Wednesday, 18 January 2017

Gender differences in Parkinson's disease depression

This is interesting and has potential relevance to mood changes in the prodromal phase of PD as well... the may be gender-specific features to depression and this may mean we need to reconsider how we measure depression in cohorts like PREDICT-PD...

Parkinsonism Relat Disord. 2016 Dec 29. pii: S1353-8020(16)30519-3. doi: 10.1016/j.parkreldis.2016.12.026. [Epub ahead of print]
Perrin AJ, Nosova E, Co K, Book A, Iu O, Silva V, Thompson C, McKeown MJ, Stoessl AJ, Farrer MJ, Appel-Cresswell S.

INTRODUCTION: 30-40% of patients with Parkinson's disease (PD) experience depression during their illness; identifying subtypes of depression and groups at risk remains a challenge in routine clinical care. One avenue that remains underexplored is the gender-specific profiles manifested in PD depression. We sought to explore this in a large sample of clinical PD patients.

METHODS: 307 patient records at a tertiary referral centre were reviewed for clinical and demographic factors. We used recursive partitioning to determine which items on the Beck Depression Inventory (BDI) were most useful in differentiating patients who scored in the depressed range (≥14) from those who scored in the non-depressed range (≤13). We also used recursive partitioning to identify those BDI items that were most effective in differentiating depressed from non-depressed patients in both genders.

RESULTS: We were able to identify a subset of items on the BDI that were most useful in partitioning depressed from non-depressed in the entire cohort. Partitioning of men and women with PD depression relied on different key BDI items, melancholy featuring prominently in women, while the more classical factors associated with depression in PD (apathy and loss of libido) featured more prominently in men.

CONCLUSION: Unique factors not previously identified as core features of depression in PD were found most useful in partitioning depressed women from non-depressed women. This raises the possibility that a female-specific depressive profile has been under-appreciated in past work. Additional studies are required to discern how this may impact future research, diagnosis and treatment.

Tuesday, 17 January 2017

PREDICT-PD: An online approach to prospectively identify risk indicators of Parkinson's disease

Here's the latest one from the PREDICT-PD team... this shows that intermediate markers (smell loss, subjective RBD and slowed finger tapping) persist in the higher risk group over three years of follow-up... but most interestingly higher baseline risk scores are associated with new diagnoses of PD at three years of follow-up. This is the strongest indicator yet that the PREDICT-PD algorithm is working...

Mov Disord. 2017 Jan 16. doi: 10.1002/mds.26898. [Epub ahead of print]
Noyce AJ, R'Bibo L, Peress L, Bestwick JP, Adams-Carr KL, Mencacci NE, Hawkes CH, Masters JM, Wood N, Hardy J, Giovannoni G, Lees AJ, Schrag A.

BACKGROUND: A number of early features can precede the diagnosis of Parkinson's disease (PD).

OBJECTIVE: To test an online, evidence-based algorithm to identify risk indicators of PD in the UK population.

METHODS: Participants aged 60 to 80 years without PD completed an online survey and keyboard-tapping task annually over 3 years, and underwent smell tests and genotyping for glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 (LRRK2) mutations. Risk scores were calculated based on the results of a systematic review of risk factors and early features of PD, and individuals were grouped into higher (above 15th centile), medium, and lower risk groups (below 85th centile). Previously defined indicators of increased risk of PD ("intermediate markers"), including smell loss, rapid eye movement-sleep behavior disorder, and finger-tapping speed, and incident PD were used as outcomes. The correlation of risk scores with intermediate markers and movement of individuals between risk groups was assessed each year and prospectively. Exploratory Cox regression analyses with incident PD as the dependent variable were performed.

RESULTS: A total of 1323 participants were recruited at baseline and >79% completed assessments each year. Annual risk scores were correlated with intermediate markers of PD each year and baseline scores were correlated with intermediate markers during follow-up (all P values < 0.001). Incident PD diagnoses during follow-up were significantly associated with baseline risk score (hazard ratio = 4.39, P = .045). GBA variants or G2019S LRRK2 mutations were found in 47 participants, and the predictive power for incident PD was improved by the addition of genetic variants to risk scores.

CONCLUSIONS: The online PREDICT-PD algorithm is a unique and simple method to identify indicators of PD risk.

Wednesday, 11 January 2017

The relevance of gender in Parkinson's disease: a review

The consistent and clear gender differences particularly in risk of being diagnosed with PD are intriguing... although I would not say one gets a clear flavour of gender-specific differences in the course of PD after diagnosis... of course when there are gender-specific differences for a disease, there is always focus on sex-hormones. At least in terms of the risk of being diagnosed with PD there is no clear evidence that HRT, contraceptive pills or surgical menopause can account for the observed gender difference...

J Neurol. 2017 Jan 4. doi: 10.1007/s00415-016-8384-9. [Epub ahead of print]
Picillo M, Nicoletti A, Fetoni V, Garavaglia B, Barone P, Pellecchia MT.

Since the official and systematic inclusion of sex and gender in biomedical research, gender differences have been acknowledged as important determinants of both the susceptibility to develop neurodegenerative diseases in general population and the clinical and therapeutic management of neurodegenerative patients. In this review, we gathered the available evidence on gender differences in Parkinson's disease (PD) regarding clinical phenotype (including motor and non-motor symptoms), biomarkers, genetics and therapeutic management (including pharmacological and surgical treatment). Finally, we will briefly discuss the role of estrogens in determining such differences. Several data demonstrate that PD in women starts with a more benign phenotype, likely due to the effect of estrogens. However, as the disease progresses, women are at higher risk of developing highly disabling treatment-related complications, such as motor and non-motor fluctuations as well as dyskinesia, compared with men. In addition, women have lower chances of receiving effective treatment for PD as deep brain stimulation. Taken together these findings challenge the definition of a more benign phenotype in women. Still, much work needs to be done to better understand the interaction between gender, genetics and environmental factors in determining the PD risk and clinical features. Improving our understanding in this field may result in implementation of strategies to identify prodromal PD and speed efforts to discern new directions for disease tailored treatment and management.

Plain English - LRRK2 G2019S Parkinson's disease with more benign phenotype than idiopathic

This research study compared patients with Parkinson's who carry the commonest gene mutation associated with the disease (called LRRK2),...