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At last, a hint at prevention

Lifestyle modification improves cognition in high-risk group

BARCELONA – For the first time, a lifestyle intervention study has shown that targeting nutrition, exercise, and metabolic and cardiovascular risk factors can improve cognition and memory in older adults at high risk of developing Alzheimer’s disease.

In fact, the program effected the greatest change in those who carried the highest risk: subjects homozygous for the apolipoprotein E–epsilon 4 allele.

“The findings were especially clear in changes on the comprehensive neuropsychological test battery,” which was the study’s primary endpoint, Dr. Miia Kivipelto of the Karolinska Institute, Stockholm, said at the Clinical Trials on Alzheimer’s Disease conference, held in Barcelona last November. “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 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.

The new data that Dr. Kivipelto described showed that people with at least one apolipoprotein E (APOE)–epsilon 4 allele reaped 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 neuropsychological test battery that was significantly higher than in noncarriers (0.17 vs. 0.10, respectively; P = .045), whereas the difference between carriers and noncarriers in the control group was not statistically significant (0.22 vs. 0.19; P = .28). Carriers in the intervention group also tended to benefit more than did noncarriers in the individual domains.

Dr. Kivipelto explored how the program might be working on a molecular level. In an analysis of 756 subjects, including 244 APOE–epsilon 4 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%.”

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 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.

01/18/16 | By: MICHELE G. SULLIVAN

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