Check this out:

http://journal.frontiersin.org/Journal/10.3389/fnsys.2014.00045/abstract

Thank you for sharing the fmri research with markers. I have worked with PD patients for years and I can honestly say that the new onset patients that are able to read about the disease are preoccupied with depression and cognitive impairment. Usually the hospitalized patients with PD are more acute and have other challenges such as the ADL's. The problem in the home is isolation and depression eventually promote more inactivity and depression (a never ending battle). Anything we can do to enhance cognition should be investigated. Good topic.

I work with mild-moderate PD, studying perception and cognition. Our research participants, who are generally high functioning and well educated, still complain of poor concentration and disorganization as well as spatial problems. Note that besides depression, anxiety is very common, as are sleep disturbances (and daytime fatigue) and subtle visual dysfunction, all of which affect cognition. Another factor affecting cognition is orthostatic hypotension, which is reasonably common and under-diagnosed. It's a complex disease and many roads (sensation and perception, mood, autonomic, sleep) lead to some cognitive compromise even in non-demented individuals, in addition to direct hits to brain areas devoted to cognitive processing.

I have had similar experiences working with people with mild to moderate PD (without dementia) investigating everyday memory and peoples awareness of their everyday memory function. In this work I have found that participants have poorer performance on tests of everyday memory function, such as prospective memory tasks, than age matched controls. Since this type of memory function is implicated in many activities of daily living; shopping, taking medication etc, it seems likely to have an impact on ADLs. Interestingly, if you take objective measures of peoples awareness of these deficits, participants do not always seem to be aware of these specific changes in their memory function. This is in contrast to some of the informal discussions I have had with participants about their thinking abilities in general, in which impairments in thinking abilities do seem to be a concern; there seems to be a desire to improve their cognition or prevent decline. I would argue that given the limited effects of pharmaceutical interventions so far, as well as continuing investigations in this field their seems to be a need to develop targeted non-pharmaceutical interventions for this group.

Absolutely, approaches that enhance cognition without drugging are needed for this terribly mistreated condition. In our experience we find the status of today's treatment of Parkinson's is extremely barbaric, bullying, and short-sighted. Symptomatic relief is not effective treatment. As time permits I will bring more to the table on this discussion. But I agree heartily with Sarah that we need to do more, and it needs to get to the reversing of underlying issues instead of superficial management of symptoms that are otherwise destined to become worse. We can do so much more for this population.

Discussions on RG have led us to conclude that the diversity of symptoms and plausible causes imply that “Parkinson’s” is “not a single entity but rather a heterogeneous neurodegenerative disorder”, as Thenganatt and Jankovic conclude in JAMA Neurol. Published online February 10, 2014. doi:10.1001/jamaneurol.2013.6233. Their paper, “Parkinson Disease Subtypes” reports an analysis of symptoms described in papers cited in PubMed between 1980 and 2013. They identify several sub-types but they are not differentiated by biomarkers and our understanding of the mechanisms underlying most of the symptoms is inadequate to provide a theoretical framework for the sub-types. (Taken from my reply to another question "One neurodegenerative diagnosis per patient? ")

Parkinson's UK estimated the prevalence of PD in the UK in 2009 and found that it (improbably) plateaued after age 85. It is more likely that older patients have other conditions that mask PD and that it is diagnosis that plateaus, rather than incidence. I modelled the prevalence from 35-64 and estimated the hypothetical prevalence if the incidence increased at the same rate throughout.

Prevalence/10 000

Age Obs. Hypoth.

40-44 0.1 0.1

45-49 1.5 1.5

50-54 5 5

55-59 11.5 11.5

60-64 24 24

65-69 46 74

70-74 83 92

75-79 130 177

80-84 172 338

85-89 171 643

90-94 171 1224

95-99 171 2328

Post Mortems might indicate which of the two columns is closer fo reality.

It is usually accepted that some 30% of PD cases are of the non-tremulous variety but tremor is still typically seen as the defining symptom of PD and I suspect that at least some of the non- tremulous cases are undiagnosed.

Any research that assumes that a sample of those diagnosed with PD is homogeneous is likely to obtain, as many others have done,only inconclusive results. It is wiser to assume that any sample of PD patients, however large, will be heterogeneous, incomplete and representative only of the diagnostic criteria employed.

