Apathy and olfactory dysfunction in early Parkinson's disease

J Mov Disord. 2015 Jan;8(1):21-5. doi: 10.14802/jmd.14029. Epub 2015 Jan 13.

Hong JY, Sunwoo MK, Ham JH, Lee JJ, Lee PH, Sohn YH.

OBJECTIVE:

Olfactory and emotional dysfunctions are very common in patients with Parkinson's disease (PD). Olfaction and emotions share common neuroanatomical substrates. Therefore, in this study, we evaluated the association between olfactory and emotional dysfunctions in patients with PD.

METHODS:

Parkinson's disease patients who had been assessed for their olfactory function and neuropsychiatric symptoms including emotional dysfunction were included. A logistic regression analysis was performed to evaluate the association between low olfaction and different neuropsychiatric symptoms.

RESULTS:

The patients with low olfaction (cross cultural smell identification test score ≤ 6) showed a higher prevalence of apathy when compared with those with high olfaction, whereas the frequencies of other neuropsychiatric symptoms were comparable between the two groups. A multivariate logistic regression analysis revealed that the presence of apathy/indifference [odds ratio (OR) = 2.859, p = 0.007], age 70 years or more (OR = 2.281, p = 0.009), and the male gender (OR = 1.916, p = 0.030) were significantly associated with low olfaction.

CONCLUSIONS:

Our results demonstrate that apathy/indifference is a unique emotional dysfunction associated with olfactory dysfunction in PD. The findings also suggest that PD patients with low olfaction have a high prevalence of apathy.

The burden of non-motor symptoms in Parkinson's disease using a self-completed non-motor questionnaire: A simple grading system.

Parkinsonism Relat Disord. 2015 Jan 5. pii: S1353-8020(14)00505-7. doi: 10.1016/j.parkreldis.2014.12.031. [Epub ahead of print]

Chaudhuri KR, Sauerbier A, Rojo JM, Sethi K, Schapira AH, Brown RG, Antonini A, Stocchi F, Odin P, Bhattacharya K, Tsuboi Y, Abe K, Rizos A, Rodriguez-Blazquez C, Martinez-Martin P.

BACKGROUND:

Non-motor symptoms (NMS) of Parkinson's disease (PD) affect virtually every patient, yet they are under-recognized and under-treated. The NMS Questionnaire (NMSQuest) is a validated 30-item self-assessment instrument useful for NMS screening in clinic.

OBJECTIVE:

Development of a straight forward grading classification of the burden of non-motor symptoms in PD based on the number of NMS as assessed by the NMS Questionnaire.

METHODS:

In an observational, cross-sectional, international study of 383 consecutive patients distribution of the declared NMS as per NMSQuest was analyzed according to previously published levels based on the Non-Motor Symptoms Scale and also the median and interquartile range (IR, percentiles 25 and 75) of the total NMSQuest scores. After post hoc checking, these values were proposed as cut-off points for estimating NMS burden based only on the accumulation of symptoms.

RESULTS:

Burden and number of NMS correlate closely (r ≥ 0.80). On the basis of this finding, five levels (0 = No NMS to 4 = Very severe) of NMSQuest grading were proposed after identification of their cut-offs by ordinal logistic regression and median and interquartile range distribution. These values coincided almost completely with those obtained by median and interquartile range in an independent sample. Concordance between this classification and HY staging was weak (weighted kappa = 0.30), but was substantial (weighted kappa = 0.68) with the Non-Motor Symptoms Scale grading.

CONCLUSION:

Completion of NMSQuest and subsequent grading of the burden could allow the health care professional to approach the severity of NMS burden using the self completed NMSQuest in a primary care setting.

Usefulness of Genetic Testing in PD and PD Trials: A Balanced Review.

J Parkinsons Dis. 2015 Jan 26. [Epub ahead of print]

Gasser T

Abstract

An increasing proportion of the individual and population risk to develop Parkinson's disease (PD) can be explained by genetic variants of different effect strength, forming a continuum from rare high penetrance gain or loss of function mutations to relatively common genetic risk variants that only mildly modify disease risk. In the coming years, further advances in molecular genetic technologies, in particular the increasing use of next generation sequencing, is likely to generate a wealth of new knowledge about the genetic basis of PD. Although specific treatments for PD based on the underlying genetic etiology will probably not be available in the near future, genetic testing is therefore likely to play an increasing role, both in the counselling of individual patients and their families with respect to the expected disease course and recurrence risks, and in the stratification of patient groups in clinical trials. Thus, the usefulness of genetic testing strongly depends on question asked and needs to be considered within each particular setting.

