Statins are underused in recent-onset Parkinson's disease with increased vascular risk: findings from the UK Tracking Parkinson's and Oxford Parkinson's Disease Centre (OPDC) discovery cohorts.

BACKGROUND: Cardiovascular disease (CVD) influences phenotypic variation in Parkinson's disease (PD), and is usually an indication for statin therapy. It is less clear whether cardiovascular risk factors influence PD phenotype, and if statins are prescribed appropriately. OBJECTIVES: To quantify vascular risk and statin use in recent-onset PD, and examine the relationship between vascular risk, PD severity and phenotype. METHODS: Cardiovascular risk was quantified using the QRISK2 calculator (high ≥20%, medium ≥10 and <20%, low risk <10%). Motor severity and phenotype were assessed using the Movement Disorder Society Unified PD Rating Scale (UPDRS) and cognition by the Montreal cognitive assessment. RESULTS: In 2909 individuals with recent-onset PD, the mean age was 67.5 years (SD 9.3), 63.5% were men and the mean disease duration was 1.3 years (SD 0.9). 33.8% of cases had high vascular risk, 28.7% medium risk, and 22.3% low risk, while 15.2% of cases had established CVD. Increasing vascular risk and CVD were associated with older age (p<0.001), worse motor score (p<0.001), more cognitive impairment (p<0.001) and worse motor phenotype (p=0.021). Statins were prescribed in 37.2% with high vascular risk, 15.1% with medium vascular risk and 6.5% with low vascular risk, which compared with statin usage in 75.3% of those with CVD. CONCLUSIONS: Over 60% of recent-onset PD patients have high or medium cardiovascular risk (meriting statin usage), which is associated with a worse motor and cognitive phenotype. Statins are underused in these patients, compared with those with vascular disease, which is a missed opportunity for preventive treatment. TRIAL REGISTRATION NUMBER: GN11NE062, NCT02881099.

High resolution magnetic susceptibility mapping of the substantia nigra in Parkinson's disease.

PURPOSE: To determine if tissue magnetic susceptibility is a more direct marker of tissue iron content than other MR markers of iron. This study presents the first quantitative, in vivo measurements of the susceptibility of the substantia nigra in patients with Parkinson's disease. MATERIALS AND METHODS: Nine patients and 11 controls were studied at 7 Tesla. Susceptibility maps were created by inverting the filtered phase maps associated with T2* weighted images. RESULTS: On average, patients showed an increase in susceptibility of the pars compacta compared with controls, which correlates with the predicted increase in brain iron in Parkinson's disease. A rostral-caudal gradient in susceptibility was also observed in controls and patients. CONCLUSION: Susceptibility mapping may provide a new tool for studying the development of Parkinson's disease.

Can spiral analysis predict the FP-CIT SPECT scan result in tremulous patients?

BACKGROUND: Previous studies have compared the accuracy of spiral analysis in distinguishing essential tremor (ET) from PD. In this study, we have used this technique to distinguish cases of tremulous PD (TDPD) (N = 24) from tremulous parkinsonian subjects without evidence of dopaminergic deficit (N = 41). METHODS: All patients were characterized on clinical and (123)I-N-ω-fluoro-propyl-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane ([(123)I] FP-CIT) SPECT scan data, which were concordant in every case. All analyses were carried out by observers blinded to the clinical details and supplied with just the spiral drawings, from which tremor severity (TS), 3-turn spiral diameter (3TD), and spiral density (SD) were measured. RESULTS: The spirals drawn by TDPD cases had significantly smaller 3TD (P = 0.029) and greater SD (P = 0.0082) than those with normal FP-CIT scans. There was no significant difference in the TS between the two groups (P = 0.11). The sensitivity and specificity of TS were 62.5% and 65.0%, 3TD were 75% and 56.7%, and SD were 30.4% and 82.5%, respectively, in predicting the correct classification. Further analyses combining these factors into pairs, showed that the respective sensitivities and specificities of (1) TS × 3TD were 75.0% and 40.0%, (2) TS/SD were 56% and 70.0%, and (3) 3TD/SD were 87.0% and 40.0%. DISCUSSION: There are significant differences in the 3TD and SD of spirals drawn by tremulous patients with normal versus abnormal FP-CIT scans. Spiral analysis may have some clinical value in helping to distinguish tremulous parkinsonian patients with normal presynaptic dopaminergic imaging from tremulous PD patients, providing results similar to those reported for expert movement disorder neurologists using standardized videotaped examinations.

