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Background: A recent Alzheimer's disease research diagnosis framework groups amyloid (A), tauopathy (T), and neurodegeneration (N) biomarkers into eight AT(N) profiles. We determined prevalence at death of each profile in the Adult Changes in Thought (ACT) community-based cohort. Within each profile, we determined dementia prevalence at death and incident dementia among those dementia free 5-7 years antemortem. Methods: Setting: prospective study of individuals ≥65 years; 25-30% consented to autopsy. Cognition was prospectively evaluated every 2 years and dementia determined using research criteria. At autopsy, A used CERAD levels (none/sparse vs. moderate/frequent), T used Braak staging (0-III vs. IV-VI), and N used absence vs. presence of lateral ventricular dilation at the temporal tip. We compared prevalent and incident dementia for each AT(N) profile. We used inverse-probability weighting to address potential selection bias, and considered the relevance of seven additional autopsy findings in predicting dementia status. Findings: Of 5,236 ACT participants, 2,870 died, and 603 had known dementia status and autopsy. The two most common profiles were A+T+(N)+ (31%) and A-T-(N)+ (22%). Dementia prevalence ranged from 14% (A-T-(N)-) to 79% (A+T+(N)+). Dementia incidence ranged from 8% (A+T-(N)-) to 67% (A+T+(N)+) and 68% (A+T+(N)-). Each additional neuropathological finding was associated with 7% (prevalence) to 9% (incidence) higher dementia risk independent of A,T and (N) (prevalence RR 1·07 (95% CI: 1·05-1·10); incidence RR 1·09 (95% CI: 1·05-1·14)). Interpretation: Dementia rates varied across AT(N) categories. Costs of determining AT(N) status may be considerable. That >30% of dementia-free people with the highest risk AT(N) categories did not develop incident dementia before death suggests restraint in population-based settings for treatments with more than trivial toxicity. Funding Statement: National Institute on Aging (US National Institutes of Health). (AG006781) Declaration of Interests: PKC reports grants from the US National Institutes of Health (NIH) and prior funding from the Alzheimer’s Association. Ethics Approval Statement: Study procedures were approved by KPW and UW institutional review boards. Participants provided written informed consent. |
