Prospective association between emotional health and clinical evidence of Parkinson's disease.

BACKGROUND AND PURPOSE: Whilst disorders of emotion are commonly comorbid with Parkinson's disease (PD), evidence concerning their association with PD risk is limited. We investigate the prospective association between selected measures of emotional health and incident suspected PD. METHODS: 20,855 men and women, considered PD-free at baseline, completed a postal assessment of major depressive disorder (MDD), generalized anxiety disorder (GAD), psychological distress [defined by the five-item Mental Health Inventory (MHI-5)], and neuroticism. PD case ascertainment was based upon PD medication use, self-report questionnaires, hospital record discharge codes, and death certification, subsequently checked against general practitioner, hospital records and neurological service records. RESULTS: 175 suspected cases of incident PD were identified in 160,725 (median 7.9) person-years of follow-up (with 43 recorded in neurological service records). MDD lifetime history, GAD lifetime history, MHI-5 and neuroticism were all significantly associated with suspected PD following adjustment for age, sex, cigarette smoking, alcohol consumption, social class and education. CONCLUSIONS: This study supports an association between measures of emotional health, assessed prior to evidence of motor symptoms, and subsequent suspected PD diagnosis. However, we were unable to determine whether our measures of personality and emotional health represent genuine premorbid risk factors or early stages of PD. Long-term prospective healthy cohort studies are required to investigate the relationship between emotional health history and the evolution of the premotor and motor phases of PD.

PINK1 mutations and parkinsonism.

BACKGROUND: PINK1 loss-of-function causes recessive, early-onset parkinsonism. In Tunisia there is a high rate of consanguineous marriage but PINK1 carrier frequency and disease prevalence have yet to be assessed. OBJECTIVES: The frequency of PINK1 mutations in familial parkinsonism, community-based patients with idiopathic Parkinson disease (PD) (non-familial PD), and control subjects was determined. Demographic and clinical characteristics of individuals with PINK1 homozygous or heterozygous variants, or without PINK1 mutations, were compared. METHODS: A total of 92 kindreds (with 208 affected and 340 unaffected subjects), 240 nonfamilial PD, and 368 control participants were recruited from the Institut National de Neurologie, Tunis. Clinical examinations included Hoehn &Yahr, UPDRS, and Epworth scales. PINK1 sequencing and dosage analysis was performed in familial index patients, the variants identified screened in all subjects. Parkin and LRRK2 genes were also examined. RESULTS: Four PINK1 homozygous mutations, three novel (Q129X, Q129fsX157, G440E, and one previously reported; Q456X), segregate with parkinsonism in 46 individuals in 14 of 92 families (15%). Six of 240 patients with nonfamilial PD were found with either homozygous Q456X or Q129X (2.5%) substitutions. In patients with familial disease, PINK1 homozygotes were younger at disease onset (36 +/- 12 years) than noncarriers (57 +/- 15 years) and more often had an akinetic-rigid presentation at examination and slow progression. CONCLUSIONS: Segregation of PINK1 mutations with parkinsonism within families, and frequency estimates within population controls, suggested only four PINK1 mutations were pathogenic. Several PINK1 sequence variants are potentially benign and there was no evidence that PINK1 heterozygosity increases susceptibility to idiopathic Parkinson disease.