Head injury, potential interaction with genes, and risk for Parkinson's disease

Are timing of injury or carrying a gene variant important for the increased risk of PD that head injury conveys??

Parkinsonism Relat Disord. 2015 Jan 8. pii: S1353-8020(15)00003-6. doi: 10.1016/j.parkreldis.2014.12.033. [Epub ahead of print]

Gao J, Liu R, Zhao E, Huang X, Nalls MA, Singleton AB, Chen H.

INTRODUCTION:

To evaluate the association between head injury and Parkinson's disease (PD), focusing on the timing of head injury, and to explore potential interactions between head injury and genetic factors in PD etiology.

METHODS:

The analysis included 507 PD cases and 1330 controls, all non-Hispanic Whites. Head injury was retrospectively asked, and genotyping was performed mainly as part of a previous GWAS.

RESULTS:

We found a positive association between head injury and PD risk. Compared with no previous head injury, the odds ratio (OR) was 1.39 (95% confidence interval [CI]: 1.00, 1.94) for one and 2.33 (95% CI: 1.25, 4.35) for two or more head injuries (P for trend = 0.0016). We further found that the higher risk was largely attributed to head injuries before age 30. Compared with no previous head injury, the OR was 2.04 (95% CI: 1.33, 3.14) for head injury that occurred before age 18, 1.39 (95% CI: 0.81, 2.36) for head injury between ages 18-<30, and 1.04 (95% CI: 0.58, 1.87) for head injury that occurred at age 30 or older (P for trend = 0.001). Exploratory interaction analyses showed a significant interaction between head injury and a SNP at the RBMS3 locus (rs10510622, uncorrected P = 0.0001). No interaction was found with GWAS tag SNPs at or near the MAPT, SNCA, LRRK2, and HLA loci.

CONCLUSION:

Our study suggests that head injury early in life may be an important risk factor for PD. The potential interaction with RBMS3 needs confirmation.

Saliva α-Synuclein and A High Extinction Coefficient Protein: A Novel Approach in Assessment Biomarkers of Parkinson's Disease

N Am J Med Sci. 2014 Dec;6(12):633-7. doi: 10.4103/1947-2714.147980.

Al-Nimer MS, Mshatat SF, Abdulla HI.

BACKGROUND:

The pathological hallmark of Parkinson's disease (PD) is the appearance of intracytoplasmic inclusions known as Lewy bodies in which its principal component is α-synuclein.

AIM:

This study aimed to determine salivary α-synuclein and the extinction coefficient of the saliva protein as biomarkers of PD.

MATERIALS AND METHODS:

This observational study was done in Department of Pharmacology, College of Medicine in cooperation with Department of Oral Medicine, College of Dentistry at Al-Mustansiriya University in Baghdad, Iraq from September 2013 to March 2014. A total number of 20 PD patients and 20 healthy subjects were enrolled in the study. Unstimulated saliva obtained from each participant obtained for determination of salivary flow rate, saliva protein and α-synuclein using enzyme linked immune sorbent assay (ELISA) technique.

RESULTS:

Total saliva protein and uncontaminated protein with nucleic acids are significantly higher in PD compared with healthy subjects. The mean extinction coefficient of that protein is 27.25 M.cm(-1) which significantly (P < 0.001) less than corresponding value of healthy subjects (33.48 M.cm(-1) ). Saliva α-synuclein level is significantly less in PD (65 ± 52.2 pg/ml) than healthy subjects (314.01 ± 435.9 pg/ml).

CONCLUSIONS:

We conclude that saliva α-synuclein serves as a biomarker for PD if its level compared with healthy subjects, and a specific protein with extinction coefficient 27.25 M.cm-1 is detected in saliva of Parkinson's patients.

Colonic mucosal α-synuclein lacks specificity as a biomarker for Parkinson disease

An important observation in light of the huge amount of research that is going on in this area right now...

Neurology. 2015 Jan 14. pii: 10.1212/WNL.0000000000001240. [Epub ahead of print]

Visanji NP, Marras C, Kern DS, Al Dakheel A, Gao A, Liu LW, Lang AE, Hazrati LN.

