Which Interventions Can Slow Cognitive Decline or Prevent Dementia?

LONDON—Cognitive training, blood pressure management, and increased physical activity could slow or delay cognitive decline, according to a new report by the National Academies of Science, Engineering, and Medicine (NASEM). The evidence is insufficient to justify a major public health campaign to encourage the adoption of these interventions, however, according to the organization.

“All the information taken together suggests that there is something that we can do to slow cognitive decline,” said Ronald C. Petersen, MD, PhD, Consultant to the Department of Neurology at the Mayo Clinic in Rochester, Minnesota, and member of the NASEM Committee on Preventing Cognitive Decline. “As these interventions have minimal risk and may be helpful for other conditions, the possible benefits are worthy of comment to the medical community.” In addition, NASEM identified areas for future research in this field, Dr. Petersen noted at the 2017 Alzheimer’s Association International Conference.

Ronald C. Petersen, MD, PhD

The NASEM review committee looked at the following three categories of cognitive decline: age-related cognitive decline, which can be a normal part of aging; mild cognitive impairment (MCI), which does not significantly impair function in daily activities; and clinical Alzheimer’s-type dementia, which denotes severe impairment and loss of functional independence. “With regard to public health messaging, it is unlikely that the general population will recognize these fine distinctions,” Dr. Petersen said.

For its report, NASEM examined a systematic review of randomized controlled trials by the Agency for Healthcare Research and Quality. For a more complete overview on which to base its recommendations, NASEM also analyzed supplementary sources, including prospective cohort studies and observational studies.

Cognitive Training

Evidence from randomized controlled trials shows that cognitive training can delay or slow age-related cognitive decline. “One study in particular, the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial, showed moderate-strength evidence of benefits,” Dr. Petersen said. “Certainly the data look good out to two years.”

The 10-year ACTIVE trial involved 2,832 subjects age 65 and older who did not have significant cognitive, physical, or functional decline at baseline. Participants were randomized to one of three 10-session training interventions (ie, for memory, reasoning, or speed of information processing) or to no contact. Each intervention improved function in the corresponding cognitive domain, but not necessarily in the other cognitive domains, the researchers found.

The study had certain limitations, however, said Dr. Petersen. “The evidence was of low strength at five years and at 10 years due to attrition and a variety of other factors. Also, there was some selection bias as to who among the study participants would receive additional booster sessions.” Other limitations were the use of no-contact controls and the lack of comparison between treatment arms. “Nevertheless, these were longitudinal data, which are uncommon for a study with these types of interventions.”

These findings may not translate to benefits for commercially available computer-based brain games, Dr. Petersen added. “In the ACTIVE study, there was a social factor, as well. These people did not just sit down at a computer screen, but they were in a group being taught various techniques.” As for supplementary evidence, NASEM identified no observational studies of cognitive training, and it found no evidence that cognitive training has a beneficial effect on MCI or Alzheimer’s-type dementia.

Blood Pressure Management

Randomized controlled trial data were inconsistent with regard to the effects of blood pressure management on the incidence of Alzheimer’s-type dementia. One of four trials, the Systolic Hypertension in Europe (Syst-Eur) trial, showed benefits of this approach.

In this study, eligible patients had no dementia, were at least age 60, and had isolated systolic hypertension. Median follow-up by intention to treat was 2.0 years. Compared with placebo (n = 1,180), active treatment (n = 1,238) reduced the incidence of dementia by 50%. The Syst-Eur trial was stopped after the second of four planned interim analyses because active treatment had reduced stroke incidence, which was the primary end point. Because of ethical issues, however, the NASEM committee questioned whether it is possible or practical to reach a definitive conclusion about the benefits of blood pressure management for dementia using randomized controlled trial data.

Supplementary evidence in favor of blood pressure management includes the link between cerebrovascular disease and dementia, Dr. Petersen said, coupled with the fact that antihypertensive drugs reduce stroke risk and subclinical cerebrovascular disease. Prospective cohort studies more consistently show an association between blood pressure lowering and improved cognitive outcomes. Furthermore, in studies that were not randomized controlled trials, NASEM’s analyses using the Bradford Hill criteria suggested a causal relationship between blood pressure management and decreased incidence of Alzheimer’s-type dementia.

Physical Activity

Although the randomized controlled trial data on the benefits of physical activity were mixed, the results suggested that physical activity could reduce the risk of age-related cognitive decline. Data on the effect of physical activity on the risks of MCI and Alzheimer’s-type dementia were insufficient, Dr. Petersen said. Generally, follow-up periods were too short to assess long-term effects, and MCI and Alzheimer’s-type dementia incidence were rarely measured as outcomes.

“Findings from studies that compared the difference between aerobic training and resistance training were somewhat inconsistent,” Dr. Petersen said. “Some people believe that a mixture of both may in fact be beneficial.” In the largest randomized controlled trial examined, the Lifestyle Interventions and Independence for Elders Pilot study, evidence was insufficient to support conclusions regarding a multicomponent intervention.

“There were observational studies and a variety of longitudinal prospective studies that would suggest that physical activity may have a positive effect on cognitive performance and dementia incidence,” Dr. Petersen said. “It could also have an impact on other conditions that may affect cognitive function, such as hypertension, depression, and diabetes.”

Future Directions for Research

While the NASEM committee recommends more research on the benefits of cognitive training, blood pressure management, and exercise training, it also urges the NIH and other organizations to support studies with improved methodologies. Such improvements include identifying patients at higher risk of cognitive decline or dementia, increasing participation of underrepresented populations, beginning interventions at younger ages, and establishing longer follow-up periods.

The committee also suggests that trials with other primary purposes measure cognitive outcomes. “For instance, if there is an ongoing study on prostate cancer, and the researchers decide midway to add some cognitive measure, that is useful,” Dr. Petersen said. “But it is not as strong as if the study had been prospectively designed to look at cognitive end points at the baseline.”

Other interventions that should be examined are new antidementia treatments; treatments for diabetes and depression; dietary, lipid-lowering, and sleep-quality interventions; social engagement interventions; and supplementation with vitamin B12 plus folic acid, said Dr. Petersen.

—Adriene Marshall

Suggested Reading

Forette F, Seux ML, Staessen JA, et al. Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet. 1998;352(9137):1347-1351.

Jobe JB, Smith DM, Ball K, et al. ACTIVE: a cognitive intervention trial to promote independence in older adults. Control Clin Trials. 2001;22(4):453-479.

LIFE Study Investigators, Pahor M, Blair SN, et al. Effects of a physical activity intervention on measures of physical performance: Results of the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study. J Gerontol A Biol Sci Med Sci. 2006;61(11):1157-1165.

National Academies of Sciences, Engineering, and Medicine. 2017. Preventing Cognitive Decline and Dementia: A Way Forward. Washington, DC: The National Academies Press; 2017.

Staessen JA, Thijs L, Birkenhäger WH, et al. Update on the systolic hypertension in Europe (Syst-Eur) trial. The Syst-Eur Investigators. Hypertension. 1999;33(6):1476-1477.