Regional vulnerability of hippocampal subfields and memory deficits in Parkinson's disease.

Neuropathological studies show the hippocampus is affected in Parkinson's disease (PD), with the second subfield of the cornu armonis (CA2) being the most involved. Our aims were to assess in vivo volumes of different hippocampal subfields in patients with PD with and without visual hallucinations using MRI and test their association with verbal learning and long-term recall. A total of 18 nondemented PD patients, 18 nondemented PD patients with visual hallucinations and 18 neurologically unimpaired elderly controls matched by age and gender were enrolled in this study. We assessed the volumes of seven hippocampal subfields on MRI, including the cornu armonis (CA) sectors, subiculum, presubiculum, and the dentate gyrus (DG) using a novel technique that enables automated volumetry. The CA2-3 and CA4-DG subfields were significantly smaller in both groups of patients, while the subiculum was only reduced in PD patients with visual hallucinations, compared to controls. Significant correlations were found between learning performance and CA2-3 as well as CA4-DG volumes in the whole patient sample. These data show there is regional atrophy of specific hippocampal subfields in PD, which is more severe and further extends to the subiculum in patients with visual hallucinations. Our findings indicate that learning deficits are associated with volume loss in subfields that act as input regions in the hippocampal circuit, suggesting that degeneration in these regions could be responsible for cognitive dysfunction 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 Parkinson's 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.

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 Parkinson's 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.

Correlations between gray matter reductions and cognitive deficits in dementia with Lewy Bodies and Parkinson's disease with dementia.

There is controversy regarding whether Dementia with Lewy Bodies (DLB) and Parkinson's disease with dementia (PDD) may or not be different manifestations of the same disorder. The purpose of the present study was to investigate possible correlations between brain structure and neuropsychological functions in clinically diagnosed patients with DLB and PDD. The study sample consisted of 12 consecutively referred DLB patients, 16 PDD patients, and 16 healthy control subjects recruited from an outpatient setting, who underwent MRI and neuropsychological assessment. Voxel-based morphometry results showed that DLB patients had greater gray matter atrophy in the right superior frontal gyrus, the right premotor area and the right inferior frontal lobe compared to PDD. Furthermore, the anterior cingulate and prefrontal volume correlated with performance on the Continuous Performance Test while the right hippocampus and amygdala volume correlated with Visual Memory Test in the DLB group. In conclusion, DLB patients had more fronto-temporal gray matter atrophy than PDD patients and these reductions correlated with neuropsychological impairment.

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 Parkinson's 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.

Structural brain correlates of verbal fluency in Parkinson's disease.

Verbal fluency tests are often used to assess cognitive dysfunction in Parkinson's disease. These tests have been found to be impaired even in initial stages of this illness. We applied voxel-based morphometry to investigate the neuroanatomic substrates of semantic and phonemic fluency impairment. Correlations between gray matter density and semantic as well as phonemic fluency performance were performed in 32 nondemented Parkinson's disease patients. We found that gray matter of temporal, frontal and cerebellar areas correlated with semantic fluency scores. In contrast, no gray matter correlations were found for phonemic fluency or for general cognitive functions. These results suggest that semantic fluency impairment is reflecting structural gray matter changes in regions involved in language networks.

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.

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

Visual hallucinations (VH) in Parkinson's 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.

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.

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

Recent neuropathological and neuroimaging studies suggest the involvement of several temporal regions in Parkinson's 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.

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

OBJECTIVE: To investigate the pattern of brain atrophy across time in a sample of Parkinson's disease (PD) patients with and without dementia using voxelbased morphometry (VBM) analysis. METHODS: The 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). RESULTS: VBM 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. CONCLUSION: 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.

Structural brain changes in Parkinson disease with dementia: a voxel-based morphometry study.

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.

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

Parkinson's 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.

Corpus callosum atrophy in adolescents with antecedents of moderate perinatal asphyxia.

BACKGROUND: The corpus callosum (CC) is a cerebral structure that reflects cognitive status in several neurological pathologies. Visual inspection of MRI has shown that hypoxic-ischemic encephalopathy(HIE) causes callosal damage. PRIMARY OBJECTIVE: To quantify the CC surface in a sample of patients with antecedents of HIE and a group of matched controls. RESEARCH DESIGN: Comparisons of CC measures among control subjects, mild HIE patients and moderateHIE patients as well as correlates of CC surface and neuropsychological performance. METHODS: Twenty-one adolescent patients with childhood antecedents of HIE were compared to 21 controls. ANALYZE software was used to semi-automatically measure the CC area. MAIN OUTCOMES AND RESULTS: Patients with moderate HIE showed corpus callosum reduction. The isthmus and genus were the most affected regions. Corpus callosum size correlated with cognitive function. CONCLUSIONS: Corpus callosum quantification provides new evidence of subtle residual deficits in subjects with HIE antecedents without apparent neurological sequelae.