well, this is my experience (mostly in the memory clinic field). It is unlikely for a patient to have two neurodegenerative diseases, so one tries to fit it in the best possible definition; for example, int he case of PD vs PSP, PSP would be the diagnosis of choice. However, in the memory clinic one large issue is the vascular damage: at some point, it is always there and it is not easy, sometimes, to say how much it contributes to the cognitive impairement. same for dlb with more or less memory impairment: how much contribution from alzheimer-like pathology is there? therefore, strict scientific criteria are not always applicable to patients in the clinic, and for biomarker study, pathological/genetic/imaging confirmation should be sought...

I will take an opposite point of view, obviously because I am a neuropathologist. Having one neurodegenerative disease doesn't protect one from having another, and indeed seeing two or even three is not that uncommon. Alzheimer's Disease pathological changes are almost always found in patient with Diffuse Lewy Body Disease (Lewy Body Dementia), and about 30 years ago Sue Mirra and CERAD showed that about 40% of AD patients had pathological (and often clinical) changes of Parkinson's also. I have seen Pick's and AD together in a single patient more than once. If one counts CJD as a neurodegenerative disease then I have seen it with Alzheimer's several times.

This is a critical point for biomarker studies and emphasizes the need for autopsy confirmation of all clinical diagnoses of these disorders to validate biomarker hypotheses. Otherwise you have biomarkers for symptoms and not underlying diseases, which can have rather different pathogenetic bases with similar or indistinguishable symptomatology and neurological examinations.

It is quite frequent that a patient receives more than 2 different diagnoses during its longitudinal follow-up. Unfortunately, some neurodegenerative disorders overlap at their initial stages, so this is a main problem for case/control studies for genetic or biomarker discovery. More, some diaghosed cases are changed or not confirmed at autopsy (when performed). So the heterogeneity/ uncertain diagnose problem do exist, the only key point is to include in experimental studies patients as much characterized as possible (more than 2/3 independent assessments etc) and never limit to short-term diagnose.

Neurotoxicity (sometimes undiagnosed and unrecognized) can cause multiple and seemingly disparate deteriorations of brain function. While a unifying diagnosis is ideal, it is often unattained.

The patient in question most likely has progressive supranuclear palsy. In general, it is possible to have two neurodegenerative processes, but having these two (PD, PSP), at the same time, in the same patient, is highly, highly unlikely. Not unlikely is erroneous clinical diagnosis of parkinsonian disorders, which averages around 20%.

in my experience, using whole brain semiserial thin sections allowing a complete mapping of all brain changes, it is very common with colliding disorders. Ageing goes with a multitude of changes (Samuelsson A S, B Bauer Alfredson , B Hagberg, G Samuelsson, B Nordbeck, A Brun, L Gustafson, J Risberg (1997). The Swedish centenarian study: A multidisciplinary study of 5 consecutive cohorts at the age of 100. Int. J. Aging and Human Devel. Vol. 45(3) 223 - 253). Frontotemporal dementia often contains additional featuers of ALS given the close relationship between these disorders. Alzheimer is more often complicated by vascular lesions than not! (Brun A, Englund E (1986): A white matter disorder in dementia of the Alzheimer type: a pathoanatomical study. Ann Neurol 1986;19:253-262.). there are more examples but in short a combinations of disorders is common.

Regards Arne Brun ( arne.brun@lsn,se )

The information for the patient is insufficient- PD patient may also develop PSP symptoms and vice versa.

We give a syndrome, and then try to give a diagnosis. In some cases it is impossible to differentiate while still living PD from other movement disorders. So we use clinical diagnosis in some diseases (possible, probable, definite).

It is possible that 1 patient develops more than 1 type of pathology, but healthy subjects also could (incidental Lewy bodies for ex.), without clinical expression.

It is accepted that vascular changes, trauma, general anesthesia etc. also play some role in the pathological process in neurodegenerative disorders. Thus and neurotoxicity- for ex. well water consumption as a risk factor for PD (fitting to the Braak`s model with olfactory and GIT as a potential “door”).

