Patients at Risk for Cognitive Decline Fared Best in Intervention

      BARCELONA — New, unpublished data from the FINGER multimodal lifestyle intervention study indicates that targeting nutrition, exercise, and metabolic and cardiovascular risk factors boosted overall cognitive performance, memory, and executive function to the greatest extent in elderly people at risk of cognitive decline who carried the APOE E ε4 allele.
      “The findings were especially clear in changes on the comprehensive neuropsychological test battery,” which was the study's primary endpoint, Miia Kivipelto, MD, PhD, of the Karolinska Institute, Stockholm, said at the Clinical Trials Conference on Alzheimer's Disease. “This is a very effective intervention that we can recommend, especially for people with this genetic risk factor.”
      The randomized, controlled FINGER (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) 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. It enrolled 1,260 participants aged 60–77 years who were cognitively normal at baseline but at risk for decline based on their CAIDE (Cardiovascular Risk Factors, Aging, and Incidence of Dementia) risk score.
      The cohort was randomized to a control program of 2 years of regular health counseling with their physician, or to the intervention, which consisted of:
      • Dietary counseling with recommendations to consume increased amounts of fruit, vegetables, whole grains, lean protein, and healthy fats.
      • Progressive aerobic exercise and weight training, conducted by physical therapists, several times each week.
      • Cognitive training several times a week with a computer program that targeted executive processes, working memory, episodic memory, and mental speed.
      • Managing metabolic and cardiovascular risk factors, including blood pressure, weight, and body mass index. This was addressed in group sessions and with visits to participants' own physicians.
      The subjects had a mean age of 69 years at baseline. About 70% reported physical activity at least twice a week. About half reported eating fish at least twice a week, and 60% reported a daily intake of vegetables. Most (65%) had hypertension and hypercholesterolemia (70%). Another 13% had diabetes, and 5% had a prior heart attack.
      The primary endpoint was change on an extended version of the neuropsychological test battery, which was conducted at baseline and at months 12 and 24. Secondary endpoints were changes on the individual components of executive function, memory, and processing speed.
      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: 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 Lancet published the study's main results earlier this year (Lancet 2015;385[9984]:2255–63).

      Carrier Benefit

      The new data that Dr. Kivipelto described showed that people with at least one APOE E ε4 allele reaped a significantly greater benefit than did those without the high-risk allele. Carriers experienced a significant improvement in the overall neuropsychological test battery score, but noncarriers did not. Carriers also benefited more in the individual domains, especially in tests of memory.
      Dr. Kivipelto explored how the program might be working on a molecular level. In an analysis of 756 subjects, including 244 APOE E ε4 carriers, she found attenuated telomere shortening in carriers in the intervention group, but not in carriers assigned to the control group or any of the noncarriers. This attenuation was also more pronounced in younger subjects, Dr. Kivipelto added.
      She also presented some preliminary data on how the intervention improved function and quality of life. “There was some decline after 2 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, she said. “We were surprised to see that after 2 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%.”

      Lasting Impact

      The program was not associated with any serious adverse events, or any adverse event at all other than musculoskeletal soreness from exercise activities. It also appeared to be practical and made a lasting impact, which was a gratifying finding, Dr. Kivipelto said. At the end of the study, intervention group participants had decreased their body mass index by about 0.8 kg/m2, which was significantly more than for control group subjects. Most reported that they were still eating fish and exercising at least twice a week and eating vegetables every day.
      “FINGER is the first long-term trial to show that a multidomain intervention like this one can maintain and improve cognitive decline,” she said. “It is important that we've also seen the program is feasible, has no obvious side effects, and that it's not limited to cognitive domains. It also has a positive impact on function and quality of life.”
      Dr. Kivipelto had no financial disclosures. The study was supported by grants from the Academy of Finland's Responding to Public Health Challenges Research Programme, La Carita Foundation, the Alzheimer's Association, the Alzheimer's Research and Prevention Foundation, the Juho Vainio Foundation, Novo Nordisk Foundation, the Finnish Social Insurance Institution, the Finnish Ministry of Education and Culture Research, Salama Bint Hamdan Al Nahyan Foundation, the Axa Research Fund, and various University Hospitals in Finland.
      Michele G. Sullivan is with the Mid-Atlantic bureau of Frontline Medical News.

      Editor's Note

      This study supports the findings of other recent research highlighting the importance of diet, and also of physical exercise, in maintaining cognitive function. But it goes even a step farther with the demonstration of actual improvement in several domains. Of course, getting people to actually implement these kinds of lifestyle changes will surely be much more difficult than getting them to take a pill or two a day — but as of now, no pills even come close to these results. So, for ourselves and for our patients, adhering to a healthy regimen of diet, physical exercise, and cognitive exercise is a good idea to keep our brains working as well as possible. Those of us who are PA/LTC clinicians probably won't need to worry about that last factor, at least until we retire.
      —Karl Steinberg, MD, CMD
      Editor in Chief