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STIMULATING LEISURE-TIME ACTIVITIES COULD STAVE OFF MILD COGNITIVE IMPAIRMENT, NEW STUDY REPORTS

Our genes certainly contribute to the development of Alzheimer disease, but so do the choices we make. Numerous studies support the idea that exercise and a healthy lifestyle may help stave off the symptoms, at least for a while.

Education also seems to postpone the appearance of Alzheimer symptoms, according to a study last month in the Journal of Neurology, Neurosurgery and Psychiatry (2006; 77:308–316), which was discussed in the March 21 issue of Neurology Today (page 1).

In that article, Nikolaos Scarmeas, MD, of the Columbia University Medical Center in New York, and his colleagues, suggest that education provides this protection by building “cognitive reserve” – a rich network of synaptic connections that enables the brain to function fairly well despite the burden of Alzheimer pathology.

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Dr. David A. Bennett: “It seems prudent to encourage people of all ages, not just the elderly, to engage in an active lifestyle that includes frequent participation in a wide range of cognitively, physically, and socially challenging activities.”

STUDY PUBLISHED IN NEUROLOGY

Now a study in the March 28 issue of Neurology (2006; 66:821–828) finds that cognitively stimulating leisure activities such as reading, socializing, playing games, and doing puzzles, are associated with a lower risk of developing mild cognitive impairment (MCI), presumably because they also increase cognitive reserve.

“I think it's important to get people engaged in these activities because there seems to be strong evidence that they might have some benefit, and there's not much downside to it,” said lead author Joe Verghese, MD, of the Albert Einstein College of Medicine in New York. “People can pick up activities they enjoy, activities that enrich their lives anyway. This might relieve loneliness and depression, and it provides a fun way of preventing dementia.”

In the same issue of Neurology, an editorial by Tatjana Rundek, MD, of Columbia University in New York, and David A. Bennett, MD, of Rush University Medical Center in Chicago, concludes that physicians should encourage their patients to engage in mentally and physically stimulating activities even though the mechanism by which such activities help the brain resist dementia remains a mystery.

“It seems prudent to encourage people of all ages, not just the elderly, to engage in an active lifestyle that includes frequent participation in a wide range of cognitively, physically, and socially challenging activities,” the authors conclude. They warn, however, that watching TV is not one of those activities. Watching television seems to increase the risk of developing MCI by about 20 percent, they report.

The claim that stimulating leisure activities can keep Alzheimer disease at bay is difficult to demonstrate because the opposite could be true – people who start to develop MCI or Alzheimer disease may drift away from cognitively demanding activities. Thus, the activities themselves would serve as an indicator, not the cause, of cognitive health.

PERSPECTIVE FROM LONGITUDINAL STUDY

Only a large longitudinal study could settle this question decisively, but Kristine Yaffe, MD, of the University of California, San Francisco, still believes that the evidence so far supports the idea that stimulating activities – both physical and cognitive – confer resistance to the symptoms of Alzheimer disease.

“Until about 10 years ago, people thought the brain was static – you couldn't change it much,” Dr. Yaffe said. “They believed, for example, that the hippocampus could not form new neurons. Now we know that there is neurogenesis later in life, and that a person can, by being active, foster synaptic connections.”

Her belief was bolstered by a study published in JAMA (2002;288:2271–2281). The Active Study Group divided 2,832 people aged 65 to 94 into four groups. Three groups received training in memory, reasoning, or speed processing. The fourth group had no training. Those who received training improved cognitive function.

“After two years improvements were domain specific and seemed to have lasted,” said Dr. Yaffe. “These studies suggest that if you stimulate your brain, you somehow foster neural connections and create a buffer against damage.”

ROLE OF PHYSICAL ACTIVITY

Dr. Yaffe also believes that physical activity can help protect the brain, probably by promoting cardiovascular health and reducing obesity. “By doing physical activities, you decrease the chance of cognitive problems that result, presumably, from vascular-mediated insults,” she said. “But there's another hypothesis – that physical activities have a direct effect on neurons. Rodents who exercise have healthier hippocampi than those who don't.”

Dr. Verghese concedes that the results of his study could be skewed if cognitively healthy older people are simply more inclined to participate in stimulating activities. “It might be that people at high risk of developing dementia are already dropping (stimulating) activities because of this subtle and gradual loss that's taking place,” he said.

