In the JournalsPerspective

BP, lipid-lowering treatments fail to affect cognitive decline in older patients

Jackie Bosch
Jackie Bosch

Rosuvastatin, candesartan plus hydrochlorothiazide or a combination of both treatments in older patients did not have significant effect on cognitive decline, according to a study published in Neurology.

“Statin use has previously been associated with cognitive impairment, but this study demonstrated that there was none, which is an important finding for those taking statins,” Jackie Bosch, PhD, director of program management at the Population Health Research Institute in Hamilton, Ontario, Canada, said in a press release.

Researchers analyzed data from 2,361 participants from the HOPE-3 trial aged at least 70 years and with intermediate CV risk. Participants were assigned 16 mg candesartan with 12.5 mg hydrochlorothiazide or placebo, and to 10 mg rosuvastatin or placebo.

Participants underwent cognitive testing at randomization and at the end of the study, which consisted of the modified 12-item Montreal Cognitive Assessment, the Digit Symbol Substitution Test (DSST) and the Trail Making Test Part B. Functional status was also evaluated at baseline and at the end of the study.

The primary cognitive outcome measure of interest was a change in DSST score. Negative scores indicate a decline, whereas positive scores indicate an improvement. Secondary outcomes of interest were the effects of treatment on mean changes in Trail Making Test Part B and modified 12-item Montreal Cognitive Assessment scores.

Participants were followed up at 6 weeks, 6 months and every 6 months thereafter until Oct. 31, 2015, for a median of 5.7 years.

Of the patients who completed cognitive assessments at baseline, 76% of those (mean age, 74 years; 59% women; 45% hypertension) completed a DSST at the end of the study.

Compared with placebo, patients assigned candesartan with hydrochlorothiazide lowered systolic BP by 6 mm Hg. The rosuvastatin group also had a reduction in LDL by 24.8 mg/dL vs. placebo.

The candesartan with hydrochlorothiazide group had a mean difference in the change in DSST of –0.91 compared with placebo (95% CI, –2.25 to 0.42). The mean difference in participants assigned rosuvastatin was –0.54 vs. those assigned placebo (95% CI, –1.88 to 0.8). Participants assigned the combination therapy had a mean difference of –1.43 compared with those assigned double placebo therapy (95% CI, –3.37 to 0.5).

Significant differences were not seen for other measures assessed in this study.

“It is possible that a treatment duration of 5.7 years may not be long enough to prevent cognitive decline, especially in a population with normal BP,” Bosch and colleagues wrote. “The slower rate of decline seen in the group with higher baseline BP and lipids and the potential benefit of longer treatment should be evaluated in future studies.” – by Darlene Dobkowski

Disclosures: This study was funded through grants from the Canadian Institutes of Health Research and AstraZeneca. Bosch reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

 

Jackie Bosch
Jackie Bosch

Rosuvastatin, candesartan plus hydrochlorothiazide or a combination of both treatments in older patients did not have significant effect on cognitive decline, according to a study published in Neurology.

“Statin use has previously been associated with cognitive impairment, but this study demonstrated that there was none, which is an important finding for those taking statins,” Jackie Bosch, PhD, director of program management at the Population Health Research Institute in Hamilton, Ontario, Canada, said in a press release.

Researchers analyzed data from 2,361 participants from the HOPE-3 trial aged at least 70 years and with intermediate CV risk. Participants were assigned 16 mg candesartan with 12.5 mg hydrochlorothiazide or placebo, and to 10 mg rosuvastatin or placebo.

Participants underwent cognitive testing at randomization and at the end of the study, which consisted of the modified 12-item Montreal Cognitive Assessment, the Digit Symbol Substitution Test (DSST) and the Trail Making Test Part B. Functional status was also evaluated at baseline and at the end of the study.

The primary cognitive outcome measure of interest was a change in DSST score. Negative scores indicate a decline, whereas positive scores indicate an improvement. Secondary outcomes of interest were the effects of treatment on mean changes in Trail Making Test Part B and modified 12-item Montreal Cognitive Assessment scores.

Participants were followed up at 6 weeks, 6 months and every 6 months thereafter until Oct. 31, 2015, for a median of 5.7 years.

Of the patients who completed cognitive assessments at baseline, 76% of those (mean age, 74 years; 59% women; 45% hypertension) completed a DSST at the end of the study.

Compared with placebo, patients assigned candesartan with hydrochlorothiazide lowered systolic BP by 6 mm Hg. The rosuvastatin group also had a reduction in LDL by 24.8 mg/dL vs. placebo.

The candesartan with hydrochlorothiazide group had a mean difference in the change in DSST of –0.91 compared with placebo (95% CI, –2.25 to 0.42). The mean difference in participants assigned rosuvastatin was –0.54 vs. those assigned placebo (95% CI, –1.88 to 0.8). Participants assigned the combination therapy had a mean difference of –1.43 compared with those assigned double placebo therapy (95% CI, –3.37 to 0.5).

Significant differences were not seen for other measures assessed in this study.

“It is possible that a treatment duration of 5.7 years may not be long enough to prevent cognitive decline, especially in a population with normal BP,” Bosch and colleagues wrote. “The slower rate of decline seen in the group with higher baseline BP and lipids and the potential benefit of longer treatment should be evaluated in future studies.” – by Darlene Dobkowski

Disclosures: This study was funded through grants from the Canadian Institutes of Health Research and AstraZeneca. Bosch reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

 

    Perspective
    Martha Gulati

    Martha Gulati

    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.