2.4. Cross‐sectional SUVR PET analysis for CN and CI participants

To comprehensively assess the performance of the cerebellum GM, centrum semiovale, and pons reference tissues in discriminating between CN or CI individuals, ROI‐ and voxelwise‐based cross‐sectional statistical analyses were performed. All baseline scans were included for cross‐sectional analysis and participants were classified as either CN (CDR = 0) or CI (CDR ≥ 0.5; Zhou et al., 2021). To investigate the sensitivity of the PET SUVR measurement in discriminating CN from CI, effects sizes were approximated using Cohen's d (Chand et al., 2020; Cohen, 1988; Lopresti et al., 2005; Sullivan & Feinn, 2012; Zhou et al., 2021) of CN and CI groups as follows:

where SDpooled represents the standard deviation of SUVR in pooled population, x represents either cerebellum GM, centrum semiovale, or pons reference tissues. Since the ¹⁸F‐FDG SUVR decreased while the ¹⁸F‐florbetapir and ¹⁸F‐flortaucipir SUVR increased with disease progression, we set group 1 to be CN and group 2 to be CI for ¹⁸F‐FDG, and group1 to be CI and group2 to be CN for ¹⁸F‐florbetapir and ¹⁸F‐flortaucipir.

For correcting the influence of covariates, the two‐sample independent t test adjusted by age, sex, and education levels were performed at voxelwise level using SPM12. For ROI‐based analysis, the generalized linear model was used to assess the group difference in SUVR for each ROI by adjusting for covariates, the Bonferroni‐corrected p‐value < .05 was defined as significant.