Excellent and sobering insights, Stephen. As a chair and committee member of PD studies I can attest that it is indeed a syndrome, not even a predictable complex that can identified beyond outward behaviors. Subsets are the key here. In one group of Young Parkinsons sufferers we were able to trace a common line of sequences, starting with Adrenal Fatigue as a result of sleeplessness, high caffeine intake, sterile, non-organic diet, high carbs, chronic dehydration, etc. leading them to their physician who promptly, without any meaningful investigation, started them on sleep medications, SSRI/SNRIs, sometimes with a psychostimulant in the mix--no changes of diet or sleep or hydration patterns--and soon the essential tremors would be treated by adding neuroleptics or other nerve deadeing medications to the mix, so that the tremor turned to intentional tremor and other abnormalities--leading to...a diagnosis of Young PD. This pattern was so common in the group we looked at that we had to rethink the pathological pathway. Poor diet, sleep, hydration leading to treatment patterns that leave the underlying causes in place but add new ones in the for of side/interaction effects until a real disease finally shows up. I mention this pattern, because now we are seeing a similar man-made pattern in many older adults--the rush to medicate has spawned an explosing in PD-type behaviors, and like you mentioned above, by 85 years of age, other chronic conditions masked the presence of the core man-made on, the PD-like syndrome. This is not to say that real PD does not exist--but if it does, what is it? In regions of our country where lead levels are high (mining, smelting, heavy industry, etc.) PD-behaviors are very prominent in the population, along with clinical depression, fibromyalgia, peripheral neuropathy, diabetes mellitus, multiple sclerosis, etc. You would think we would be working to pre-empt these diseases in such easily identified areas of environmental assaults, but instead our system is a wait-and-see, and therefore the disease must appear before action (usually with drugs) is taken, making matters worse. Most of this, of course, is a subject for public health. But that is not where see it going. They, too, seem to have bought into the fix-it-after-it-breaks scenario. But, as you say, PD is in the mix and difficult to identify simply it has too many pathways. Pre-emption, also known as preventative, care is needed. But first awareness of underlying causes so that we can work on those and see what's left over.

The phenomenon of Parkinson's disease dementia is well-known, illustrated by the apparently arbitrary diagnostic cutoff between parkinson's disease dementia and lewy body dementia.

Many of us working in the field routinely prescribe cholinesterase inhibitor drugs for our patients with PDD. The outcomes are usually much better than what we would expect when treating a similar degree of impairment in Alzheimer's disease patients. I suspect, therefore, that big pharma investing $$$ to specifically improve cognition in PDD would not be a major goal, as effective drug treatments for the cognitive symptoms already exist. of course, these are symptomatic treatments without lasting benefit as they currently stand, and are not disease-modifying....

Thank you all, for your thoughtful comments.

1. I think while there is no doubt that there are significant cognitive deficits in PD and this may in part be made worse by other non-motor symptoms like depression, anxiety, sleep disturbances etc. I still think there is very little work done to show how this impacts on functional outcome such as activities of daily living. We need to do more research in this area.

This is important for those of us involved in drug discovery because the FDA and other regulatory authorities want us to demonstrate an effect of the drug not only on cognition as measured by various cognitive tasks, but also some measure of functional outcome. They will not approve a drug for cognition unless there is a change in activities of daily living.

2. I agree with the comments made about PD being a heterogeneous disorder. I think one would need to define the sub-group of patients that would most benefit from the drug by focussing on a specific phenotype that is common regardless of the underlying mechanism. For example, one could focus on the PD-MCI group with executive deficits and for this group one would aim to develop drugs that increase cortical dopamine.

While cholinesterase inhibitors such as Rivastigmine is approved for PD-dementia, the efficacy is rather modest and there is still an unmet need for drugs with substantially greater efficacy.

3. I agree that the way forward is to develop disease modifying drugs that target the underlying pathology (for example, an antibody for alpha-synuclein), but I think there is still room for symptomatic treatments and one could potentially achieve greater improvements in cognition with a combined treatment approach. Furthermore, I agree that we should think about non-pharmacological approaches that might work synergistically with pharmacological treatments for cognition (i.e. cognitive training + drugs that enhance synaptic plasciity).

