What does it take to stay healthy past 100?: Commentary on “No disease in the brain of a 115-year-old woman”

The description of an 115-year-old woman without dementia or Alzheimerʹs disease (AD) is remarkable, but fits well with previous accounts of aging and AD. Several similar non-demented cases aged 85–105 years have been reported previously, who had neurofibrillary tangles in the medial temporal lobe, but no deposition of amyloid plaques. Together with observations on other aging and very mild AD cases, these can be related to a model of aging and AD. In this model, tangles develop independently but relatively slowly during aging; these represent neurodegeneration, but by themselves may not represent AD. In contrast, amyloid may be the driving factor in AD, exacerbating neurofibrillary changes and other neurodegeneration. There is a pre-clinical period when the process has begun but has not produced sufficient degeneration to produce clinical symptoms. Critical questions raised by the present report include what genetic or other factors allowed healthy survival to age 115 year, and whether anti-amyloid therapies will allow more general survival in good mental health beyond age 100?