We also identify differences distinctive to the ASYMAD group that may help maintain cognitive GSK461364 purchase ability in the face of accumulating neuropathology, and we describe changes distinctive to CI group that likely contribute to CI over time in this group. Materials and Methods Subjects In this study we used PET data from 19 older participants in the neuroimaging substudy

(Resnick et al. 2000) of the BLSA who underwent postmortem evaluation of the brain Inhibitors,research,lifescience,medical (four female, 15 male). Approximately half the BLSA neuroimaging substudy participants have agreed to autopsy, a rate that is similar to that in the BLSA as a whole. These groups have similar ages, male/female distribution, years of education, and number of APOE e4 alleles (data not shown). The mean (SD) age at PET baseline was 76.0 (SD 7.1) years and age at death was Inhibitors,research,lifescience,medical 85.9 (SD 5.3) years. Subjects had to have at least two PET scans, although the majority had more than seven scans (n= 15). At autopsy, subjects were determined to meet pathologic criteria for one of the three study groups and individuals were not included if they had evidence of a non-Alzheimer neurodegerative disorder (e.g., non-AD tauopathy,

Parkinson disease, or vascular dementia). All individuals remained in good physical and cognitive health during the Inhibitors,research,lifescience,medical period of PET data collection with no history of central nervous system disorders, major psychiatric disorders including depression, or severe cardiovascular disease (Table 1). Table 1 Subject characteristics (mean [SD]). This study was approved by the local Institutional Review Boards. All participants provided written informed consent prior to each Inhibitors,research,lifescience,medical assessment. Study design This study examines serial CBF measurements starting many years prior to death. Participants underwent PET scanning sessions at baseline and annually for up Inhibitors,research,lifescience,medical to eight follow-up visits (mean interval 7.2 years). Participants died on average

2.8 years after the last PET scan included in this study and underwent autopsy at that time. The study groups were determined based on the combination of antemortem clinical diagnosis and autopsy findings (see below). The imaging tuclazepam analyses were subsequently performed comparing these three groups. Cognitive assessment All participants were followed annually and were reviewed at a consensus conference if their Blessed Information Memory Concentration score was ≥4, or if their informant or subject Clinical Dementia Rating (CDR) score was ≥0.5. Dementia diagnosis was determined according to Diagnostic and Statistical Manual of Mental Disorders, 3rd Ed., Revised (DSM-III-R) criteria. Mild CI (MCI) diagnosis was based on the Petersen (Petersen 2004) criteria. A battery of neuropsychological tests was administered annually and performance levels were used to determine clinical diagnosis (see Kawas et al. 2000 for detailed description).