Neuroprotective effect of lifelong mental activity

A new study, published today in the open access journal PLoS One, provides evidence that remaining mentally active throughout life reduces the rate of age-related neurodegeneration and may therefore stave off Alzheimer’s Disease and other forms of dementia.

Valenzuela et al used the Lifetime of Experiences Questionnaire (LEQ) to estimate the extent to which 37 healthy older individuals had engaged in complex mental activity throughout their lives. They also performed functional magnetic resonance imaging (fMRI) to measure hippocampal volume in the participants, at the beginning of the study when they completed the questionnaire, and again three years later.

A strong correlation was found between the level of mental activity, as evaluated with the questionnaire, and the rate of atrophy in the hippocampus. Those participants with a high LEQ score experienced an average loss of 3.6% of hippocampal volume in the 3 year period over which the study was carried out, whereas those with low scores exhibited an average of 8.3% hippocampal volume loss over the same period (see figure below).


Moreover, there was a negative correlation between LEQ scores and shrinkage of the hippocampus – in other words, the higher an individual’s score on the questionnaire, the less their hippocampus had atrophied over the duration of the study.

These findings are not at all surprising, but they are significant, because the hippocampus and surrounding medial temporal lobe structures are the first to degenerate in Alzheimer’s Disease (AD); the rate of hippocampal atrophy begins to increase before the onset of clinical symptoms, and subsequently leads to the memory impairments that are characteristic of the condition.

Thus, engaging in complex mental activity throughout life evidently has a neuroprotective effect which specifically reduces the rate of hippocmapal atrophy. However, the cellular and molecular mechanisms by which it does so is as yet unclear. It is possible that mental activity stimulates neurogenesis (the generation of new nerve cells) in the hippocampus; it may also promote the survival of newly generated cells.

Regardless, this study adds more weight to the idea that the risk of Alzheimer’s can be significantly reduced by making lifestyle changes. For example, recent studies suggest that adhering to a Mediterranean diet may reduce the risk of AD, and that socializing may preserve memory.


Valenzuela, M.J. et al. (2008). Lifespan Mental Activity Predicts Diminished Rate of Hippocampal Atrophy. PLoS ONE 3 (7), e2598. DOI: 10.1371/journal.pone.0002598

2 thoughts on “Neuroprotective effect of lifelong mental activity

  1. How did the authors distinguish cause and effect? If neurodegeneration actually occurs over a very long period of time, and starts with subtle phenotypes we aren’t measuring, perhaps people that have their mental capacities slip a bit choose less mental activity.

  2. I think the second paragraph of the discussion answers your question:
    The possibility that preclinical AD change was differentially affecting our high and low LEQ groups at the start of the study was addressed in two ways. Firstly, baseline volume was controlled for in all multivariate change analyses. Second, a re-analysis restricted to LEQ scores in the Young Adulthood and Mid-Life epochs found that correlations with hippocampal volume loss were fully conserved.

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