In a study of more than 700 elderly, community-dwelling individuals, a cognitively inactive person was 2.6 times more likely to develop Alzheimer's disease (AD) than a cognitively active person. Frequent cognitive activity during old age — such as reading a newspaper, going to see a play, or playing chess or checkers — was also linked with a reduced incidence of mild cognitive impairment. Brain autopsies in 102 study subjects who died found no link between the level of cognitive activity and neuropathologic lesions typical of dementia.

These findings, by lead author R. S. Wilson, PhD, and colleagues at Rush University Medical Center, in Chicago, Illinois, were published online June 27 in Neurology.

D. A. Bennett, MD, commented to Medscape that this means that the level of cognitive activity in these elderly subjects was not a consequence of the neuropathological changes of Alzheimer's disease. On the other hand, cognitive activity might reduce the amount of brain changes of Alzheimer's disease. He stressed: "The most important thing, we think, is that keeping yourself mentally active throughout your life is protective for developing mild or severe memory loss."

The group writes that several large, prospective studies showed that older people who keep mentally active seem to stave off memory loss and Alzheimer's disease. But from these studies it was not clear which came first: a decline in cognitive activity or Alzheimer's disease. It was also unclear whether declining mental agility in old age is related to a low level of cognitive activity and/or socioeconomic disadvantage in early life.

To examine these issues, the group analyzed data from the Rush Memory and Aging Project, an ongoing study in which elderly participants from the Chicago area agreed to undergo an annual clinical evaluation and donate their brain to research when they died.

More Than 700 Seniors Followed to 5 Years

At the time of the analysis, 931 study participants had baseline evaluations that showed no dementia then. A total of 775 of these individuals had complete follow-up data for up to 5 years. In this subgroup, 75% of the subjects were women and 91% were white. They had a mean age of 80.4 years and a mean baseline Mini Mental State Examination score of 28.0 and had received a mean of 14.5 years of education.

At baseline, the study subjects answered a questionnaire that probed how often they performed cognitively stimulating activities when they were younger (30 questions) and currently (9 questions); they also replied to questions about their current social interaction and physical activity and past socioeconomic status. At each annual examination, the participants answered the 9 questions about current cognitive activity and underwent 20 cognitive tests (administered in about 1 hour).

A total of 90 participants developed Alzheimer's disease during the study follow-up.

In the 102 participants who died, brain autopsies were performed to quantify (globally and in specific regions of the brain) the lesions most commonly associated with dementia: amyloid plaques, neurofibrillary tangles, Lewy bodies, and cerebral infarction.

Less Brain Stimulation, Greater Alzheimer's Disease Risk

Compared with their cognitively inactive peers, the elderly subjects who frequently participated in mentally stimulating activities were less likely to develop Alzheimer's disease (relative risk, 0.58; 95% CI, 0.44 – 0.77), independent of age, sex, and education. This relationship remained the same when also adjusted for past cognitive activity, lifetime socioeconomic status, and current social and physical activity.

Similarly, more frequent cognitive activity was associated with a reduced incidence of mild cognitive impairment.

Brain Pathology Not Linked to Level of Brain Activity

In the brain autopsy studies, the composite measures of amyloid, tangles, Lewy bodies, and infarction were not related to the level of cognitive activity prior to the study start, at baseline, or during the study.

"The most direct evidence that infrequent cognitive activity is a consequence of AD would be an association between cognitive activity and the pathology underlying the disease," the group writes. They did not find this correlation.

Important Societal Implications

"The implications are much more from a public health perspective than a clinical perspective," said Dr. Bennett. "As a society, how do we encourage all people, not just seniors, to engage in cognitive activities?" he asked.

He noted that clearly, cognitive activity is just 1 aspect of staving off memory loss. Physical activity and social activity play a role. The group published a study last year showing that cognitive function was higher in individuals with larger social networks (Bennett DA et al. Lancet Neurol. 2006;5:406-412).

In some communities, there are not many opportunities for seniors to interact socially, Dr. Bennett observed, adding that social interaction is very demanding on the brain, since it requires following a conversation, watching for verbal and nonverbal clues, and responding "in the moment."

He concluded by extending thanks to the currently more than 1200 individuals who agreed to participate in this study.