Neuropsychiatric disorders constitute the largest class ofillness causing disability to mankind and, within these,the dementias have emerged as a subgroup of the great-est epidemiological magnitude. The current issue of Dia-logues in Clinical Neuroscience endeavors to present per-spectives on key issues in the diagnosis and treatment ofthe dementias.In the State of the art, Ramit Ravona-Springer, MichaelDavidson, and Shlomo Noy (page 7) discuss the polemicsof the distinction between Alzheimers disease (AD) andvascular dementia. They suggest various cardiovascularmechanisms that may contribute to the overlap betweenthe dementias, and discuss the implications for diagno-sis and treatment.Two Basic research articles appear in this issue. The firstarticle, which is contributed by Ya-Ping Tang and Elliot S.Gershon (page 17), reviews genetic studies in AD. Itextensively covers the role of the three genes (APP, PS1,and PS2) that have been incriminated as being causativeof AD. It also postulates the various polymorphic mech-anisms that are emerging as significant in the pathogen-esis of AD.In the Basic research second article, Christoph Hock(page 27) depicts the role of abnormal protein aggre-gates in the biochemistry of dementia. He speculates onthe therapeutic targets that are likely to result from thedecryption of the processes of protein deposition in thebrain. The efficacious treatment of AD is one of the most chal-lenging tasks of modern medicine. In his Pharmaco-logical aspects article, Alistair Burns (page 35) delin-eates the role of the array of anticholinesterases as wellas alternative agents, such as N-methyl-D-aspartate(NMDA) receptor antagonists, in alleviating the cognitiveimpairment that is the hallmark of AD.The decision tree in the diagnosis of dementia by JulieLoebach Wetherell and Dilip V. Jeste in the Poster (page44) brings to the busy clinicians office the algorithm forsifting through the diagnostic uncertainties that con-found the dementias. The issue thus integrates epi-demiological, methodological, genetic, biochemical,diagnostic, and therapeutic aspects of the dementias ina manner that should be useful to researchers and clin-icians alike.Five articles in Clinical research cover diagnostic andhistorical aspects of dementia. In the first, Franz Müller-Spahn (page 49) highlights the behavioral disturbancesthat are prominent in dementia and discusses the com-plex interaction between the cognitive deficits andbehavioral abnormalities. The article covers the underly-ing biochemical mechanisms, diagnostic issues, andtherapeutic strategies in the management of these dis-orders.Christian Gilles negotiates through the hazy territory ofmild cognitive deficits (page 61). The article lends clari-ty to the blur between optimal and pathological aging,and contributes toward the goal of offering early treat-ment to patients whose dementias are in early stages ofprogression.Keith A. Wesnes and John E. Harrison critically reviewthe instruments used in diagnosing dementias and theimplicit regulatory considerations (page 77). They advo-cate the use of automated cognitive tests in early diag-nosis. Structural and functional imaging has become an inte-gral element in the diagnosis of AD. Daniel E. Wollmanand Isak Prohovnik examine the sensitivity and specifici-ty of various neuroimaging modalities (page 89). Theyfocus on the greater accuracy of neuroimaging com-pared with clinical diagnosis, and discuss the limitationsas well as indications of resorting to the imaging tech-nologies.Finally, Hanns Hippius and Gabriele Neundörfer narrateAlois Alzheimers role in the eponymous disorder (page101). The tale incorporates the elements of curiosity,clinical excitement, politics, and delayed recognition,which are frequently the ingredients of many epic con-tributions in medicine.5I n t h i s i s s u e . . .Rajesh M. Parikh, MD