that nothing is ever fully understood. But this uncertainty is less a detriment of science than a testament to what science strives to do. The concept of “proof” is what underlies science but maybe not from the perspective that people usually think of. In science, definitively “proving” something to be true is very challenging and some would argue impossible. This isn’t necessarily why you might think, though. Science, through deductive and inductive reasoning via hypotheses and experimentation, strengthens claims which allows scientists to increase their confidence of whether or not something is true. It is easier to prove something is false than it is to prove something is true. A key consideration in science — and therefore discussions about connections between the environment and health conditions and clinical research — is whether a hypothesis is falsifiable. This means that the researcher, in order to glean conclusions from the experiment, should develop a hypothesis that can be proven false. The concept of falsifiability can be pretty easily explained when we consider dogs. If a scientist were to hypothesize that all dogs have brown fur, proving that would require the experimenter to observe every dog on the planet. Alternatively, a single counterexample of a dog with black (or any other color) fur would prove this claim is false. This is true of science more broadly; when we hypothesize something, there should be an experiment that could reasonably and logically capture the scope of what the hypothesis is. It should be noted that falsifiability is not the end-all-be-all in science. A single counter-example to a theory or hypothesis does not invalidate the whole pretense of the theory. Humans, after all, are capable of drawing the wrong conclusions from experimentation or theories which can influence future hypothesizing; when evidence doesn’t support a particular theory, the evidence should be used as a part of the whole body of evidence to inform analyses, conclusions, and further hypotheses and experimental design. If you found a dog a black fur, you would not then change your hypothesis to “all dogs have black fur,” nor would you change it to “no dogs have brown fur.”
This might sound a bit disconcerting, especially when we’re discussing something like causal connections between the environment and health conditions. Correlations might be spurious in that certain observations might show preliminary promise but later prove to be false upon further research. But correlations between two environmental factors and health conditions shouldn’t be viewed in the same light as evidence for or against the use of therapeutics. Ultimately, what all research is seeking out to do is get closer and closer to a fundamental truth. In clinical research, this can be shown when we consider a therapeutic. The clinical research process is founded upon the scientific method and requires many, many steps between the genesis of a new proposed therapeutic before it ever reaches full approval. This process, like science itself, is not perfect but it is very effective at giving researchers the knowledge needed to effectively discern connections. If early phase 1 or phase 2 trials show a therapeutic does not seem to have many promising effects or that its side effects are negative, the compound will likely not advance much further in the process. In those cases, researchers will usually say that the compound is not very effective; this is because it’s easier to discern when a drug is not doing anything than to definitively say a drug is correlated with the benefits. For compounds where clinical research is ongoing, even if they show initial promise, researchers and clinicians will usually be very hesitant to say much other than that it’s promising but not definitely helpful. In clinical research, the hypothesis would be “this compound will improve” the specified outcomes as part of the condition, and it would be falsifiable by demonstrating that the compound has no influence (or a negative influence) on the outcomes.
When researching how environmental factors influence outcomes, teasing out specifics is a bit different than evaluating a specific compound’s effects. The goals are similar, as are the ways we develop studies, but unfortunately, there are additional factors that must be considered. First, environmental factors are themselves nebulous and influenced by other factors. Things like diet, air pollution, and gingivitis are not singular factors. Our diets can be dramatically different from one another; not only do we consume different ratios of carbohydrates, proteins, and fats, but those ratios of macromolecules come from different sources which have other ratios of vitamins and minerals. Further, our metabolisms differ, as do our bodies’ needs. Sure, metabolism and individualism are factors that can influence how our body responds to a medication, but since the independent variable, medication vs food, remains unchanged per person (aside from perhaps dose, but clinical trials control for dosages), there are fewer factors that influence the independent variable and its comprised subcategories. Additionally, such external factors are harder to control than a medication or therapy. It is not at all reasonable to ask or expect researchers or trial participants to live in a dome where the air can be completely controlled, nor is it reasonable to think that researchers can control every bit of a person’s diet. Finally, when you consider the complexity of Alzheimer’s disease and just how much more there is to learn about its etiology and manifestations, it becomes clear just how complex environmental factors are in and of themselves and the immense challenge it is for researchers to fully understand the implications of environmental factors on both the individual and the community more broadly. On the bright side, however, researchers are attempting to accomplish these challenges!
Despite the enormity and seriousness of these challenges, there are two very positive silver linings. The first is that researchers are even attempting to understand these connections. The second, and probably more positive silver lining, is that we don’t necessarily need to have evidence that there is a definitive connection for us to make judgment calls that will likely help reduce our chances of developing Alzheimer’s.
