Beatriz Mejia-Constain

Mild cognitive impairment is linked with faster rate of cortical thinning in patients with Parkinson’s disease longitudinally

Previous studies have shown greater atrophy in grey and white matter of various brain regions in patients with Parkinsons disease with mild cognitive impairment than in those without. These anatomical differences likely account for the distinct clinical profiles observed between those groups, but do not account for the evolution of regional brain degradation observed as the disease evolves. Although we have shown recently that cortical thinning correlates significantly more with disease duration in Parkinsons patients with mild cognitive impairment than in those without, to the best of our knowledge no study to date has explored this longitudinally. The present study investigated the longitudinal changes of the cortical and subcortical grey matter in patients with Parkinsons disease with and without mild cognitive impairment. Additionally, these two groups were compared with healthy controls. We found a higher rate of cortical thinning in the temporal, occipital, parietal and supplementary motor area, in patients with Parkinsons disease with mild cognitive impairment compared with both cognitively stable patients and healthy controls. On the other hand cognitively stable patients had only one lateral occipital and one fusiform cluster with increased rate of thinning compared with healthy individuals. Correlating the rate of change of cortical thickness with the results of Montreal Cognitive Assessment scores revealed significant thinning associated with cognitive decline in the group of all patients, in similar regions including temporal and medial occipital lobe. Finally, a significant decrease in the volume of the amygdala and nucleus accumbens was observed specifically in patients with Parkinsons disease with mild cognitive impairment. These results indicate that the early presence of mild cognitive impairment in patients with Parkinsons disease is associated with a faster rate of grey matter thinning in various cortical regions as well as a significant diminishment of limbic subcortical structures. This specific pattern of brain degradation associated with the early presence of mild cognitive impairment might serve as a marker of development toward dementia.

Effect of mild cognitive impairment on the patterns of neural activity in early Parkinson's disease

We have previously observed decreased activation of corticostriatal loops involved in planning (cognitive loop) and execution (motor loop) of a set shift in patients with early Parkinsons disease (PD) compared with control subjects. Here, we aimed to assess whether cognitive impairment in PD could drive these differences. Nondemented patients underwent a comprehensive neuropsychological evaluation and participated in our Wisconsin Card Sorting task functional magnetic resonance imaging protocol. Patients were separated into 2 groups according to the presence of mild cognitive impairment (MCI). Patients with MCI displayed reduced activity in the cognitive corticostriatal loop, which includes the caudate nucleus and prefrontal cortex while planning a set shift, whereas non-MCI patients exhibited activation patterns similar to those of healthy participants from our previous studies. Furthermore, reduced activation was observed in the premotor cortex of the MCI patients. Finally, hippocampal activity, correlated with individual memory scores, suggesting a compensatory mechanism in patients with preserved memory. These results suggest that the presence of MCI in PD affects activity in the prefrontal cortex and caudate nucleus as well as motor-related regions.

Mild cognitive impairment in patients with Parkinson's disease is associated with increased cortical degeneration

Mild cognitive impairment (MCI) can occur early in the course of Parkinsons disease (PD), and its presence increases the risk of developing dementia. Determining the cortical changes associated with MCI in PD, thus, may be useful in predicting the future development of dementia. To address this objective, 37 patients with PD, divided into 2 groups according to the presence or absence MCI (18 with and 19 without) and 16 matched controls, underwent anatomic magnetic resonance imaging. Corticometry analyses were performed to measure the changes in cortical thickness and surface area as well as their correlation with disease duration. Compared with healthy controls, the PD‐MCI group exhibited increased atrophy and changes of local surface area in the bilateral occipital, left temporal, and frontal cortices; whereas the PD non‐MCI group exhibited only unilateral thinning and decreased surface area in the occipital lobe and in the frontal cortex. In addition, a comparison between the PD‐MCI and PD non‐MCI groups revealed increased local surface area in the occipital lobe, temporal lobe, and postcentral gyrus for the cognitively impaired patients. It is noteworthy that, in the PD‐MCI group, cortical thickness had a significant negative correlation with disease duration in the precentral, supramarginal, occipital, and superior temporal cortices; whereas, in the PD non‐MCI group, such a correlation was absent. The findings from this study reveal that, at the same stage of PD evolution, the presence of MCI is associated with a higher level of cortical changes, suggesting that cortical degeneration is increased in patients with PD because of the presence of MCI.

