Subscribe to eTOC

Multiple Interventions Found to Improve or Maintain Cognitive Function in At-Risk Elderly People

ARTICLE IN BRIEF

Figure

No caption available.

In a two-year study, elderly individuals at risk for dementia who followed an intervention involving diet, exercise, cognitive training, and vascular monitoring fared better on neuropsychological tests than those who received general health advice only.

An intervention strategy involving diet, exercise, cognitive training, and vascular monitoring appears to improve or maintain cognitive functioning in at-risk elderly people, according to a report published in the March 12 online edition of The Lancet.

The large, population-based Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was able to detect small individual effects of the multidomain intervention that, when spread over a population, were significant. The two-year randomized, controlled trial was conducted at six centers in Finland.

“FINGER targeted the at-risk segment of the general elderly population, not patients in a clinical setting,” said Miia Kivipelto, MD, a professor of clinical geriatric epidemiology at the Karolinska Institute in Sweden. “Results are thus most appropriately interpreted in a public health context, where small long-term changes can have large effects.”

STUDY METHODOLOGY, RESULTS

Dr. Kivipelto and colleagues enrolled older individuals aged 60 to 77 recruited from previous national surveys. To be eligible, participants had to have a CAIDE (Cardiovascular Risk Factors, Aging and Dementia) risk score of at least six points and cognition at a mean level or slightly lower than expected for age. (CAIDE, an ongoing study launched in 1998 in Finland, examines social, lifestyle, and cardiovascular risk factors and their relation to cognition, dementia, and structural changes in the brain. Finnish investigators have used the data to develop a scale that can predict the likelihood that a middle-aged person will develop dementia in 20 years.)

For the FINGER study, the investigators randomly assigned 1,260 individuals to a multidomain intervention involving diet, exercise, cognitive training, and vascular monitoring (n=631) or to a control group that received general health advice (n=629).

At baseline, all participants were given oral and written information and advice on maintaining a healthy diet and engaging in physical, cognitive, and social activities that help manage vascular risk factors and prevent disability. Blood samples were collected at baseline and at six, 12, and 24 months, and the results — with discussion on any clinically important implications — were sent to all participants with advice to contact primary health care professionals if needed.

Figure

DR. MIIA KIVIPELTO: “FINGER targeted the at-risk segment of the general elderly population, not patients in a clinical setting. Results are thus most appropriately interpreted in a public health context, where small long-term changes can have large effects.”

The intervention group also received individual and group counseling sessions and advice on how to maintain a healthy, low-fat diet, and participated in discussions and practical exercises for facilitating lifestyle changes. They were prescribed an exercise program guided by physiotherapists that consisted of muscle training (one to three times per week) and aerobic exercise (two to five times per week). They also participated in individual and group cognitive training sessions, including computer-based training at their home or study sites, and in educational programs on activities that could enhance memory and reasoning strategies.

The investigators assessed cognition through an extensive neuropsychological test battery (NTB) at baseline and at 12 and 24 months after randomization. Participants who dropped out during the study were invited to a final visit at 24 months to evaluate the outcomes.

The primary outcome was a change in cognitive performance measured with NTB total score, a composite score based on results from 14 tests calculated as “z scores,” with higher scores suggesting better performance. Secondary outcomes included NTB domain z scores for executive functioning, processing speed, and memory. The z score is a statistical measurement of a score's relationship to the mean in a group of scores.

The researchers found an estimated mean change in the NTB total z score at two years of 0.20 in the intervention group and 0.16 in the control group. That indicates changes that are small at the individual clinical level, but which can translate to a significant public health effect on the population burden of dementia.

They also noted a significant intervention effect for the secondary cognitive outcomes of executive functioning and processing speed. Improvement in executive functioning and processing speed were 83 percent and 150 percent higher, respectively, in the intervention group than in the control group.

EXPERTS COMMENT

“This is the first time such a trial has been done, and the results are encouraging in that they are statistically significant and go in the right direction,” said Mary Ganguli, MD, MPH, a professor of psychiatry, epidemiology, and neurology at the University of Pittsburgh. “The results suggest that multiple risk factors have to be modified at the same time to produce a discernible effect. So when clinicians advise patients to adopt these lifestyle modifications, they will now be doing so on an empirical basis, not just because it ‘feels good’ or has no downside.”

