Alzheimer's Protein Lower in Brains More Stimulated

Abstract

C stimulating activity, particularly in early and midlife, is associated with lower brain deposition of the major protein constituent of amyloid plaques in Alzheimer’s disease later in life, a cross-sectional study indicates. The association between cognitive activity and beta-amyloid (A-beta) protein suggests that the lifestyles of people with greater cognitive engagement may play a role in the onset and progression of Alzheimer’s disease (AD), Susan M. Landau, Ph.D., of the University of California, Berkeley, and her colleagues said online in the Archives of Neurology. PET imaging of the binding of the radiopharmaceutical carbon 11–labeled Pittsburgh Compound B ([11C]PiB) to A-beta protein showed comparable A-beta deposition in older adults in the highest cognitive activity tertile and young controls. On the other hand, older adults in the lowest cognitive activity tertile had mean cortical [11C]PiB uptake comparable with the Alzheimer’s patients (Arch. Neurol. doi:10.1001/archneurol.2011.2748). The researchers defined cognitively demanding activities in terms of activities that depended minimally on socioeconomic status, such as reading books or newspapers, writing letters or e-mails, and playing games. The greatest association was seen between higher cognitive activity from ages 6 to 40 years and lower [11C]PiB uptake, but the association between cognitive activity and lower [11C]PiB uptake existed across the life span after age, sex, and years of education were taken into account, the investigators noted. The findings “suggest a novel mechanism in which increased cognitive activity may play a direct role in reducing A-beta before disease onset,” they wrote. “Our cognitive activity measurement is likely just one of a variety of interrelated lifestyle factors that are difficult to quantify. Cognitive activity and (marginally) years of education were associated with [11C]PiB uptake (although cognitive activity and years of education were not related to one another), suggesting that these measurements may reflect a broader underlying tendency to engage in intellectual, occupational, social, and recreational activities,” Dr. Landau and her coauthors wrote. The study included 65 healthy participants with normal cognition and a mean age of 76 years and 10 with Alzheimer’s disease who had a mean age of 75 years. The 11 control participants had a mean age of 24.5 years. The healthy older adults underwent [11C]PiB PET imaging and completed an extensive neuropsychological battery between Oct. 31, 2005, and Feb. 22, 2011. They self-reported their levels of cognitively demanding activities and physical activity. Although physical activity was associated with cognitive activity in this study, it was not associated with [11C] PiB uptake. The addition of physical activity to the model also did not reduce the association between cognitive activity and PiB. This indicates that cognitive activity was the primary variable driving the association because physical activity was measured as a current function and cognitive activity was assessed as a lifelong engagement. It is plausible, they said, that people who participate in a variety of cognitively stimulating activities throughout life may develop more efficient neural processing that results in less A-beta deposition – an idea supported by findings in transgenic A-beta–expressing mice. “It is unlikely that our results reflect a single unitary cause of AD, which is a complex disease with many potential pathogenetic processes. ... However, the present findings extend previous findings that link cognitive stimulation and AD risk (an indirect downstream effect of A-beta) by providing evidence that is consistent with a model in which cognitive stimulation is linked directly to the AD-related pathology itself,” they concluded. The authors reported no relevant financial conflict of interest. CfA