Do not forget the most common- essential tremor. It is accepted, finally, as a neurodegenerative disorder. ET may coexist with or transform into PD. The number, however, of neuropathological studies of ET is far lesser.

And, unfortunately, we are still far from clinical biomarkers and early detection of neurodegenerative diseases.

A neuropathologist, I once observed, as did Douglas Miller, instances of what I published as an association of CJD and AD (GACHES J., SUPINO-VITERBO V., FONCIN J.-F. : Association des maladies d'Alzheimer et de Creutzfeldt-Jakob. Acta Neurol. Belg. 1977 77 202-212.). But the occurence of a further case in one family, and the molecular study then made possible, showed the patients were in fact affected with a single disease, namely AD due to a PS1 A163G mutation (EL HACHIMI K.H., CERVENAKOVA L., BROWN P., GOLDFARB L.G., GAJDUSEK D.C., FONCIN J.-F. : Mixed features of Alzheimer's disease and Creutzfeldt-Jakob disease in a family with presenilin 1 mutation in chromosome 14. Amyloid: Intl. J. Exp. Clin. Inv. 1996 3 223-233.). The "biomarker" asked for by Douglas Miller was, in that instance, DNA, a pre-emptive one ! I think that the nosology of "neurodegenerative disesases" is in its infancy, and that what we now call "a disease" is in fact a family of diseases, each disease species to be ultimately defined by its cause (FONCIN J.-F. : Réflexions à partir de l’importance de la notion de cause dans la classification des « maladies ». In : Peut-on classer le vivant ? Linné et la systématique aujourd’hui D. Prat, A. Raynal-Roques, A. Roguenant (Édit.), pp.99-105, Éditions Belin, Paris, 2008). As in the above-mentioned case, various occurences of association between clinico-pathologic features of distinct "diseases" should mostly be a manifestation of a "Jordanian" (as distinct from "Linnean") disease species with specific features. Of course, association of a frequent disease such as AD (sensu lato) with other frequent diseases, such as vascular brain disease, is due to chance, compounded by the earlier manifestation of symptoms due to the synergic effect of both diseases.

Regards, J.-F. Foncin ( [email protected] )

This may get us a bit far from the original question, but I agree with Professor Foncin that some cases of what seem to be CJD are in fact, AD. I recently had a case in a 38 year old sent to me for autopsy as R/O CJD who had only AD, and who had a presenilin 1 mutation with no family history. However, the cases of AD + CJD I have diagnosed pathologically have had abnormal prion proteins proven by western blot plus the typical beta-amyloid plaques and tau-tangles of AD. Of interest in these cases is that the spongiform changes which characterize CJD can be more numerous around the edges of beta-amyloid plaques, somewhat mimicking the appearance of the "florid plaques" of variant CJD. It should be clear that a patient can have both disorders, just as I have seen at least one case with both Pick's and AD, based on the presence of typical plaques and tangles plus typical Pick Bodies, ballooned neurons, etc. I would be prepared to believe (to return a bit closer to the original question) that a patient could have both PSP and Parkinson's Disease, if the brain had Lewy Bodies AND tangles in the appropriate places without any senile plaques, but I have not seen such a case in 30 years.

My view arises from my research on Multiple Sclerosis. In Orkney Islands, Optic Neuritis is almost 100% followed by Multiple Sclerosis. Why? Ask me for a copy of my copyrighted, and soon to be published (in the next quarter of this 2014 year) reports on the causes, including the vectors of most neurological diseases. I am choosing the publishers at this moment.

Multiple neurological diseases can be expected where there is one diagnosed.

Thanks to ResearchGate for the question, without which, there would be no succinct answer.

The question asked is timely and allows to awake neurologists about the concept of a new taxonomy. The need to integrate several parameters to be considered including genetic tests becomes evident without neglecting the autopsy which seems to be more and more neglected/forbidden. Thanks all for this discussion which should be synthesized and gather in a review article.

