Showing papers by "Francesco E. Pontieri published in 2012"

The progression of non-motor symptoms in Parkinson's disease and their contribution to motor disability and quality of life.

Abstract: Non-motor symptoms are gaining relevance in Parkinson’s disease (PD) management but little is known about their progression and contribution to deterioration of quality of life. We followed prospectively 707 PD patients (62 % males) for 2 years. We assessed non-motor symptoms referred to 12 different domains, each including 1–10 specific symptoms, as well as motor state (UPDRS), general cognition, and life quality. Hoehn & Yahr (HY III moderate; IV–V severe). We found that individual non-motor symptoms had variable evolution over the 2-year follow-up with sleep, gastrointestinal, attention/memory and skin disturbances (hyperhidrosis and seborrhea) becoming more prevalent and psychiatric, cardiovascular, and respiratory disorders becoming less prevalent. Development of symptoms in the cardiovascular, apathy, urinary, psychiatric, and fatigue domains was associated with significant life-quality worsening (p < 0.0045, alpha with Bonferroni correction). During the observation period, 123 patients (17 %) worsened clinically while 584 were rated as stable. There was a fivefold greater increase in UPDRS motor score in worse compared with stable patients over 24 months (p < 0.0001 vs. baseline both in stable and worse group). The total number of reported non-motor symptoms increased over 24 months in patients with motor worsening compared to stable ones (p < 0.001). Thirty-nine patients died (3.4 % of patients evaluable at baseline) with mean age at death of 74 years. Deceased patients were older, had significantly higher H&Y stage and motor score, and reported a greater number of non-motor symptoms at baseline. In conclusion, overall non-motor symptom progression does not follow motor deterioration, is symptom-specific, and only development of specific domains negatively impacts quality of life. These results have consequences for drug studies targeting non-motor features.

Hippocampal abnormalities and memory deficits in Parkinson disease A multimodal imaging study

Abstract: Objectives: Investigating in a case-control study whether the performance scores of a group of patients with Parkinson disease (PD) without dementia on tests of declarative memory could be predicted by hippocampal volume reduction (as assessed by automatic segmentation of cerebral magnetic resonance [MR] images) or by the rate of microstructural alterations (as evaluated by diffusion tensor analysis of MR images). Method: Twenty-five individuals with PD and 25 matched healthy control subjects underwent a 3-T MRI protocol with whole-brain T1-weighted and diffusion tensor imaging and a neuropsychological assessment. Images were processed to obtain indices of macrostructural (volume) and microstructural (mean diffusivity [MD]) variation of bilateral hippocampi. Neuropsychological evaluation included tests of verbal memory (15-minute delayed recall of a 15-word list) and visuospatial memory (20-minute delayed reproduction of Rey complex figure). Results: MD in the hippocampi of patients with PD was significantly increased with respect to that of the group of control subjects. Moreover, patients with high hippocampal MD values obtained low memory scores. In contrast, no difference emerged between patients with PD and healthy control subjects for hippocampal size, and no relationship could be found between hippocampal volumes and memory scores. Conclusions: These data confirm that the declarative memory impairment in patients with PD without dementia may be predicted by the rate of microstructural alterations in the hippocampal formation as detected by diffusion tensor imaging analysis.

Psychosis associated to Parkinson's disease in the early stages: relevance of cognitive decline and depression

Abstract: Objective To evaluate the prevalence of psychosis associated with Parkinson9s disease (PSY-PD) in its early stages, its incidence over a 24 month follow-up period and the association with motor and non-motor clinical features. Methods PRIAMO is a 2 year longitudinal observational study that has enrolled patients with parkinsonism in 55 Italian centres. A cohort of 495 patients with early disease stage PD (baseline Hoehn and Yahr score ≤2, disease9s duration (median) 3.4 years) were followed for 2 years. PSY-PD was evaluated by means of a clinician rated questionnaire and defined as the presence of at least one of the following symptoms occurring for at least 1 month: illusions, hallucinations, jealousy ideas and persecutory ideas. Patients with and without PSY-PD were compared on several clinical variables, encompassing motor and non-motor features. Results The prevalence of PSY-PD at baseline was 3%; the incidences at 12 and 24 months were 5.2% and 7.7%, respectively. Longer disease duration and prescription of dopamine agonists at baseline were associated with the development of PSY-PD over the 24 month period. At this follow-up time, worse disease severity, decline in cognitive performances, presence of depressive symptoms and anxiety were more frequently observed in PSY-PD. Conclusions Psychotic type symptoms may occur in the early stages of PD although less frequently than in later stages. Beyond dopaminergic treatment, there are disease related factors, such as disease severity and the occurrence of cognitive and depressive symptoms, which may underlie the onset of psychotic type symptoms from the earliest stages.

