The differences between CI and other groups, however, still result from greater decline in CBF in the CI group. Within the regions of longitudinal change, there were no significant differences in baseline

(year 1) CBF with one exception. The anterior cingulate region (BA 32), which showed greater longitudinal decline in the CI group relative to the CN and ASYMAD groups, had KPT 330 baseline CBF levels that were significantly different across groups (P = 0.04). This effect was driven by higher initial baseline levels in the CI group than the ASYMAD group Inhibitors,research,lifescience,medical (P = 0.01). Discussion In this study, we compared longitudinal changes in rCBF in BLSA participants classified as CN, ASYMAD, and CI based on clinical data and neuropathological findings at autopsy. Across the groups, we observed significant differences in brain activity over time measured many years before death and while all participants were CN. The ASYMAD and CI groups differed from CN in several areas, suggesting that some regions show similar functional loss due to neuropathologic Inhibitors,research,lifescience,medical changes in the brain. Changes distinctive Inhibitors,research,lifescience,medical to either ASYMAD or CI groups were also noted. Because these differential patterns of CBF were identified years prior to the development of CI and death, these functional changes may be related to the difference in subsequent cognitive ability between these groups. The CI and ASYMAD Inhibitors,research,lifescience,medical groups exhibited

similar amounts of neuropathology at autopsy. The CI and ASYMAD groups not only had identical scores for NPs, which is based on the current criteria used in the neuropathologic diagnosis of AD, but they also had similar cortical burdens of pathology by quantitative assessments of β-amyloid. Additionally, Braak scores were not significantly different between these groups, indicating a comparable distribution of NFTs, which was strengthened by the demonstration Inhibitors,research,lifescience,medical of similar quantitative assessments of cortical tau (NFTs and threads) in the ASYMAD and CI groups. Based on these results, it could be hypothesized that the CI and ASYMAD groups would show similar

differences in brain function when compared to pathologically normal individuals. Indeed, both of the groups with AD pathology showed similar longitudinal declines in rCBF in the precuneus, lingual gyrus, and middle temporal regions. As the precuneus and middle temporal regions demonstrated similar mean area fractions many of amyloid and tau in both CI and ASYMAD groups, these results suggest that premorbid function in these regions may decline with the accumulation of the neuropathology over time. However, the functional decline in these regions is likely not the primary contributor to the subsequent differences in cognitive ability, as the declines occur in individuals who maintain cognitive ability as well as those who develop impairments.