OBJECTIVE:

To determine the utility of detecting α-synuclein (αSyn) in colonic mucosal biopsy tissue as a potential diagnostic biomarker for Parkinson disease (PD).

METHODS:

We used the paraffin-embedded tissue (PET) blot, which degrades physiologic nonaggregated αSyn using proteinase K and enhances antigen retrieval allowing sensitive and selective detection of remaining protein aggregates, to detect αSyn in colonic mucosal biopsies from 15 patients with early PD (<3 years), 7 patients with later PD (>5 years), and 11 individuals without PD. αSyn and serine 129-phosphorylated αSyn (Ser129p-αSyn) were assessed by PET blot and conventional immunohistochemistry.

RESULTS:

PET blot-resistant aggregated αSyn and Ser129p-αSyn was present in 12 of 15 individuals with early PD, 7 of 7 individuals with later PD, and 11 of 11 control subjects. The number of biopsies positive by PET blot relative to conventional immunohistochemistry was significantly lower in both PD groups compared with the control group for both αSyn and Ser129p-αSyn, whereas routine immunohistochemistry was positive more often in PD, but was positive in as many as 9 of 11 control individuals.

CONCLUSION:

Strong evidence of the presence of aggregated hyperphosphorylated αSyn in individuals with and without PD, using such a sensitive and specific method as the PET blot, suggests that colonic deposition of αSyn is not a useful diagnostic test for PD. The utility of detecting αSyn in the colon as a biomarker in combination with other assessments remains to be determined.

A panel of nine cerebrospinal fluid biomarkers may identify patients with atypical parkinsonian syndromes.

Good bit of CSF biomarker research from my good friend and colleague...

http://jnnp.bmj.com/content/early/2015/01/14/jnnp-2014-309562.abstract

J Neurol Neurosurg Psychiatry. 2015 Jan 14. pii: jnnp-2014-309562. doi: 10.1136/jnnp-2014-309562. [Epub ahead of print]

Magdalinou NK, Paterson RW, Schott JM, Fox NC, Mummery C, Blennow K, Bhatia K, Morris HR, Giunti P, Warner TT, de Silva R, Lees AJ, Zetterberg H.

BACKGROUND:

Patients presenting with parkinsonian syndromes share many clinical features, which can make diagnosis difficult. This is important as atypical parkinsonian syndromes (APSs) such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal syndrome (CBS) carry a poor prognosis, compared with patients with Parkinson's disease (PD). In addition, there is overlap between APS and dementia diseases, such as Alzheimer's disease (AD) and frontotemporal dementia (FTD).

OBJECTIVE:

To use a panel of cerebrospinal fluid (CSF) biomarkers to differentiate patients with APS from PD and dementia.

METHODS:

A prospective cohort of 160 patients and 30 control participants were recruited from a single specialist centre. Patients were clinically diagnosed according to current consensus criteria. CSF samples were obtained from patients with clinical diagnoses of PD (n=31), PSP (n=33), CBS (n=14), MSA (n=31), AD (n=26) and FTD (n=16). Healthy, elderly participants (n=30) were included as controls. Total τ (t-τ), phosphorylated τ (p-τ), β-amyloid 1-42 (Aβ42), neurofilament light chain (NFL), α-synuclein (α-syn), amyloid precursor protein soluble metabolites α and β (soluble amyloid precursor protein (sAPP)α, sAPPβ) and two neuroinflammatory markers (monocyte chemoattractant protein-1 and YKL-40) were measured in CSF. A reverse stepwise regression analysis and the false discovery rate procedure were used.

RESULTS:

CSF NFL (p<0.001), sAPPα (p<0.001) and a-syn (p=0.003) independently predicted diagnosis of PD versus APS. Together, these nine biomarkers could differentiate patients with PD from APS with an area under the curve of 0.95 and subtypes of APS from one another. There was good discriminatory power between parkinsonian groups, dementia disorders and healthy controls.

CONCLUSIONS:

A panel of nine CSF biomarkers was able to differentiate APS from patients with PD and dementia. This may have important clinical utility in improving diagnostic accuracy, allowing better prognostication and earlier access to potential disease-modifying therapies.

