Sep 03 2010

Dementia and Mental Activity

With our aging population diseases and disorders that increase dramatically with age are of special concern. Among such disorders is dementia, the most common cause of which is Alzheimer’s disease. There has been a suggestion in the research that increased mental activity decreases the risk of developing dementia, or at least delays its onset. It certainly would be nice if playing sudoku could stave off dementia – that is a fairly risk-free intervention and it may actually reduce the burden of a terrible and costly disease on society. But the research, while highly suggestive of a protective effect, is not yet definitive.

A new study published in the September issue of the online version of Neurology, adds to the research and follows subjects for longer than previous studies (11 years on average). They found that mental activity does delay the onset of dementia, but when they continued to follow subjects they also found that mental activity increases the rate of progression of dementia once it starts:

On clinical evaluation, 614 people had no cognitive impairment, 395 had mild cognitive impairment, and 148 had AD. During follow-up, the annual rate of global cognitive decline in persons without cognitive impairment was reduced by 52% (estimate = 0.029, SE = 0.010, p = 0.003) for each additional point on the cognitive activity scale. In the mild cognitive impairment group, cognitive decline rate was unrelated to cognitive activity (estimate = -0.019, SE = 0.018, p = 0.300). In AD, the mean rate of decline per year increased by 42% (estimate = 0.075, SE = 0.021, p < 0.001) for each point on the cognitive activity scale.

This is a very interesting result. If true, it means that mental activity would tend to compress the duration of dementia – delaying onset but then hastening progression, so individuals would spend less time in a demented state.

The study is a longitudinal cohort study – subjects are recruited then followed with clinical evaluations and self-reporting of their mental activity. The methods and size of the study are reasonable, but it is an observational study and therefore subject to confounding factors. A follow up study in which subjects are randomized to various treatment groups is needed. While subjects would not be blinded to the intervention, they would not necessarily know what intervention was being studied, and therefore a control group where subjects are instructed to alter some other behavior, but not one that would increase their mental activity, could be used. It would also be interesting to see, once subjects develop dementia, if decreasing their mental activity would slow progression, or if the effect of increased mental activity has already occurred.

Another interesting question, assuming the effect described in this study is genuine, is what is the mechanism – how does mental activity delay but then progress dementia? Perhaps mental activity recruits neural stem cells to make more connections, and this provides more of a buffer so onset of dementia is delayed. But then once dementia begins it progresses more quickly because there are fewer stem cells remaining to replace lost neurons. The pattern certainly fits the broader concept that some resource is being mobilized by mental activity, delaying onset of dementia, but then there are fewer of those resources (whatever they are) remaining to fight the dementia once it starts.

If researchers can identify what those resources are (neural stem cells seem like a good candidate, but there are other possibilities) then that might also provide a clue leading to a biological treatment for dementia.

Regardless of mechanism, this study supports prior research showing a delaying effect for dementia from being mentally active. It also adds the longer term follow up showing another aspect to this effect. And, as always, I like to point out the importance of interpreting a research program, not just individual studies in isolation.

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