I agree with the view of Dr.Borislav Ivanov .

I would be surprised if Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP) don't share molecular networks. Consequently, I doubt that a single biomarker will help. The disease progression from PD to PSP (or other neurological diseases) needs to be taken into account. Accordingly, different marker profiles will reassure you whether your patient has "just" PD or an assembly of neurological diseases.

I am not a clinician. I trained as a chemist but did a D Phil in chemical pathology and subsequently briefly taught biochemistry at Oxford. I was diagnosed with PD at the age of 71 in 2010 on the basis of a few tests from the UPDRS. Two doctors from the Monument Discovery Project carried out thorough UPDRS assessments in June 2012 and Dec 2013 and doubted that I had enough symptoms to have PD.

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 there 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.

Clinicians and researchers of course have different priorities but so much research is focussed on finding a cure that there is no systematic attempt to understand how the diversity of forms that PD takes arise. Most of the science is looking at protein misfolding and clinicians are, in the absence of any alternative, looking for ways to categorise PD on the basis of its symptoms of which they take, from a patient’s perspective, a sometimes simplistic view.

It seems to me to be futile to try and define PD in terms of characteristic symptoms until we know a great deal more about the underlying pathology.

Analysis of symptoms can nevertheless provide useful information but there is no routine system for collecting data.

A register of patients with neurodegenerative disorders that listed the diagnosis, date of diagnosis, date at which symptoms were first apparent and symptoms at regular intervals would provide an invaluable database for researchers and clinicians. The data could be provided by the patient and/or carer and might include the patient’s occupation, past and present residences and any other chronic or significant medical conditions or events.

From a lay point of view, and taking something from the not to long ago headlines--the Sandy Hook Elementary shooter was diagnosed with Asperger and OCD, which may have masked a more malevolent type of neuropathy.

I'm neurologist mainly dedicated to cognitive neurology, specially dementias, only a clinician. I strongly support giving one diagnosis to one person. However often it depends.Sometimes it's a question of hierarchy. I mean, following the exemple of the question: I've not seen any patient with a clear diagnosis of PD being re-labelled to PSP. However, the last PSP cases I've diagnosed all of them were previously diagnosed as FTD -ok, a sensu lato diagnosis, but the most likely one to date. Then you have PSP as a part of FTD complex, I think this is a possible 'evolutive' diagnosis. I think it is not the case of PD and PSP. Typical PD and PSP cases are different by the very first beginning, I think; against classical classification of neurological entities can suggest strong similarities because that broad spectrum concept when diagnosing 'parkinsonism'. But 'parkinsonism' is not 'Parkinson's Disease'!

If you have such a case that seems to have two different neurodegenerative diseases you must to reconsider both diagnosis, this is obvious when you have a patient with both PD and AD features perhaps you could diagnose Difusse Lewy Body Disease. A similar situation occurrs not only with clinical features but also with pathological features like coexistence of AD and CJD features in PSEN1 mutations as other investigators have showed.

So I think a single answer to the question does not exist. It depends on diseases and situations, often varying by the certainty of diagnosis, the hierarchy of the entities to be diagnosed and its sensitivity/specificity criteria, and so on

Finally, in common practice, it depends of the likely benefit of available potential treatments too. Not every case fits the clinical standard criteria for diagnosis; however, in clinical practice, you must proceed with the patient and it's possible to try some actions with a possible, but not quite certain, diagnosis. So we give value to some alterations and outcomes and sometimes does not consider any other features. Diagnosis is not the same thing in common practice that it's in research; the clinical diagnosis often is not valid for research purposes.

Fitting cases in diagnosis often is not an easy matter, so what can be said if you ask for multiple diagnoses!! I think I'll go on trying to avoid multiple diagnosis

No, you shoudn't "give a diagnosis" to a patient. A patient "carries a diagnosis", and often, in the case of neurodegenerative diseases, he does so since the zygote stage. One of the task of the physician should be to unveil that diagnosis, or at least to quantify its probability (Bayesian epistemology). Unfortunately, the current diagnosis system is not congruent with that task. Diagnoses are now defined, not by the nature of things (the realist attitude), but by the name attributed empirically by an authority (the nominalist atitude), enabling any trained physician to "give a diagnosis" - and, if two diagnoses are simultaneously "valid" (the word "true" is obsolete), never mind !

