Objective
The objective of this work was to investigate survival, dementia, and genotype‐phenotype correlations in patients with Parkinson's disease (PD) with and without mutations on the ...glucocerebrosidase gene (GBA).
Methods
We included 2,764 unrelated consecutive PD patients: 123 GBA carriers (67 mild‐p.N370S and 56 severe mainly p.L444P) and 2,641 noncarriers. Brain perfusion and dopamine transporter imaging was analyzed, including dementia with Lewy Bodies (DLB) as an additional control group.
Results
Multivariable analysis adjusted by sex, age at onset, and disease duration attributed to GBA carriers a greater risk for dementia (hazard ratio HR = 3.16; p < 0.001) and death (HR = 1.85; p = 0.002) than noncarriers. When dementia was introduced in the model as a time‐dependent covariate, the mortality risk remained greater in carriers (HR = 1.65; p = 0.016), suggesting that other clinical features are likely to contribute to reduced survival. At last examination, GBA carriers had worse motor symptoms, particularly nondopaminergic features. Carriers of severe mutations had greater risk for dementia compared to mild mutations (p < 0.001), but similar mortality risk. Consistent with clinical data, GBA carriers showed reduced posterior parietal and occipital cortical synaptic activity and nigrostriatal function than PD noncarriers. Neuroimaging features of carriers of mild mutations overlapped with PD noncarriers, whereas carriers of severe mutations were closer to DLB.
Interpretation
Survival is reduced in GBA carriers compared to noncarriers; this seems to be partially independent from the increased risk for early dementia. The risk for dementia is strongly modulated by type of mutation. In the clinical continuum between PD and DLB, patients with GBA mutations seem to localize midway, with carriers of severe mutations closer to DLB than to idiopathic PD. Ann Neurol 2016;80:662–673
Abstract Background Swallowing disturbances are an important issue in Parkinson's disease (PD) as several studies have shown that they are associated with increased risk of aspiration pneumonia and ...mortality. Information about factors related to swallowing disturbances, such as disease duration, age at assessment and concomitant dementia, is limited and would be useful for their management. Methods All consecutive PD out-patients evaluated at a movement disorders clinic over a 7-year period (2007–2014), were included in the present retrospective study. Presence of symptomatic swallowing disturbances was assessed using the specific item of the Non Motor Symptom Questionnaire. Results In the whole PD population ( N = 6462), prevalence of symptomatic swallowing disturbances was 11.7% (95%CI, 10.9–12.5). Multivariable logistic regression analysis (adjusted for education) disclosed a significant interaction between disease duration and gender ( P = 0.009). In both gender strata, swallowing disturbances were significantly associated with longer disease duration and dementia ( P < 0.001 for all). A significant effect for age at assessment was also found in male patients. In non-demented patients, swallowing disturbances were associated with male gender, age and disease duration ( P < 0.02 for all). In demented patients an association was found only with male gender ( P = 0.018) and disease duration ( P < 0.001). Conclusions Gender, age, disease duration and dementia all seem to contribute to the occurrence of swallowing disturbances independently. However, the role played by these factors in sub-groups of patients stratified by gender and concomitant dementia suggests that swallowing disturbances are likely related to different neuro-degenerative patterns within the brain. The underlying mechanisms deserve further investigation.
Background and Objectives: Although the growing literature is now focusing on the long-term effects of Deep Brain Stimulation (DBS) in Parkinson’s disease (PD), there is still a large gap of ...knowledge about its long-term implications in rehabilitation. Therefore, this study aimed at investigating the effects of rehabilitation in PD patients years after DBS implantation. Materials and Methods: This retrospective case–control study analyzed records from Moriggia-Pelascini Hospital, Italy from September 2022 to January 2024. Data of PD patients (n = 47) with (DBS group, n = 22) and without (control group, n = 25) DBS were considered. All study participants underwent a daily rehabilitation program lasting four weeks, including warm-up, aerobic exercises, strength training, postural exercises, and proprioceptive activities. The outcomes assessed were the Unified Parkinson’s Disease Rating Scale (UPDRS), Berg Balance Scale (BBS), Timed Up and Go (TUG), 6 Min Walk Test (6MWT), and Self-Assessment Parkinson Disease Scale (SPDDS). Results: DBS group showed significant improvements in terms of all outcome measures after the rehabilitation intervention (UPDRS III: −7.0 (−11.5 to −1.0); p = 0.001; UPDRS I II IV: −12.0 (−19.0 to −4.5); p = 0.001; BBS: 7.0 (3.8 to 10.3); p < 0.001; TUG (s): −2.8 (−5.7 to −1.1); p < 0.001; SPDDS: −8 (−13.0 to −4.0); p < 0.001; 6MWT (m): 81 (37.3 to 132.3); p < 0.001). No differences were reported in the between-group analysis (p: NS). Conclusions: This study emphasizes positive rehabilitation effects on PD patients irrespective of DBS status. Further research is essential to elucidate long-term effects of DBS on rehabilitation outcomes of PD patients.
