Neuropsychological test performance and CSF levels of monoamine metabolites in healthy volunteers and patients with Alzheimer's dementia.

Fifteen patients (51-78 yrs) with mild to moderately severe Alzheimer's dementia and 18 healthy subjects of the same age were examined by clinical rating scales and a battery of neuropsychological tests. Levels of the monoamine metabolites homovanillic acid (HVA), 3-methoxy-4-hydroxyphenyl glycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in the lumbar cerebrospinal fluid (CSF). Correlations between clinical, psychological and biochemical measures were calculated in order to elucidate whether monoaminergic mechanisms are of importance for the maintenance of cognitive abilities in normal and pathological aging. The patients' performance was severely impaired in all neuropsychological tests. The mean levels of monoamine metabolites, however, did not differ between patients and volunteers. The correlations between psychological test scores and CSF metabolite levels were generally low, but mostly negative, associating a poor performance to a high activity of brain monoaminergic neurons. Thus, among the volunteers high 5-HIAA and MHPG levels correlated with poor performance in the Picture completion and the Trail making tests--measures of visuo-perceptual and visuo-motor skills. In the demented patients poor performance in the memory tests was associated with high levels of HVA and 5-HIAA. The results indicate that monoamine neuron activity is not a primary determinant for cognitive abilities in healthy elderly subjects or in demented patients. The slight negative correlation between cognitive function and metabolite concentrations in the patients may reflect a disturbance in a dopaminergic-cholinergic balance due to degenerative changes of central cholinergic pathways.