The prodromes of Parkinson's

Following on nicely from our last post, we are delighted to publicise our latest peer-reviewed publication.

This will come out in a special edition of the European Journal of Neuroscience, dedicated to the memory of Tom Isaacs. Tom was the founder and leader of the Cure Parkinson's Trust - a truly dynamic leader and a real disruptive presence (in all the right ways) within  Parkinson's research. We are honoured to have our names and our ideas as testimonial to him in this way.

It is clear that Parkinson's is more of an umbrella condition than one single entity. For instance, some people have significant tremor, while others have none. Some progress very slowly, and a decade from diagnosis have barely any more symptoms - others progress more quickly. For many Parkinson's affects mainly movement while others have many non-motor symptoms. It is likely (although not yet proven) that these different subtypes of Parkinson's have a different underlying process causing them.

It therefore stands to reason that the earliest phases are also different. In our article we lay out the evidence that Parkinson's that comes from people with a particular kind of sleep disorder (REM sleep behavioural disorder), smell loss, and genetic forms do all look different. The evidence is not bomb-proof, but in Predict-PD we will be able to shed light on both the sleep disorder, smell loss and try and pick apart differences in the general population.

To see the article, please see the journal website. Please also remember to talk to friends and family to read more about the study and sign up themselves: www.predictpd.com

RNR

Do thinking problems develop before Parkinson's?

Many of the blog posts from the PREDICT team have highlighted the fact that Parkinson's affects many more aspects of life than just movement. Whilst the core features are still thought of as slowing down, becoming stiff and developing tremor, problems such as constipation, sleep difficulties and thinking and memory problems are all commonly seen. 

The thinking problems may even be present before diagnosis - testing for specific difficulties could be helpful in the efforts to pick up people at the earliest stages. This research paper used data from a large international study of healthy people who we know are at risk of Parkinson's including people with a sleep disorder strongly related to Parkinson's, people with smell loss and people with genetic mutations associated with Parkinson's.

They found that people with the sleep disorder performed worse on tests of attention and visual function than all the other groups. The groups with smell loss and genetic mutations performed at a similar level across tests and were comparable to people who had already developed Parkinson's. Unfortunately there was no comparison to people without these risk factors, so we can't make any conclusions about whether these groups perform worse than the general population.

I think this finding points to the fact that, just as Parkinson's disease is different in every individual, the route into the disease is also likely to be different. It is also helpful in pointing us towards the specific tests which may be useful in the earliest stages - we have included short tests of attention and memory in the new online PREDICT-PD study www.predictpd.com and I will be very interested to see how our findings compare to these results.

-anna

https://www.ncbi.nlm.nih.gov/pubmed/30125297 

Cognition among individuals along a spectrum of increased risk for Parkinson's disease.

Chahine LM, Urbe L, Caspell-Garcia C, Aarsland D, Alcalay R, Barone P, Burn D, Espay AJ, Hamilton JL, Hawkins KA, Lasch S, Leverenz JB, Litvan I, Richard I, Siderowf A, Coffey CS, Simuni T, Weintraub D; Parkinson’s Progression Markers Initiative. 

Several characteristics associated with increased risk for Parkinson's disease (PD) have been identified, including specific genotypes and various non-motor symptoms. Characterizing non-motor features, such as cognitive abilities, among individuals considered at-risk for PD is essential to improving prediction of future neurodegeneration. METHODS: Participants belonging to the following cohorts of the Parkinson Progression Markers Initiative (PPMI) study were included: de novo PD with dopamine transporter binding deficit (n = 423), idiopathic REM sleep behavior disorder (RBD, n = 39), hyposmia (n = 26) and non-PD mutation carrier (NMC; Leucine-rich repeat kinase 2 (LRRK2) G2019S (n = 88) and glucocerebrosidase (GBA) gene (n = 38) mutations)). Inclusion criteria enriched the RBD and hyposmia cohorts, but not the NMC cohort, with individuals with dopamine transporter binding deficit. Baseline neuropsychological performance was compared, and analyses were adjusted for age, sex, education, and depression. RESULTS: The RBD cohort performed significantly worse than the hyposmia and NMC cohorts on Symbol Digit Modality Test (mean (SD) 32.4 (9.16) vs. 41.8 (9.98), p = 0.002 and vs. 45.2 (10.9), p<0.001) and Judgment of Line Orientation (11.3 (2.36) vs.12.9 (1.87), p = 0.004 and vs. 12.9 (1.87), p<0.001). The RBD cohort also performed worse than the hyposmia cohort on the Montreal Cognitive Assessment (25.5 (4.13) vs. 27.3 (1.71), p = 0.02). Hyposmics did not differ from PD or NMC cohorts on any cognitive test score. CONCLUSION: Among individuals across a spectrum of risk for PD, cognitive function is worse among those with the characteristic most strongly associated with future risk of PD or dementia with Lewy bodies, namely RBD.