According to the somatic marker hypothesis, autonomic measures and arousal modulation can reveal a difference in subgroups of patients developing impaired decision‐making because of addictions. ...Previously, pathological gambling (PG) and Parkinson's disease (PD) have been associated with differential arousal levels during gambling behavior. However, no research considered the specific autonomic responses of Parkinson's disease patients with pathological gambling and with a previous history of gambling. Thus, this study investigated skin conductance responses (SCRs), skin conductance level (SCL) and heart rate (HR) during the Iowa Gambling Task (IGT) in two groups of PD patients with gambling disorder, active (PD Gamblers; n = 14) or remitted (PD Non‐Gamblers; n = 13) and a control group of patients with Parkinson's disease only (n = 13). Anticipatory autonomic responses to disadvantageous decks and advantageous decks during the Iowa Gambling Task were measured for each participant. The PD Gamblers group performed worse than the PD Non‐Gamblers and the control groups at the IGT task and exhibited lower SCRs, SCL, and HR during the decision‐making processing of cards belonging to disadvantageous decks. The role of autonomic and behavioral measures was considered.
Previously, Pathological Gambling and Parkinson’s Disease (PD) have been associated with differential arousal levels during gambling behavior. However, no research compared the specific autonomic responses of PD Gamblers to those of PD patients with a previous history of gambling. Here, PD Gamblers exhibited lower Skin Conductance Responses, Skin Conductance Level and Heart Rate than the PD Non‐Gamblers and the PD control groups, during the decision‐making processing of Iowa Gambling Task disadvantageous decks.
•Pre-feedback and post-feedback processes were analyzed in decision-making.•Gambling patients (PDG) remitted patients (PDNG) and controls (PD) were compared.•Delta and Theta EEG bands increased in ...frontal area for PDG.•PDG opted for more risky choices, whereas PDNG choices were more similar to control PD.•PDG were correlated to high BAS and BIS-11 components.
Psychopathological components, such as reward sensitivity and impulsivity, and dopaminergic treatment are crucial characteristics related to the development of Pathological Gambling (PG) in Parkinson's Disease (PD). The aim of the present study is to investigate the differences in decision-making in PD patients with or without PG considering both neurophysiological and behavioral aspects. The IOWA Gambling Task (IGT) and electroencephalographic (EEG) activity were considered to elucidate the decision and post-feedback processes in PG. The sample included fifty-two PD patients, divided in three groups: 17 PD patients with active gambling behavior (PD Gamblers, PDG); 15 PD patients who remitted from PG (PD Non-Gamblers, PDNG); and a Control Group (CG) composed by 20 patients with PD only. EEG and IGT performance were recorded during decision and post-feedback phase. Results showed worse performance and an increase of the low frequency bands in the frontal area for the PDG group compared to the other two groups. In addition, higher BAS (Behavioral Activation System) and BIS-11 (Barratt Impulsiveness Scale) personality components were correlated to groups’ behavioral response. These results show an anomalous behavioral (IGT) and cortical response of PDG patients related to their inability to use adequate control mechanisms during a decision-making task where reward mechanisms (BAS) and impulsivity (BIS-11) are relevant.
•MSA phenotype shows a challenging overlap with dominant polyglutamine diseases.•Utility of polyQ genetic screening in Italian MSA population.•MSA-C had higher percentage of longer normal SCA1 ...alleles compared to other groups.•One MSA-C patient carried an expanded SCA2 allele, suggesting possible misdiagnosis.
Multiple system atrophy (MSA) is an adult onset, progressive, neurodegenerative disorder of unknown etiology characterized by autonomic dysfunction, parkinsonism (MSA-P) and cerebellar ataxia (MSA-C). The phenotypic spectrum may present overlapping features with other neurodegenerative diseases, particularly the autosomal dominant inherited polyglutamine disorders.
To investigate the possible contribution of CAG expansions in the MSA phenotype, we analyzed the triplet repeat length in the autosomal dominant causative genes for spinocerebellar ataxia (SCA) type 1, 2, 3, 6, 7, 17, dentatorubral-pallidoluysian atrophy (DRPLA) and Huntington disease (HD) in a cohort of 246 Italian MSA patients. As comparison, 223 controls were also analyzed. The alleles were classified on the basis of CAG repeat length as “normal”, “intermediate” or “expanded” according to literature.
The MSA patients (101 men/145 women) had a mean age at onset of 58 years and a mean age at genetic testing of 63 years. MSA-C patients had significantly younger age at onset and at examination in comparison to MSA-P (p < 0.0001). We identified a SCA1 intermediate allele in a MSA-C subject (36 CAG), a SCA2 intermediate allele in a MSA-P patient (31 CAG), and a pathologically expanded SCA2 allele (36 CAG) in a patient initially misdiagnosed as MSA-C.
No intermediate or expanded SCA alleles were detected in controls. The distribution of CAG repeat length was similar among groups except for SCA1 gene that showed a higher percentage of longer normal alleles in MSA-C as compared to MSA-P and controls (p < 0.0001).
