The cognitive status of patients with Parkinson’s disease (PD) who developed pathological gambling (PG) during dopamine replacement therapy has been poorly explored. We compared clinical and ...cognitive features of 21 consecutive PD patients with active PG (PD–PG) versus 42 PD controls of similar disease duration without any impulse control disorder. All patients underwent full neuropsychological testing to evaluate executive and other frontal lobe-related functions, attention, learning and memory, language, visuospatial abilities and neuropsychiatric status using Geriatric Depression Scale (GDS) and Neuropsychiatric Inventory (NPI) as well as the South Oaks Gambling Screen Scale (SOGS). PD–PG were younger (60.4 vs. 64.9,
p
= 0.01) and more frequently of male gender (85 vs. 57%,
p
= 0.02). The two groups did not differ in medication dosages and kind of dopamine agonist. PD–PG had higher MMSE (29.1 vs. 27.4,
p
= 0.02) and performed better at Rey Auditory Verbal learning Test (45.9 vs. 40.4,
p
= 0.04), verbal phonemic fluencies (38.7 vs. 31.8,
p
= 0.02), verbal semantic fluencies (44.9 vs. 37.4,
p
= 0.01) and attentive matrices (47.6 vs. 43.5,
p
= 0.05) while the remaining cognitive performances were comparable to controls. Moreover, based on the NPI, PD–PG had higher aggressiveness, irritability, disinhibition and eating disorders than controls. In conclusion the occurrence of PG in our cohort of patients with PD was associated with preserved executive functions.
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
Quantitative evaluation of midbrain atrophy may be useful in differentiating progressive supranulear palsy (PSP) from Parkinson disease (PD); however, this finding is not specific of PSP, and ...quantitative measurements are not always practical. We determined whether an abnormal superior midbrain profile (flat or concave aspect) is a more practical diagnostic parameter for PSP.
MR imaging studies of 25 patients with PSP and 27 with PD were reviewed by means of five parameters: midbrain superior profile on midsagittal T1-weighted images, midbrain atrophy, tegmental abnormal T2 hyperintensity, abnormal T2 putaminal hypointensity or hyperintensity on axial proton density-weighted images. We also measured the anteroposterior diameter of the midbrain on axial T2-weighted sections at the level of the superior colliculus.
The finding of an abnormal superior profile of the midbrain had 68% sensitivity and 88.8% specificity. Midbrain atrophy had 68% sensitivity and 77.7% specificity. Tegmental T2 hyperintensity had 100% specificity but poor sensitivity (28%). Only 14.8% of patients with PD and 24% of those with PSP had abnormal putaminal T2 hypointensity; none had proton-density hyperintensity. With PSP, the average midbrain diameter was smaller than that with PD, but an important overlap was observed. Reader discordance was lower for the midbrain superior profile sign (eight of 52 cases); this was similar for tegmental hyperintensity (nine of 52 cases) and higher for midbrain atrophy (16 of 52 cases).
An abnormal superior profile of the midbrain facilitates the distinction of PSP from PD and may support the clinical differential diagnosis of parkinsonism.
Abstract Background Age is considered an important risk factor for Parkinson's disease (PD). However, although life-expectancy has increased considerably, incidence rates of PD appeared to be stable ...over the last two decades. Accordingly, an increase in mean age at onset over time could be expected. We investigated the changes in age at onset in PD over the last two decades. Methods All consecutive PD patients assessed over a 18-year period (1995–2013) in a single tertiary outpatient clinic were included in the present retrospective cohort study. Results After adjusting for several confounders (gender, positive family history for PD, education, smoking at onset and past exposure to environmental/occupational pollutants), 5-year cohorts of year of disease onset were associated with increasing age at onset in both prevalent ( N = 6996) and incident ( N = 4172) cases (for trend, P < 0.001). From 1995–2000 to 2010–2013 there was an increase in predicted age of 4.1 years (95% CI, 3.0–5.2) and 3.9 years (95% CI, 2.7–5.1) in prevalent and incident cases, respectively. However, the change in predicted age at PD onset, across cohorts of year at onset, showed a steeper increase than the corresponding sex and cohort-matched mean age from the official Italian statistics. Conclusions Over the last two decades, age at onset of PD appeared to shift progressively towards more advanced age. However, sequential, high-quality population-based incidence studies are required. To establish whether there is a trend towards increase in age at onset over and above general population ageing and to assess whether the increase is associated with improved medical and socio-economic conditions.
We analysed the
Leucine-Rich Repeat Kinase 2 (
LRRK2) gene for the G2019S mutation in 1245 consecutive, unrelated patients with primary degenerative parkinsonism, and collected information on medical ...history, motor, cognitive and neuropsychiatric functions to characterize the clinical phenotype associated to the G2019S mutation. The mutation was detected in heterozygous state in 19 probands (1.7%), and in five additional affected relatives. Clinical features in carriers were those of typical, idiopathic Parkinson's disease. However, behavioural abnormalities were frequent (87%), suggesting a more widespread limbic involvement in G2019S carriers.
Abstract The α-synuclein gene ( SNCA ) multiplication causes autosomal dominant Parkinson Disease (PD): triplication is associated with early-onset rapidly progressing parkinsonism with a strong ...likelihood of developing dementia, while duplication is associated with a less severe phenotype similar to idiopathic PD. We tested for SNCA multiplication 144 unrelated PD patients with a dominant family history. We identified one patient with SNCA duplication (0.7%). The SNCA -duplicated patient was a woman of 45 years of age with PD onset at 41 years of age. She experienced a rapidly progressive disease with early motor complications (on/off fluctuations and dyskinesias). Medical records confirmed that the proband's mother developed PD at 47 years of age and died at 63 with dementia. She experienced rapid progression in both motor and cognitive symptoms: development of dementia at 54 years of age, 7 years after onset. Although SNCA duplication is an unusual cause of familial PD testing for it is worthwhile. The clinical presentation of duplicated cases may be more aggressive than usual.
This multicentre randomised double blind crossover trial tested the short term efficacy of intravenous immunoglobulin (IVIg) 2.0 g/kg given over 24 or 48 hours in patients with paraproteinaemic ...demyelinating neuropathy (PDN). Twenty-two patients were randomised and completed the trial. After 2 weeks, the overall disability grade decreased during both IVIg treatment and placebo but neither change was significant nor was the mean difference between the treatment effects. After 4 weeks the overall disability decreased by a mean of 0.55 0.67 grades during the IVIg period (p = 0.001) while it was substantially unmodified during the placebo period. The mean difference between the treatment effects was significant (p = 0.05). Overall during the IVIg period 10 patients improved and 11 were stable and one got worse. During the placebo period 4 patients improved, 4 deteriorated and 14 were stable. Many secondary outcome measures, including Rankin scale, time to walk 10 metres, grip strength, sensory symptoms score were significantly better during IVIg treatment. Two serious adverse events occurred during the trial, both during placebo treatment. In conclusion the trial showed some short-term benefit of IVIg in about half of the patients confirming previous observation.
