When I realized what study this was, I will be honest and say I was hoping for a more significant finding; I was predicting that treating ASCVD risk factors was going to improve outcomes. We have known for some time that there is a link between ASCVD risk factors that impact cognitive decline. This association has linked dementia, Alzheimer’s and cognitive decline to being related to vascular disease. But association isn’t causation, of course. The question remains that despite this relationship, if we can treat aggressively with preventive measures, will we actually impact outcomes or even potentially prevent dementia, Alzheimer’s or any cognitive decline as we age?
Before I read the study in its entirety, I immediately read the conclusion, where I saw that by lowering BP and cholesterol, there was not a reduction in cognitive decline in older people. At that age, it is possible that the vascular effects had already caused the damage. Additionally, the follow up period was only 5.7 years of follow-up, a relatively short duration. I hope that in HOPE-3 or in other studies that they include patients who are younger and follow them out longer to see if at an earlier stage if you can treat these risk factors and prevent the decline.
Additionally, there was a significant proportion of patients that did not complete the cognitive assessment at baseline. I do not know why that was, but a part of me wonders if they already knew that they had some cognitive decline and didn’t want to fill it out. They only included those who filled out their cognitive questionnaire at baseline and follow-up, and there were some lost from analysis because they didn’t fill out the follow-up questionnaire: Perhaps those with cognitive impairment were the ones who could not be assessed in this way.
What we do not know is if treatment at that age is going to prevent cognitive decline. Certainly, this study didn’t show that. The study for the future may need to be done in a younger cohort and following them for some time to see the impact of preventive therapies on cognitive declines. We did not find a difference in this study. Perhaps if they had followed these patients longer, or looked at the younger population.
People that are enrolled in trials at that age do tend to be a healthier cohort. They know they need to go for follow-up, they usually have to be a little more mobile or self-sufficient, depending more on themselves to participate in a trial. That always is a limitation of every study, especially for this particular question. It was a very small number that eventually developed dementia, only 16, four of whom were institutionalized by the end of the study. This is more evidence that this was a healthier cohort.
Some studies have given us a signal that CV prevention can abate cognitive decline, but studies have been inconsistent and conflicting in their results. The reason it is important for us is that all over the world, people are living longer. All of us want to live healthy lives with functional cognitive abilities. We want to able to make decisions for our ourselves and not be reliant on other people as much as possible. Independence is a big part of aging and aging well. We need to know what the things we can do to preserve cognitive function.
All we can say right now is that this study hasn’t shown that treating hypertension and high cholesterol has had impact on cognitive decline. There have been some data supporting that the people with higher BP and higher cholesterol may benefit the most, but it is a small number within any of the studies. We have to start looking at and following populations at younger ages and following them longer, because I am not sure age 70 is the time to start preventive therapy. Certainly this was not the primary purpose of HOPE-3, as this was a secondary analysis, but that is what we need. In the older population, we have evidence for controlling their BP, but not as much for treating high cholesterol when we are taking about primary prevention.
For the practicing physician, you are still stuck. You do not know if you are doing something good necessarily by treating an older population with statins just from a primary prevention standpoint.
The message to physicians and to patients is to keep looking for the right data. Right now, these data do not support treating BP and cholesterol to prevent cognitive decline (there are other reasons to treat both). We just need a well-done study looking at this. I suspect that there will be others.
We are probably needing a population study on what is the natural history is of people well-treated vs. people that are undertreated so that we can determine how best to prevent cognitive decline.
Martha Gulati, MD, MS, FACC, FAHA
Division Chief of Cardiology
University of Arizona College of Medicine Phoenix
Physician Executive Director for the Banner University Medicine Heart Institute
Editor in Chief, ACC CardioSmart
Disclosures: Gulati reports no relevant financial disclosures.