Blanca Ramirez-Ruiz

Amygdalar and hippocampal MRI volumetric reductions in Parkinson's disease with dementia

Parkinsons disease (PD) involves neuropathological changes in the limbic system that lead to neuronal loss and volumetric reductions of several nuclei. We investigated possible volumetric reductions of the amygdala and hippocampus associated to PD. We carried out magnetic resonance imaging (MRI) volumetric studies in 16 patients with PD and dementia (PDD), 16 patients with PD without dementia (PD), and 16 healthy subjects. The general analysis of variance (ANOVA) showed a significant group effect (for the amygdala, P = 0.01; for the hippocampus, P = 0.005). A post‐hoc test demonstrated that the differences were due to PDD and control group comparisons for the amygdala (P = 0.008) and for the hippocampus (P = 0.004). In nondemented PD subjects, we observed an 11% reduction in the amygdala and a 10% reduction in the hippocampus compared with that in controls. In summary, demented PD patients have clear amygdalar and hippocampal atrophy that remains statistically significant after controlling for global cerebral atrophy. Nondemented PD patients also showed a degree of volumetric reduction in these structures although the differences were not statistically significant.

Longitudinal evaluation of cerebral morphological changes in Parkinson's disease with and without dementia

AbstractObjectiveTo investigate the pattern of brain atrophy across time in a sample of Parkinsons disease (PD) patients with and without dementia using voxelbased morphometry (VBM) analysis.MethodsThe initial sample comprised thirteen non–demented PD patients and sixteen demented patients. Longitudinal cognitive assessment and structural MRI were performed. The mean follow–up period was 25 months (SD = 5.2). From this initial group, eight PD patients with dementia (5 men and 3 women) and eleven PD patients without dementia (7 men and 4 women) were reevaluated. MRI 3D structural images were acquired and analyzed by means of the optimized VBM procedure with Statistical Parametric Mapping (SPM2).ResultsVBM analysis showed a progressive grey matter volume decrease in patients with PD without dementia in limbic, paralimbic and neocortical associative temporooccipital regions. In patients with dementia the loss mainly involved neocortical regions.ConclusionVBM 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.

Cerebral atrophy in Parkinson's disease patients with visual hallucinations

Although visual hallucinations (VH) are relatively frequent in Parkinsons disease (PD) patients, their neural substrates are only known from neuropathological and functional magnetic resonance studies. The aim of this study was to investigate possible structural brain changes on MRI in non‐demented PD patients with VH using voxel‐based morphometry. Eighteen PD patients with VH were compared to 20 patients with PD without VH and 21 healthy controls. Compared with both controls and the non‐hallucinating PD group, PD patients with VH had grey matter volume reductions in the lingual gyrus and superior parietal lobe. Structural changes in these areas involved in higher visual processing may be important in understanding the VH and visual deficits in PD patients.

Hippocampal head atrophy predominance in Parkinson's disease with hallucinations and with dementia.

We studied regional gray matter density in the hippocampus in Parkinson’s disease (PD) patients. We obtained magnetic resonance scans in 44 PD patients (PD patients with dementia (PDD) = 9, non-demented PD patients with visual hallucinations (PD + VH) = 16, and PD patients without dementia and without visual hallucinations (PD - VH) = 19) and 56 controls matched for age and years of education. A region of interest (ROI) of the hippocampus following voxel-based morphometry (VBM) procedures was used to perform group comparisons, single-case individual analysis and correlations with learning scores. Group comparisons showed that PDD patients and PD+VH patients had significant hippocampal gray matter loss compared to controls. In PDD patients, hippocampal gray matter loss involved the entire hippocampus and in PD+VH this reduction was mainly confined to the hippocampal head. 78 % of PDD patients, 31 % of PD+VH patients and 26 % of PD-VH patients had hippocampal head gray matter loss when compared to controls. These results suggest that in PD the neurodegenerative process in the hippocampus starts in the head of this structure and later spreads to the tail and that, in addition, memory impairment assessed by Rey’s Auditory Verbal Learning Test (RAVLT) correlates with hippocampal head gray matter loss.

Neuropsychological deficits in Parkinson's disease patients with visual hallucinations.

Recent neuropathological and neuroimaging studies suggest the involvement of several temporal regions in Parkinsons disease (PD) patients with visual hallucinations (VH). We examined 24 nondemented PD patients with VH, 21 PD patients without VH, and 21 healthy controls using a battery of tests assessing different aspects of temporal lobe function. PD patients with VH showed poorer performance in language, verbal learning, semantic fluency, and visuoperceptive functions compared to controls and PD patients without VH. Differences in verbal learning and visuoperceptive functions were independent of general cognitive status, disease severity, and depression. We suggest that a wide range of neuropsychological deficits can contribute to the emergence of VH in PD.

