Defining and describing the pre-dementia stages of familial Alzheimer's disease.

With the prospect of prevention trials for familial Alzheimer's disease on the horizon, understanding the natural history of the illness has never been so important. Earlier this year in The Lancet Neurology, Acosta-Baena and colleagues published the results of the largest and longest retrospective study of pre-dementia clinical stages in familial Alzheimer's disease to date. By reviewing serial neuropsychological assessments of individuals from a large Colombian kindred affected by the E280A mutation in the Presenilin 1 gene, they defined three stages of pre-dementia cognitive impairment. Using survival analyses, the authors estimated the median age at onset and rate of progression through each of these stages towards dementia and ultimately death. Their study provides valuable insights into the time course of cognitive decline associated with this mutation. Furthermore, the study highlights some of the challenges of defining pre-dementia clinical stages in familial Alzheimer's disease and the need for the field to develop a consistent terminology.