The effects of scopolamine (anticholinergic) and methysergide (antiserotonergic) on memory and long-latency auditory cognitive evoked potentials (EPs) were tested in 16 normal adults. Recent memory was impaired by both drugs. In contrast, scopolamine, but not methysergide, significantly delayed P3 latency and decreased P3 amplitude. Immediate memory and the earlier EP components (i.e., N1 and P2) were unaffected. The findings support the hypothesis that cholinergic neurons are important in the neuronal networks generating the P3 potential. Serotonergic neurons do not appear to play a major role in the networks that generate the P3.

In the first part of the study, a comparison of 19 patients with Alzheimer''s disease (AD) with 19 age-matched controls was performed to establish diagnostic criteria of AD with positron emission tomography and ¹⁸F-2-fluoro-2-deoxygIucose. Patients had a mean age of 60.6 ± 7.1 years, and a mean score of 14.5 ± 7.3 in Mini Mental Status examination, and of 4.9 ± 0.9 on the Global Deterioration Scale. They fulfilled current research criteria (NINCDS-ADRDA) for probable AD and had been screened rigorously to exclude other potentially dementing conditions, in particular cerebrovascular disease. Regional glucose metabolism was always abnormal in temporoparietal association areas, at least unilaterally, and in most patients also in fronto-lateral association areas. Regional metabolism relative to whole-brain metabolism was always normal in cerebellum, brain stem, and lentiform nucleus, and in most patients also in visual and sensorimotor cortex. A metabolic ratio of typically affected to typically unaffected regions was designed to represent this characteristic pattern. It provided a complete separation of AD patients from normals. In the second part of the study, the diagnostic power of this ratio was tested in an independent sample of 56 patients with a mean age of 59.9 ± 11.3 years. Eight of these patients had subjective memory complaints, but were found completely normal at neuropsychological and clinical examination. Twenty-two had cognitive deficits due to diseases other than AD, among them 7 with cerebrovascular disease, and 26 had probable AD. The classification by the metabolic ratio as AD or non-AD was correct in 85%, with a sensitivity of 92, and a specificity of 80%.

A cognitive evoked potential, the P3, is commonly altered in dementia states but little is known of the specific neuronal generators that are the source of this potential. Event-related evoked potentials and neuropsychological testing were obtained in six normal subjects during neuropharmacological manipulation of the central cholinergic system. Scopolamine (an anticholinergic) impaired recent memory, prolonged P3 latency and decreased P3 amplitude. These abnormalities were partially reversed by physostigmine (an anticholinesterase). The results imply that the cholinergic system is involved in the generation of the P3 potential.

Single photon emission computerised tomography (SPECT) was used to measure regional brain uptake of technetium-99m hexamethylpropyleneamine oxine (Tc99m-HMPAO) in elderly patients with Alzheimer's disease (AD), multi-infarct dementia (MID) and normals (n = 20 in each group). Different patterns of uptake were found between groups when cortical uptake was normalised to cerebellar uptake. Reductions occurred in all regions in AD, being most marked in temporal and posterior parietal areas. Significant correlations were found in AD between memory impairment and decreased temporal uptake bilaterally, and between duration of illness and reduced uptake in most brain regions. MID patients showed higher uptake in the anterior parietal region than did the other groups. A variable comparing anterior to posterior uptake significantly discriminated the two patient groups.

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