Ten patients with idiopathic Parkinson's disease and motor fluctuations were rated for mood changes during discrete "off," "on," and "on with dyskinesia" periods. The Profile of Mood States and visual analogue scales were used. Significant changes in mood and anxiety were found to parallel changes in motor fluctuations. One patient rated his moods as consistently improving from the "off" state to the "on" state and finally to the "on with dyskinesia" state, a finding that is consistent with concomitant central dopaminergic changes. All other patients showed moods that improved significantly from the "off" state to the "on" state but then worsened significantly in the "on with dyskinesia" state, a finding that is consistent with the fact that patients feel worse when impaired by dyskinesias. It is suggested that these results argue for multiple etiologies of depression in Parkinson's disease. The literature on dopamine and depression in Parkinson's disease is briefly reviewed and the opportunity provided by "on-off" phenomena to study the effect of dopamine on mood changes is discussed.

Affect↗

PubMed1990

Parameters of cholinergic neurotransmission in the thalamus in Parkinson's disease and Alzheimer's disease.

Loss of cholinergic cells in the basal forebrain is associated with commensurate reductions in cortical acetylcholine-related enzyme activities in both Alzheimer's disease (AD) and Parkinson's disease (PD). Nerve cell loss from the cholinergic pontine tegmental nuclei also occurs. As the latter nuclei project to the diencephalon, we used frozen tissue from 5 controls, 5 PD and 5 AD cases to study the distribution of ChAT, AChE and [3H]nicotine binding in the thalamus and subthalamic nucleus. The anterior nuclear group and the mediodorsal nucleus showed high activities of ChAT and AChE together with relatively high levels of [3H]nicotine binding. The centromedian nucleus and subthalamic nucleus contained equally high levels of ChAT but negligible levels of [3H]nicotine binding. There were no significant changes in the levels of ChAT, AChE and nicotine binding in the PD and AD groups indicating that involvement of the pedunculopontine tegmental nucleus is likely to be a secondary retrograde phenomenon rather than part of a systematic cholinergic fibre degeneration.

Acetylcholine↗

PubMed1990

Distribution of neurofibrillary tangle formation and [3H]-D-aspartate receptor binding in the thalamus in the normal elderly brain, in Alzheimer's disease and in Parkinson's disease.

The overactivity of glutamatergic neurons may underlie some neurodegenerative disorders, including Alzheimer's disease (AD). We explored the relationship between glutamatergic transmission and neurofibrillary tangle formation by measuring [3H]-D-aspartate binding activity and the proportion of neurons containing tangles within individual thalamic nuclei in five AD cases. Five elderly normal and five Parkinson's disease (PD) cases were used as controls. A highly significant correlation between [3H]-D-aspartate binding and tangle counts in Alzheimer's disease suggests that those thalamic nuclei which normally receive a relatively dense glutamatergic afferent input are predisposed to tangle formation. There were no significant differences in individual thalamic nuclear [3H]-D-aspartate binding between controls and the AD and PD groups.

Aged↗

PubMed1990

Evidence of a monoaminergic-cholinergic imbalance related to visual hallucinations in Lewy body dementia.

Senile dementia of Lewy body type is characterized clinically by a relatively acute onset of fluctuating memory loss and confusion, frequently accompanied by visual hallucinations. Neurochemical analyses of temporal cortex has revealed a distinction between hallucinating and nonhallucinating patients in both cholinergic and monaminergic transmitter activities. In contrast with the cholinergic enzyme choline acetyltransferase, which was more extensively reduced in hallucinating individuals, serotonergic S2 receptor binding and both dopamine and serotonin metabolites were significantly decreased in nonhallucinating cases. These results suggest that an imbalance between monaminergic and cholinergic transmitters is involved in hallucinogenesis in the human brain.

Acetylcholine↗

PubMed1990

Cholinergic and dopaminergic activities in senile dementia of Lewy body type.

Analyses of brain tissue in a recently identified group of elderly demented patients suggest a neurochemical basis for some of the clinical features. Senile dementia of the Lewy body type (SDLT) can be distinguished from classical Alzheimer disease (AD) clinically by its acute presentation with confusion frequently accompanied by visual hallucinations, and neuropathologically by the presence of Lewy bodies and senile plaques (but not generally neurofibrillary tangles) in the cerebral cortex. Reductions in the cortical cholinergic enzyme choline acetyltransferase were more pronounced in individuals with (80%) compared to those without (50%) hallucinations and correlated strongly with mental test scores in the group as a whole. In the caudate nucleus, dopamine levels were related to the number of neurons in the substantia nigra, there being a 40-60% loss of both in SDLT--probably accounting for mild extrapyramidal features in some of these cases--compared with an 80% loss in Parkinson disease and no change in AD. The cholinergic correlates of mental impairment in SDLT together with the relative absence of cortical neurofibrillary tangles and evidence for postsynaptic cholinergic receptor compensation raise the question of whether this type of dementia may be more amenable to cholinotherapy than classical AD.

Aged↗

PubMed1989