Depression and quality of life in monogenic compared to idiopathic, early-onset Parkinson's disease.

Quality of life (QoL) is decreased in PD and is linked with depression and anxiety. However, little is known about QoL in monogenic PD. Subjects with mutations in PD genes were recruited from ongoing family and genetic studies (manifesting carriers, n = 23; nonmanifesting carriers, n = 19). For comparison purposes, we included patients with idiopathic PD (IPD; n = 128; early onset, n = 38; late onset, n = 90), healthy controls (n = 127), and data on depressive symptoms of 144 patients with major depression (treated controls). Depression affected 31% of early-onset PD cases, 21% of late-onset cases, and 44% of manifesting carriers of mutations in PD genes, but was rare in the nonmanifesting carriers (7%) and healthy controls (5%). Subjects with Parkinson-associated depression reported fewer feelings of guilt or self-doubt than treated controls, but the occurrence of suicidal ideation was associated with severity of depression only. Social phobia (P = 0.018) and agoraphobia (P = 0.059) were more common in manifesting carriers than in any other group. QoL was decreased in the Parkinson groups, particularly in the early-onset cases (P < 0.001), and QoL correlated with depression in all analyses. In our study, monogenic and IPD cases were comparable in QoL and depression characteristics. The QoL and, possibly, overall prognosis of all PD patients can be improved by appropriate attention and treatment for depression, sleep impairments, and anxiety, even if the treatment of the motor problems cannot be further optimized.

Impaired sense of smell and color discrimination in monogenic and idiopathic Parkinson's disease.

Olfaction is typically impaired in idiopathic Parkinson's disease (IPD), but its role is uncertain in monogenic PD. Diminished color discrimination has been suggested as another early sign of dopaminergic dysfunction but not been systematically studied. Furthermore, it is unknown whether both deficits are linked. We examined 100 patients with IPD, 27 manifesting mutation carriers (MC), 20 nonmanifesting mutation carriers (NMC), and 110 controls. Participants underwent a standardized neurological examination, the University of Pennsylvania Smell Identification Test (UPSIT), the Farnsworth-Munsell (FM) color discrimination test, and mutation testing in known PD genes. The monogenic group consisted of 15 Parkin (6MC/9NMC), 17 PINK1 (10MC/7NMC), 8 LRRK2 (4MC/4NMC), 3 SNCA (MC), and 4 ATP13A2 (MC) carriers. Olfaction was most impaired in IPD (UPSIT percentiles 10.1 ± 13.5) compared with all other groups (MC 13.8 ± 11.9, NMC 19.6 ± 13.0, controls 33.8 ± 22.4). Within MC, carriers of two mutations in Parkin and PINK1 showed higher UPSIT percentiles than LRRK2 and SNCA carriers. Color discrimination was reduced in IPD (FM total error score 134.8 ± 92.7). In MC (122.4 ± 142.4), the reduction was most pronounced in LRRK2, NMC (80.0 ± 38.8) were comparable with controls (97.2 ± 61.1). UPSIT and FM scores were correlated in the control (r = -0.305; P = 0.002) and the IPD group (r = -0.303; P = 0.006) but not among mutation carriers. First, we confirmed olfaction and color discrimination to be impaired in IPD and suggest olfaction to be a premotor sign. Second, olfaction differed between carriers with one and two mutations in Parkin/PINK1-associated PD. Third, olfaction and color discrimination impairment do not necessarily evolve in parallel.

Nonmotor symptoms in genetic Parkinson disease.

OBJECTIVES: To review current knowledge on nonmotor symptoms (NMS), particularly psychiatric features, in genetic Parkinson disease (PD) and to provide original data for genetic and idiopathic PD. DATA SOURCES: A MEDLINE search using Parkinson and known PD genes focused on the presence of depression, anxiety, hallucinations, and dementia was performed. Original data from 82 outpatients with idiopathic (n = 55) and genetic (n = 27) PD were obtained. STUDY SELECTION: All studies including information on NMS and patients with genetic PD. DATA EXTRACTION: Study methods and clinical and genetic information were summarized. DATA SYNTHESIS: The literature search yielded 1855 citations; 305 included genetic information on PD patients, of which 119 also contained information on any type of NMS (990 cases). Availability of information varied by gene and type of NMS; studies differed by recruitment and examination method. Literature search and original data showed high frequencies of the following NMS: depression, 8% to 37% (literature) and 33% to 40% (our data); anxiety, 7% to 37% (literature) and 10% to 22% (our data); hallucinations, 3% to 23% (literature) and 23% to 29% (our data); and dementia, 5% to 26% (literature), absent in our own data. CONCLUSIONS: Data on NMS in genetic PD are limited. Specific data needs include a systematic approach to NMS assessment reporting permitting comparability of studies. Overall, the frequency of NMS in genetic PD does not appear to be higher and may even be lower than in idiopathic PD. Nonmotor symptoms have a high impact on the patients' quality of life and caregiver burden and should be considered important and often treatable concomitant features of genetic PD.