Clinical diagnosis of CBD; autopsy showed CJD

In case you needed more evidence that CBD mimics other disorders… This is a case of a 73-year-old Japanese woman who “showed slowly progressive aphasia, apraxia and dementia. She had no family history of prion disease or dementia. One year later she showed parkinsonism and corticobasal degeneration was initially suspected. … The patient developed myoclonus and an akinetic mutism state 15 months and 22 months after onset, respectively.”

She died at age 81. A brain autopsy was performed. It revealed she had a genetic form of Creutzfeldt-Jakob disease.


Neuropathology. 2011 Jan 27. [Epub ahead of print]

An autopsied case of V180I Creutzfeldt-Jakob disease presenting with panencephalopathic-type pathology and a characteristic prion protein type.

Iwasaki Y, Mori K, Ito M, Nagaoka M, Ieda T, Kitamoto T, Yoshida M, Hashizume Y.
Departments of Neurology Pathology, Oyamada Memorial Spa Hospital Department of Neurology, Yokkaichi Municipal Hospital, Yokkaichi Division of CJD Science and Technology, Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Aichi, Japan.

A 73-year-old Japanese woman showed slowly progressive aphasia, apraxia and dementia. She had no family history of prion disease or dementia.

One year later she showed parkinsonism and corticobasal degeneration was initially suspected. On MRI, the left temporal neocortex seemed swollen on T2-weighted images in the initial stage, and a later high-signal intensity region was observed in the cerebral cortex in diffusion-weighted images.

The patient developed myoclonus and an akinetic mutism state 15 months and 22 months after onset, respectively. Consecutive electroencephalography revealed no periodic sharp-wave complexes.

Prion protein (PrP) gene analysis revealed a valine to isoleucine point mutation at codon 180, and methionine homozygosity at codon 129.

This patient’s clinical symptoms and disease course were atypical for Creutzfeldt-Jakob disease (CJD), and a stable state with nasal tube-feeding lasted several years.

She died of respiratory failure at the age of 81, 102 months after the onset.

Autopsy revealed widespread spongiform degeneration with weak synaptic-type PrP deposition, confirming the diagnosis of genetic CJD. Neurons in the cerebral cortex were relatively preserved in number and hypertrophic astrocytosis was generally moderate for such long-term disease, but cerebral white matter showed diffuse severe myelin pallor with tissue rarefaction suggestive of panencephalopatic-type pathology. The cerebellar cortex was relatively well preserved with observation of mild spongiform change in the molecular layer, moderate neuron loss in the Purkinje neuron layer, and scattered small plaque-like PrP deposition. Western blot analysis of protease-resistant PrP showed a characteristic pattern without a diglycoform band.

V180I CJD is an interesting form of genetic CJD with regards to the clinicopathologic, molecular and genetic findings.

© 2011 Japanese Society of Neuropathology.

PubMed ID#: 21269331 (see for this abstract only)

Clinical-pathological correlates in PSP (and MSA)

This is a terrific little study done comparing brain tissue of 15 PSP cases, 12 MSA cases, 8 PD cases, and 8 healthy controls, and correlating the pathology with clinical variables (age at onset, disease duration, and symptoms).

The study was done in Australia using tissue donated to the Sydney Brain Bank. I say it was a “little” study because the previous clinical-pathological correlation study in MSA and PSP had much larger numbers — 110 PSP cases and 83 MSA cases. That larger Queen Square Brain Bank (UK) study “did not consider the pathological severity of disease or assess pathological correlations to clinical features.” (This is O’Sullivan’s “Clinical outcomes” article published in the journal Brain in 2008.  We have posted about that here.)

The symptoms studied include the:

“presence or absence of…bradykinesia and rigidity, resting tremor, postural instability, response to levodopa (L-dopa) therapy, dementia as indicated from the last Clinical Dementia Rating (CDR) score, early falls (within the first 2 years of onset), supranuclear vertical gaze abnormalities (abnormal or slow vertical gaze and/or supranuclear gaze palsy), dysarthria, dysphagia, postural hypotension, autonomic and urinary dysfunction, and gait ataxia. The severity of parkinsonism was assessed using the last Hoehn and Yahr (H&Y) score prior to death.”

