Possible trajectories of the conversion process from cognitively normal to Alzheimer's disase (AD)-type dementia. (A) Three different possible trajectories of the conversion to dementia in a group of cognitively normal (CN) individuals (100% of non-demented subjects at t0), at risk of AD. In the first trajectory (red line), the group comprises at baseline (t0) CN individuals at different stages of preclinical AD, with roughly the same number of subjects at each stage. The total conversion time (the time between appearance of an early AD marker and dementia onset) is constant and is the same for all subjects (t), and the number of converters in a given period is constant. In the second scenario (green line), the group comprises peole with preclinical AD, with a Gaussian distribution of the individuals at different stages of advancement (most individuals being at the intermediate stage). The total conversion time is constant and the same for all the individuals (t). Most of the group converts to dementia at around t1/2. Finally, the black line shows the group comprising CN at preclinical AD, with the constant conversion rate (proportion of the individuals that develop dementia in a given time period). Most individuals convert to dementia early, and the mean time of conversion is higher than the respective median. (B) Preclinical AD individuals with a passive compensatory mechanism that delays conversion for a given time (Δt), until the mechanism is exhausted. Subsequently, all patients convert to dementia, following one of the trajectories presented on the panel A. (C) Preclinical AD individuals with an active compensatory mechanism that prevents, in a certain proportion of cases (p), conversion to dementia, whichever trajectory the conversion process follows.
Lazarczyk et al. BMC Medicine 2012 10:127 doi:10.1186/1741-7015-10-127