Alzheimer's and other neurodegenerative diseases are generally incurable and often difficult to diagnose accurately. Yet early and accurate diagnosis of a neurodegenerative disease can potentially contribute to more effective treatment. Hence research efforts are moving towards early identification of high risk subjects and prevention of disease progression with biomarkers. Unfortunately dementia and biomarker studies are hampered by variables such as drop outs, challenges in comparing data sets, discordant biomarker sets, availability of histopathological confirmation at death, validity of cognitive testing, and nonlinear fluctuations in cognitive domains as disease pr o g r e s s e si nv i v oi ns u b j e c t s .T h i sc h a p t e ri s an assessment of the challenges in the early diagnosis of dementia, as well as a presentation of the issues faced in conducting dementia and biomarker studies.