| Stage 1 | Evidence of amyloid accumulation (positive amyloid PET or reduced CSF Aβ42/Aβ40) |
| Stage 2 | Evidence of amyloid accumulation PLUS subtle cognitive decline |
| Stage 3 | Evidence of amyloid accumulation, cognitive decline, AND subtle functional changes |
| Amyloid accumulation | Begins 20-30 years before expected clinical symptoms |
| Tau pathology | Begins approximately 10-15 years before symptoms |
| Neurodegeneration | Begins 5-10 years before symptoms |
| Cognitive changes | Subtle changes detectable 3-5 years before MCI |
| Amyloid-positive cognitively normal | Approximately 10-30% of individuals aged 50-70, increasing with age |
| Autosomal dominant AD | Nearly 100% develop preclinical changes by middle age |
| Sporadic AD risk | Approximately 20-40% of cognitively normal elderly are amyloid-positive |
| Aβ42/Aβ40 ratio | Reduced ratio reflects cortical amyloid deposition |
| Aβ42 | Historically used, now largely replaced by ratio |
| Databases | OMIMOrphanetClinicalTrialsPubMed |
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