CSF cholinesterase activity in demented and non-demented subjects

Samples of cerebrospinal fluid (CSF) were examined, looking mainly at total cholinesterase (ChE) and acetyl-cholinesterase (AChE) levels from 139 living subjects. At the completion of the study, 35 of the 139 patients had died and pathological confirmation of the presence of dementia had been obtained. These results, together with results from other laboratories, provide evidence that a low CSF ChE level presenting in demented patients may indicate a depletion of the brain AChE system, and this may confirm a clinical diagnosis of AD as well as other types of dementia which are associated with an alteration of the brain AChE system. The overlap in the levels of CSF biochemical markers between demented and non-demented subjects which has led to many conflicting reports has always disappointed investigators. It is suggested that some 'control' subjects with CSF ChE activity indistinguishable from that in AD patients may have an abnormal ageing process in their brains (brain at risk), although the symptoms of dementia have not yet been detected. Recognition of a pre-clinical or incubation period is very beneficial for explaining discrepancies in biochemistry and pathology in the literature, and must be considered for both the treatment and the prevention of dementia. The long used treatment, which was designed to inhibit AChE, should no longer be used: treatment must be designed to enhance the activity of the neuronal AChE system, or slow its degeneration.