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Monday, January 23, 2012

Association of Lifetime Cognitive Engagement and Low Amyloid Deposition

The recent development of the radiopharmaceutical carbon 11–labeled Pittsburgh Compound B ([11C]PiB)  has made it possible to image fibrillar forms of the β-amyloid (Aβ) protein, which is the major constituent of the amyloid plaque in Alzheimer disease (AD). Studies applying this technique have demonstrated [11C]PiB accumulation throughout cortex in most patients with AD. More important, 20% to 30% of healthy, cognitively normal older individuals  also display significant PiB uptake, which is consistent with evidence that some older individuals who were cognitively intact during life show substantial numbers of Aβ plaques post mortem.  Greater understanding of the factors associated with Aβ variability in the healthy older population could have important consequences for disease prevention.

Recent evidence indicates that lifestyle practices, such as increased physical exercise, are associated with reduced Aβ deposition based on [11C]PiB positron emission tomography (PET) and cerebrospinal fluid Aβ42 measurements.  Participation in cognitively stimulating activities has also been linked to reduced risk of late-life cognitive decline and AD. An individual's tendency to engage in physically and cognitively stimulating activities is likely related to a broad set of lifestyle factors that are difficult to quantify but include occupational, social, community, and recreational practices. Researchers assessed engagement in cognitive and physical activities and hypothesized that greater levels of engagement may be associated with less Aβ later in life.

They investigated this hypothesis by performing [11C]PiB PET and neuropsychological testing in a sample of cognitively normal older participants. Aβ deposition, characterized as mean cortical [11C]PiB PET uptake, was examined in healthy older participants and comparison samples of young participants and patients with AD. A variety of neuropsychological and lifestyle measurements were also obtained and assessed in relation to Aβ deposition for healthy older participants only, including frequency of engagement in cognitively demanding activities, frequency of engagement in physical and leisure activities, and current episodic memory function.

Their data are consistent with the observation that participation in cognitively stimulating activities in early to middle life is associated with lower Aβ accumulation regardless of whether cognitive activity is evaluated as a continuous or categorical variable or whether Aβ is assessed as a global [11C]PiB index or by voxelwise analysis. More important, this association was not affected by the inclusion of possible confounding variables, such as current episodic memory ability, age, sex, and years of education.


Landau SM, Marks SM, Mormino EC, et al. Association of Lifetime Cognitive Engagement and Low {beta}-Amyloid Deposition. Arch Neurol:archneurol.2011.748. http://archneur.ama-assn.org/cgi/content/abstract/archneurol.2011.2748

Objective To assess the association between lifestyle practices (cognitive and physical activity) and {beta}-amyloid deposition, measured with positron emission tomography using carbon 11-labeled Pittsburgh Compound B ([11C]PiB), in healthy older individuals.

Design Cross-sectional clinical study.

Setting Berkeley, California.

Participants Volunteer sample of 65 healthy older individuals (mean age, 76.1 years), 10 patients with Alzheimer disease (AD) (mean age, 74.8 years), and 11 young controls (mean age, 24.5 years) were studied from October 31, 2005, to February 22, 2011.

Main Outcome Measures Cortical [11C]PiB average (frontal, parietal, lateral temporal, and cingulate regions) and retrospective, self-report scales assessing participation in cognitive activities (eg, reading, writing, and playing games) and physical exercise.

Results Greater participation in cognitively stimulating activities across the lifespan, but particularly in early and middle life, was associated with reduced [11C]PiB uptake (P < .001, accounting for age, sex, and years of education). Older participants in the highest cognitive activity tertile had [11C]PiB uptake comparable to young controls, whereas those in the lowest cognitive activity tertile had [11C]PiB uptake comparable to patients with AD. Although greater cognitive activity was associated with greater physical exercise, exercise was not associated with [11C]PiB uptake.

Conclusions Individuals with greater early- and middle- life cognitive activity had lower [11C]PiB uptake. The tendency to participate in cognitively stimulating activities is likely related to engagement in a variety of lifestyle practices that have been implicated in other studies showing reduced risk of AD-related pathology. We report a direct association between cognitive activity and [11C]PiB uptake, suggesting that lifestyle factors found in individuals with high cognitive engagement may prevent or slow deposition of {beta}-amyloid, perhaps influencing the onset and progression of AD.