Here’s some key data on the clinical variables:

Age at onset
PSP: 67 years +/- 9 years

Disease duration
PSP: 7 years +/- 4 years

Phenotype (parkinsonian: parkinsonian-plus)
PSP: 5:10

% L-dopa responsive
PSP: 47%

% demented
PSP: 67%
MSA: 0%

% early falls
PSP: 93%

% gaze abnormalities
PSP: 73%

% dysarthria
PSP: 60%

% autonomic dysfunction
PSP: 47%

% gait ataxia
PSP: 40%

The researchers divide cases by phenotype — parkinsonian or parkinsonian-plus. My assumption is that, for PSP, the parkinsonian phenotype is called PSP-Parkinsonism and the parkinsonian-plus phenotype is called RS (Richardson’s Syndrome).

“As expected, response to L-dopa was associated with a parkinsonian phenotype across all groups, although resting tremor was not associated with either phenotype. The presence of supranuclear vertical gaze abnormalities and early falls was associated with a parkinsonian-plus phenotype across groups, although autonomic dysfunction and gait ataxia were not associated with either phenotype.”

I’ve copied the abstract below.



Movement Disorders. 2011 Jan 21.

Clinical correlates of similar pathologies in parkinsonian syndromes.

Song YJ, Huang Y, Halliday GM.
Neuroscience Research Australia and the University of New South Wales, Randwick, New South Wales, Australia.

BACKGROUND: There have been no previous studies assessing the severity of regional atrophy, cell loss and lesion densities between the overlapping conditions of Parkinson’s disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) and relating these pathologies to different clinical features.

METHODS: Clinical indices and basal ganglia, brainstem, and cerebellar pathology from 43 longitudinally studied cases (PD = 8, PSP = 15, MSA = 12, controls = 8) were compared. A point-counting method was used to evaluate subregional volumes, and alpha-synuclein and phospho-tau immunohistochemistry was used to assess pathological inclusions and stage disease severity. Logistic regression analyses were used to identify pathological associations with clinical features.

RESULTS: All PD, PSP, and MSA cases had severe degeneration of the substantia nigra. Clinical features correlated with tissue loss and the severity of inclusion pathologies. Levodopa responsiveness and a lack of resting tremor was associated with preservation of pallidal volume, the presence of gait ataxia was associated with atrophy of the putamen, and the parkinsonian-plus phenotype with early falls and supranuclear vertical gaze abnormalities had more substantial midbrain atrophy and greater inclusion pathology in the caudate nucleus.

DISCUSSION: This is the first study to compare the severity of regional pathologies across parkinsonian conditions. The data show that tissue loss and inclusion densities in certain regions correlate with clinical indices, with regional volume changes likely to be the best indicator of clinical progression of disease.

Copyright © 2011 Movement Disorder Society.

PubMed ID#: 21259341 (see for the abstract only)

Alpha-synuclein in spinal fluid isn’t a parkinsonism biomark

Dutch researchers found that the amount of alpha-synuclein in cerebrospinal fluid (CSF) is not a tool for differentiating those who have Parkinson’s Disease from those who have an atypical parkinsonism disorder (MSA, DLB, PSP, CBD, and vascular parkinsonism). Alpha-synuclein in CSF is also not a tool for differentiating among the atypical parkinsonism disorders. The search for a biomarker continues.

Neurobiology of Aging. 2011 Jan 12. [Epub ahead of print]

CSF alpha-synuclein does not differentiate between parkinsonian disorders.

Aerts MB, Esselink RA, Abdo WF, Bloem BR, Verbeek MM.
Department of Neurology, Parkinson Center Nijmegen (ParC), and Alzheimer Centre Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, the Netherlands.

Differentiating between Parkinson’s disease (PD) and atypical Parkinsonism (AP) is clinically relevant but challenging.

A timely and correct diagnosis might result in better targeted treatment strategies, adequate patient counseling, and early recognition of disease-specific complications.

We aimed to investigate whether cerebrospinal fluid (CSF) concentrations of alpha-synuclein are of additional diagnostic value. We examined 142 consecutive patients with parkinsonism, mean disease duration 39.7 mo (Parkinson’s disease (PD), n = 58; MSA, n = 47; dementia with Lewy bodies (DLB), n = 3; VaP, n = 22; progressive supranuclear palsy (PSP), n = 10; CBD, n = 2).

Gold standard was the clinical diagnosis established after 2 years of clinical follow-up.

CSF concentrations of alpha-synuclein, blood pigments and the erythrocyte count were determined.

No differences between CSF alpha-synuclein concentrations of patients with PD with the reference values from our laboratory were observed.

We neither found significant differences between patients with PD and AP nor between AP subgroups. Adjustment for age, disease severity or presence of erythrocytes or blood pigments in CSF did not alter these results.