Dr. Ganguli added that the study is also important because it looked at a sample drawn from the general population. The z scores represent an average, so some individuals will experience more or less effect from the intervention, and the individual effects could be greater over five or 10 years rather than the two years measured by FINGER, she noted.

“This study should be viewed from a public health perspective rather than an individual perspective,” she said. “Even if the change for the individual is small, spread across the whole population it could be a substantial effect. This is analogous to the well-known estimate that if we can delay dementia symptom onset in individuals by two years, we can reduce the prevalence and population burden of dementia by 25 percent.”

But how durable would the effect of this multidomain intervention be? Dr. Ganguli noted that the effects of many of these exposures, such as diet and exercise, are likely dependent on timing and duration; for example, they may have to occur during early or middle adulthood and continue for decades to confer real protection, and it's not possible to conduct randomized, controlled trials for that long. In addition, she pointed out that a single factor such as diet may not be enough to have an effect on its own.

“Perhaps for these reasons, most previous non-drug randomized, controlled trials have shown no or minimal benefits,” Dr. Ganguli said.

Walter A. Rocca, MD, MPH, a professor of epidemiology and neurology at the Mayo Clinic in Rochester, MN, agreed with Dr. Ganguli's assessment. “This trial did not address the question of durability,” he said, “but the authors have planned to do a seven-year extended follow-up study to examine the long-term effects of the regimen.

“As noted by the authors, this is a proof-of-concept study, and the results should be interpreted in a public health context, not in a clinical or personal context. In a public health context, even small but long-term effects may have a large population impact. This clinical trial is an exciting first step in a new direction of research on the prevention of cognitive decline.”

He added that the study is one of the first clinical trials to report results for the pre-clinical phase of cognitive decline and dementia, and one of the first to test a multidomain intervention to prevent dementia. “The study is convincing and the results match intuitive expectation,” he said. “The difference between groups suggests a genuine effect above and beyond the practice and placebo effects.”

Dr. Rocca said further studies on the timing of such interventions may be important. “For example, nutritional intervention and physical exercise at an earlier age may reduce the incidence of metabolic and vascular risk factors at a later age, in turn reducing the risk of cognitive decline further along,” he said. “The timing for cognitive training is less clear. This study opens a new series of important questions about multidomain interventions and optimal timing of the interventions.”

Dr. Kivipelto and colleagues said a seven-year extended follow-up will be done to assess the intervention's effect on the incidence of dementia and Alzheimer's disease and related functional outcomes.

“Postponing the onset of Alzheimer's disease by five years has been estimated to decrease its prevalence by up to 50 percent in 50 years,” they wrote. “About a third of cases of Alzheimer's disease worldwide could be attributable to low education, physical inactivity (the highest population-attributable risk in the USA, Europe, and the UK), obesity, hypertension, diabetes, smoking, and depression. The worldwide prevalence of Alzheimer's disease could be reduced by 8.3 percent by 2050 with relative reductions of 10 percent per decade in the prevalence of each of these factors. Such small changes imply large effects, and if the beneficial effects on cognition observed in FINGER will lead to even a modest delay in onset of dementia and Alzheimer's disease, it would have a huge effect on both individual and societal levels.”

EXPERTS: ON A MULTIDOMAIN INTERVENTION FOR ELDERLY PEOPLE AT RISK FOR DEMENTIA

Figure

DR. MARY GANGULI: “This is the first time such a trial has been done, and the results are encouraging in that they are statistically significant and go in the right direction. The results suggest that multiple risk factors have to be modified at the same time to produce a discernible effect. So when clinicians advise patients to adopt these lifestyle modifications, they will now be doing so on an empirical basis, not just because it ‘feels good’ or has no downside.”

Figure

DR. WALTER ROCCA: “As noted by the authors, this is a proof-of-concept study, and the results should be interpreted in a public health context, not in a clinical or personal context. In a public health context, even small but long-term effects may have a large population impact. This clinical trial is an exciting first step in a new direction of research on the prevention of cognitive decline.”

LINK UP FOR MORE INFORMATION:

•. Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): A randomised controlled trial http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2815%2960461-5/abstract. Lancet 2015: Epub 2015 March 12.
    •. Cardiovascular Risk Factors, Aging and Dementia (CAIDE): http://bit.ly/CAIDE-NT