What is the role of baseline cognitive ability in the pathophysiology of Alzheimer disease (AD) in Down syndrome (DS)?

Updated: Nov 13, 2019
  • Author: Norberto Alvarez, MD; Chief Editor: Jasvinder Chawla, MD, MBA  more...
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Epidemiologic and brain imaging studies of patients with AD without DS have led to observations that patients with limited education or diminished baseline cognitive abilities are at increased risk for AD. These data have led to the cognitive reserve hypothesis, which suggests that patients with better baseline cognitive abilities can tolerate more AD pathology and neuronal loss than patients with worse baseline cognitive abilities. Because most patients with DS have mental retardation and limited baseline cognitive ability, the cognitive reserve hypothesis would suggest that patients with DS are at increased risk for developing AD.

Originally, this was mostly a quantitative concept. In a simple way, having more neurons with more connections, for example, will allow the individual to tolerate more brain pathology before showing symptoms. A more modern explanation of the concept of cognitive reserve suggests that the presence of higher cognitive abilities allows the brain to have a better compensatory system. In that sense, the cognitive reserve is more related to brain function than size or number of neurons. [49]

Studies in persons with AD but not DS suggest that the risk of AD is 2.2 times higher in individuals with less than 8 years of education as well as for those working occupations that require lower skill level. Interestingly enough, the same studies also suggest that in those with supposedly higher cognitive reserve when the disease starts, the decline is faster. [49]

Following this line of reasoning, we could assume that people with DS who function at a lower cognitive level should have a higher risk for AD. However, at the present time there is no evidence supporting this assumption, and in fact there is some evidence against it. [50]

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