Fig. 4. Early Braak stages are associated with isolated memory dysfunction and late Braak stages are associated with dementia severity.

a, Memory, executive, language and visuospatial composite Z scores according to PET-based Braak stage (n = 291 individuals with neuropsychological evaluation available). Memory function begins to decline at Braak stage II, while other cognitive domains remain unaffected. Memory continued to decline with increasing Braak stage. Language and visuospatial domains remain relatively spared until late Braak stages. b, Summary cognitive assessments according to PET-based Braak stage. Little change in MMSE scores were observed from Braak stages 0 to III. Steeper declines in MMSE score were observed at Braak stages V and VI. Changes in MOCA score were detectable by stage IV. Braak stages 0–II were largely compatible with the absence of dementia as assessed by the CDR. Braak stages III and IV consisted almost exclusively of individuals with CDR = 0.5 (very mild dementia). Braak stage V and VI were incompatible with normal cognition, with Braak stage VI being associated with increased dementia severity (n = 324 with summary cognitive assessments). c, In a subsample of individuals with autosomal dominant AD (PSEN1 mutation carriers; n = 14, total of 21 tau-PET scans including follow-ups), PET-based Braak stage was associated with estimated years to the onset of symptoms. Shapes indicate means, and error bars indicate s.d. Summary statistics for all cognitive outcome comparisons are reported in Supplementary Table 6. Statistics were conducted with two-sided ANOVA using Dunnett’s correction for multiple comparisons. PSEN1, Presenilin-1.