Magnetic resonance T1w/T2w ratio: A parsimonious marker for Parkinson's disease

I love it when something simple yet really effective...

We are in an era when imaging and laboratory investigations are ever more complex and expensive, and here we have a wonderful study showing that a very simple, cheap and easily-obtained ratio from an MRI scan can be used to accurately diagnose Parkinson's. Importantly the researchers were not satisfied with showing this once and went on to demonstrate similarly impressive results in a separate patient and control group.

Now it is important for other researchers to replicate these findings and to work how far back they go... could it be used to detect people in the pre-symptomatic/pre-diagnostic phase??

Du G, Lewis MM, Sica C, Kong L, Huang X

Ann Neurol 2018 Nov 8

https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.25376

Objective

Newer MRI techniques have shown promise in capturing early Parkinson's disease (PD)‐related changes in the substantia nigra pars compacta (SNc), the key pathological loci. Their translational value, however, is hindered by technical complexity and inconsistent results.

Methods

A novel yet simple MRI contrast, the T1w/T2w ratio, was used to study 76 PD patients and 70 controls. The T1w/T2w ratio maps were analyzed using both voxel‐based and region‐of‐interest approaches in normalized space. The sensitivity and specificity of the SN T1w/T2w ratio in discriminating between PD and controls also were assessed. In addition, its diagnostic performance was tested in a subgroup of PD patients with disease duration ≤2 years (PDE). A second independent cohort of 73 PD and 49 controls was used for validation.

Results

Compared to controls, PD patients showed a higher T1w/T2w ratio in both the right (cluster size=164 mm3, p<0.0001) and left (cluster size=213 mm3, p<0.0001) midbrain that was located ventrolateral to the red nucleus and corresponded to the SNc. The region‐of‐interest approach confirmed the group difference in the SNc T1w/T2w ratio between PD and controls (p<0.0001). The SNc T1w/T2w ratio had high sensitivity (0.908) and specificity (0.80) to separate PD and controls (AUC=0.926), even for PDE patients (AUC=0.901, sensitivity=0.857, specificity=0.857). These results were validated in the second cohort.

Interpretation

The T1w/T2w ratio can detect PD‐related changes in the SN and may be used as a novel, parsimonious in vivo biomarker for the disease, particularly early stage patients, with high translational value for clinical practice and research.

Why does Parkinson's cause constipation?

When people think of Parkinson's disease they often think of tremors however often people who actually have Parkinson's are more concerned by the symptoms that are not to do with movement and tremors (non-motor symptoms). The commonest of these symptoms are constipation, tiredness, difficulty sleeping, anxiety and needing to pass urine multiple times at night. These symptoms are not always as immediately obvious to people without Parkinson's but they can be extremely troubling. In this blog I want to talk a bit more about constipation and why people with Parkinson's get constipation.

Constipation is when it is more difficult to go for a poo or when the amount of time between opening your bowels increases. Usually your poo will become a lot harder when this happens and sometimes can result in a bloated feeling and pain in your tummy. So the question is how does Parkinson's, a brain disease, affect your bowels in this way?

The answer lies in looking at the large intestine. This is a large pipe near the end of the path from your mouth to your bum (the GI tract). By the time your dinner reaches the large colon it has mainly been digested and had all of the useful vitamins, protein and carbohydrates removed from it. This means that when your dinner reaches the large colon it is made up of waste products (poo) and lots of water; in fact it is so watery at this point that it is completely liquid. The role of the large colon is to turn this liquid into a solid poo and to get the water out of it so that you can stay hydrated. So what changes in Parkinson's disease?

In Parkinson's disease if you measure the amount of time it takes a piece of food to move from the beginning of the large intestine to exiting out of your bum it would take double the amount of time that it would take a healthy person. In other words: poo moves through the large intestine at half the speed if you have Parkinson's. Because the large intestine is so good at draining water from your poo, the poo becomes much drier and harder as the large intestine has double the amount of time to remove as much water as possible. This explains why people with Parkinson's have drier harder poos and subsequently have more constipation.

