Fig. 6: Longitudinal memory change analyses.

Exclusively longitudinal data was used to estimate individual-specific age-relative and absolute change in CVLT task performance (PC1 across subtests), modelling the adult lifespan trajectories using GAMMs with random individual-specific slopes. a Adult lifespan trajectory analysis for CVLT memory performance from 30–89 years. Lines connect longitudinal observations. b Estimated absolute memory change per individual (datapoints) in CVLT task performance plotted as a function of their mean age (across timepoints). c Estimated age-relative change per individual in CVLT task performance (individual-specific slopes) as a function of mean age. For each participant with memory change data, black stroke indicates whether or not genetic data was available. d The linear association between the principal component across the four PRS-AD scores and the principal component of age-relative change across the first 50 ADNI-derived features (listed in Fig. 4a) was used to define four quadrant groups representing the conjunction of brain and genetic risk factors. e Memory change for individuals with both memory change and genetic data within the quadrant groups (colours in d-e depict groups). Linear models found that individuals with higher PRS-AD who also exhibited more age-relative brain change in AD-sensitive features (in pink) showed significantly more age-relative (left plot) and absolute (right plot) change in memory across the healthy adult lifespan, relative to high PRS-AD individuals estimated to show less relative brain change. These significant group differences survived FDR-correction for multiple comparisons (applied across six one-sided tests; Methods; two-sided p-values shown). The distributions are visualized for these two groups; datapoints corrected for covariates including mean age and APOE-ε4 carriership [Methods] (see also Supplementary Fig. 17). Error bands depict 95% CI. Summary-level source data are provided as a Source Data file.