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Objective: To compare survival, life expectancies (LE), and the anticipated age at the time of death (AAD), in a community-based cohort of Parkinson's disease (PD) patients with and without significant cognitive impairment, with an age sex matched population of England and Wales., Methods: The age- and sex-specific standardised mortality ratios (SMR) were calculated and stratified by dementia status. The LE and AAD estimations were calculated from the SMRs of the 2003 UK population, using a modified Gompertz function., Results: In total, 166 PD patients participated in the investigation, of which 91 died by the 4-year follow-up. The overall SMR was 2.09 (95% CI 1.68 to 2.57). Demented patients had significantly higher SMRs than non-demented patients (SMR 3.10, 95% CI 2.39 to 3.96 vs SMR 1.15, 95% CI 0.75 to 1.69, p<0.001). In our cohort, the LE in younger-onset demented patients (55-74 years) was much lower than in non-demented patients (7.5; SD 3 vs 12.4; SD 7). Likewise, the estimated AAD in younger onset patients with dementia was also much lower (demented 72.4; SD 4 vs not demented 77.8; SD 7). In older-onset patients with dementia (>75 years), the differences in LE (demented 2.1; SD 1 vs not demented 4.7; SD 4) and AAD were less apparent (demented 89.5; SD 6 vs not demented 92.2; SD 6)., Conclusion: The survival, LE and AAD in patients with PD are much lower compared with the general population, apart from those patients who do not develop dementia, who appear to have near normal population mortalities. However, dementia and younger onset of PD appear to be important determinants of survival, LE and AAD.

Genetic classification of Parkinson's disease (PD) subtypes may become the preferred diagnostic tool for neurologists. Herein we compare clinical features from a large cohort of patients with familial PD of unknown aetiology or attributable to distinct genetic forms. Comprehensive neurological examinations were performed in 231 familial PD patients from Tunisia. Analysis was previously performed to screen for mutations in leucine rich repeat kinase 2 (LRRK2), PTEN induced kinase 1 (PINK1) and parkin (PRKN). Clinical features were compared between patients with genetically undefined PD (n=107) and those with LRRK2 (n=73) and PINK1 (n=42) mutations using regression analyses adjusted for gender, age of onset and disease duration. PRKN cases (n=9) were too few for meaningful statistical analysis. In comparison with genetically undefined patients, LRRK2 mutation carriers had more severe motor symptoms (median Unified Parkinson's Disease Rating Scale scores approximately 1.6 times higher, p<0.001), a higher rate of dyskinesia (OR 4.21, p=0.002) and use of dopamine agonists (OR 3.64, p<0.001), and less postural tremor (OR 0.21, p<0.001). PINK1 mutation carriers presented an increased rate of drug induced dyskinesia (OR 3.81, p=0.007) and a lower rate of postural tremor (OR 0.16, p<0.001) than genetically undefined patients. As expected, PINK1 patients had younger ages and ages at disease onset, and a longer disease duration compared with LRRK2 mutation carriers and genetically undefined patients. Clinical differences between LRRK2, PINK1 and genetically undefined familial PD appear more pronounced than previously appreciated, and may prove useful in clinical practice. As future therapies are targeted to specific protein abnormalities, identifying the genetic causes and associated clinical and pathological features will determine diagnosis, preventative medicine and drug intervention strategies.