Much like physical exercise and a healthy diet, might doctors start recommending brainteasers as part of our lifelong daily routine? A new study suggests that cognitive stimulation in early and midlife protects from amyloid plaque deposition—known to be associated with Alzheimer's disease. Susan Landau, University of California, Berkeley, and colleagues published their results online January 23 in the Archives of Neurology. "Cognitive engagement may allow people to delay the onset of Alzheimer's disease or reduce their risk overall," said Landau.

Landau and colleagues recruited 65 healthy older adults (average age 76.1 years), all of whom were cognitively normal, to take part in the study. Each volunteer filled out a survey to assess how often in the past (at ages six, 12, 18, and 40), and in their current routine, they took part in common brain-stretching activities, such as reading books, writing letters/e-mails, or playing games (see Wilson et al., 2003). A five-point scoring system gave top marks for completing the activity daily, a 4 for several times a week, 3 for several times a month, 2 for several times a year, and a 1 if they did the activity once a year or fewer. Compiling survey answers, the researchers assigned each person scores for past, current, and lifetime cognitive activity. The nice thing about this survey, said Landau, is that it assessed common activities that, unlike education, do not depend on socioeconomic status. The volunteers then underwent a positron emission tomography scan with the C11-labeled Pittsburgh Compound B (PIB-PET) to image the amyloid deposits in their brains. Landau recruited two control groups to straddle the data on either side—10 older adults with AD (average age 74.8 years) and 11 young controls (mean age 24.5 years). These groups provided PIB comparisons, but were not assessed for cognitive engagement.

It turns out that past cognitive activity, not current or total, correlated best with PIB binding. The higher the activity score, the lower the amyloid a person had in later life, and vice versa. Participants with the lowest cognitive activity scores had comparable levels of PIB binding to the control group with Alzheimer's, while volunteers with the highest scores had levels more like the young controls. Past score correlated with plaques better than education or ApoE4 allele status, two factors that modulate the risk for dementia or plaque deposition (see ARF related news story on Roe et al., 2008 and ARF related news story).

Previous research suggested that greater participation in cognitive activities protects against dementia (see ARF related news story on Wilson et al., 2002). The predominant hypothesis is that greater cognitive reserve with more education allows the brain to tolerate more amyloid, said Landau. "Our study puts a different angle on the idea of cognitive reserve," she said. "Instead of modifying the brain's response to amyloid, cognitive activity may prevent amyloid accumulation itself." Diminished amyloid accumulation seems to be a recurring theme in the literature these days, said William Jagust, a coauthor on the paper, pointing out that increased exercise (see Liang et al., 2010) and decreased vascular risk (see Reed et al., 2011) have also recently been associated with less amyloid accumulation in people's brains. "A lot of things that we thought were mediated through resistance to the effect of amyloid turn out to be more related to amyloid itself," he said.

An intriguing idea, said Yaakov Stern, Columbia University, New York. But even if these factors do decrease amyloid, the theory of cognitive reserve could still hold, he suggested. "It doesn't negate the idea that, once they have the pathology, some people can cope with it better than others," he said. Additionally, this is just one paper with a small, selected population, so longitudinal and prospective studies are needed to confirm the results, he added.

What explains the correlation between cognitive engagement and plaque deposition? Landau and colleagues point out that increased neuronal activity has been associated with more plaque deposition (see ARF related news story on Bero et al., 2011). They suggest that brain-challenging activities make synapses more efficient, so they do not have to fire as much (see Jagust and Mormino, 2011). “It could be that people who engage in the most frequent reading and writing activities don't have to recruit as many neural resources," Landau explained, "so they have less synaptic activity, which would then result in less amyloid deposition.” Differential efficiency of cognitive networks is a valid idea, said Stern, and relates to the idea of cognitive reserve as well (see Tucker and Stern, 2011). An alternative explanation for the correlation might be found in research from John Cirrito’s lab at Washington University, St. Louis, Missouri. Cirrito and colleagues found that, while synaptic activity releases Aβ, very high activity, as might occur in people who are cognitively engaged, suppresses it (see ARF related news story). Landau's group plans to follow these healthy people to find out if those with more amyloid and less past cognitive activity show an earlier decline in cognitive function.—Gwyneth Dickey Zakaib


  1. Landau et al. present very intriguing work. Their cross-sectional results suggest that cognitive activity before the age of 40 years may influence fibrillar amyloid plaque deposition. I was frankly surprised to see how high the Spearman correlation was (r = -.37) between lifetime cognitive activity and amyloid uptake, and would be interested to know the magnitude of this correlation when confined to early and midlife cognitive activity. The finding that both past cognitive activity and educational level (p = .052) were associated with PIB uptake is logically congruent and strengthens confidence in these results.

    I look forward to seeing the results of longitudinal studies along these lines. I imagine that Landau et al. will follow these participants forward in time to see whether those with higher PIB uptake are, in fact, faster to develop AD (which is likely based on other research), and to determine whether, in line with the cognitive and brain reserve hypotheses (e.g., Stern, 2006; Mortimer, 1997), greater early-life cognitive activity is also associated with a slower time to development of AD after controlling for amount of amyloid uptake level. Our Adult Child Study, led by John Morris, may also help to inform these questions. We are assessing AD biomarkers along with cognitive and physical activity in middle-aged adults, and are following these adults forward in time to examine predictors of incident dementia. If the results of Landau et al. can be confirmed in longitudinal studies, this would strengthen the increasingly hard-to-ignore argument that lifestyle factors, and individual differences, are important influences in the development of symptomatic AD.


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    View all comments by Cathy Roe

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News Citations

  1. Imaging Studies Support Cognitive Reserve Theory
  2. More ApoE4 Means More Amyloid in Brains of Middle-Aged
  3. Add Mental Exercise to Potential AD Protection
  4. Do Overactive Brain Networks Broadcast Alzheimer’s Pathology?
  5. Brain Activity and Aβ—The Interstitial Plot Thickens

Paper Citations

  1. . Assessment of lifetime participation in cognitively stimulating activities. J Clin Exp Neuropsychol. 2003 Aug;25(5):634-42. PubMed.
  2. . Alzheimer disease and cognitive reserve: variation of education effect with carbon 11-labeled Pittsburgh Compound B uptake. Arch Neurol. 2008 Nov;65(11):1467-71. PubMed.
  3. . Participation in cognitively stimulating activities and risk of incident Alzheimer disease. JAMA. 2002 Feb 13;287(6):742-8. PubMed.
  4. . Exercise and Alzheimer's disease biomarkers in cognitively normal older adults. Ann Neurol. 2010 Sep;68(3):311-8. PubMed.
  5. . Coronary risk correlates with cerebral amyloid deposition. Neurobiol Aging. 2012 Sep;33(9):1979-87. PubMed.
  6. . Neuronal activity regulates the regional vulnerability to amyloid-β deposition. Nat Neurosci. 2011 Jun;14(6):750-6. Epub 2011 May 1 PubMed.
  7. . Lifespan brain activity, β-amyloid, and Alzheimer's disease. Trends Cogn Sci. 2011 Nov;15(11):520-6. PubMed.
  8. . Cognitive reserve in aging. Curr Alzheimer Res. 2011 Jun;8(4):354-60. PubMed.

Further Reading

Primary Papers

  1. . Association of Lifetime Cognitive Engagement and Low β-Amyloid Deposition. Arch Neurol. 2012 Jan 23; PubMed.