Multipronged Lifestyle Change Reduces Cognitive Impairment

Susan Jeffrey

July 16, 2014

COPENHAGEN, Denmark — Results of a randomized trial suggest lifestyle intervention that addresses a variety of risk factors simultaneously can have cognitive benefits for people at risk for cognitive impairment and Alzheimer's disease (AD).

The 2-year trial, called the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), showed that an intervention including nutritional guidance, physical exercise, cognitive training, social activities, and management of cardiac risk factors resulted in better overall cognitive performance on a comprehensive neuropsychological test battery vs regular health advice. The advantage for this approach was seen on each of the individual cognitive domains tested as well, including memory, executive function, and psychomotor speed, the researchers report.

"In conclusion, I would say that the FINGER study is a kind of proof-of-concept study because it reports the first result from a large, long-term multidomain study showing that it is possible to reduce the risk of cognitive impairment in an at-risk population," lead author Miia Kivipelto, MD, PhD, professor at the Karolinska Institutet, Sweden, and the National Institute for Health and Welfare, Helsinki, Finland, told attendees here.

The multidomain intervention seemed to be feasible, she added, with a low drop-out rate of only 11% over 2 years. "Importantly, of course, we need to have longer-term follow-up time, she added, to really understand what the effect is on the incidence of dementia and Alzheimer's disease."

Dr. Kivipelto presented the results at the Alzheimer's Association International Conference (AAIC) 2014.

Dr. Miia Kivipelto

Multidomain Approach

It's known that several modifiable risk factors have been linked with cognitive impairment and AD in observational studies, she noted. "What is needed now is evidence from randomized, controlled trials, long-term studies, showing that this is really important, if it's possible to prevent Alzheimer's disease," she said. "Given that Alzheimer's disease is a multifactorial disorder, targeting several risk factors simultaneously may be needed to get the optimal preventive effect."

The main aim of FINGER, then, was to reduce cognitive impairment in an at-risk population using a 2-year, multidomain lifestyle intervention that included nutritional guidance, physical activity, cognitive training and social activities, and monitoring and management of all metabolic and vascular risk factors, including hypertension, dyslipidemia, obesity, and impaired glucose tolerance.

Participants included 1260 people from 6 cities in Finland, aged 60 to 77 years. They were randomly assigned to receive the intensive intervention or regular heath advice. Participants were recruited from earlier nonintervention population-based studies, Dr. Kivipelto noted, providing "a very unique baseline database that is normally not available in these kinds of trials."

The intervention was completed in February 2014, with a 7-year extension follow-up starting in 2015.

Features of the intensive intervention included the following:

  • Seven group sessions on nutrition and 3 individual sessions;

  • Exercise supervised by a physiotherapist with increasing intensity, from muscle training 1 to 2 times per week plus aerobic training 2 to 4 times per week, to muscle training twice per week plus aerobic training 5 to 6 times per week;

  • Computer-based cognitive training offered in both group and individual training settings; and

  • Monitoring of vascular risk factors, with a nurse visit every 3 months, and a physician consult at 3 additional visits.

Controls were given regular health advice over 13 visits during the study, she noted, amounting to a kind of "mini-intervention."

They aimed to include people at risk for cognitive decline and dementia, and so they used as an inclusion criterion a dementia risk score of 6 or more points on a scale developed and published by Dr. Kivipelto's group in 2006. This score indicated that these people had several risk factors for dementia.

The second criterion was cognitive performance at mean level or slightly lower than expected for age based on the Consortium to Establish a Registry for Alzheimer's Disease test battery. However, participants with any symptoms of cognitive impairment at baseline were excluded.

Data were presented here on the primary outcome, cognitive performance as measured on the modified Neuropsychological Test Battery (mNTB), which has been shown to be sensitive to mild changes of both Alzheimer's and vascular types.

"Our study was powered to detect a difference of about 45% to 50% in the change between these 2 groups, and we think that is quite a tough goal because even lower (levels of) change may be meaningful in everyday life," Dr. Kivipelto said.