I say, we should first go to underlying causes (nutrition, hydration, removal of heavy heavy metals--esp. lead accumulations, food sensitivities, environmental toxins, unhealed injuries, subclinical infections, exercise, sleep, medication side effects, etc.) and see what's left over to treat. To ignore these and go into the depth of each is, though it be common practice, an abrogation of our duty to sufferers of PD. In our experience, once sufficient attention and remediation is given to the foregoing, what's left over can be addressed on a more solid footing.

"..... our ability to redefine Parkinson's disease is hampered by its complexity and heterogeneity in genetics, phenotypes, and underlying molecular mechanisms; the absence of biochemical markers or ability to image Parkinson's disease-specific histopathological changes; the long prodromal period during which non-motor manifestations might precede classic motor manifestations; and uncertainty about the status of disorders diagnosed clinically as Parkinson's disease but without Lewy pathology. " from the abstract of "Changing the research criteria for the diagnosis of Parkinson's disease: obstacles and opportunities", Berg, Lang et al.(http://www.thelancet.com/journals/laneur/article/PIIS1474-4422%2813%2970047-4/abstract)

I agree with this (although I didn't invest $31 in the full text) but we have known it for some time. What we need is a strategy and a research programme to establish some facts about PD. At the moment the funding agencies are passive, relying on submissions of project proposals by research groups for funding. This leads to a fragmented body of knowledge. The situation is hard to change because established groups get continuity of funding and the large gaps are never filled. I'm afraid, however, that administrators lack the knowledge and understanding to design a coherent programme.

Dance for PD is one of the better approaches for cognition, mood regulation, and self-esteem/confidence issues, as well as motor function, balance, and dexterity.

Excellent suggestion, Tumay. The exercise side of the equation is often overlooked for a magic pill that really doesn't exist. Instead, rebuilding myelin, albeit the floating myelin of astroglia of the brain, and immunology, are among the benefits of strategic exercise for sufferers of PD.

The sub-cortical nature of cognitive deficits seen in PD disadvantages PD patients on many of the standard cognitive assessments. Specific cognitive tests for subcortical cognitive impairment would seem a good option. Dopamine has been shown to have some benefit in cognition in PD, and leads me to think that it may be possible to assess treatment efficacy more accurately by assessing cognition, rather than using motor function.

Good point, Brett. In our observations with actual PD patients and in cognitive studies of same, we find the motor component secondary in just about every case, although it garners the most attention from both patients and clinicians. Etiology is important, yet varies so much from individual to indvidual, that just treating behavioral symptoms is not doing much to address underlying causes. We find a vast array of etiologies, from heavy metal accumulations, long-term acidosis, and chronic semi-dehydration to nutrition deficiencies, developing idiopathic neuropathy, and medication-inspired pathologies, such as in multiple diuretics and statins. So many cases start as PD-like condition only to end up conclusing into real PD behaviors if nothing is done to interrupte the cascade of progression. Our conclusion at this time is that much of what creates PD can be addressed in the early formative stages, but not by covering of symptoms with prescription drugs.

Dance for PD, as well as Tai Chi, tango, boxing, Irish dance, and other exercises that demand focused attention to the quality of movement have shown neuroprotective benefit. Thank you, Tumay for mentioning this. It seemed to take about 6-7 years to convincingly demonstrate the benefits, however. I agree with Max that changes in diet and lifestyle that reduce exposure to environmental toxins are essential. Along with prevention, and addressing underlying causes of neurodegenerative changes, inflammation and autophagy. Those choices don't come with bells and whistles.

I am curious why more attention has not been given for PD improvements from research such as:

1. Mindfulness based intervention in Parkinson's disease leads to structural brain changes on MRI: A randomized controlled longitudinal trial (https://www.researchgate.net/publication/258252171)

2. Meditation to change gene expression for inflammation: http://www.investigatinghealthyminds.org/pdfs/KalimanRapidPNEC.pdf

3. Meditation and Neurodegenerative Diseases "Meditation techniques present an interesting potential adjuvant treatment for patients with neurodegenerative diseases and have the advantage of being inexpensive" (https://www.researchgate.net/publication/255705545)

4. Subramanian, et al. Real-Time Functional Magnetic Resonance Imaging Neurofeedback for Treatment of Parkinson's Disease.