Systematic review and meta-analysis of hydrocarbon exposure and the risk of Parkinson's disease

http://www.prd-journal.com/article/S1353-8020(14)00491-X/abstract

Parkinsonism Relat Disord. 2014 Dec 26. pii: S1353-8020(14)00491-X. doi: 10.1016/j.parkreldis.2014.12.017. [Epub ahead of print]

Palin O, Herd C, Morrison KE, Jagielski AC, Wheatley K, Thomas GN, Clarke CE.

BACKGROUND:

There is no consensus on the association between exposure to hydrocarbons and the risk of Parkinson's disease (PD). We conducted a systematic review and meta-analysis to summarise the epidemiological evidence and included a new large case-control study.

METHODS:

Data were extracted following a predefined protocol. Risk estimates regarding the association between hydrocarbon exposure and PD were consolidated to produce a summary odds ratio (OR), 95% confidence intervals (CI), and p-value. In our case-control study, 1463 PD patients and 685 controls were recruited from clinical trials and completed a structured questionnaire describing their previous working exposure to hydrocarbons and other demographic measures. The association between exposure to hydrocarbons and risk of PD was evaluated using logistic regression.

RESULTS:

The systematic search identified 13 case-control studies matching the inclusion criteria. The meta-analysis included 3020 PD cases and 6494 controls. The summary OR was 1.32 (95% CI 1.08-1.62, p = 0.006) for hydrocarbon exposure (ever versus never). In the PD GEN study, occupational exposure to hydrocarbons significantly increased the risk of PD (OR = 1.61; 95% CI 1.10-2.36, p = 0.014), and risk dose-dependently increased for subjects exposed greater than 10 years compared to subjects never exposed (OR = 2.19; 95% CI 1.13-4.26, p = 0.021). The addition of PD GEN data increased the total numbers to 4483 PD cases and 7179 controls and strengthened the significant association (summary OR = 1.36; 95% CI 1.13-1.63, p = 0.001).

CONCLUSIONS:

This systematic review supports a positive association between hydrocarbon exposure and PD. Data from prospective studies are required to reinforce the relationship between hydrocarbon exposure and PD.

Alpha-synuclein biology in Lewy body diseases

http://alzres.com/content/6/5/73

Alzheimers Res Ther. 2014 Oct 27;6(5):73. doi: 10.1186/s13195-014-0073-2. eCollection 2014.

Kim WS, Kågedal K, Halliday GM.

Abstract

α-Synuclein is an abundantly expressed neuronal protein that is at the center of focus in understanding a group of neurodegenerative disorders called α-synucleinopathies, which are characterized by the presence of aggregated α-synuclein intracellularly. Primary α-synucleinopathies include Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy, with α-synuclein also found secondarily in a number of other diseases, including Alzheimer's disease. Understanding how α-synuclein aggregates form in these different disorders is important for the understanding of its pathogenesis in Lewy body diseases. PD is the most prevalent of the α-synucleinopathies and much of the initial research on α-synuclein Lewy body pathology was based on PD but is also relevant to Lewy bodies in other diseases (dementia with Lewy bodies and Alzheimer's disease). Polymorphism and mutation studies of SNCA, the gene that encodes α-synuclein, provide much evidence for a causal link between α-synuclein and PD. Among the primary α-synucleinopathies, multiple system atrophy is unique in that α-synuclein deposition occurs in oligodendrocytes rather than neurons. It is unclear whether α-synuclein originates from oligodendrocytes or whether it is transmitted somehow from neurons. α-Synuclein exists as a natively unfolded monomer in the cytosol, but in the presence of lipid membranes it is thought to undergo a conformational change to a folded α-helical secondary structure that is prone to forming dimers and oligomers. Posttranslational modification of α-synuclein, such as phosphorylation, ubiquitination and nitration, has been widely implicated in α-synuclein aggregation process and neurotoxicity. Recent studies using animal and cell models, as well as autopsy studies of patients with neuron transplants, provided compelling evidence for prion-like propagation of α-synuclein. This observation has implications for therapeutic strategies, and much recent effort is focused on developing antibodies that target extracellular α-synuclein.

