Anne-Louise Lafontaine

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.

L-Dopa Medication in Parkinson's Disease Restores Activity in the Motor Cortico-Striatal Loop but Does Not Modify the Cognitive Network

Background The goal of this study was to evaluate the effects of L-Dopa medication in Parkinsons disease (PD) on brain activation during the performance of a set-shifting task. Using fMRI, we have previously studied the patterns of activity observed in patients with PD after overnight removal of dopaminergic medication compared with control participants during the performance of different stages of the Wisconsin Card Sorting Task (WCST). The results revealed decreased cortical activity in the PD group compared to controls in the conditions that significantly required striatum, while increased cortical activity was observed when striatum was not involved. However, the effect of dopaminergic medication in PD patients on those patterns of activity has not yet been studied. Methodology/Principal Findings Here, eleven PD patients at early stage of the disease taking L-Dopa medication were recruited and underwent two fMRI sessions while performing the WCST: one session while taking their normal dose of medication and the other following overnight dopaminergic medication withdrawal. We found that L-dopa medication helped restoring a normal pattern of activity when matching and not planning was required, by increasing cortical activity in the premotor cortex. This effect was even stronger in the motor loop, i.e. when the putamen was required for controls, when matching following negative feedback. However, the medication did not change the pattern of activity in conditions relying primarily on a cognitive loop, i.e. when the caudate nucleus was required. Conclusions/Significance These studies provide explanation at the neural level regarding the relatively poor effects of L-Dopa on the cognitive deficits observed in PD.

Reduced cognitive function in patients with Parkinson disease and obstructive sleep apnea

Objective: To assess the association between obstructive sleep apnea (OSA) and nonmotor symptoms (NMS), including cognitive dysfunction, in patients with Parkinson disease (PD). Methods: Patients with idiopathic PD, recruited from a movement disorder clinic, underwent overnight polysomnography. OSA was defined as an apnea-hypopnea index (AHI) ≥15/h. PD severity was assessed using the Hoehn & Yahr (H&Y) scale and the Movement Disorder Society Unified Parkinsons Disease Rating Scale (MDS-UPDRS). NMS were assessed using the Montreal Cognitive Assessment (MoCA), Epworth Sleepiness Scale (ESS), Fatigue Severity Scale, Apathy Scale, Beck Depression Inventory, Hospital Depression and Anxiety Scale, and PD sleep Scale. Results: Sixty-seven patients (61.2% male), mean age 64.4 (SD 9.9) years and motor MDS-UPDRS 21.9 (12.6) using levodopa equivalent dose (LED) 752.4 (714.6) mg/d, were studied. OSA occurred in 47 patients (61.6%, mean AHI 27.1/h, SD 20.2/h), and NMS in 57 patients (85%). ESS and MoCA were associated with the AHI (ESS β = 0.0670, p = 0.031; MoCA β = −0.0520, p = 0.043, adjusted for age, sex, body mass index, LED, and H&Y). ESS was associated with respiratory arousals (β = 0.1015, p = 0.011) and intermittent hypoxemia (β = 0.1470, p = 0.006). MoCA was negatively associated with respiratory arousals (β = −0.0596, p = 0.049) but not intermittent hypoxemia. Conclusions: OSA is associated with sleepiness and cognitive dysfunction in PD, suggesting that OSA may be a reversible contributor to these NMS. Further studies will be required to evaluate whether OSA treatment can improve excessive sleepiness and cognitive dysfunction in PD.

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.

Diagnosis of Obstructive Sleep Apnea in Parkinson’s Disease Patients: Is Unattended Portable Monitoring a Suitable Tool?

Purpose. Obstructive sleep apnea (OSA) is frequent in Parkinsons disease (PD) and may contribute to nonmotor symptoms. Polysomnography (PSG) is the gold standard for OSA diagnosis. Unattended portable monitoring (PM) may improve access to diagnosis but has not been studied in PD. We assessed feasibility and diagnostic accuracy in PD. Methods. Selected PD patients without known OSA underwent home PM and laboratory PSG. The quality of PM signals (n = 28) was compared with matched controls. PM accuracy was calculated compared with PSG for standard apnea hypopnea index (AHI) thresholds. Results. Technical failure rate was 27.0% and airflow signal quality was lower than in controls. Sensitivity of PM was 84.0%, 36.4%, and 50.0% for AHI cut-offs of 5/h, 15/h, and 30/h, respectively, using the same cut-offs on PM. Specificity was 66.7%, 83.3%, and 100%, respectively. PM underestimated the AHI with a mean bias of 12.4/h. Discrepancy between PM and PSG was greater in those with more motor dysfunction. Conclusion. PM was adequate to “rule in” moderate or severe OSA in PD patients, but the failure rate was relatively high and signal quality poorer than in controls. PM overall underestimated the severity of OSA in PD patients, especially those with greater motor dysfunction.