I have seen some modest functional improvements in my PD patients using mindfulness, exercise and meditation. Because these increase a sense of empowerment, and offer self-regulation of brain activity, they also address emotional and QoL issues. However, these are not likely to attract pharmaceutical investment. Would it take 6-7 years of research to convincingly demonstrate the benefit of these approaches?

Article Mindfulness based intervention in Parkinson's disease leads ...

Article Meditation and neurodegenerative diseases

May I propose an indirect answer by repeating a link I recently posited in another ResearchGate blog ?

I apologize for the delay in my suggestion, Mauro Colombo

By no means do all PD Patients suffer from cognitive impairment.  Different sources quote the (eventual) incidence of MCI in PwP as 30%, 40% 60% and 80% but it is not clear how many of these are really PD-related MCI. It is possible to be demented without Lewy Bodies and to have Lewy Bodies without Dementia so we have no categorical method for predicting dementia and therefore no way of identifying patients who should be given preventative treatment or advice.  In fact there is no systematic data on PD symptomology - what symptoms are always associated and which are mutually  exclusive,  which always respond to l-dopa and which do not.  The diagnosis of PD and Parkinsonism is so arbitrary that I now tell people that I have PSD (Parkinson's spectrum (or syndrome) disorder).  Much is made of the association between PD and protein tangles and much research is directed at protein misfolding but the underlying assumption of a causal relationship is conjectural and has not been proven, much less a relationship between protein misfolding and particular symptoms.  The fragmented sources of R&D funding, each with a different emphasis and an over-emphasis on "finding a cure" has prevented the pursuit of a single strategy to understand the condition. But without a basic understanding of the cause(s) and mechanisms of the Parkinsonian syndrome progress in therapy is likely to be slow.

As Stephen pointed out, manifestaton of cognitive loss in PD cases is quite variable. One of the doctoral dissertation projects I chaired was on PD and depression--in which the investigator used cognitive measures. A surprising finding was that the higher education level the lower the loss of cognitive functions. In the population studied (Sun CIty, AZ, in this case) incidence of cognitive decline was lower than any other we looked at. By comparing education/cognitive relationships in several studies we found a strong association between them, and the Sun City group, which had a high number of grad school graduates (masters/doctorate) with PD that showed almost no cognitive loss.  

Rosi's suggestions on spatial activities (dancing) as beneficial in enhancing cognitive function has to be a good one, for incease of vascularization, oxygenation, immunology stimulus, not to mention the psychosocial aspects altogether would benefit PD patients.

Max - I have no (discernable!) loss of cognitive function and certainly no depression.  But I have an MA (chemistry) and a DPhil in Biochemistry from Oxford (in 1964!). I have bradykinesia but no tremor, severe speech impairment and double vision but no response to l-dopa apart from benefits to mood and sociability.   I see a neurologist at a local hospital for about 10 minutes every 12-18 months.  He is not indifferent but too busy.   I guess about half his patients have dementia and about 7% have PD, most of whom are much worse than I am.  I feel well and not particularly disabled so I have no complaints.  I participate in several research projects but most are poorly designed and executed by amateurs ( I spent 25 years in R & D, the last 20 in industry).   I recently reviewed a proposal for a trial of a substance to slow the progress of Alzheimer's.  I was quite critical but this kind if input is unwelcome because it would have either made the project more expensive or else undermined the credibility of its results.  My opinion of much medical research is low!