Dopamine transporter SLC6A3 genotype affects cortico-striatal activity of set-shifts in Parkinson’s disease

Parkinsons disease is a neurodegenerative condition that affects motor function along with a wide range of cognitive domains, including executive function. The hallmark of the pathology is its significant loss of nigrostriatal dopamine, which is necessary for the cortico-striatal interactions that underlie executive control. Striatal dopamine reuptake is mediated by the SLC6A3 gene (formerly named DAT1) and its polymorphisms, which have been largely overlooked in Parkinsons disease. Thirty patients (ages 53-68 years; 19 males, 11 females) at early stages of Parkinsons disease, were genotyped according to a 9-repeat (9R) or 10-repeat (10R) allele on the SLC6A3/DAT1 gene. They underwent neuropsychological assessment and functional magnetic resonance imaging while performing a set-shifting task (a computerized Wisconsin Card Sorting Task) that relies on fronto-striatal interactions. Patients homozygous on the 10R allele performed significantly better on working memory tasks than 9R-carrier patients. Most importantly, patients carrying a 9R allele exhibited less activation than their 10R homozygous counterparts in the prefrontal cortex, premotor cortex and caudate nucleus, when planning and executing a set-shift. This pattern was exacerbated for conditions that usually recruit the striatum compared to those that do not. This is the first study indicating that the SLC6A3/DAT1 genotype has a significant effect on fronto-striatal activation and performance in Parkinsons disease. This effect is stronger for conditions that engage the striatum. Longitudinal studies are warranted to assess this polymorphisms effect on the clinical evolution of patients with Parkinsons disease, especially with cognitive decline.

Neuroimaging studies of different cognitive profiles in Parkinson's disease

It is now clear that cognitive deficits exist even early in Parkinsons disease, having a significant impact on daily activities. However, the nature and the neural origins of cognitive dysfunction in PD are still under debate. Furthermore, a great heterogeneity seems to exist with respect to the cognitive profiles found in patients at the early stages of the disease, and these initial differences are likely predictive of distinct outcomes regarding the later occurrence of dementia. These include the early presence of Mild Cognitive Impairments, the nature and number of domains affected, as well as the occurrence of depression or apathy. Here, we will review studies involving anatomical and functional neuroimaging, and neuropsychological evaluation that have attempted to address these issues. Recommendations for future work will also be discussed.

Depressive symptoms in Parkinson’s disease correlate with cortical atrophy over time

Introduction Depressive symptoms are very common in patients with Parkinson’s disease (PD) and have a significant impact on the quality of life. Methods The present study analyzed the correlations between over‐time changes in depressive symptoms and gray matter parameters of cortical thickness and subcortical volumes in non‐demented PD patients. Results A significant correlation was observed, between increased scores for depression over time and lower cortical thickness over time in the right temporo‐parietal junction, right occipital medial region, right dorsolateral prefrontal cortex, right posterior cingulate region, left middle temporal as well as left supplementary motor area. Furthermore, the presence of depressive symptoms at baseline predicted increased cortical thinning over time in the left middle temporal, left anterior cingulate, right posterior cingulate and right parahippocampal cortices. Finally, a statistically significant negative correlation has been revealed between the thalamus’ volume changes over time and the change in depressive symptoms scores. All other analyzed subcortical structures didn’t reveal any significant correlations. Conclusion These results suggest that depressive symptoms in PD patients are associated with gray matter cortical thinning and thalamus volume shrinkage over time and higher scores of depressive symptoms at baseline correlate with a higher rate of cortical thinning longitudinally. The present study highlights the importance of addressing depressive symptoms in PD patients early in the disease. HighlightsEarly presence of depressive symptoms in PD is a marker of faster neurodegeneration.Depressive symptoms in PD correlate with a higher neurodegeneration rate over time.These preliminary results indicate that even mild depressive symptoms should be treated early in PD.

Patterns of Longitudinal Neural Activity Linked to Different Cognitive Profiles in Parkinson's Disease

Mild cognitive impairment in Parkinsons disease (PD) has been linked with functional brain changes. Previously, using functional magnetic resonance imaging (fMRI), we reported reduced cortico-striatal activity in patients with PD who also had mild cognitive impairment (MCI) vs. those who did not (non-MCI). We followed up these patients to investigate the longitudinal effect on the neural activity. Twenty-four non-demented patients with Parkinsons disease (non-MCI: 12, MCI: 12) were included in the study. Each participant underwent two fMRIs while performing the Wisconsin Card Sorting Task 20 months apart. The non-MCI patients recruited the usual cognitive corticostriatal loop at the first and second sessions (Time 1 and Time 2, respectively). However, decreased activity was observed in the cerebellum and occipital area and increased activity was observed in the medial prefrontal cortex and parietal lobe during planning set-shift at Time 2. Increased activity in the precuneus was also demonstrated while executing set-shifts at Time 2. The MCI patients revealed more activity in the frontal, parietal and occipital lobes during planning set-shifts, and in the parietal and occipital lobes, precuneus, and cerebellum, during executing set-shift at Time 2. Analysis regrouping of both groups of PD patients revealed that hippocampal and thalamic activity at Time 1 was associated with less cognitive decline over time. Our results reveal that functional alteration along the time-points differed between the non-MCI and MCI patients. They also underline the importance of preserving thalamic and hippocampal function with respect to cognitive decline over time.

White matter degeneration profile in the cognitive cortico-subcortical tracts in Parkinson's disease: White Matter Tractography in PD-MCI

Background: In Parkinsons disease cognitive impairment is an early nonmotor feature, but it is still unclear why some patients are able to maintain their cognitive performance at normal levels, as quantified by neuropsychological tests, whereas others cannot. The objectives of this study were to perform a cross‐sectional study and analyze the white matter changes in the cognitive and motor bundles in patients with Parkinsons disease.