Thirteen participants remained CN by consensus criteria (Kawas et al. 2000) through the last available cognitive evaluation (last evaluation on average was 14.8 months prior to death, range
3–30 months). The remaining six individuals developed some degree of CI (last evaluation on average 2.8 months prior to death, range 1–5 months) by consensus criteria. One declined to amnestic MCI (Petersen 2004), one to possible AD (n= 1), two to probable AD, one to dementia of undetermined etiology that was consistent with probable AD on pathology (n= 1), and one to mixed vascular dementia and AD (n= 1) (Table Inhibitors,research,lifescience,medical 2). Table 2 Cognitively impaired subjects. Autopsy diagnostic evaluation All brains from subjects with CI had NP CERAD age-related BVD-523 concentration plaque scores of B and
NFT Braak scores of III (n = 2), IV (n = 3), and V (n = 1). Among the 13 subjects that remained CN, six had substantial AD pathology, Inhibitors,research,lifescience,medical that is, NP age-related scores of B and NFT Braak scores of II (n = 1), III (n = 2), or IV (n = 3). The remaining seven CN subjects had NP CERAD age-adjusted plaque scores of 0 (n = 6) or A (n = 1), and NFT Braak scores of II (n = 3), III (n = 1), or IV (n = 3) Inhibitors,research,lifescience,medical (Table 3; Braak and Braak 1991; Mirra et al. 1991). Table 3 CERAD and Braak scores. Ten (4/6 CI, 1/6 ASYMAD, 5/7 CN) participants had evidence of remote microinfarcts or lacunes at the time of autopsy. The majority of these were located in the basal ganglia or cerebellum. One subject in the CI group had an acute infarct in the distribution of the right middle cerebral artery. A number of other pathologies were found in subjects in the CN, each occurring in one subject. These included: Inhibitors,research,lifescience,medical LB pathology limited to rare LB in the substantia nigra, the amygdala, and temporal cortex corresponding to a brainstem distribution of α-synuclein pathology (McKeith et al. 2005); inactive demyelinating lesions consistent with multiple sclerosis, which were incidentally discovered; focal perivascular cuffing with mononuclear cells in a few vessels in the basal ganglia; and focal areas of tau positive astrocytes in the Inhibitors,research,lifescience,medical amygdala and substantia nigra. In all cases,
NP and NFT evaluations and quantitative stereology were performed in tissue sections not affected by these non-AD-related findings. Definition first of groups according to clinical/cognitive-pathological correlations Based on the clinical and neuropathologic diagnoses, we divided the 19 participants into three groups: CN (n = 7, 7 males, 0 females), asymptomatic Alzheimer’s disease (ASYMAD; n = 6, 4 males, 2 females), or cognitively impaired (CI; n = 6, 4 males, 2 females). CN were CN individuals by clinical consensus criteria (Kawas et al. 2000) and also had none to sparse numbers of NP (CERAD age-related plaque score 0 or A), Braak scores ranging from II to IV, and received a neuropathologic diagnosis of normal with respect to AD by CERAD criteria (Mirra et al. 1991).