Thanks for sharing that, Stephen. Quite a resume and your experience matches many of those looked at in the study I mentioned. I wanted to comment on the amyloid plaque model on which the cholinesterase inhibitors since I just read Pradeep's comments on it (from March 21st)--I think that class of medicine has been a miserable failure and its promoters were barking up the wrong tree since day one in terms of its purported attempt to improve cognitive function (of course, later the fallback position was to "slow down" progression of cognitive loss). But in our work early on we could see the plaques as a rough substitute for the loss of astroglia to bring about a sort of "minefield" for offending unpaired molecules we typically call free radicals. My doctoral students, some of whom were MDs going after their research degree in my courses were particularly adamant that those drugs were based on the wrong model of cause and effect, and were disturbed that they were so aggressively promoted in the medical community. We have great need treatments that bring down the inflammatory sector of the PD and AD--and the opening salvo of any such treatment protocol must include dramatic improvements in diet, hydration, nutrition, removal of stored heavy metals (lead, in particular, which is more egregious in our later years), avoidance of toxins like the current crop of artificial coloring, flavoring, enhancers, perservatives, etc. that permeate the food supply, at least in the US., and resolution of any subclinical infections (sepsis of teeth and jaw come to mind on this one, but are typically overlooked as the serious offenders they can be). But, resolving these issues as a starting point, we are finding is not even on the radar, going instead to the jugular of pyschopharmacology, which brings more assualts on the PD patient. Anyway, we have a long way to go, and I appreciate that we have astute scientests like you to help get on the inside of such serious conditions that you describe. 

I agree, Stephen, there is not a single medication that has been brought to the fore to-date that provides substantive, long-term benefits for cognitive improvemenst in ether the PD or AD patient. That is because the underlying causes are not being addressed and because of the toxicity of the drugs and faulty behavioral models on which they are designed. A huge waste of time and resources. I've never understood why sincere research has not been shined more on mitochondria's abiity to put things right--except that the profit margins are not a lot to write home about.

Good observations, Susan. We know from clinical experience that we can rehyrdrate and retrain brains in AD, and correction of hearing is a major and terribly overlooked solution, also. It seems we ignore the elephants in the living room as we search for the microscopic culprits. 

Susan - Because l-dopa doesn't  improve my motor symptoms I do not have the usual reminder to take a tablet.  Playing duplicate bridge one evening a few days ago, my concentration fell to pieces, together with my hand-eye coordination and balance.  When I got home I found I'd missed two tablets due at 11.30 and 15.30.  Now I take a lot more care but I was interested to find hat I get more benefit from l-dopa than I'd realised.  If you've never played yourself .....  duplicate bridge, where you play 24 hands in 3 hours, gives you an average of 5-6 seconds to remember what cards have been played,  calculate the probability of which cards each player holds and play each trick with sometimes unforgiving partners and opponents, is a pretty severe test of your cognitive competence ... and under stress!

My consultant and the Parkinson's Nurse each keep urging me to increase the dose but Wiliam Wilson (you can find him on RG) has reminded me that the biochemistry of dopamine and serotonin are linked through the enzyme cofactors and the whole biochemical network is highly integrated and delicately balanced.  If one step, such as the conversion of tyrosine to l-dopa, is impaired then the precursor(s) accumulate and inhibit their own production.  If you then flood the neurons with l-dopa there will be other consequences and side effects.

These are described in the attached paper but William has a low opinion of the research because it relies on measuring small molecule concentrations in urine, which are notoriously variable.  (Is it worth trying concentrations in saliva?) Nevertheless the principles of biochemical balance and feedback are true and important.

Susan - Thanks for this. No, I don’t take 5-HTP with l-dopa because first I want to map the biochemical relationships that affect PD and work out what supplements and what dose would be reasonable. On the advice of William Wilson, however, I did change the folic acid supplement I was taking to L-5-methylfolate which I think improved things a little but PD is so variable it’s hard to tell. I presume your interest in therapies is on behalf of your friend rather than yourself.

There are several drugs that improve motor symptoms in some patients but none is as effective as l-dopa and all have side effects. Deep Brain stimulation seems to offer a long(ish) term easing of the tremor but stem cell injections (to replace the dopaminergic neurons) is hopeful rather than proven.

There have been some good results and some bad ones and some without effect. Many workers find the association with misfolded proteins and PD convincing but I do not ... yet. If they are right this adds to pessimism about stem cells because the misfolding has the prion-like property of being infective and able to pass between neurons. This would cast doubt on the likely long term effectiveness of stem cell treatment.

Other substances have been suggested as possible inhibitors of protein misfolding or possibly being of some benefit but the abstract and press reports are usually far more optimistic than a critical analysis of the research would suggest.