Self-reported adherence to the program was quite high, the researchers found, with highest adherence seen in the dietary and vascular risk factor control, both over 90%, but slightly lower for the cognitive training, possibly because it was computer based and may have been more difficult for this older population, she said.

Importantly, more than 70% of participants were able to adhere to interventions for all 4 domains, she said, "indicating that the multidomain approach is feasible and people are able to follow it."

On the primary endpoint at 2 years, the researchers reported a highly statistically significant beneficial effect for the intervention on overall cognitive performance assessed using the mNTB (P < .001 for time-by-group interaction).

"We also saw the same result for each cognitive domain," Dr. Kivipelto said, including memory (P < .05), executive function (P < .0.5), and processing speed (P < .05).

In prespecified subgroup analyses, the benefit of intervention was more pronounced among the elderly (<70 years) and those with worse cognitive function at baseline, possibly because the change was easier to detect in these groups, she speculated.

"At the same time, I think this is very positive news; it seems to be possible even for elderly persons and those who have worse cognition to get the benefit of the intervention," she said.

The responses to the training did not differ between men and women.

Although there were more drop-outs among participants in the intervention group, no serious adverse events and no hospitalizations occurred during the study. Adverse events with the intervention were mainly slight musculoskeletal pain related to the exercise.

Future secondary analyses will include dementia at 7 years, depressive symptoms (Zung scale), vascular risk factors, morbidity and mortality, a disability questionnaire, quality of life, utilization of health resources, and blood biomarkers (inflammation, lipid and glucose metabolism, telomere length), as well as brain MRI in 200 participants and positron emission tomography in 60 participants.

Dr. Kivipelto told Medscape Medical News that they are particularly interested in quality of life. "That will also be important to learn how they feel," she said. Their spontaneous feedback to the program has been very positive, she added, particularly the social aspects of getting out and having interaction with others. "I suspect that the effect will be not only on cognition, but will be on the well-being in general."

They will also be looking at issues of cost-effectiveness, "but it's not expensive. The things that we're doing are already there; the infrastructure is there," she noted. "So I hope this will be a model that, with some modification, can be used in different societies."

Never Too Late

Dr. Ralph Nixon

Ralph Nixon, MD, chair of the Alzheimer's Association Medical and Scientific Advisory Council, professor of psychiatry and cell biology, former director of the NYU Comprehensive Center on Brain Aging, the Silverstein Alzheimer's Institute at New York University School of Medicine, and director of research at the Center for Dementia Research at the Nathan S Klein Institute for Psychiatric Research, moderated a press conference featuring these results here.

Asked for comment on these new findings, Dr. Nixon said the study "tells us that it's never too late to start to change lifestyle in a way that will improve diet and cardiovascular health and physical activity, to hedge against the risk of developing cognitive decline in older age.

"This is important because in the 60s and 70s you're at greatest risk for the disease, and there may be changes in the brain that are suggesting early Alzheimer's proclivity. It's been known for some time that adopting that lifestyle in midage has a benefit, but now we hear that even at age 60 or in your 70s, you can still make these changes and have some impact," Dr. Nixon said. This should be encouraging to Baby boomers, for example, who may think they have "missed the boat" on this kind of preventive approach.

He found the magnitude of the effect seen on cognition "quite impressive, especially in the context of a treatment that is safe, and is in theory, something that people should want to do anyway," he told Medscape Medical News. "To get benefits from it that go beyond just feeling better from doing these things, those are important issues, and why I think this is very encouraging."

The study received grant support from the Academy of Finland, Novo Nordisk Foundation, Alzheimer's Research and Prevention Foundation, Alzheimer Association, VR, La Carita säätiö, The Social Insurance Institution of Finland and Juho Vainio Foundation.

Alzheimer's Association International Conference (AAIC) 2014. Abstract O1-05-04. Presented July 13, 2014.

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