The large intestine pushes food along it by tensing the muscles around it in a rhythmic way that propels the poo downstream. Like the rest of the body, in Parkinson's, these movements become much slower. The reason for this is not as clear but is probably due to the layer of nerve cells around the gut wall called the enteric nervous system. Studies where they have looked at samples of the gut wall have found build ups of Lewy Bodies (the characteristic thing found in the brain in Parkinson's) also in the gut wall. It is possible that this build up is what also causes the slowness in the gut.

It is important to remember that there are many other things that cause constipation other than Parkinson's. There are many medications that can be tried to help improve constipation but some of the simple things that can help are increasing the amount of water you drink or increasing the amount of fibre that you eat, but discuss with your doctor if this is a problem for you.

Curr Treat Options Neurol. 2018 Oct 25;20(12):54. doi: 10.1007/s11940-018-0539-9.

Gastrointestinal Dysfunction in Parkinson's Disease.

Pfeiffer RF

Author information

Abstract

PURPOSE OF REVIEW:

During the past 25 years, there has been an explosion of information regarding the occurrence of gastrointestinal dysfunction in Parkinson's disease. In this review, the clinical features of gastrointestinal dysfunction in Parkinson's disease will be described and information regarding the potential role of the enteric nervous system and the gut microbiome in the genesis of Parkinson's disease will be addressed.

RECENT FINDINGS:

Recognition is growing regarding the role that gastroparesis and small intestinal dysfunction may play in Parkinson's disease, especially with regard to erratic responses to anti-Parkinson medication. The presence of enteric nervous system involvement in Parkinson's disease is now well established, but whether the enteric nervous system is the starting point for Parkinson's disease pathology remains a source of debate. The potential role of the gut microbiome also is beginning to emerge. Gastrointestinal dysfunction is a prominent nonmotor feature of Parkinson's disease and dysfunction can be found along the entire length of the gastrointestinal tract. The enteric nervous system is clearly involved in Parkinson's disease. Whether it is the initial source of pathology is still a source of controversy. There also is growing recognition of the role that the gut microbiome may play in Parkinson's disease, but much more research is needed to fully assess this aspect of the disorder.

PLAIN ENGLISH: Does removal of the appendix impact the risk of Parkinson's Disease?

Multiple large news organisations yesterday were reporting the results of a study showing that people who have had appendectomies (surgical removal of the appendix) have a lower chance of developing Parkinson's disease. Its a neat paper which links large amounts of data from medical databases and histology results (looking at tissue under the microscope) on a much smaller number of patients.

First they looked at the Swedish National Patient Registry, a database of 1,698,000 people followed up for 52 years, and identified anyone who had a history of an appendectomy (551,647 people). They then matched these patients to two 'control' patients who had not had appendectomies but were similar in age, sex and geographical to the original patients. They interestingly found that the chance of having Parkinson's disease was 19.3% lower in the participants with appendectomies than the 'control' participants who had not had appendectomies. They also found that the participants who had appendectomies and developed Parkinson's on average developed Parkinson's 1.6 years later than the Parkinson's patients who still had their appendix. Interestingly this effect was not observed in participants who had known genetic mutations causing their Parkinson's suggesting that if the appendix has any effect on the development of Parkinson's it is only in patients whose Parkinson's has an 'environmental' trigger or cause.

This part of the study was not novel or new and previous similar studies have been done and found no association between appendectomy and PD. In a Canadian study they actually found a higher rate of PD in patients who had appendectomies in the past 5 years. So despite the results of this study being very interesting they are not backed up by previous studies.

The novel part of this study is the histological analysis where the researchers analysed the 48 peoples appendixes under the microscope. These participants did not have PD. The appendixes were analysed under the microscope for clumps of protein which have stuck together that we call 'aggregates of α-syneuclein'. These are the key feature of PD that can be found in PD patients brains at autopsy. In other words the misfolded protein that causes PD when it is seen in the brain can be seen in young, healthy peoples appendix. These misfolded proteins were detected in both young and old people.

There are some problems with this study; first is that in large databases it is very difficult to know the accuracy of the Parkinson's diagnosis and previous studies investigating the reliability of this found only a 70.8% chance that it is reliable. They also only examined the appendix under the microscope and did not check any other tissues to compare.

This study does provide some food for thought; at the end of the paper the authors hypothesise that the appendix is the source of the misfolded protein that then spreads through the gut and up the vagus nerve to the brain thereby causing Parkinson's disease. This gut to brain model of the development of Parkinson's disease is often discussed and is a popular research topic at the moment. However the results of this study should still be taken with a pinch of salt because there are a number of large scale similar studies that precede this study that do not come to the same conclusion, that doesn't stop it being interesting though!