This study supports the utility of polyQ genetic testing in the differential diagnosis of MSA, and may suggest a possible role of SCA1 repeat length as risk factor for MSA-C. SCA1 and SCA2 genetic screening is recommended in MSA Italian patients.
Parkinson's disease beyond 20 years Cilia, Roberto; Cereda, Emanuele; Klersy, Catherine ...
Journal of neurology, neurosurgery and psychiatry
86, Številka:
8
Journal Article
Recenzirano
A very limited number of studies report data on the clinical features of Parkinson's disease (PD) 20 years after onset and beyond.
To characterise PD 20 years after onset, investigating the impact of ...age at onset and disease duration on the clinical picture and the predictors of outcomes in patients reaching the 20-year time point.
We conducted a retrospective, cross-sectional study and a longitudinal study. All case visits of patients with a disease duration ≥20 years (N=401) were stratified by disease duration (20-22, 23-25, ≥26 years) and by age at onset (cut-off, 50 years). Patients with a disease duration of 20-22 years (N=320) were prospectively followed up for a median of 45 months (IQR 23-89) for the new occurrence of fracture, percutaneous endoscopic gastrostomy, institutionalisation, confinement to a wheelchair or bed and death.
Older age at onset and longer disease duration were independently associated with a higher prevalence of major motor and non-motor milestones of disease disability (no interaction observed). In the longitudinal study, the most frequent outcomes were death (N=92), confinement to a wheelchair or bed (N=67) and fracture (N=52). Mortality was associated with the gender: male, older age, dysphagia, orthostatic hypotension, postural instability, fractures and institutionalisation. Fracture was associated with postural instability. Predictors of permanent confinement to a wheelchair or bed were older age, postural instability and institutionalisation. Comorbid dementia at the 20-year examination did not predict any of the outcomes.
Age at onset and disease duration are independent determinants of the clinical features of PD beyond 20 years. Non-motor symptoms depend more on age at onset rather than the disease duration itself. Non-levodopa-responsive axial symptoms are the main predictors of all relevant outcomes.
Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is ...Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP (cases) and 3,247 controls (stage 1) followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the stage 1 SNPs that yielded P ≤ 10−3. We found significant previously unidentified signals (P < 5 × 10−8) associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component.
Dopamine dysregulation syndrome (DDS) refers to a compulsive pattern of dopaminergic drug misuse complicating Parkinson's disease (PD). To date, few data are available on DDS risk factors, cognitive ...profile and long-term outcome.
In this retrospective case-control study, consecutive PD outpatients fulfilling criteria for DDS were assessed over a 6-year period (2005-2011). They were compared with 70 PD cases matched for age at onset, gender and disease duration, and with 1281 subjects with motor fluctuations and dyskinesias. DDS patients and matched controls underwent extensive neuropsychological assessment. Strategies for DDS patients management and the outcome at the last follow-up visit were recorded.
Thirty-five patients with DDS were identified, reporting history of depression, family history of PD and drug abuse, greater difference between 'Off' versus 'On' motor symptoms compared to age-matched controls. They had younger age at onset (but not any gender difference) compared to general PD population. Cognitive profile of DDS did not show major abnormalities, including executive functions. DDS patients have been followed up for 3.2±2.1 years and remission was recorded in 40% of cases. Negative DDS outcome was significantly associated with poor caregiver supervision. Sustained remission occurred more commonly on clozapine and on duodenal levodopa infusion and subthalamic nucleus deep brain stimulation (STN-DBS) than on apomorphine pump treatment.
Clinicians should be aware of risk factors predisposing to DDS. Duodenal levodopa infusion and, less consistently, STN-DBS were more commonly associated with DDS remission. Effective caregiving plays a key role in long-term behavioural outcome.
Abstract Background The rates of cognitive decline in patients with Parkinson's disease (PD) are higher than in the general population. Age and disease duration have been associated with increasing ...rates of dementia in PD. However, the role of other factors including gender has been poorly investigated. We investigated the relationship between dementia and gender along with other established risk factors, such as age and disease duration. Methods We conducted a cross-sectional retrospective study including all consecutive patients diagnosed with idiopathic PD attending a single out-patient tertiary clinic over an 18-year period (1995–2013). Dementia was diagnosed according to DSM-IV criteria. Results Prevalence of dementia was 11.5% (95%CI, 10.8–12.3) and 13.5% (95%CI, 12.7–14.5) in the whole population (N = 6599) and in those aged ≥60 years (N = 5373), respectively. Age and disease duration were independently associated with dementia, and the latter was associated with dementia up to 84 years of age. Male gender was an independent risk factor. In addition, while the rate of dementia increased in males over all age strata, we found that in females prevalence began to increase steadily after the age of 65 years, reaching male estimates only after 80 years of age. Higher rates in male gender were observed between 60 and 80 years of age. Conclusion Age and PD duration are confirmed risk factors for dementia. However, disease duration appeared to be a less important factor in cognitive decline in patients aged ≥85 years. As opposed to gender-specific estimates in the general population, male gender is likely associated with higher rates of dementia in PD patients.
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