Pathology clearly supports the frequent existence of mixed neurodegenerative processes. However, it also supports the existence of non-dementing neurodegenerative lesions. Which lesions in a mixed case contribute to dementia is an empiric question. My research suggests that this depends more on their location than their aggregate "burdens". Pathology of the Default Mode Network (DMN) and its nodes may be most relevant. So I think you might be able to make a single diagnosis in a mixed case regardless of whether the total clinical presentation arises from one pathology or both.

Royall DR, Palmer R, Mulroy A, Polk, MJ, Román GC, David J-P, Delacourte A. Pathological determinants of clinical dementia in Alzheimer’s disease. Experimental Aging Research 2002;28:143-162.

Royall DR, Palmer RF, Vidoni ED, Honea RA, Burns JM. The Default Mode Network and related right hemisphere structures may be the key substrates of dementia. Journal of Alzheimer’s Disease, 2012;32:467-478.

Royall DR, Palmer RF. Some Neurofibrillary Tangles Co-evolve with Neuritic Plaques in Space: Implications for NP-related and Independent Tauopathies. Journal of Alzheimer’s Disease, in press.

Our experience of reviewing Brains Bank navara Biomed.This happens especially with neurodegenerative diseases in elderly patients. Sending a paper by Dr Echávarri.

Multiprotein Deposits in Neurodegenerative Disorders: Our Experience in the Tissue Brain Bank of Navarra. The Anatomical Record

Volume 294, Issue 7, pages 1191–1197, July 2011

Endeavouring to perform as a clinical gerontologist, let me quote the following abstract:

Neuropathological profile of mild cognitive impairment from a population perspective.

Alzheimer Dis Assoc Disord. 2012 Jul-Sep;26(3):205-12 PMID: 21946014

Stephan BC1, Matthews FE, Hunter S, Savva GM, Bond J, McKeith IG, Ince P, Brayne C; Medical Research Council Cognitive Function and Ageing Study (MRC CFAS).

Whether the neuropathological profile of mild cognitive impairment (MCI) reflects an intermediate state between normal aging and dementia is not clear. Identifying which phenomena initiate disease and which occur secondary to the neuropathological process is important for targeted disease prevention. Current definitions of MCI include amnestic (aMCI), nonamnestic (nMCI), and multidomain (mMCI) subtypes. In an unbiased population-based cohort of brain donors, we have determined how many individuals fulfill these criteria in the period leading up to death [n=10 (5 multidomain MCI, 4 amnestic MCI, 1 nonamnestic MCI)]. All MCI cases were collapsed into 1 group and we tested whether their pathologic profile, including markers of Alzheimer disease (AD) and vascular disease (VD), is intermediate to individuals (matched for age, sex, and education) without cognitive impairment (n=20) or dementia (n=20). The main findings are of a significant linear trend in the odds of neuritic plaques (entorhinal/hippocampus), atrophy (hippocampal and cortical), infarcts, and small vessel disease (SVD) with increased cognitive impairment. Neuropathologically, MCI is complex, with 10% of MCI brains classified as normal, 10% as VD, 10% as AD, and 40% as mixed AD/VD, with the remaining showing other pathologies. Rather than pure pathologic changes, several different factors seem to contribute to the impairment of MCI. In MCI, both AD and non-AD pathology should be considered as possible intervention targets.

To me, the paper shows the difficult trade-off between clinical work and neuropathology data ("valid" / "true" they are: Wiener Kreis is off, but "positive heuristics still works ...)

Best regards, Mauro Colombo

Nice and realistic conclusion.