There is far too much emphasis on finding a cure (which is very unlikely) and far too little on understanding the condition and identifying the underlying cause. As a result much of the published research is of the “let’s try this!” type, from which we learn nothing except that substance x doesn’t work either.

Even the epidemiology is poor (see one of my blog posts below).

My experience working with dozens of Parkinsonians 3-4.5 hours a week over a 12 year period, many have cognitive deficiencies, the disease creates many distracting symptoms through out their bodies along with the obvious tremors etc. and some of the medication causes the hallucinations..

Vera, my experience is similar but from a research and consulting standpoint. I find far too many medications given at once to this population. The problem is practically no one is paying attention to overlay and interaction effects of medications for statins (should never be given with PD meds), hypertension meds (which piled 2-4 high on PD meds present terrible conseguences), and neuroleptics and opiates (should NEVER be used in PD cases in my opinion)...but then I am describing most of the PD cases out there---overmedicated and underlying causes being virtually ignored. If we want to help PD patients we will first get them healthy (yes it can be done) and remove everything that is addressable and then we will find the PD far less, as CVD, hyperlipidemia, non-PD neuropathies resolved, etc. As in all disease, we start with getting healthy in a true and natural manner, reducing toxic, immune suppressing medication as quickly as feasible, and watching what's left over much more manageable.    

Max - Why should statins not be taken with l-dopa?

Good question. They block Co-Q10 production and weaken muscles all over the body, and have demonstrated affect on motor control. I do not like that class of meds at all. If a person wants to step over the cause of hyperlipidemia and just improve cholesterol readings of the blood there are plenty of more gentle, organic ways of doing so---E-Toco (4 tocotrienals, 4 tocopherols), Ubiquinol CoQ10, Medical Grade Red Yeast Rice, eating an apple a day, apple cider vinegar capsules, there are a number that accomplish the task without the damage of synthetic statins. 

Thanks, Max.  I had a mild attack of unstable angina a few weeks before diagnosis of PSD (Parkinson's Spectrum Disorder) I have some marked PD symptoms but no tremor, no MCI, no depression and good sense of smell.  I had an aortic stent fitted and have taken bisoprolol (2.5 mg), ramipril (2.5 mg), aspirin (75 mg) and simvastatin (40 mg) every day since.  Since October 2011 I have taken Sinemet, which is of no benefit to motor symptoms but helps concentration, alertness and coordination.  I resist my consultant's advice to increase the dose to 4 x 1.5 tablets/day (600 mg) because 5 x 1 tablet is enough and I think 9 x 0.5 tablets will be better because smaller more frequent doses will cause less metabolic disruption.

Do you think I should try leaving out the statin?

I go to the Gym for 90 minutes three times a week but finish tired and sore jointed.

Well, of course, I cannot tell you not to take it. But I would not. Forty miligrams is in the range we find motor issues and most definitely blocking of CoQ10. No informed physician would give any patient more than 10 mg, of a synthetic statin without prescibing a high quality CoQ10. We have published and harped on the egregious use of statins for so long that we note that lately physicians are being advised to go to the less risky 5mg and 10mg doses--of course, the Pharmaceuticals make about as much per dose at any size. But we still hold this medication, regardless of the pop culture and dubious data supporting it, as unnecessary as long as there are less risky natural ways to resolve the problem. Inflammation of the blood vessels is a far greater risk for CVD events than elevated lipids ever were. The relationship of the latter is, at best, correlational and definitely not causal.  

I'll give statins a miss for a while.  I'm not taking your advice - I've been thinking about doing this for some time and this conversation just fired the gun.  Any idea how long it might be before I ought to notice any change?

Well, change from what? All medications interfere with PD. So does microwaving one's food, or missing micronutrients that no longer exist in the food supply, and many additives to food and water. In our practice and in our research our goal is ever to remove all possible stressors and see what is left over. Usually, in doing so, adding in proper hydration, exercise, and restful, not drug induced, sleep, and we find not a whole of one's health complaints still exist afterwards.

Dear all, let me post a note collateral to cognitive enhancement, pertaining behaviours in PD. Recently - elsewhere in ResearchGate - Linda Hershey posted a paper about smoking & PD [see alleged].