Preventive Neurology Unit Showcase

Yesterday alongside the launch of the second phase of PREDICT-PD (a new drive to recruit 10'000 participants to the study!) was the showcase of the Preventive Neurology Unit. The Preventive Neurology Unit is a new and exciting unit that is part of the Wolfson Institute at Queen Mary University London. The Wolfson Institute of Preventive Medicine has a proud history of leading the way in terms of cancer prevention and epidemiology with many high impact publications. Now, thanks to Barts Charity, we are trying to replicate some of the successful preventive techniques used in cancer and apply them to neurological diseases.

The showcase yesterday gave the three senior clinical lecturers the opportunity to explain some of their work and objectives as well as hearing from Professor Jack Cuzick and Professor Gavin Giovannoni about their hopes for this new unit.

The showcase began by Dr Charles Marshall explaining his work regarding the benefits and difficulties of diagnosing Alzheimer's disease as early as possible. Current research suggests that amyloid deposits can begin accumulating in patient's brains up to 20 years before they have any symptoms of dementia. This period before symptoms begin would be the ideal time to intervene with medications to prevent the onset of dementia but unfortunately there is no way to easily identify these people. Dr Marshall explained how the use of 'Brain Stress tests' could help to identify patients before they develop any symptoms of dementia and how his work will use these tests to see if people who will go onto develop Alzheimer's dementia can be identified earlier and therefore start treatments sooner.

Next up was Dr Alastair Noyce who explained the PREDICT-PD project which I am sure most readers of this blog are familiar with. Dr Noyce explained how the project evolved from a keyboard tapping test called the BRAIN test and now has 1000 participants who have been taking part over 5 years and will soon have 10'000 participants! The benefits of this research could be huge if we can begin to identify patients who are highly likely to develop Parkinson's before they suffer from any symptoms then we can begin to start trying to prevent Parkinson's in the first place. Dr Noyce also explained some fascinating results about Exenatide (a diabetes medication) which has recently been shown to potentially have some neuroprotective effect in Parkinson's and could be the first disease modifying medication for Parkinson's disease. Medications such as this would be ideal to use in further studies if PREDICT-PD can successfully identify those at high risk of Parkinson's.

The final talk about preventive approaches to Multiple Sclerosis was delivered by Dr Ruth Dobson. The complex links between EBV, childhood obesity and vitamin D levels were examined. Dr Dobson explained some of the intriguing results regarding EBV infection and Multiple Sclerosis and some of the difficulties of interpreting this relationship. The audience was also fascinated to hear about the links between foetal and neonatal vitamin D levels and MS. The main point that Dr Dobson emphasised is that a preventive approach to MS has to happen much earlier than the couple of years prior to diagnosis; the most important potential modifiable risk factors are all in early childhood or potentially in-utero!

Overall the showcase was very successful and the audience provided lots of insightful questions and interesting discussion. It is an exciting time to be working on preventive approaches to neurological disease and yesterday definitely highlighted that.

We have lift-off

PREDICT-PD has been going since 2011, and during that time we have had around 1,300 participants complete annual surveys, and we have done around 500 in-person assessments all around the UK.

This year we have also started our imaging project, where we are using the PREDICT-PD model with cutting edge MRI and ultrasound techniques to 'see' Parkinson's at the very earliest stages.

We have also been paying special attention to two special groups within PREDICT-PD: people who have lost their sense of smell, and people with a certain kind of sleep disorder. We have been seeing individuals who have been referred to us from specialist clinics, and doing in-person assessments with them to see if we can tease out what features put some people in these groups at increased risk of Parkinson's.

All of this has been taking place while we have been working tirelessly to create a new online platform on which to continue the study. The website has an entirely new design and set up, with a really robust 'back end' to safely and securely store participants data. This has come during the implementation of GDPR, to add to the complexity.

However, the exciting news of the day is that we have officially launched the second phase of PREDICT-PD!! We are now aiming to recruit at least TEN THOUSAND new participants.

So if you have not been part of this journey, please visit www.predictpd.com to find out more, and when you're ready, press 'TAKE PART'. It takes about 20 minutes to register, and go through the questionnaires and assessments. Now is your chance to join in with a truly groundbreaking research study, from the comfort of your own home. If you have already joined us, thank you. Please talk about it with friends and neighbours, encourage as many people as you can to join in. We take all comers (as long as they're between 60-80, and do not have Parkinson's disease (to their knowledge).