Neurodegenerative conditions such as Parkinson’s disease (PD), multiple symptom atrophy (MSA) and supranuclear palsy (PSP) can manifest similar clinical symptoms although the underlying pathology may be different. This is reflected in the metabolic imaging topographies of parkinsonian syndromes derived with positron emission tomography (PET) that indicate disease networks that are distinct but can overlap in many areas. Automated diagnostic imaging tools that measure the expression of these characteristic networks in individual patients can assist clinicians to differentiate difficult to diagnose cases. The outcomes from these routines can be accompanied by a percent probability for each of several possible conditions indicating which is most likely, often reaching greater than 90%, but there is sometimes a high probability that another condition is also likely. Refining these algorithms to give more definitive answers at early stages of disease is an ongoing objective.

All these discussions rest on the postulate that PD, MSA, PSP, not to mention AD and many other "neurodegenerative" diseases, each are "bona fide" entities, and not more or less arbitrary groupings created to be used by statisticians and, hopefully, therapy-oriented physicians. In fact, each of the above-mentioned conditions is a collection of many distinct entities, many of them currently unrecognized, but each one ultimately to be defined by its cause, as evidenced by the numerous distinct genetic instances they already include.

I fully agree with Douglas Miller and Arne Brun, combined diseases are common!

I want to stress the point by DM that autopsy confirmation is very important, especially in the light of a variable and sometimes surprisingly low concordance between clinical diagnosis in a specialist setting and the neuropathology findings.

All neuropathologists will agree with the precedent messages: when a "degenerative disorder" diagnosis is considered by a physician, "mixed dementia" is the usual finding and a "pure" degenerative or vascular or any other complex disorder such as Creutzfeldt-Jakob or any other variant of "prion" induced disorder is a quite exceptional diagnosis (for vascular and mixed dementias, see "Hauw JJ, De Girolami U, Zekri D. The neuropathology of vascular and mixed dementia and vascular cognitive impairment. In C Duyckaerts, I Litvan (eds) Handbook of Clinical Neurology, Vol 90 (3rd series), Edinburgh, Elsevier, 2008 p 687-703.). What is important is to take into account, for the patient, the therapeutic possibilities and also, for the physician, the unique infection control problem caused by prion diseases.

Prefer to give a single, most likely , diagnosis in an established category, say PD vs PSP. While I agree that as of now, the postmortem examination is the safest . For the most likely clinical diagnosis , I rely on the question , how sure am I? for instance stating that a patient has PSP. The constellation of clinical findings and response to therapy makes me gain a level of certainty,.

Regarding the example ,for instance , cognitive impairment primarily manifested in visuospatial impairment is likely to be associated with PD. Posture is another helpful mark.Clinical eye movement exam , looking for saccadization of pursuit is helpful. .RESPONSE TO SYMMETREL therapy IS A HELPFUL GUIDE TO DIAGNOSE PD..

How my current thinking will change with the future availability of easily obtainable biomarkers, such as examination of the saliva , the eye ...time will tell.

We know that the world has a rapidly ageing population. Neurodegenerative diseases (ND) are strongly linked with age, with older peoples more at risk. Therefore the prevalence of ND is increasing dramatically. The major problem with ND is its difficulty to be diagnosed early.

From the perspective of the treatment of any disease is crucial setting its accurate diagnosis. The same is true for its clinical neurologists and patients who would be ideal if it were possible to set the person's lifetime unique reliable diagnosis of any neurological disease, as well as neurodegenerative.

Symptoms are similar to those of Parkinson's disease have a large number of other neurodegenerative diseases caused by infections, toxins, drugs, and the structural damage to the brain, and it is sometimes impossible to distinguish from a Parkinson's disease by clinical symptoms. A thorough medical history and diagnostic tests such as neuroimaging can assist in setting distinguishing diagnosis.

When they problems exist between only the two neurodegenerative diseases, the procedure of their distinction with the modern complementary diagnostics will be easier, but if we consider that only the differential diagnosis of parkinsonism implies a potential for about twenty different clinical-pathological entity, with a dozen more specific diagnostic subgroupes, all of which must carefully considered and the rationale to accept or reject them, in order to reach the final correct diagnosis.

