Background: Parkinson disease with dementia (PDD) results from neuropathological changes in cortical and subcortical brain regions. Voxel-based morphometric analysis of magnetic resonance images can contribute to in vivo identification of the cerebral regions predominantly involved in PDD.Objective: To identify structural cerebral regions most closely related to the presence of PDD.Design: Magnetic resonance images were obtained from 16 patients who had PDD, 13 patients with PD without dementia, and 13 age-matched healthy control subjects. Gray matter volumes were compared using optimized voxel-based morphometric analyses.Results: Compared with healthy controls, patients with PDD showed gray matter volume decreases in several of the following regions: bilateral putamen, accumbens nuclei, left side of the thalamus, bilateral hippocampus, parahippocampal region, and anterior cingulate gyrus. Patients with PD also showed gray matter reductions compared with healthy controls in the right side of the hippocampus, left anterior cingulate gyrus, and left superior temporal gyrus. Conclusions:The hippocampus, thalamus, and anterior cingulate are the regions most affected in PDD. Our results agree with recent neuropathological findings suggesting the involvement of the limbic and cortical areas in PD.

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VBM revealed a significant loss of grey matter volume in PD patients with and without dementia with disease progression. The decrease in limbic and paralimbic regions is widespread in non-demented patients. Neocortical volume reduction is the most relevant finding in patients with dementia. This suggests that the neocortex is a substrate for dementia in Parkinson disease.

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Dopamine (DA) acts as a key neurotransmitter in the brain. Numerous studies have shown its regulatory role in motor and cognitive function. However, the impairment of emotional processes in neurologic and psychiatric pathologies involving the dopaminergic system (Parkinson disease, schizophrenia, autism, Attention Deficit Hyperactivity Disorder, Huntington disease, frontal lobe lesions), as well as the influence that administration of dopaminergic agonists/antagonists exert on the processing of emotion, suggest a role for DA in emotional processes. Moreover, emotional processes are dependent upon a variety of structures, the majority of which form part of the limbic system and are subject to DA innervation. In reviewing the literature, the amygdala emerges as a brain structure critical for emotional processing. It may also be implicated in deficits in emotional recognition found in two major disorders where DA's implication is clear: Parkinson disease and schizophrenia. In addition, the amygdala's response to emotional tasks is likely to be altered by the administration of both agonist and antagonist dopaminergic drugs. Experimental studies reinforce the idea of a dopaminergic contribution to emotional response, as suggested by biochemical, pharmacologic, and lesion experiments. Although the implication of the dopaminergic system in emotional processing appears to be clearly documented, the contribution of specific DA receptor subtypes, or of the DA cotransmitters cholecystokinin and neurotensin, or even glutamate, is, however, still unclear. Altogether, these observations suggest that DA has, undoubtedly, a direct and/or indirect role in the full emotional process.