| Many factors are thought to contribute to Alzheimer's disease (AD) risk. Among them are possession of allele &egr;4 of Apoliprotein E gene (APOE4), advanced age, increased cardiovascular risk, thinning of the entorhinal cortex, poor memory and executive function performance, and presence of amyloid plaques and neurofibrillary tangles (the pathological hallmarks of AD) in the brain. Evidence suggests that AD-related changes may occur years before clinical symptoms of AD are present. In these studies, we examined cognitive and functional changes associated with AD risk in an effort to better understand the relationship that each has with brain function. In the first experiment using functional magnetic resonance imaging (fMRI) we found that areas preferentially activated in those with increased cardiovascular risk were similar to areas previously found to activate more in those with a genetic risk for AD. In the second experiment, we found that those having thicker left entorhinal cortex showed more fMRI activity in anterior frontal regions and anterior cingulate during memory retrieval. These results were stronger in those who performed poorly on the Stroop Interference task, a task known to recruit anterior cingulate. In the third experiment, we found that older participants who performed well on a cued recall task showed more fMRI activation in regions of their hippocampus during memory retrieval, when compared with older adults who performed more poorly. Comparisons with younger adults suggest that these increases are both compensation for other aging-related changes in the brain in those who performed well, and decreases in activity in those who performed poorly. Those with APOE4 showed reduced activity in one hippocampal area, suggesting a decreased ability to compensate. In the final experiment, we used PET imaging with FDDNP, a probe that labels plaques and tangles. FDDNP signal in many brain regions associated with AD degeneration was significantly correlated with a composite cognitive score. The effects of AD risk may be obscured by normal variability and presence of other factors that affect cognition in aging. Future exploration of AD risk using large samples and longitudinal studies would help illuminate which brain differences may represent incipient AD. |