Clinical-pathological studies have shown the possibility of several neurodegenerative diseases in the same patient in many cases, what is so far in the discussion of the question given already quite competent and answers.

Compared to studies of biomarkers and the need to confirm the autopsy findings of clinical diagnosis of these disorders on biomarker validation hypothesis, it must be pointed out that in some instances they are the symptoms but not the confirmation of the underlying disease, which further complicates the decision-definite conclusion, and thus the precise answer the question.

In this particular example, search for answers to this question can be accepted as correct placement of both diagnoses, with the first alleged that she was set up earlier (PD) and the other (PSP) as clinically appropriate and unlikely.

Milorad - Parkinson's Disease (PD) is among the most difficult conditions to diagnose with confidence. Patients may have any combination of over 30 symptoms, many of which appear entirely unrelated to each other, but nearly all of which can be traced to a lack of dopamine and many of which can be attributed easily to old age. One website supporting self diagnosis gave a list of 8 symptoms of which, they said, you had to have at least 3 to be diagnosed with PD! These arbitrary rules without any foundation give clinical science a bad name.

I think there is a case for giving any patient with more than three (even mild) symptoms a provisional diagnosis of PSD (Parkinson's Spectrum Disorder) or PTD

(Parkinson's Type Disorder). The patient could then be sent , if (s)he wished to a regional centre for a thorough assessment. I think PD is probably underdiagnosed in the over 75s in the UK (see the attached file).

While any PD symptoms are ameliorated with dopaminergic therapy, others ,(such as olfactory dysfunction, visuopsatial dysfunction, logical memory deficits, losing weight, indistinct speech) are not helped with dopaminergic therapy. The question is whether or not the cardinal symptoms respond to dopaminergic therapy. PSP symptoms don't.

The "arbitrary rules are probably related to experience with the diagnosis on the long run, but this would be worth edtanlishin.

A minor note: the arbitrary rules are giving perhaps a bad name for clinical diagnostic acumen, but I do not think they denigrate 'clinical science".

I find it necessary to add the previous answer a few important data as useful guidelines in practical work with patients in whom there is diagnostic confusion .

Clinical criteria for Parkinson's disease ( PD ) include the following neurological cardinal signs : bradykinesia ; tremor at rest ; rigidity ; postural instability ; and clinical features of PD are in the later course of the disease are present : cognitive disorders ; dementia ; autonomic disorders ; frequent falls ; dysphagia ; dysarthria ; freezing; depression .

Exclusion criteria for the PB : supranuclear paresis views ; cerebellar signs ; and expressed early autonomic disorders ; early dementia ; signs of damage to the cortico - spinal path; lack of response to L -dopa ; previous therapy with neuroleptics .

Criteria and cardinal signs for the diagnosis of PSP are slowly progressive disorder ; beginning ≥ 40 years ; supranuclear vertical gaze palsy or slowing of vertical saccades together and postural instability with falls within the first year of the disease; no other disease that would explain these symptoms could .

Suggesting signs are retrokolis ; puzzled look ; sign of applause ; Early motor blocks ; " Dignified" gait ( falls back ) ; frontal lobe syndrome .

Exclusion criteria for PSP were : alien limb and Graphesthesia ; early cerebellar signs ; Early autonomic disorders ; hallucinations wound ( without D therapy ) ; pronounced asymmetry and early cortical dementia type.

The symptoms that support the diagnosis of PSP are symmetrical bradykinesia and rigidity ( proximal > distal ) ; abnormal disturbance door , particularly retrokolis ; absent or poor response to L - dopa therapy ; early occurrence of dysphagia and dysarthria ; early occurrence of cognitive impairment , including at least two of the following : apathy , damaged abstract thought , decreased verbal fluency, imitation or utilización behavior , signs of frontal disinhibition .