Flying the flag, and raising support

At PREDICT-PD nothing we do would be possible without our funding from Parkinson's UK. In clinic, we know how invaluable the support they give to people with Parkinson's all over the UK.

I have just received a wonderful phone call from Parkinson's UK, offering me one of their places in the London Marathon 2019. 

Please help me make groundbreaking research a reality, bring us closer to a cure, and provide life changing support to people with Parkinson's, by sponsoring me at here 

I'm aiming for a Good For Age time of under 3 hours, smashing over 20 minutes from my previous record. Every donation will spur me on through training in the long winter months between now and April. Follow my progress on Strava. Last weekend was my first 20 miler since the 2015 London marathon, and this Sunday I'm running in the Wimbledon Half marathon.

Wish me luck!

RNR

Why more Parkinson's might not be such a bad thing

This week, the Lancet Neurology have published the "Global, regional, and national burden of Parkinson’s disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016", a very large and very complex analysis of the amount of Parkinson's all over the world.

As can be seen from the map below, there are huge differences in the rate of Parkinson's. Some of the reasons for this are clear, and some are less well understood.

Worldwide rates of people with Parkinson's (age-standardised prevalence per 100,000 population in 2016)

What is more interesting is the rates of change. Parkinson’s was the fastest growing condition in terms of prevalence, disability and death of all neurological conditions. Since 1990, the prevalence (number of people with a condition), mortality, and disability-adjusted life-years (One DALY can be thought of as one lost year of "healthy" life. Read more about DALYs here), have more than doubled. In part this is because of the population of the world getting older. This figure shows the rates of Parkinson’s for men and women at different ages.

The percentage of men (red) and women (blue) with Parkinson's by age. The line is  the current estimate, with the shaded area being the region of uncertainty in which the 'true' figure lies.

Although there are many reasons why this increase is being seen, one reason is that the prevalence is related to two things: how many people receive a new diagnosis, but also how long people with a condition live with it. If the rate of new diagnoses has not significantly changed (the evidence remains unclear), in a generation we have enabled people with Parkinson’s to live longer. The authors remind us that this is only partly due to drugs like levodopa, and also due to the general increase in sanitation, food security, general health improvement, vaccination etc. as well as attention to things like physiotherapy, speech and language therapy etc.

So as we go forward, lets hope that the number of people with Parkinson’s continues to increase, but the DALYs decrease. And lets continue to work hard so we can at last make a real change to the incidence of Parkinson’s.

RNR

GBD 2016 Parkinson's Disease Collaborators. Global, regional, and national burden of Parkinson's disease, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology. 2018 Oct 1;17(11):939–53. 

What does ethnicity have to do with Parkinson's disease?

I have recently started working at the Preventive Neurology Unit (QMUL) on a new project called the East London Parkinson’s Project. It has been exciting to be starting a new project, especially when the subject is so interesting; the way that ethnicity can affect Parkinson’s disease (PD). This is really important to study because up until now most studies of PD have been based on white participants or a single ethnic group that does not allow us to compare any differences between different ethnicities. Unfortunately due to the lack of research in this area we know very little about even some of the most basic information regarding PD and ethnicity.

For example there is not even a consensus as to whether people from different ethnicities have a different chance of developing PD. This is usually one of the first things that we learn about any condition. Previously PD was thought of as more common in white people and some studies have confirmed this, however other studies have found that people of all ethnicities have similar rates of PD. The results seem to vary depending on the way the study was carried out and there is a distinct lack of large scale multi-centre studies to more accurately answer this question.

If we are still struggling to determine something as simple as the rates of PD in different ethnicities then you can imagine how difficult is to work out more complicated relationships between ethnicity and PD. For example a study in Israel looked at differences in PD between Ashkenazi Jews (a distinct group of Jews who have lived throughout Europe since the 7^th/8^th century) and Yemenite Jews (a group of Jews who evolved completely separately to the rest of the Jewish population after arriving in Yemen around the second century). The study showed that Yemenite Jews with PD had more severe symptoms and the PD progressed faster than in Ashkenazi Jews. This is interesting because all the participants live in Israel now so have a relatively similar environment raising the possibility that the differences observed are genetic. Having said that Yemenite and Ashkenazi Jews have different diets and lifestyles to each other and it is possible that this could be having an effect. This is just one study out of hundreds I could have discussed but I think it demonstrates some of the interesting trends we notice between ethnicity and PD but also some of the complications when trying to analyse these differences.