Figure

Dr. Kristine Yaffe: “Until about 10 years ago, people thought the brain was static – you couldnt change it much. They believed, for example, that the hippocampus could not form new neurons. Now we know that there is neurogenesis later in life, and that a person can, by being active, foster synaptic connections.”

STUDY PROTOCOLS

To guard against that possibility, he excluded 51 participants who showed signs of dementia or MCI. The remaining 437 subjects were deemed free of dementia or MCI when they joined the study. The subjects were selected from the Bronx Aging Study, which recruited 488 people older than 75 who lived in the community, and were free of dementia initially.

Subjects were examined every 12 to 18 months, and took tests for memory, IQ, and depression. Their physical and cognitive activities also were measured and assigned a value. During a median follow-up of 5.6 years, 58 of the 437 participants developed amnestic mild cognitive impairment (aMCI). While there was no correlation between conversion to aMCI and scores on the Physical Activity Scale, there was a correlation with the Cognitive Activity Scale.

“A 1-point increase in the Cognitive Activity Scale score was associated with a 5 percent reduced risk of aMCI,” the paper states. “The observed association remained robust even after adjusting for potential confounders such as age, sex, education, chronic illnesses, depression, and baseline cognitive status. Our results suggest a dose-response effect; subjects with scores in the highest third on the Cognitive Activity Scale had a 54 percent reduced risk of development of aMCI compared with those with scores in the lowest third.”

The authors of the study acknowledge that people in the earliest stages of dementia may cut back on their leisure activities. “A reduction of leisure activities even years before a diagnosis of aMCI may reflect the undetected pathologic presence of dementia given that the pathologic process begins years, perhaps decades, before the onset of clinically evident symptoms,” they write.

To guard against this possibility, they removed eight subjects who converted to dementia within two years of developing aMCI, but the correlation between mentally stimulating leisure activities and cognitive health remained strong.

“This is the second paper in a series,” Dr. Verghese said. “In our previous paper (N Engl J Med 2003;348:2508–2516), we excluded people who developed dementia in the first six or seven years of the study. In this paper we looked at what would happen if we excluded those who convert from MCI to dementia within a two-year period. In both instances, the results seem to hold true.”

THE THEORY OF ‘COGNITIVE RESERVE’

A growing body of circumstantial evidence supports the theory that education and other stimulating cognitive activities somehow confer protection against the symptoms of mild cognitive impairment and Alzheimer disease. The theory of cognitive reserve makes intuitive sense, and is supported by animal studies. (Rats raised in an “enriched” environment containing toys, wheels, and other objects develop brains with much denser synaptic connections than the brains of rats kept in a barren environment.)

For now, however, cognitive reserve remains a theory that could be undercut by further research. Still, with dementia looming as a public health crisis, anything that can ameliorate risk is welcome, especially something as simple as mental activity, which can be inherently enjoyable.

“Cognitive function is complex and not well understood,” said Dr. Rundek, one of the authors of the editorial in Neurology. “I think we're beginning to understand it better. Meanwhile, we can engage in physical and mental activities. At least they're fun.”

News from the 2006 AAN Annual Meeting

Neurology Today will offer extensive coverage of the AAN Annual Meeting plenary, platform, and poster sessions. Expect coverage of major advances – with input from experts in the field – on the AAN Science Committee “picks” for notable advances this year:

  • Safety data for natalizumab for multiple sclerosis
  • Effect of diet and exercise on diabetic neuropathy
  • Gene therapy for Parkinson disease
  • Monoclonal antibodies to treat prion protein
  • Pathological gambling and Parkinson disease
  • Alginate-based capillary hydrogels promote axon regeneration in spinal cord injury
  • PET imaging of apoptosis in a stroke model
  • New model for myasthenia gravis using muscle-specific kinase
  • New methods for generating neurogenic stem cells
  • New treatment for Wilson disease

ARTICLE IN BRIEF

  • ✓ Cognitively stimulating leisure activities such as reading, socializing, playing games, and doing puzzles, are associated with a lower risk of developing mild cognitive impairment.

REFERENCE

• Verghese J, LeValley A, Lipton RB, et al. Leisure activities and the risk of amnestic mild cognitive impairment in the elderly. Neurology 2006;66:821–827.
    • Rundek T, Bennett DA. Cognitive leisure activities, but not watch TV, for future brain benefits. Neurology 2006:66:794–795.