You should bear in mind the data of applied epidemiology in this area and know that the frequency of Parkinsonian syndromes in daily practice as follows: Idiopathic PB 85 % ; Neuroleptic parkinsonism 7 % -9 % ; MSA ~ 2.5 % ; PSP ~ 1.5 %, and the prevalence of different Parkinsonian syndrome per 100,000 population: the PB 150 ; MSA 6-8 , 4-6 PSP , Dementia with Lewy bodies 0.5 and cortico - basal degeneration 1-2 .

Lawrence - ". ....... all patients with Parkinson's ... had ..more dementia ......some froms of Parkinsonism may be variants [modifications] of senile dementia of the Alzheimer type."

I couldn't find the reference (vol 3 is too old?) but:

How were PwP defined - ie what criteria for diagnosis were used? The swirch from PD to P'ism is unexplained. Are the forms of Parkinsonism considered to be variants of Parkinson's Disease?

[I should say that I was diagnosed with P'ism in 2010 after symptoms going back to 2008 or even 2006. I am now considered to have PD although I lack many of its characteristic symptoms (no MCI as far as I can tell!) and colleagues on ResearchGate tell me that I definitely do not have PD. ]

Personally I have concluded Parkinsinism should be diagnosed initially as Parkinson's Spectrum Disorder (PSD) until the diagnosis can be refined. The association between PD and AD is well established and PD is under-diagnosed in the 80+age range.

Here is a blog post about the under-diagnosis of PD.

I would like to post the following inter/multi-disciplinary example in this intriguing discussion

Mauro Colombo

I prefer one diagnosis . In the example I would chnage PD to PSP. HOWEVER, I also recognize that in many patients giving one diagnossi may or does

not cover all the signs and symptoms. realistically , that is also true even if we are confident of a single diagnosis. The problem of developing neuroprotective medications should not influence diesease categorization at this stage. Oncea neuroprotective medications , based on pathobiology , are developed, the issue of treating symptomatic diagnostic categories will become mote..

Mauro, I like this idea of using the pattern of deterioration as an indicator of multiple causes of dementia but we would need evidence of the repeatability of shape of the deterioration curve for different causes of dementia. PD does not inevitably lead to dementia but maybe we should say that all forms of PSD do not inevitably lead to dementia. Is PD dementia always associated with Lewy Bodies (and vice versa)?

Really we need more data from functioning brains in living people.

I think using symptoms as criteria for a diagnosis is arbitrary unless we know for certain that they have a common specific cause. In PD we are a long way from this.

Of course, all patients dying with dementia shoud "benefit", after competent clinical observation, from a complete neuropathological post mortem study. Only then would the nosology of dementing disease provide a firm, rooted in reality, basis for progress. Instead, in place of a nosology we have a categorisation, a nominalist process "rooted" in definitions by "authorities". English being a splendid poetic language, but not a good philosophical one (we lost the best one with scolastic Latin), I published in French a discussion of these problems (FONCIN J.-F. : Réflexions à partir de l’importance de la notion de cause dans la classification des "maladies". In : Peut-on classer le vivant ? Linné et la systématique aujourd’hui D. Prat, A. Raynal-Roques, A. Roguenant (Édit.), pp.99-105, Éditions Belin, Paris, 2008).

Jean- your English is excellent!  Your phrase ... dying with dementia .... is precise and accurate but few naive speakers would realise this and even fewer would understand why it is important.  Educated English can be very precise if sentences are properly constructed but unfortunately  they often are not.  it is almost impossible to write an unintentionally ambiguous sentence in Latin because of its  case structure and German is simlilar.  Russian shoiuld be at least as good but is not because many Russian speakers fnd their own lanuage difficult to learn and it becomes corrupted, as English does, by slang.  It is said that Chekhv went out to buy a pair of gloves and came back empty handed becasue he could not recall the (partitiive)genitive plural of glove!  Chinese (Mandarin) is notoriously ambiguous bcause it is tenseless and has no cases so the listener must rely heavily on context to capture meaningl

