Alzheimer's disease and senile dementia: Biochemical characteristics and aspects of treatment

Alzheimer's disease (AD) and senile dementia (SD) are often classified together, but there are genetic, biochemical, neuropathological and clinical arguments for separating them.The well-known Alzheimer lesions in the brains of patients with AD and SD are described, as is the loss of neurons in the locus coeruleus. White matter changes in brains from patients with dementia are discussed and related to AD and SD.Biochemical changes in brains of patients with AD and SD include reduced activity of acetylcholineesterase (AChE) and choline-acetyltransferase (CAT), indicating reduced activity in the acetylcholinergic system. There is also, however, reduced activity in the dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) system. The active amines are decreased while the end metabolites are decreased to a lesser extent or normal. The levels of the active amines are thought to reflect the number of neurons, while the levels of end metabolites reflect the rate of turnover in the system. 3-Methoxy-4-hydroxyphenylglycol (MHPG) is increased to levels above normal, which may indicate an increased rate of turnover in the NA system.Monoamine oxidase B (MAO-B), which is increased in advanced age, is further increased in patients with AD and SD. It is assumed that this enzyme is localized in extraneuronal tissue, and therefore the increase may reflect a gliosis.In brains from patients with AD and SD neuropeptides are also studied. Only somatostatin and substance P, however, seem to be reduced, indicating selective damage to the neuropeptides.The biochemical changes can be given pathogenetic importance. Disturbances in the acetylcholinergic system may explain memory disturbances, disturbances in the DA system may explain parkinsonlike symptoms and disturbances in the NA and 5-HT systems may explain mood disturbances and emotional symptoms in the disorder. The biochemical changes may also suggest a line of treatment. At present, several attempts have been made to activate the neurotransmitter systems. The progress of these studies is, however, not very encouraging.