To me it has been a true lesson in neuroepidemiology & neurochemistry, but also of clinical epistemology, unmasking an example of reverse causality.

I found also some connection with Cloninger’s visions of low novelty-seeking & reward depending versus high harm avoiding (pre-morbid) personality in PD.

Best regards, Mauro Colombo

Max - This is a somewhat lofty position to hold.  PD has many symptoms, all of which rarely, if ever, appear in a single patient.  The symptoms all seem to vary in severity more or less independently on timescales of hours, days, weeks and longer periods;  few, if any, are simple on/off or yes/no variations. PD research is plagued by reports of effects that cannot be replicated and by conjecture masquerading as fact.  A recent report claims that the risk of AD is doubled if you have recurring herpes simplex. The authors hypothesise that the herpes virus triggers the onset of AD and suggest that antiviral drugs may arrest the progress of the disease!  It is legitimate to conjecture a mechanism for an observed effect and to suggest experiments to test the hypothesis but not to encourage speculative trials.  Of course these experiments and trials are difficult because it is hard to measure the progress of AD and PD over timescales less than 6 - 12 months.  For PD there are large differences in the progression of the condition between individuals, which means that a very large experimental cohort is required. 

If your claim is to achieve wide acceptance it would need a lot more than a few individual case studies.

It is Known that slight cognitive deficits are very common in early and mid-stage PD, together  with depression. On the paharmacological ground, I often observed positive effects with   selegiline, for motor, affective and, to a lesser degree, also cognitive domains.

Of course, I think there is room for investing in research for specific cognitive enhancers drugs in PD, and may be also also for cognitive stimulation tecniques, better if addressed to specific defcits (i.e executive/attentional ones) 

In my experience spending several hours weekly over a period of years with the same PD'ers.  Some of the cognitive reactions are similar to oppositional defiance disorders.

Vera - can you expand on this a little?  Do you mean that MCI associated with PD can look like contrariness as it develops?   I have a Parkinson's Spectrum Disorder and I am dismayed at clinicians attitude towards symptoms, in which their interest seems to be only in using them as diagnostic tools. 

"Do you still have a sense of smell?" 

"Well.....  yes." 

"Then you probably haven't got PD!"

" Do you have a tremor, REM sleep disturbance, depression?" 

"Ummm no."

"Then you definitely don't have PD." 

"So what abut my bradykinesia, distonia, postural instability, double vision, soft speech, slurred speech and festination?" 

"Sounds like Parkinsonism."

"What's Parkinsonism?" 

"It is caused by something - a drug, a substance you've been exposed to in the past ....  Parkinson's Disease is idiopathic it has no known cause."

" What's the difference between an idiopathic illness and one with a large and variable overlap of the same symptoms, which you think has a cause but you don't know what it is?"

This is why I say I have PSD.

Symptoms are the only window we have into what goes wrong in PSD and yet clinicians seem uninterested in how patients experience their symptoms.  Hence my interest in some analysis of how patients experience MCI other than as a score in a test.  Is there anything to suggest that MCI (perhaps) means different things in different illnesses?

Excellent foray for assessment (screening), Stephen. We see so much mis-over-diagnosis among those to sent to us with "PD". It's incredible, almost a free for all. We even find some of these cases arising strictly from the medications given them...ostensibly...for...PD when they don't even have it. 

Max - I stopped taking simvastatin 4 weeks ago and am astonished at the consequences.

1. I felt better the first day and have been improving ever since, which means it is very unlikely to be just the usual Parkinsonian fluctuation. By "better" I mean no tiredness, no aches and pains.

2. After struggling to maintain performance at the Gym for two years, after 4 weeks I am equalling or surpassing the levels of 2 years ago.

3. When I fall (about 1-2 times/month - I walk 3-4 dogs over rough country for an hour most days) I used to be able to get up without assistance but had to lie there for a minute or two and work out how to do it first. The last two times I simply got up without thinking about it.

4. None of my Parkinson’s symptoms has gone, or even improved but the pain and weakness that I wrongly attributed to PD have gone completely.

BUT ...

When I enter “simvastatin +PD) into Google I get a lot of references on how simvastatin protects against PD (eg http://www.sciencedaily.com/releases/2013/07/130724195945.htm).

