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Visuospatial impairment in Parkinson's disease (PD) heralds the onset of a progressive dementia syndrome and might be associated with cholinergic dysfunction. It remains unclear however, whether degeneration of the cholinergic basal forebrain is directly related to cognitive decline, or whether relationships between this region and cognitive function are mediated by closely related brain structures such as those in the medial temporal lobe. To evaluate relationships between structure of the cholinergic basal forebrain, medial temporal lobe and cognition, 27 PD patients without dementia and 20 controls underwent neuropsychological assessment and MRI. Volumes of the cholinergic basal forebrain nuclei, the entorhinal cortex, the hippocampus and its subfields were measured. Regression models utilised basal forebrain and hippocampal volumetric measures to predict cognitive performance. In PD, visuospatial memory (but not verbal memory or executive function) was correlated with hippocampal volume, particularly CA2-3, and basal forebrain subregion Ch1-2, but not Ch4. In addition, hippocampal volume was correlated with Ch1-2 in PD. The relationship between Ch1-2 and visuospatial memory was mediated by CA2-3 integrity. There were no correlations between cognitive and volumetric measures in controls. Our data imply that the integrity of the cholinergic basal forebrain is associated with subregional hippocampal volume. Additionally, a relationship between visuospatial function and cholinergic nuclei does exist, but is fully mediated by variations in hippocampal structure. These findings are consistent with the recent hypothesis that forebrain cholinergic system degeneration results in cognitive deficits via cholinergic denervation, and subsequent structural degeneration, of its target regions.

Background: Late onset depression is characterised by pronounced cognitive impairment, more somatic complaints and psychomotor retardation. Psychomotor slowing may be due to impairment in either motor or cognitive domain. Electrophysiology may be particularly convenient as a tool in studies of psychomotor retardation, as it can separate central cognitive processing from the motor processing. Subjects and methods: In this study we compared event related potentials (ERP) in the two groups of patients with late onset depression and psychomotor slowing as measured by reaction time (RT): a group of patients with lower RT was compared to a group with a higher RT. Twenty patients with late onset depression were included in the study after they had reached remission. Four weeks after reaching remission patients were reevaluated clinically using Hamilton Depression Rating Scale, Mini Mental State Examination, and with a computer version of the Stroop task. ERP, accuracy and RTs were simultaneously recorded. Both groups of patients aditionaly underwent a perfusion SPECT imaging. Results: There were no differences between the short and long RT groups of patients in amplitudes of the late positive Stroop related potentials. The group of patients with longer RTs showed significant hyperperfusion in precentral gyrus, parietal regions, cuneus and hypoperfusion within insular, frontal, temporal and limbic (parahyppocampal gyrus and anterior cingulate) cortices, as well as cerebellum. Conclusion: We found no ERP differences between the two groups suggesting that although patients may differ on psychomotor retardation measured as RT, their cognitive abilities may be quite similar. Perfusion SPECT imaging however revealed a significant difference between them. This may be due to a process of compensation and applying different strategies to cope with cognitive impairment in the two groups.

Cholinergic degeneration is a key feature of dementia in neurodegenerative conditions including Alzheimer's disease (AD) and Parkinson's disease (PD). Quantitative electro-encephalography (EEG) metrics are altered in both conditions from early stages, and recent research in people with Lewy body and AD dementia suggests these changes may be associated with atrophy in cholinergic basal forebrain nuclei (cBF). To determine if these relationships exist in predementia stages of neurodegenerative conditions, we studied resting-state EEG and in vivo cBF volumes in 31 people with PD (without dementia), 21 people with mild cognitive impairment (MCI), and 21 age-matched controls. People with PD showed increased power in slower frequencies and reduced alpha reactivity compared to controls. Volumes of cholinergic cell clusters corresponding to the medial septum and vertical and horizontal limb of the diagonal band, and the posterior nucleus basalis of Meynert, correlated positively with; alpha reactivity in people with PD (p< 0.01); and pre-alpha power in people with MCI (p< 0.05). These results suggest that alpha reactivity and pre-alpha power are related to changes in cBF volumes in MCI and PD without dementia.