Accuracy of clinical diagnosis in tremulous parkinsonian patients: a blinded video study.

BACKGROUND: This study examines the clinical accuracy of movement disorder specialists in distinguishing tremor dominant Parkinson's disease (TDPD) from other tremulous movement disorders by the use of standardised patient videos. PATIENTS AND METHODS: Two movement disorder specialists were asked to distinguish TDPD from patients with atypical tremor and dystonic tremor, who had no evidence of presynaptic dopaminergic deficit (subjects without evidence of dopaminergic deficit (SWEDDs)) according to (123)I-N-ω-fluoro-propyl- 2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane ([(123)I] FP-CIT) single photon emission computed tomography (SPECT), by 'blinded' video analysis in 38 patients. A diagnosis of parkinsonism was made if the step 1 criteria of the Queen Square Brain Bank criteria for Parkinson's disease were fulfilled. The reviewer diagnosis was compared with the working clinical diagnosis drawn from the medical history, SPECT scan result, long term follow-up and in some cases the known response to dopaminergic medications. This comparison allowed a calculation for false positive and false negative rate of diagnosis of PD. RESULTS: High false positive (17.4-26.1%) and negative (6.7-20%) rates were found for the diagnosis of PD. The diagnostic distinction of TDPD from dystonic tremor was reduced by the presence of dystonic features in treated and untreated PD patients. CONCLUSION: Clinical distinction of TDPD from atypical tremor, monosymptomatic rest tremor and dystonic tremor can be difficult due to the presence of parkinsonian features in tremulous SWEDD patients. The diagnosis of bradykinesia was particularly challenging. This study highlights the difficulty of differentiation of some cases of SWEDD from PD.

Variation in Recent Onset Parkinson's Disease: Implications for Prodromal Detection.

BACKGROUND: The detection of prodromal Parkinson's disease (PD) is desirable to test drugs with neuroprotective potential, but will be affected by known disease variations. OBJECTIVE: To assess the prevalence of four key non-motor prodromal PD markers, and evaluate the sensitivity of case detection when non-motor screening tools for prodromal PD are implemented in an early clinical PD cohort. METHODS: Hyposmia (University of Pennsylvania smell identification test ≤15th centile or Sniffin' Sticks at or ≤10th centile corrected for age and sex), rapid-eye movement sleep behaviour disorder (RBD questionnaire >4), constipation (<1 daily spontaneous bowel motion) and depression (Leeds >6) were recorded in recent onset PD cases, and proposed non-motor screening criteria applied. RESULTS: In 1,719 PD cases, mean age 68.6 years (SD 8.1), 65.5% male, mean disease duration 1.3 years (SD 0.9), 72.2% were hyposmic, 43.3% had RBD, 22.1% depression, and 21.5% constipation. 11.6% of cases had no key non-motor features, 38.8% one, 32.1% two, 15.5% three, and 2.0% all four. Increasing numbers of non-motor features were associated with younger age (p = 0.019), higher motor scores (p < 0.001), more postural instability gait difficulty (PIGD) (p < 0.001), greater cognitive impairment (p < 0.001) and higher total non-motor burden (p < 0.001). Cases with hyposmia alone were younger (p < 0.001), had less severe cognitive (p = 0.006) and other non-motor features (p < 0.001). All screening criteria selected younger patients (p = 0.001, p < 0.001), three of four greater overall non-motor burden (p = 0.005, p < 0.001), and inclusion of RBD more cognitive impairment (p = 0.003, p = 0.001) and PIGD (p = 0.004, p = 0.001). CONCLUSIONS: Varying sensitivity levels, and age and phenotype selectivity, are found when different non-motor screening methods to detect prodromal PD are applied to an early clinical PD cohort.