Can you give me reference to the downside of simvastatin in relation to PD and l-dopa (Sinemet Plus)?

Stephen I know of no credible studies that truthfully conclude that synthetic statin drugs are protective against PD. I know of tons of conflict of interest and biased studies and those that are for short periods of time on otherwise healthy younger people. We have seen consistent improvements in PD and other neuropathies in older adults when they replace synthetic statins for gentler, more natural ways for lowering triglycerides and VLDL cholesterol. Optimized CoQ10, medical grade E-Toco and EPA-DHA, ginger in several forms, red yeast rice, the list goes on--anything but muscle-wasting, CoQ10-blocking, superficially beneficial statin drugs is better for just about anyone in our book. But then the money is not in that corner of the contest, so you won't see the robust studies we think we see in the other corner. But the absence of evidence does not prove the null of a hypothesis. To the contrary, honest, objective case studies of each approach side by side is the only data that matters. And winner for title of Damage to One's Health Over the Long Term is clearly in the synthetic camp.   I'm glad you are feeling better--as well as the countless multitude who are finding the same outcome. 

dear Stephen Warren,

first I'm glad too you feel better; maybe a simple answer to your question lies in the "number needed to treat" [in a wide and consciously improper meaning] that relates PD risk to statins. Obviously I agree with Max Stanley Chartrand about improper pressure, also acknowledging and favouring more natural ways to improve own health.

Thank you for your posting explicitly your intriguing story, Mauro Colombo

In my experience cognitive decline is initially not perceived as disturbing by PD patients, in line with lacking awareness of the "littleness" of movements (decrement of movement amplitude, voice volume, etc), hence interference with ADL is by the patient not seen as a problem, more so by the carer/spouse. Furthermore, cognitive decline is associated with axial symptoms of movements with more pronounced symmetrical gait disturbances (freezing) or posture abnormalities (camptocormia, Pisa). Therefore, treatment with e.g. rivastigmine also targets awareness of motor performance trying to increase alertness. Have a look at the ReSPonD trial. 

Max

I've just seen this:

Statins Do Not Lower Risk of Parkinson's - Monday February 23, 2015

(https://nwpf.org/stay-informed/news/2015/02/statins-may-not-reduce-chances-of-parkinsons/)

Florin

I have a non-tremulous form of PD in which motor symptoms are completely unresponsive to l dopa (Sinemet) but after 2-3 days without it I become socially withdrawn. I am restored to normal within 30 minutes of taking a single 100 mg tablet. I play duplicate bridge (which requires absolute concentration and alertness for 3 hours continuously, and involves memory of all the conventions [codes] used in bidding to give your partner information about your hand and understand what (s)he is telling you about his/her hand, assessing your opponents hand from their bidding, remembering all the playing conventions [codes] and what cards have been played in the past few minutes, from which you deduce which player is holding what cards and his likely response to cards played by others and incorporating all this information into the decisions and judgements you make) in which you play 24 hands in 3hours or less so on average you have about 5 seconds to play each card.

When I’m playing I have to take 50 mg Sinemet every 2 hours. If not I lose concentration and alertness and start to make mistakes leading to funny looks from my partner and ultimately to the cardinal sin in bridge of a revoke, when you play a card of the wrong suit.

Since l-dopa is a metabolite rather than a drug, it looks as if concentration, attention and alertness actually consume l-dopa (or dopamine). The temporary loss of these attributes could easily be taken for MCI.

So I take 100 mg Sinemet when I wake up and when I go to bed and in between I aim to take 50 mg every 120-150 minutes.

Stephen, thanks for the link. I've always maintained that drugs like synthetic statins are best used temporarily until underlying issues that have elevated blood lipids (GERD, alkaline liver, diabetes, and other digestive and metabolic disorders) can be rectified. All of these studies that try to show benefits relative to heart health, memory retention, warding of Parkinson's, are looking at very narrow, weak relationships that may make little difference in individual's health when translated to application, or may mean introducing new problems in the long term that are not being measured at all. Health professions, in my feeling, should be looking at natural, gentle, and organic ways to resolve health problems.

I do agree

treat the disease(s) / care for the patient ... Mauro Colombo