Cognitive reserve in ageing and Alzheimer's disease

Abstract

The concept of cognitive reserve provides an explanation for differences between individuals in susceptibility to age-related brain changes or pathology related to Alzheimer's disease, whereby some people can tolerate more of these changes than others and maintain function. Epidemiological studies suggest that lifelong experiences, including educational and occupational attainment, and leisure activities in later life, can increase this reserve. For example, the risk of developing Alzheimer's disease is reduced in individuals with higher educational or occupational attainment. Reserve can conveniently be divided into two types: brain reserve, which refers to differences in the brain structure that may increase tolerance to pathology, and cognitive reserve, which refers to differences between individuals in how tasks are performed that might enable some people to be more resilient to brain changes than others. Greater understanding of the concept of cognitive reserve could lead to interventions to slow cognitive ageing or reduce the risk of dementia.

Figure 1

This hypothetical figure illustrates how memory function changes over time in individuals with high and low reserve. In the absence of AD pathology, it is likely that individuals with higher reserve will perform better on memory tests, although this has not been universally observed. AD pathology begins to advance prior to any observation of change in memory performance. However, at some point the pathology is sufficient to begin to cause noticeable declines in memory test scores. This point where performance begins to decline is later in individuals with higher reserve because they can tolerate more pathology before it affects performance. The figure hypothesizes a point where pathology is so severe that memory performance is nil. This point is the same for both individuals with high and low reserve. Given this common endpoint, the figure hypothesizes that once memory decline does begin, the rate of decline should be more rapid in individuals with higher reserve than in those with lower reserve. This theoretical model can explain observations of more rapid clinical decline in AD patients with higher reserve. According to this model, this differential rate of decline can be observed both in individuals who already have diagnosed AD as well as in those for whom memory has begun to decline.

Figure 2

Clinical implications of cognitive reserve. This figure describes the theoretical effects of different levels of AD pathology, on the x-axis, and clinical severity, on the y-axis. When AD pathology is mild, individuals with lower levels of reserve might already appear to be clinically demented, while those with higher reserve might appear clinically normal. At higher levels of pathology, both groups might appear to be clinically demented. Still, those with higher reserve will appear to be less clinically severe than those with lower reserve.

Figure 3

This is a figure from our first study that tested the idea that at any given level of clinical severity, AD patients with higher CR should have more advanced AD pathology. In this study, we used a measure of cerebral blood flow as a proxy for AD pathology. The figure summarizes three groups of 20 AD patients, all carefully matched for clinical severity as measured by mental status and activity of daily living assessments. Note that the group with the highest educational level has the darkest blue in the parietotemporal area, indicating the lowest level of blood flow and in turn the most advanced AD pathology. This figure suggests that even though the three groups are matched for clinical severity, those with higher levels of education have greater levels of underlying pathology.