The P300 event-related potentials in dementia of the Alzheimer type. Correlations between P300 and monoamine metabolites.

We studied auditory event-related potentials (ERPs) in 40 patients with dementia of the Alzheimer type (DAT). Peak latencies and amplitudes of N100, P200 and P300 components were measured. To study the possible relationships between the ERPs and monoaminergic neurotransmitter functions, CSF neurotransmitter metabolites were also analyzed. In patients with DAT, the P300 amplitude was significantly reduced and the P300 latency was prolonged. CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were decreased. The P300 amplitude was significantly correlated with the 5-HIAA concentration. There were no correlations between the P300 components and the HVA concentration. These findings suggest that the serotonergic system modulates the P300 component of ERPs in patients with DAT.

Analysis of somatosensory evoked potentials in peroneal nerve palsy.

The peroneal nerve SEPs over the CZ' of the scalp were studied in patients with peroneal nerve palsy. The initial positive peak latencies of P27 (to popliteal fossa stimulation), P30 (to fibular neck stimulation) and P37 (to dorsum of the foot stimulation) were measured. The latency difference P30-P27 was prolonged in all patients with the fibular head lesions. In patients with the superficial peroneal nerve lesions at the foreleg, P37-P27 was prolonged whereas P30-P27 was normal. Clinical application of peroneal nerve SEPs was useful in deciding the site of the lesion causing the peroneal nerve palsy.

Pathologic laughing and crying treated with levodopa.

Levodopa or amantadine hydrochloride was administered to 25 patients with pathologic laughing and/or crying. This symptom was markedly improved in ten cases, most of which were devoid of a cortical atrophy or a periventricular lucency in computed tomographic scan and also devoid of a severe dementia or a disturbance in activity of daily living. The concentration of homovanillic acid in the CSF of the patients was significantly decreased, whereas the concentration of 5-hydroxyindoleacetic acid remained within the normal limit. Because part of pathologic laughing and crying seems to be caused by the decreased function of the dopaminergic neuron, levodopa or amantadine is worth trying.

Dopamine-beta-hydroxylase activities in serum and cerebrospinal fluid of aged and demented patients.

Age-related changes in dopamine-beta-hydroxylase (DBH) activities in serum and cerebrospinal fluid (CSF) were determined. In normal subjects, serum DBH activity increased gradually from the 3rd to the 8th decade, but decreased prominently in the 9th decade. DBH activity in CSF did not differ between younger and older subjects. Serum DBH activity decreased significantly in senile dementia of Alzheimer's type (SDAT, 12.2 +/- 8.8 nmoles/min/ml, P less than 0.05), but not in multi-infarct dementia (MID, 13.9 +/- 9.1 nmoles/min/ml) compared to control subjects (17.1 +/- 9.5 nmoles/min/ml). The decrease of serum DBH in SDAT was more prominent in patients with severe dementia and/or severe brain atrophy. DBH activity in CSF was much lower than that in serum and did not correlate with each other. DBH activity in CSF obtained from SDAT patients (1.60 +/- 0.94 nmoles/h/ml) and from MID patients 2.01 +/- 0.99 nmoles/h/ml) were both lower than that from other neurological diseases without dementia (4.04 +/- 3.81 nmoles/h/ml). DBH in CSF from SDAT patients was significantly lower (P less than 0.05) than that from controls, but that from MID did not differ from controls. Noradrenergic nervous dysfunction is partly associated with pathophysiology and life expectancy of senile dementia of Alzheimer's type (SDAT).

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.

Purification and properties of 2'-nucleotidase from mammalian brain.

A nucleotidase specific for 2'-nucleotides was localized in both the soluble and the synaptosomal fractions of rat brain. The enzyme was partially purified from the soluble fraction of bovine brain. The s20,w was 4.9 S with an estimated molecular weight of about 70 000. The optimum pH was 8.0 and Km value for 2'-AMP was 5.5 . 10(-4) M. The substrate and inhibitor specificities of the enzyme were examined. The nucleotidase has an absolute requirement for Mg2+ but neither Fe3+ nor Ca2+ acted as replacement ions. In fact, Mn2+ and Ca2+ inhibited the Mg2+-dependent 2'-nucleotidase.