I will give my opinion from the perspective of the results obtained in brain banks. It is very rare that after exhaustive studies including all sorts of proteins responsible for neurodegeneration,  amyloid, tau At 8,  4r , 3r, ubiquitin, alpha-synuclein, p62, TDP43, PrPSc, PAS etc, we can say that the patient has one disease responsible for the all clinical symptoms. Each brain that will be included as controls in older patients In the brains of these patients we see deposits over more than a single abnormal protein, sometimes three or even four.Only in young or middle aged patients. Therefore comparative studies between patients and control patients are required to be very rigorous. In my opinion in the report issued by the neuropathologist, should describe each and every one of the observed diseases and their distribution in the parenchyma. Adding further vascular damage, whether small or large vessel.

Teresa - This is very interesting.  Is there any evidence of an age-related trend in the pathologies?

In the UK the onserved incidence of PD appears to drop to zero at age 75.  Disbelieivng the reality of this I looked at the data and estimated a true prevalence similar to what you observe (se the attachment).  Many GPs still see the tremor as the key symptom for a diagnosis of PD.  If tremor were less common in PD occuring at a later age this might partially account for an underdiagnosis of PD.  If the pathology also changed in later onset PD this might give a useful clue relating symptom to pathology.   Yes, I know there are two or three big "if"s but the potential rewards justify the small effort involved.

Incidentally in your report,  do you mean "abnormal proteins" or "abnormal forms of  (normal) proteins"?

One neuogenerative diagnosis per patient....  I am a clinical neurologist and am aware t hat many late onset  dementias I diagnose  may be mixed- vascular and Alzheimers . It is also increasingly becoming clear from clinical and neuropathological correlations that a growing number of autoimmune disorders - particularly MS may have a treatable /reversible autoimmune component - before degeneration sets in. another example- several patients treated for autoimmune dementias have brain biospsy showing neurofibrillary tangles. So in a broad sense more than one underlying process can coexist and we may label them clinically as a single  entity or vice versa.

Lekha - how often do you diagnsoe a 75+ year old with Parkinson's.  What defining criteria would/do you use?  Parknson's comes in so many forms that I now tell people that I have a Parkinson's Spectrum Disorder (PSD) because, although I have  several of the symptoms characteristic of PD, I lack more of them than I have.

When I am with a patient, I focus on the diagnosis that makes the most sense in that particular patient. This is important, since the natural Hx of PSP and PD, for example, are very different.  The tremor in PSP does not usually respond to Sinemet in the same way as the tremor in PD.  I may still use Sinemet, but with the understanding that I will not get the same response.  The life expectancy of these two diseases is very different, so this is also an important difference in counselling the pt about thier Dx.

In an elderly patient with Parkinsonism , I look for asymmetry in clinical presentation (even historically is good enough), classical resting tremors, involvement of postural reflexes in upper extremities, unremarkable deep tendon reflexes and lack of vertical eye movement disorders to make a diagnosis of Parkinsons disease. It always helps that in the history there is no suggestion of early cognitive imapirment /Hallucinations or early falls . With this check list I hope to avoid PSP, Lewy body dementia, vascular PD and MSA.  Occassionally a wide based gait has helped me pick up MSA-C.  But in an occassional patient you still are not sure what you are treating..

To TERESA, her contribution 2 days ago : Neuropathology is not an inventory of proteins, but an analysis of lesions and their paterns. Moreover, the ultimate nosological criterium is not (neuro)pathology, but the cause of the disease. Tuberculosis is the many-sided disease caused by the Koch bacillus. To our current theme: affected members with betaA4 as well as prion plaques of the family we published (EL HACHIMI K.H., CERVENAKOVA L., BROWN P., GOLDFARB L.G., GAJDUSEK D.C., FONCIN J.-F. : Mixed features of Alzheimer's disease and Creutzfeldt-Jakob disease in a family with presenilin 1 mutation in chromosome 14. Amyloid: Intl. J. Exp. Clin. Inv. 1996 3 223-233.) are affected with Alzheimer's disease, period, because they carry a pathogenic A163G mutation in the PSEN1 gene.