• CME DISCLOSUREVicki Brower, CME Writer, MedPage Today; Robert Jasmer, MD, Associate Clinical Professor of Medicine, University of California, San Francisco, Reviewer; and Dorothy Caputo, MA, BSN, RN, Nurse Planner have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity. The staff of Projects In Knowledge®, Inc. and the staff of MedPage Today have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity.

Target Audience and Goal Statement:

Internists, family medicine specialists, neurologists, and cardiologists

The goal of the study was to determine whether older adults with mild cognitive impairment but no dementia and cardiovascular risk factors can improve executive functioning, memory, and verbal fluency by adding moderate, regular aerobic exercise, and/or the the Dietary Approaches to Stop Hypertension (DASH) diet.

Questions Addressed:

What are the independent and additive effects of aerobic exercise (AE) and the DASH diet on executive functioning (primary endpoint), and on measures of language/verbal fluency and memory (secondary endpoint) in adults at risk for cardiovascular disease and who have mild cognitive impairment?

Study Synopsis and Perspective:

In a randomized clinical trial of exercise and diet in 160 sedentary adults with mild cognitive impairment but no dementia (CIND) and cardiovascular risk factors, regular aerobic exercise three times a week for 6 months resulted in significant improvements in executive function, but not in memory or language/verbal fluency domains, James Blumenthal, PhD, of Duke University Medical Center in Durham, N.C., and colleagues for the ENLIGHTEN trial reported.

The researchers employed a 2-by-2 factorial design (exercise/no exercise and DASH/no DASH) to compare the independent effects of exercise and diet on a range of cognitive abilities. At baseline, participants had subjective memory complaints, objective evidence of cognitive impairment, and at least one additional cardiovascular disease risk factor besides being sedentary. They had a mean age of 65.4, and 66% were female.

The team randomly assigned 160 inactive men and women to 6 months of either exercise alone (n=41), DASH diet alone (n=41), combined exercise and DASH diet (n=40), or a no-exercise, no-diet control group that received weekly phone calls about health-related topics (n=38). Effect sizes were measured with the Cohen’s d to indicate the difference between means.

Participants in the exercise group worked out under supervision three times a week for 35 minutes at 70% to 85% of their initial peak heart rate reserve for 3 months, then continued exercising at that rate at home, documenting activity in weekly exercise logs. DASH diet group members received education about the DASH diet and frequent feedback about adherence from a nutritionist.

At the end of 6 months, individuals who engaged regularly in aerobic exercise (beta coefficient 4.2, 95% CI 0.2-8.2, d=0.32, P=0.046), not those only in the DASH group (beta coefficient 3.7, 95% CI −0.2 to 7.7, d=0.30, P=0.059), demonstrated significant improvements in the executive function domain. There were no significant improvements in the memory or language/verbal fluency domains, however.

The largest improvements in executive functioning occurred for participants in the combined exercise and DASH diet group (d=0.40, P=0.012) compared with controls. To illustrate the potential clinical significance of this, the authors estimated that participants had average scores for select subtests of executive function consistent with 93-year-old people at baseline — 28 years older than their chronological age. After 6 months, people who exercised and followed the DASH diet had average executive function scores corresponding to 84-year-olds, a 9-year improvement. In contrast, executive function scores for control group participants worsened by a half year (which actually was the duration of the study).

Follow up examination of specific CVD risk factors showed that participants on the DASH diet had reductions in total cholesterol, reduced weight and LDL lipoprotein, and a reduction in the number of hypertensive medications taken. There were no significant differences in systolic blood pressure. Individuals in the exercise and exercise + DASH diet showed greater improvements in insulin compared with those who did not exercise.

Regarding neurocognitive function, while researchers saw no significant changes in executive function for those on the DASH diet, those in the aerobic arm of the trial saw significant improvement in executive function. Reduced sodium intake was also associated with improved executive function, changes in potassium, magnesium, and calcium were not related to executive function.

“Individuals with CIND — cognitive impairment, no dementia — are at risk for developing dementia over time,” Blumenthal said. “Currently there are no known treatments to prevent the progression of this disorder, so findings from this study are very important by suggesting that regular exercise can improve cognitive function and potentially delay the onset of dementia in these individuals.”

Although study researchers conducted APOe4 genotyping, they did not comment on genotype status and outcomes for individuals, although they did control for APOE genotype as well as education and CVD medication burden, and long-term use of anti-inflammatory medications. Participants were evenly divided between whites and minorities.

Source Reference: Neurology Dec. 19, 2018; DOI:10.1212/WNL.0000000000006784

Study Highlights: Explanation of Findings

In the ENLIGHTEN trial, 6 months of regular aerobic exercise led to improved executive functioning in adults at risk for cognitive decline, researchers reported. And while the DASH diet boosted the executive functioning benefits of exercise, it did not show any cognitive function benefit by itself, the study authors wrote in Neurology.

Blumenthal and colleagues observed that this trial may be the first randomized study to investigate the independent and combined effects of a diet and aerobic exercise on neurocognitive function in older adults at elevated risk for progressive decline in cognitive functioning. Results of previous meta-analyses of randomized trials have been inconsistent, they noted.

“An interesting finding is that the DASH diet alone did not provide any benefit for cognitive function, even though the DASH diet did improve cardiovascular health,” observed Teresa Liu-Ambrose, PhD, PT, of the University of British Columbia in Vancouver, who was not involved with the study. “However, it should be noted that aerobic exercise not only improves cardiovascular health, but also induces the release of growth factors that are beneficial for neuronal health.”

While participants who engaged in both aerobic exercise and DASH demonstrated the most improvement in executive functions, the difference in the magnitude of benefit — of exercise alone vs exercise plus DASH — was 25%, Liu-Ambrose told MedPage Today. “As adoption and adherence to health habits is often a challenge for individuals, one may consider adopting one habit first, i.e., exercise, and then slowly incorporating the second habit, i.e., diet,” she said. In the combined exercise and DASH group, greater aerobic fitness, reduced cardiovascular disease (CVD) risk, and reduced sodium intake were associated with executive function improvements.

Researchers pointed out that “because there is considerable overlap in risk factors for CVD and dementia, strategies designed to reduce CVD risk may also be effective in improving neurocognition and reducing the risk of developing dementia.”

“These findings raise the possibility that adopting a healthy lifestyle of diet and exercise can not only reduce the risk of heart disease, but also reduce the risk of developing dementia later in life,” he added. “Future studies, with larger samples followed over more extended time periods are needed, along with studies that examine the mechanisms by which these lifestyle modifications improve cognitive functioning,” he told MedPage Today.

The ENLIGHTEN trial may have been underpowered to detect differences between aerobic exercise and DASH diet alone, Blumenthal and co-authors noted; because of this potential limitation, they provided limited evidence of the relative benefits of these two interventions. The study also was only 6 months long and longer-term effects of exercise and diet on cognitive outcomes are unknown. No one dropped out of the study and trial results may not apply to less motivated groups, they added.

Judy George wrote the original story for MedPage Today

Source:

by Vicki Brower, CME Writer, MedPage Today December 23, 2018