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Figure 29.1. Scatter Plots with Linear Regression for Numerical Synaptic Density versus Subject's Age at the Time of Death for Both Lamina 3 and 5 of the Frontal Cortex (Brodmann Area 9). A minimum of five subjects were available for each decade of life and all subjects were considered cognitively normal at the time of death. There were no significant correlations (p > 0.1) for either lamina suggesting that in normal aging the frontal cortex manifests a plasticity response that maintains normal synaptic numbers.

We have also obtained additional cases from individuals older than 89 who also met the short PMI, education and neurologically intact, criterion. These additional five cases might represent individuals who could be considered "survivors" since they were outside of the normal human life expectancy33. The results of the entire group are shown in Figure 29.1. In this very objective study, we failed to observe any significant association between age and packing density of synapses in this Brodmann area, suggesting that the number of synapses remains stable in cognitively normal individuals. In addition there were no significant sex effects indicating that both males and females had equivalent packing densities. When comparing individuals in the ninth decade of life with those of the second and third decades, the very old group had significantly lower synaptic densities, suggesting that mechanism(s) that maintain synaptic numbers begin to wane in the oldest old, similar to other findings34,35. These results support the idea that cognitively normal individuals maintain synaptic connectivity throughout the normal life expectancy. Although individuals greater than 89 demonstrated a decline in synaptic numbers, they still were functioning at a fairly high cognitive level. It is tempting to categorize this as a case of cognitive reserve36,37.

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