BARCELONA—New, unpublished data from a multimodal lifestyle intervention study indicates that targeting nutrition, exercise, and metabolic and cardiovascular risk factors improves overall cognitive performance, memory, and executive function to the greatest extent in elderly people at risk of cognitive decline who have the APOE ε4 allele.
“The findings were especially clear in changes on the comprehensive neuropsychologic test battery,” which was the study’s primary end point, said Miia Kivipelto, MD, Professor of Clinical Geriatric Epidemiology at the Karolinska Institutet in Stockholm, at the Clinical Trials on Alzheimer’s Disease conference. “This is a very effective intervention that we can recommend, especially for people with this genetic risk factor.”
The FINGER Trial
The randomized, controlled Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) trial was a proof-of-concept study designed to show how a multimodal lifestyle intervention might not only slow or prevent cognitive decline, but also help improve cognition among patients who are already experiencing decline. Investigators enrolled 1,260 participants between ages 60 and 77 who were cognitively normal at baseline but at risk for decline based on their Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) risk score.
The cohort was randomized to a control program of two years of regular health counseling with their physician, or to the intervention, which consisted of four parts. The first part was dietary counseling, including recommendations to consume increased amounts of fruit, vegetables, whole grains, lean protein, and healthy fats. The second part was progressive aerobic exercise and weight training, conducted by physical therapists several times each week. The third part was cognitive training, which took place several times per week with a computer program that targeted executive processes, working memory, episodic memory, and mental speed. The fourth part was managing metabolic and cardiovascular risk factors, including blood pressure, weight, and BMI. This part was addressed in group sessions and with visits to participants’ own physicians.
The subjects had a mean age of 69 at baseline. About 70% reported physical activity at least twice per week. About half of the population reported eating fish at least twice per week, and 60% reported a daily intake of vegetables. Most participants (65%) had hypertension and hypercholesterolemia (70%). Another 13% of participants had diabetes, and 5% had a prior heart attack.
The primary end point was change on an extended version of the neuropsychologic test battery, which was conducted at baseline and at months 12 and 24. Secondary end points were changes on the individual components of executive function, memory, and processing speed.
Intervention Had Neuropsychologic Benefits
By the end of the study, subjects in the intervention group experienced a significant, 25% greater improvement on the overall score than did those in the control group. Improvements on the secondary measures were significant for the intervention group as well. That group performed 150% better than the control group in processing speed, 83% better in executive functioning, and 40% better in short-term memory.The risk of cognitive decline increased by 30% in the control group by the study’s end, whereas subjects in the intervention group experienced no increased risk. The study’s main results were published in Lancet earlier this year.
The new data that Dr. Kivipelto described showed that people with at least one APOE ε4 allele had a significantly greater benefit than did those without the high-risk allele. In the intervention group, carriers had an estimated mean change z-score on the overall neuropsychologic test battery that was significantly higher than that in noncarriers (0.17 vs 0.10), whereas the difference between carriers and noncarriers in the control group was not statistically significant (0.22 vs 0.19). Carriers in the intervention group also tended to benefit more than did noncarriers in the individual domains.
Attenuated Telomere Shortening
Dr. Kivipelto offered a theory about how the program might work on a molecular level. In an analysis of 756 participants, including 244 people with APOE ε4, she found attenuated telomere shortening in carriers in the intervention group, but not in carriers assigned to the control group or in any of the noncarriers. This attenuation was also more pronounced in younger subjects, Dr. Kivipelto added.
She also presented preliminary data on how the intervention improved function and quality of life. “There was some decline after two years in the control group, but the intervention group remained stable,” Dr. Kivipelto said. “There was also significant improvement in general health, mental function, and social function in the intervention group.”
General daily function was good for the entire cohort at baseline, but by the end of the study, significant differences had emerged. “We were surprised to see that after two years, the control group actually had a 50% increased risk for at least one new difficulty with activities of daily living, and for those with no difficulties at baseline, the increased risk was even stronger: 76%,” said Dr. Kivipelto.