ABSTRACT
BACKGROUND: Half of all amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD) patients are classified as cognitively impaired, of which 10% have frontotemporal dementia (FTD), and an additional 40% suffer from a frontotemporal syndrome not severe enough to be described as dementia (cognitively impaired/ALSci). As changes in cerebral function measured by resting-state magnet resonance imaging (rs-fMRI) are known in ALS, we investigated whether group differences in resting-state functional connectivity (RSFC) networks could be observed between ALS patients with different cognitive profiles against healthy controls (HC). Furthermore, we correlated cognition and motor functioning with network connectivity. METHODS: Healthy controls, 69, and 97 ALS patients underwent functional MRI scanning and cognitive assessment. The ALS patients were categorized as non-impaired (ALSni; n = 68), cognitively impaired (ALSci; n = 21), and ALS-FTD (n = 8). Group differences in connectivity of the default mode network (DMN), motor network (MN), and ventral attention network (VAN) were investigated using a full-factorial model; correlations between global cognitive performance, shifting, and motor symptom severity were established using Pearson's correlation. RESULTS: At a liberal alpha level of uncorrected p < 0.005 and a cluster size exceeding 20 voxels, we found widespread decreases in functional connectivity in all three networks when comparing ALS patients to HC. Similar patterns of hypoconnectivity in the bilateral motor cortices and frontotemporal emerged when comparing the ALSci and ALS-FTD patients to those not cognitively impaired. Hyperconnectivity in the DMN temporal gyrus correlated with worse global cognition; moreover, hyperconnectivity in the VAN thalamus, insula, and putamen correlated with worse shifting ability. Better-preserved motor function correlated with higher MN connectivity. Only the motor-related effects prevailed at a more conservative significance level of p FDR < 0.001. CONCLUSION: Resting-state functional connectivity differs between cognitive profiles of ALS and is directly associated with clinical presentation, specifically with motor function, and cognitive shifting.
ABSTRACT
BACKGROUND: Several studies examined the influence of subthalamic nucleus-deep brain stimulation (STN-DBS) on quality of life (QoL) in patients with Parkinson's disease (PD). However, it is unclear whether this effect differs between age groups and disease durations and whether it stays consistent over time. OBJECTIVES: We assessed the influence of stimulation duration, disease duration, and age at surgery on QoL after STN-DBS. METHODS: We systematically searched for studies reporting the results of the Parkinson's Disease Questionnaire 39 or 8. Studies were included if they investigated the time passed since STN-DBS or if their study cohort fell into the range of one of the following age groups: younger than 60 years or between 60 and 70 years. For each condition, a standardized mean difference meta-analysis was performed. Furthermore, all studies were categorized into short or long disease duration at surgery using a median split. RESULTS: A total of 23 studies reporting the cumulative outcome of 76 to 802 PD patients were included in this analysis. The results demonstrate a substantial improvement of QoL after DBS that remains stable over 36 months. QoL falls to preoperative scores 60 months after surgery. However, only 3 studies could be included in this analysis. Both younger and older PD patients profit in QoL from STN-DBS, independent of the disease duration. CONCLUSIONS: The results of this analysis show an impressive improvement in QoL after STN-DBS, with a loss of QoL 60 months after DBS surgery. This highlights the need to explore the factors influencing QoL after STN-DBS to prevent or delay a decline in QoL.
