Brain tau deposition is now trackable in vivo using serial positron emission tomography (PET). Characterization of brain tau accumulation rates and anatomy in clinically normal (CN) or cognitively impaired (CI; Mild Cognitive Impairment or mild Alzheimer's disease) populations may be informative to the design of clinical trials. We sought to optimize regional sampling of PET data with respect to measurement of tau accumulation rates. Baseline clinical assessments, amyloid PET (11C-PiB cortical DVR), and serial tau PET (18F-Flortaucipir; FTP) were assessed in several subgroups (full cohort N=70): low-PiB CN, high-PiB CN (combined as all CN), and CI (Table 1). Partial-volume-corrected SUVR (80–100 min; cerebral white matter reference; GTM correction), SUVR change/year (cSUVR), and coefficient of variation (COV=SD/mean) were calculated in FreeSurfer-defined regions (ROI) and volume-weighted aggregates. The following ROI measurements yielded significantly nonzero group mean FTP cSUVRs across the full cohort and each subgroup: inferior temporal (IT; all p≤0.0006), with COVs ranging from 65%-146%; the LTLF aggregate (all p≤0.0015), with COVs ranging from 59%-159%; and a global aggregate (34 bilateral ROIs; all p≤0.0021 across the full sample, CI, all CN, high-PIB CN; low-PiB CN p=0.0475), with COV ranging from 87% − 269% (Table 1, Figure 1). Change rates in CI were consistently higher compared to CN (Table 1, Figure 1). Group mean cSUVR in IT, fusiform, LTLF, and the MOLT aggregate were significantly correlated to PiB FLR DVR at baseline in the full cohort, all CNs, and high-PiB CNs, but not in low-PiB CNs or CI (Table 2). Baseline SUVR was also significantly associated with cSUVR in high-PiB CNs across IT, fusiform, and MOLT (all Pearson's r≥0.39, all p≤0.0415; LTLF p=0.0611, Global p=0.577). Tracking cSUVR in MOLT would enable a 28.5% minimum detectable effect with 80% power over one year of study in 200 high-PiB CN subjects per treatment arm using a two-point model (Figure 2), though more general statistical modeling (e.g., mixed effects) will likely yield estimates having greater power. Significant annual FTP signal increase indicates that tau accumulation is detectable in regions with elevated signal at baseline, in impaired and unimpaired subjects, and is related to higher amyloid burden. cSUVR by ROI, amyloid burden, and subgroup * Denotes p<0.05 in independent sample t-tests for group comparisons between MCI/AD and all CN group means (upper level) or between high-PiB and low-PiB group means (lower level). Grey COVs are for all CN and MCI/AD groups; COVs for high- and low-PiB CN groups are given according to the figure legend. Nonzero mean single-sample t-test p value levels: p>0.05, 0.001<p≤0.05, p≤0.001 Sample size estimation using ROIs and aggregates in target populations for clinical drug trials. Sample Size estimation per treatment arm is shown for a significance level of 0.05 in a two- tailed t-test with 80% power, using mean and SD values in either the high PiB CN or MCI/AD subgroups. ROIs and aggregates with the lowest COVs for each subgroup were chosen for comparison; solid lines are ROIs while dotted lines are aggregates. Other region/subject group combinations yield similar results in proportion to reported COVs.