Preclinical Alzheimer's disease: diagnosis and prediction of progression

Background From the modest but important breakthroughs in the treatment of Alzheimer's disease (AD), diagnostic focus has increasingly shifted to the accurate detection of the earliest phase of the illness. The challenge of distinguishing preclinical AD from changes of normal ageing or established AD, has been recognised in several attempts at clinical classification. Of these attempts, Mayo Clinic's mild cognitive impairment (MCI) has received significant attention, although it has not been internationally accepted. Not all people diagnosed as having MCI will develop AD, hence there is a need to reliably predict progression. Recent developments Research in the identification of people with MCI who will develop AD via the use of neuropsychological tests, neuroimaging (both structural and functional), CSF analysis, and other biomarkers, either in isolation or in combination, has progressed rapidly. In this article we summarise findings from relevant recent longitudinal studies. Where next? There are increasing calls to recognise the pathological nature of MCI and to develop international diagnostic guidelines. Such uniform application of MCI criteria can then lead to clearer evidence of its diagnostic and therapeutic benefit. In developing these guidelines, the crucial presence of functional deficit arising from cognitive decline (which diagnoses dementia and excludes MCI) needs to be investigated in a standardised manner. Also needed are good-quality normal-values data on the various tests used to predict progression in preclinical AD.