MAPT and Cognitive impairment: Later on, tau deposition extends to the neocortex and cognitive impairment sets in, initially with moderate neocortical tau burden (biological stage C) and mild cognitive impairment (clinical stage 3) and finally with severe neocortical tau burden (biological stage D) and dementia (mild, moderate, and severe corresponding to clinical stages 4–6).2 Neurodegeneration is closely related in time and topography to tau deposition and is not featured in the model.