Alexithymia is a non-motor symptom of Parkinson disease.

Abstract: Objectives To investigate whether alexithymia is linked to the disease process or to psychopathology, particularly depression, in Parkinson disease (PD) patients. Design Cross-sectional study. Setting Neuropsychiatry outpatient clinic. Participants One hundred PD patients and 100 comparison subjects (CS). Measurements PD patients and CS underwent a clinical and neuropsychiatric evaluation. Alexithymia was assessed with the 20-item Toronto Alexithymia Scale (TAS-20). Severity of depressive symptoms was measured with the Beck Depression Inventory. A structured psychiatric interview was used to diagnose major and minor depression. Logistic regression analyses with 95% confidence intervals (CI) were used to assess the association between alexithymia and PD. Results Alexithymia occurred twice as often in PD patients (22%) as in CS (11%) and major depressive disorder occurred twice as often in CS (30%) than in PD (16%). The frequency of minor depression was almost identical (about 40%) in the 2 groups. Alexithymia was also associated with PD independently from depression. Indeed, after adjustment for sociodemographic factors, antidepressant use and depression severity, PD patients had an almost fourfold higher risk of having alexithymia (OR: 3.9, 95% CI: 1.5–10.0) and 24 times increased odds of having high scores on the TAS-20 items assessing difficulty in identifying emotions than CS (OR: 23.7, 95% CI: 10.1–55.6). Conclusions Our findings suggest that alexithymia is a depression-independent phenomenon in PD patients and may be associated with the disease process. Alexithymia is an important nonmotor symptom of PD and should be considered in patient assessment and management.

Regional cortical thickness and cognitive functions in non-demented Parkinson's disease patients: a pilot study.

Abstract: Background and purpose: The pathology of neuropsychological deficits in Parkinson’s disease (PD) is incompletely defined. Methods: We investigated cortical thickness and neuropsychological performances in non-demented patients with PD and healthy controls. Results: Patients showed significant cortical thinning in right middle temporal and left fusiform cortices. Verbal memory performance was related with left fusiform thinning. Conclusions: Cognitive and cortical changes in non-demented patients with PD are detectable and clearly related.

Frontal assessment battery scores and non-motor symptoms in parkinsonian disorders

Abstract: Using data from the PRIAMO study, we investigated non-motor symptoms (NMS) versus frontal lobe dysfunction in patients with idiopathic Parkinson disease (PD); 808 patients with PD and 118 with atypical parkinsonisms (AP) were consecutively enrolled at 55 Centers in Italy. Twelve categories of NMS were investigated. Cognitive impairment was defined as a Mini-Mental Status Evaluation score ≤ 23.8 and frontal lobe dysfunction as a Frontal Assessment Battery (FAB) score ≤ 3.48. Multivariable logistic regression was used to identify predictor of frontal lobe dysfunction in 524 PD patients, and a generalized linear model was used for each of the six FAB items. Not only the total FAB scores but also the single FAB items were lower in AP versus PD (p ≤ 0.005). Age (OR = 1.05), cognitive impairment (OR = 9.54), lack of cardiovascular symptoms (OR = 3.25), attention or memory problems (OR = 0.59) and treatment with L: -DOPA (OR = 5.58) were predictors of frontal lobe dysfunction. MMSE was negatively associated with all FAB items (β ≤ -0.16) and age with all FAB items but prehension behavior (β ≤ -0.01). Previous use of L: -DOPA was negatively associated with verbal fluency (β = -0.32) possibly acting as surrogate marker of disease duration. Cognitive impairment is a predictor of frontal lobe dysfunction. Among NMS, lack of attention or memory problems were negatively associated with frontal impairment. Further studies are nonetheless needed to better identify the predictors of frontal impairment in PD patients.