Differential progression of brain atrophy in Parkinson's disease with and without visual hallucinations

Objective To determine the course of cognitive deficits and the regional progression of brain atrophy in patients with Parkinsons disease (PD) with and without visual hallucinations (VH). Methods The authors performed MRI and neuropsychological assessment at entry to the study and at follow-up (mean±SD=29.91±5.74 months) in a sample of initially non-demented 12 PD patients with VH, 14 PD patients without VH and 12 healthy controls (HC). Grey-matter changes over time were assessed by means of voxel-based morphometry (VBM) and cognitive changes by an extensive neuropsychological battery. Results At follow-up, 75% of patients with VH developed dementia. The greatest decline was observed in verbal memory, semantic fluency, language comprehension and visuoperceptive functions. None of the patients without VH met criteria for dementia and did not show any worsening in cognitive functions over time. Patients with VH showed widespread limbic, paralimbic and neocortical grey-matter loss, whereas in the PD without VH group, grey-matter loss was restricted to a small region in the frontal cortex and cerebellum. The authors also found significant correlations between the changes in several cognitive functions and grey-matter loss over time in PD patients with VH. Conclusion The presence of VH in PD determines a different cognitive outcome and a different pattern of progressive brain atrophy. PD patients with VH, unlike PD without VH, frequently develop dementia and show a widespread atrophy involving limbic, paralimbic and neocortical areas.

Neuroanatomical substrate of visuospatial and visuoperceptual impairment in Parkinson's disease.

To determine magnetic resonance imaging patterns of gray matter (GM) atrophy underlying visuospatial and visuoperceptual impairment in Parkinsons disease (PD), we applied voxel‐based morphometry to 36 nondemented PD patients and correlated their whole brain GM density with performance on three visuospatial and visuoperceptual tests. In addition, group comparisons between patients and 20 healthy controls were also performed. Correlations between visuospatial performance and GM density were found in the superior parietal lobules and the superior occipital gyrus of PD patients. Poor performance on visuoperceptual tests was also found to be significantly associated with GM decreases in the fusiform, the parahippocampus, and the middle occipital gyrus. Finally, group comparisons between controls and patients showed widespread GM cortical reductions in PD, involving posterior temporal and parietal regions. Taken together, these findings suggest that visuospatial and visuoperceptual dysfunctions reflect structural GM changes in temporo‐parietal cortical regions of PD patients.

Cognitive Changes in Parkinson’s Disease Patients with Visual Hallucinations

Objective: To evaluate the decline in specific neuropsychological functions in nondemented Parkinson’s disease (PD) patients with a history of visual hallucinations (VH). Methods: Twenty PD patients with VH, 20 PD patients without VH and 18 normal controls were followed up over a 1-year period and assessed for cognitive decline. Results: Forty-five percent of nondemented hallucinating PD patients developed dementia during the 1-year period between baseline and follow-up evaluations. Of the nondemented hallucinating PD patients nearly 70% showed impairment in multiple cognitive domains. The progressive decline in hallucinating PD patients affected mainly visual memory for faces and visuoperceptive-visuospatial functions. Conclusion: Our results support a fast impairment of complex visual functions in hallucinating PD patients, but also a progressive decline in multiple cognitive domains, which have been identified as a risk of developing dementia in PD.

Frontal and associative visual areas related to visual hallucinations in dementia with Lewy bodies and Parkinson's disease with dementia.

Visual Hallucinations (VH) are among the core features of Dementia with Lewy Bodies (DLB), but are also very frequent in demented patients with Parkinsons Disease (PDD). The purpose of this study was to investigate the pattern of gray matter and cognitive impairment underlying VH in DLB and PDD. We applied voxel‐based morphometry and behavioral assessment to 12 clinically diagnosed DLB patients and 15 PDD patients. Subjects with VH showed greater gray matter loss than non‐hallucinators, specifically in the right inferior frontal gyrus (BA 45) in the DLB patients and in the left orbitofrontal lobe (BA 10) in the PDD patients. Comparing the two subgroups with VH, DLB patients had greater decrease of the bilateral premotor area (BA 6) than PDD patients. Furthermore, decreased volume in associative visual areas, namely left precuneus and inferior frontal lobe, correlated with VH in the DLB but not in PDD patients. VH were related to impaired verbal fluency, inhibitory control of attention and visuoperception in the DLB group and to visual memory in the PDD group. In conclusion, DLB and PDD patients with VH had more frontal gray matter atrophy than non‐hallucinators, the impairment being greater in the DLB group. The patterns of structural and functional correlations were different in both pathologies.

Brain response to complex visual stimuli in Parkinson's patients with hallucinations: a functional magnetic resonance imaging study.

Visual hallucinations (VH) in Parkinsons disease (PD) have been associated with gray matter reductions in visual associative areas and with abnormal patterns of brain activation in posterior and frontal regions. However, all previous fMRI studies have used simple visual stimuli. The objective of our study was, therefore, to compare the pattern of brain activation during a one‐back face detection task. We examined 10 PD patients with VH, 10 PD patients without VH, and 10 controls matched for age and education. The fMRI task consisted in three blocks of 21‐face stimuli (activation condition) and three blocks of 21‐colored mosaics (control condition). Subjects were asked to press a key when two identical stimuli were presented consecutively. During the face condition, compared with patients without VH, hallucinating PD patients showed significant reductions in the activation of several right prefrontal areas, such as the inferior (BA 10,47), superior (BA 6/8), middle frontal (BA 8), and anterior cingulate gyrus (BA 31/32). In the control condition, we found a hyperactivation in the hallucinating PD sample compared with the nonVH patients in the right inferior frontal gyrus. A dysfunction of the frontal areas associated with the control of attention could predispose to VH through an abnormal processing of relevant and irrelevant visual stimuli.