Predictors for mild parkinsonian signs: A prospective population-based study

http://www.prd-journal.com/article/S1353-8020(14)00495-7/abstract

Parkinsonism Relat Disord. 2014 Dec 31. pii: S1353-8020(14)00495-7. doi: 10.1016/j.parkreldis.2014.12.021. [Epub ahead of print]

Mahlknecht P, Kiechl S, Stockner H, Willeit J, Gasperi A, Poewe W, Seppi K.

OBJECTIVE:

Mild parkinsonian signs (MPS) are common in the elderly population and are associated with a wide range of adverse health outcomes, including incident Parkinson's disease (PD). We aimed to prospectively evaluate potential risk factors for incident MPS.

METHODS:

Participants of the population-based Bruneck Study representative for the general elderly community underwent a baseline assessment of substantia nigra (SN)-echogenicity with transcranial sonography, olfactory function with the Sniffin' Sticks identification test and vascular risk according to the Framingham risk score as well as a baseline and 5-year follow-up neurological examination. MPS were defined according to established criteria based on the entire motor section of the Unified PD Rating Scale. Participants with PD at baseline or follow-up and subjects with MPS at baseline were excluded. A logistic regression analysis adjusted for age and sex was used to detect risk factors for incident MPS in the remaining 393 participants.

RESULTS:

SN-hyperechogenicity and hyposmia were related to the development of MPS with odds ratios of 2.0 (95%CI, 1.1-3.7) and 1.6 (95%CI, 1.0-2.7), respectively, while increased vascular risk was not. Having both, SN-hyperechogenicity and hyposmia, was associated with an odds ratio of 3.0 (95%CI, 1.2-7.7) for incident MPS. Among the various motor domains, increased SN-echogenicity predicted the development of bradykinesia and rigidity, whereas diminished olfactory function predicted the development of impaired axial motor function.

CONCLUSIONS:

In addition to their established roles as risk factors for PD, SN-hyperechogenicity and hyposmia are associated with an increased risk for MPS in the general elderly community.

Google Glass for Parkinson’s disease: benefits and drawbacks

WHAT IS GOOGLE GLASS

Google Glass is a wearable technology that looks like a set of designer glasses. It was developed by Google and works in the same way as a smart-phone, displaying information on its lens. However the difference is it is mostly voice-operated, which makes it easier to use- compared to a touch-screen- for Parkinson’s patients experiencing tremor and “off” periods of medication.

HOW CAN GLASS HELP WITH PARKINSON’S

For now researchers have focused on two aspects of Parkinson’s that Glass might be useful with: preventing gait disturbances and enabling patients to live more independently.

In 2013 researchers in the Netherlands from the University of Twente have started developing new apps to improve the gait and prevent falls in patients with Parkinson’s. It is already established that the gait of patients improves with regular visualisation and/or hearing of a pattern. Technology such as Google Glass can be used to provide visual overlays, in form of shapes or stripes that the person would see through the glasses or patters of music, which they would hear through the device’s earphone.

In UK in 2014, doctors at Newcastle University started looking at how the Google Glass technology can be used to help control behaviours associated with Parkinson’s. The idea is that the device can be used to provide discrete prompts such as to swallow in order to prevent drooling and to speak up when people’s voice and volume gets affected by the disease. In addition, the device could also be used as a reminder about when exactly to take the different medications during the day. Researchers are also taking on the work done by scientists in the Netherlands and exploring how Glass’s motion sensors can help patients experiencing “freezing”, the blocking of movement which is a common symptom in Parkinson’s disease.

WHAT ARE GLASS’S SHORTCOMINGS FOR PARKINSON’S DISEASE USERS

As mentioned earlier, people suffering of Parkinson’s experience alteration to their voice, therefore it is felt that the Glass voice recognition system needs improvement. "The fact that it wasn't recognising what I wanted was very irritating and very frustrating," said one of the Newcastle study participants.
Patients also had trouble with navigation gestures, a mixture of tapping on the device’s side and swiping to navigate the menus.
Lastly a drawback of Google Glass is that it stands out: participants of the study felt that members of the public had various reaction to the device, which varied from some not noticing it to others starting suspiciously at the Glass user as if they were up to something bad.

CONCLUSION

Google Glass is a device with a lot of potential for being a tool to help people with Parkinson’s disease, however to make the most of this technology researchers need to continue working in partnership with people living with the condition. Only they can give valuable feedback to the researchers as to what needs working on to meaningfully improve their lives.

 View the full press release from University of Newcastle here.