BPSD and the Psychosis of AD: Treatment Possibilities

Meeting of the Psychopharmacological Drugs Advisory Committee on the " Various psychiatric and behavioural disturbances associated with dementia. " Purpose: " Can we identify appropriate clinical entities or targets of drug development in this area? " I would like to begin by congratulating the FDA for giving considered and thoughtful attention to this very important public health problem. AD is the major form of dementing disorder and its also the best understood. Therefore in addressing the question, " Can we identify appropriate clinical entities or targets of drug development in this area? " , it is useful to focus on AD. In focusing on AD, it is also useful to note that conclusions for AD will frequently apply to other dementing entities. For example, cerebrovascular dementia consists primarily of patients with AD and notable concomitant cerebrovascular disease (mixed dementia). Also, cerebrovascular disease is now believed to represent a continuum of relevance for AD as well as for cerebrovascular dementia. Similarly, Lewy body dementia is frequently noted to be accompanied by AD neuropathologic concomitants, and is sometimes seen to be a Lewy body variant of AD. 7 In comparison with other major psychiatric disorders, much is known about AD. For example, AD is known to be accompanied by brain changes. These include: (a) accumulation of tau positive paired helical filaments in neurons of the neocortex; (b) accumulation of amyloid plaques in the neocortex comprised in part, of the ß-amyloid protein; (c) cellular and volume losses in the hippocampus and to some extent in other brain structures. Clinically, AD is recognized to be a progressive disorder with linear declines in cognition and functioning extending over a period of up to approximately 20 years. AD has also long been know to be accompanied by " Behavioral and Psychological Symptoms " (BPSD), including psychotic symptoms. 8-10 For example, in Alois Alzheimer's classic case description, he noted BPSD in approximately half of his clinical description. 8 He noted, in part, that his patient believed " that people were out to murder her " , seems to have auditory hallucinations " , " dragged objects here and there and hid them " , and that " often she screams for many hours in a horrible voice. " Therefore, Alzheimer identified delusions, hallucinations, activity disturbances, and aggressivity, as part of the clinical presentation in his classic case. Frequently, BPSD in AD are: (1) disturbing to family members …