2010 Alzheimer’s Disease Progress Report: A Deeper Understanding

The advent of PiB imaging brought with it the surprising finding that many cognitive normal older people carry substantial loads of brain amyloid. Is it possible that some people are relatively resistant to the accumulation of brain amyloid and, despite accumulating it, never develop problems with cognitive function?

The answer to that question seems to be a qualified “no.” Researchers at Washington University, St. Louis, used PiB imaging to look at 159 cognitively normal people with a mean age of 72 and then tested their cognition for up to 5 years (Morris et al., 2010). Those with higher amounts of beta-amyloid on their initial PiB scans were significantly more likely to develop Alzheimer’s symptoms than those who showed little or none.

An NIA-led study found similar results, using PiB imaging to examine 57 people (average age 79) who had undergone annual cognitive testing for the previous 8 to 12 years (Resnick et al., 2010). All had been cognitively normal when they first entered the study but had shown varying degrees of cognitive decline during the subsequent years. PiB scanning showed that the participants with higher brain beta-amyloid levels had also experienced greater losses in cognition and memory during the years prior to their scans.

Finally, a Washington University study of 68 cognitively normal older people and 35 people with Alzheimer’s used PiB imaging as well as functional MRI (fMRI), which looks at brain function while doing tasks (Sheline, Morris et al., 2010). Even the cognitively normal people with elevated beta-amyloid levels showed reduced connectivity among brain cells in the default-mode network (brain areas used when the mind “wanders,” such as when daydreaming or retrieving memories), compared to individuals with low beta-amyloid. In fact, the disruptions of default-mode network connectivity seen in the cognitively normal participants were similar to those of the people with Alzheimer’s disease. Together, these studies suggest that beta-amyloid accumulation signals the presence of preclinical Alzheimer’s, even in people free of symptoms.

At the same time, however, evidence shows that some people seem better able to bear the burden of beta-amyloid accumulation than others, despite the likelihood of advancing disease. For some time, scientists have thought this might be due to “cognitive reserve,” or an ability of the brain to function effectively despite loss of brain cells or other damage. A number of studies have suggested that higher levels of education and intelligence (as measured on standardized tests) contribute to cognitive reserve and confer some protection against Alzheimer’s disease.

Those factors also appear to moderate the effect of beta-amyloid on cognitive function. Researchers at Harvard University, Cambridge, MA, found higher beta-amyloid levels were associated with worse performance on tests of memory, language, vision, and navigation in a study of 66 cognitively normal older people and 17 with Alzheimer’s (Rentz et al., 2010). However, elevated beta-amyloid levels had a weaker effect on cognitive function in people who were more highly educated and scored higher on an intelligence test.

• Lachman ME et al. (2010) Frequent cognitive activity compensates for education differences in episodic memory. Brandeis University. Supported by NIA.