To make any headway with this difficult issue we need more studies that explore this tangled relationship between PD and ethnicity.

J Neural Transm (Vienna). 2008 Sep;115(9):1279-84. doi: 10.1007/s00702-008-0074-z. Epub 2008 Jul 30.

Clinical characteristics of Parkinson's disease among Jewish Ethnic groups in Israel.

Djaldetti R, Hassin-Baer S, Farrer MJ, Vilariño-Güell C, Ross OA, Kolianov V, Yust-Katz S, Treves TA, Barhum Y, Hulihan M, Melamed E.

Yemenite Jews in Israel are a distinctive ethnic division of the Jewish diaspora. Clinical findings, disease course and genetic tests for the LRRK2 6055G > A (G2019S) mutation were compared between Ashkenazi and Yemenite Israeli patients with Parkinson's disease (PD). Age of onset was significantly younger in the Yemenites (P < 0.001). There were no differences in the distribution of initial symptoms, environmental risk factors or rate of motor/non-motor phenomena. The Yemenite group had a more severe disease (P < 0.001), and a more rapid disease course (P = 0.006). The frequency of Lrrk2 substitution was 12.7% in the Ashkenazi group and was not observed in the Yemenites. These results show that there are differences between Israeli Jewish ethnic groups in the severity and progression of PD, but not in clinical symptoms. The high frequency of Lrrk2 G2019S in the Ashkenazi and its absence in the Yemenite Jews suggests a specific ancestral pattern of inheritance in Ashkenazi Jews.

Why gout might be surprisingly good for the brain

There has been quite a lot of interest in the role of uric acid in Parkinson's Disease. Uric acid is a by-product of normal cell function, and a normal part of urine. In medicine uric acid is well recognised for its role in gout, where high levels in the blood lead to joint swelling and pain.

However, in Parkinson's Disease, uric acid seems to have a protective value. The study I've looked at here took 200 Koreans who had newly been diagnosed with Parkinson's, testing their thought processes as well as smell and uric acid levels in the blood. They found that there was a significant link with uric acid - higher levels were associated with better scores on tests of cognitive function.

from nhsdirect.wales.nhs.uk 

from memorangapp.com

vs

Does this mean that uric acid is somehow neurologically protective? This study looks at one point in time, but in large groups where uric acid has been measured and the participants followed up for diagnosis of Parkinson's, those with higher levels are less likely to go on to develop the disease. Recent findings have suggested that uric acid is particularly associated with those who have cognitive problems, who tend to have more severe disease.

Other possibilities are that there are other factors related to both urate levels and risk of parkinson's - for example diet or smoking, or that lower urate levels could be caused by the disease itself.

However, this is a promising avenue and a good example of how potential treatments can result from studies looking at risk factors. A trial with a drug designed to increase urate levels, Inosine, has so far shown that it is effective and safe, although will require close monitoring for the known side effects of high urate.  I will be particularly interested to see how this drug affects thought processes as it is studied further.

-Anna

 https://www.researchgate.net/publication/328022951_Cognition_Olfaction_and_Uric_Acid_in_Early_de_novo_Parkinson's_Disease

Cognition, Olfaction and Uric Acid in Early de novo Parkinson's Disease.

Lee HR, Park JH, Han SW, Baik JS

OBJECTIVE: Cognitive impairment is one of the nonmotor symptoms in Parkinson's disease (PD), and olfactory dysfunction is used as a marker to detect premotor stages of PD. Serum uric acid (sUA) levels have been found to be a risk factor for PD. Our objective in this study was to examine whether sUA levels are associated with cognitive changes and olfactory dysfunction in early de novo PD patients.

METHODS: The study participants included 196 de novo PD patients. We assessed cognitive function by the Korean versions of the Mini-Mental State Examination and the Montreal Cognitive Assessment and assessed olfactory function by the Korean version of the Sniffin' Sticks test.

RESULTS: The mean sUA level was 4.7 mg/dL and was significantly lower in women than in men. Cognitive scores were lower in women, suggesting that sUA levels were related to cognitive function. The olfactory functions were not related to sUA level but were clearly associated with cognitive scores. Olfactory threshold, odor discrimination, and odor identification were all significantly related to cognitive scores.

CONCLUSION: We conclude that lower sUA levels were associated with cognitive impairment, not olfactory dysfunction, in de novo PD patients. This finding suggests that UA is neuroprotective as an antioxidant in the cognitive function of PD patients.