Evidence, Potential Explanation, and Implications
Just as we saw with air pollution and gingivitis, it probably sounds strange that there could be a connection between what we eat and a condition as complex and pervasive as Alzheimer’s. But also like we saw with the other two environmental factors, the potential connection makes more sense than one might think at first glance.
The National Institute on Aging (NIA), the NIH institute that covers Alzheimer’s disease, has documented a lot of the evidence and ongoing studies on diet and Alzheimer’s. Interestingly, the NIA opens their article by asking the question: “Can eating a specific food or following a particular diet help prevent or delay dementia caused by Alzheimer’s disease?” Note their use of “help prevent or delay dementia.” This question is posed differently than the questions around gingivitis and air pollution where we asked if air pollution or gingivitis can cause the development of Alzheimer’s (as a reminder, the evidence suggests that it’s… complicated). This article is instead asking if diets can prevent or delay Alzheimer’s. This distinction might seem minor or even irrelevant, but these are different questions in the same way we discussed falsifiability and definite proof above.
The article notes that brain changes happen before symptoms which is one of the reasons Alzheimer’s is such a pernicious condition, since the onset of symptoms can be so far removed from the anatomical causes that precede — and precipitate — the clinical manifestations. This issue is of particular importance because this major temporal gap between changes and symptoms makes it more challenging to tease out cause-and-effect, and more directly related to the patient, makes it more challenging to do much to reduce or treat progression. But as the article goes on to state, this gap, or as they call “a possible window of opportunity,” gives researchers a chance to indeed investigate modifiable risk factors that could end up slowing progression. This point underscores the importance of early detection of brain changes.
The NIA explains possible mechanisms for how our diets affect our brains. If you read the Unseen Links blog about gingivitis, pay close attention to the last possible mechanism.
It’s possible that eating a certain diet affects biological mechanisms, such as oxidative stress and inflammation, that underline Alzheimer’s. Or perhaps diet works indirectly by affecting other Alzheimer’s risk factors, such as diabetes, obesity and heart disease. A new avenue of research focuses on the relationship between gut microbes — tiny organisms in the digestive system — and aging-related processes that lead to Alzheimer’s.
The NIA then goes on to recount the evidence which contains two types of information: First, clinical trials that investigated specific diets compared to rates of cognitive decline or rates of Alzheimer’s; secondly, studies that recounted changes in the parts of the brain that are usually affected by Alzheimer’s. These two strategies are useful because they help the community more broadly zero in on the connection from different angles.
The main diets that have been studied are really quite similar. There’s the Mediterranean diet, which you’ve probably heard of and has a long history of being researched, and a descendent of the Mediterranean diet called the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. The MIND diet integrates the “Dietary Approaches to Stop Hypertension” (DASH) eating plan into the Mediterranean diet. As you might notice, the DASH eating plan is useful for lowering high blood pressure, which is a risk factor for Alzheimer’s. Clinical research into these diets have produced some compelling data. Across different studies, both of which had data doe four to five years, those who followed the MIND diet closely had a “53% reduced rate of Alzheimer’s disease compared to those who did not follow the diet closely” and “substantial slowing of cognitive decline.” In a different study of “cognitively normal adults,” the participants who followed the Mediterranean diet had “thicker cortical brain regions than those who did not.” Subsequent studies into that same population showed “lower glucose metabolism and higher levels of beta-amyloid protein.” Shrunken cortical brain regions, high glucose metabolism, and high levels of beta-amyloid protein are all hallmarks of Alzheimer’s disease. Other diets, including the ketogenic diet, are also being researched.
Does this evidence definitely demonstrate that certain diets cause Alzheimer’s? Most certainly not, nor does this evidence definitely prove that Mediterranean or MIND diets prevent, delay the onset of, or slow the progression of Alzheimer’s. What the evidence shows is that there seems to be some link between certain diets and preventing Alzheimer’s, which is about the same as what we saw with reduced air pollution or reduced rates of gingivitis. This might not completely comfort anybody who is concerned about the risk of developing Alzheimer’s, but when you consider the overall evidence for these unseen invisible links to Alzheimer’s, it would be worth considering being aware of air pollution in your area (and wearing masks on days with worse air pollution), taking your dental health seriously, and implementing a Mediterranean or MIND diet. If we modify the risk factors that we can, we are doing the most we can do to reduce our chances of developing Alzheimer’s. That counts for something.
Ongoing clinical trials investigating connections between Alzheimer’s and diet
- Enhanced Mediterranean Diet for Alzheimer’s Disease Prevention
- Multicultural Healthy Diet to Reduce Cognitive Decline
- Brain Energy for Amyloid Transformation in Alzheimer’s Disease