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.

Reference:
Landau SM, Marks SM, Mormino EC, Rabinovici GD, Oh H, O'Neil JP, Wilson RS, Jagust WJ. Association of Lifetime Cognitive Engagement and Low β-Amyloid Deposition. Arch Neurol. 2012 Jan 23. Abstract