Neurotransmitters in dementia

Changes in the activity of neurotransmitters in dementia were studied by measuring the activities of each of choline acetyltransferase (CAT), dopamine-beta-hydroxylase (DBH) and hydroxylase cofactor (tetrahydrobiopterine; BPH4), and the concentrations of homovanillic acid (HVA) and vasopressin. CAT activity was low in the cerebral cortex of patients with senile dementia of Alzheimer's type (SDAT). The CAT activity was high in the nucleus basalis, which correlated well with the CAT activity in the cerebral cortex, Brodmann areas 22 and 17. DBH activity was lower in the cerebrospinal fluid (CSF) of SDAT and multi-infarct dementia (MID) patients than in that of control subjects. No age-related change was observed in control subjects. Serum DBH activity was decreased in patients with SDAT but not in patients with MID. DBH activity was especially low in the serum of SDAT patients with a low dementia rating score and/or severe brain atrophy shown on computed tomography (CT) scan. Serum DBH activity was also decreased in older normal subjects (greater than or equal to 80 years). The concentration of HVA in the CSF of control subjects decreased with the advance of age, but the decrease in HVA concentration was more pronounced in the CSF of SDAT patients, which would reflect the lowered dopaminergic activity in SDAT. BPH4 activity was also decreased in the CSF of SDAT patients. Arginine-vasopressin was widely demonstrated in the cerebral cortex of control subjects but could not be detected in many areas of the cerebral cortices of demented patients. These results suggest that a deficit of dopamine, noradrenaline or vasopressin as well as acetylcholine may occur in the brain of SDAT patients. The evidence presented points toward areas for consideration in the search for methods of therapy or prevention of SDAT.