Our results imply that CSF alpha-synuclein is currently unsuitable as biomarker to differentiate between PD and AP.

Copyright 2011 Elsevier Inc. All rights reserved.

PubMed ID#: 21236518 (see for abstract only)

“Applause sign” may be due to frontal lobe impairment

PSP and CBD folks –

This is further evidence that the “applause sign” is not a very useful tool when diagnosing PSP or, by inference, CBD. This research shows that the applause sign can occur in FTD (only the behavioral variant of FTD was included) and AD. (Previously others have argued that it is unique to PSP. More recently, researchers have argued that it is specific to parkinsonian disorders.)

Here’s a description of the applause sign from the article: “The applause sign was detected using the three clap test which was administered and scored according to the literature: subjects were asked ‘to clap three times as quickly as possible after demonstration of the examiner’. The subject’s performance was considered normal when he/she clapped three times (score=3), abnormal when the subject clapped more than three times (2=four times, 1=five to ten times; 0= more than 10 times).”

“An abnormal applause sign was present in all patient groups (80% in PSP, 70% in FTD and 31% in AD) while it was absent in normal controls. …[P]oor specificity and low positive predictive value of the applause sign should raise questions about its diagnostic usefulness.”


Journal of Neurology, Neurosurgery and Psychiatry. 2011 Jan 18. [Epub ahead of print]

Applause sign: is it really specific for Parkinsonian disorders? Evidence from cortical dementias.

Luzzi S, Fabi K, Pesallaccia M, Silvestrini M, Provinciali L.
Department of Neuroscience, Polytechnic University of Marche, Ancona, Italy.


The applause sign, originally reported as a specific sign of progressive supranuclear palsy (PSP), has recently been found in several parkinsonian disorders. Its nature is still uncertain. It has been interpreted as a motor perseveration or a form of apraxia.

The present study aims to: (a) verify the specificity of the applause sign for parkinsonian disorders, examining the presence of the applause sign in cortical dementias which should be error free and (b) clarify the nature of the applause sign (resulting or not from apraxia).

77 subjects were included: 10 PSP, 15 frontotemporal dementia (FTD), 29 Alzheimer’s disease (AD) and 23 normal
controls. The presence of apraxia was an exclusion criterion. All patients underwent a detailed neuropsychological examination, and cognitive performance was correlated to the applause sign.

All patient groups showed the applause sign and differed significantly from normal subjects who were error free.

No difference was found when comparing PSP with FTD and FTD with AD.

AD differed significantly from PSP but they were not error free (31% of patients with AD showed the applause sign).

The only correlation with background neuropsychology was found for measures of executive functions.

The presence of the applause sign in cortical dementia does not confirm the specificity of the applause sign for parkinsonian disorders. The applause sign should be interpreted as a sign of frontal lobe dysfunction rather than a form of apraxia, and can likely be detected in any kind of disease which involves frontal lobe structures to some extent.

Pub Med ID#: 21245475 (see for this abstract only)

Patterns of brain atrophy – PSP, MSA, PD

This paper from Italian researchers addresses the amount of atrophy in various regions of the brain in those with clinical diagnoses of Parkinson’s Disease (PD), PSP, and MSA. I *think* standard MRIs were given and the volumetric analysis is done by software.

Researchers concluded: “Volumetric data obtained with automated segmentation of cerebral regions show a significant atrophy of different brain structures in parkinsonisms rather than in PD. Our study also demonstrates that the atrophy of the thalamus only occurs in PSP while the enlargement of the whole ventricular system characterizes both PSP and MSA-P.”


Parkinsonism and Related Disorders. 2011 Jan 12. [Epub ahead of print]

Patterns of brain atrophy in Parkinson’s disease, progressive supranuclear palsy and multiple system atrophy.

Messina D, Cerasa A, Condino F, Arabia G, Novellino F, Nicoletti G, Salsone M, Morelli M, Lanza PL, Quattrone A.
Institute of Neurological Sciences, National Research Council, Piano-Lago, Mangone, Italy; Institute of Neurology, University “Magna Graecia”, Germaneto, Catanzaro, Italy.

BACKGROUND AND PURPOSE: Quantitative analysis of brain atrophy may be useful in differentiating Parkinson’s Disease (PD) from Progressive Supranuclear Palsy (PSP) and parkinsonian variant of Multiple System Atrophy (MSA-P); the aim of this study was to identify the volumetric differences of subcortical structures in patients with PD, PSP and MSA-P using a novel and validated fully-automated whole brain segmentation method.

METHODS: Volumetric MRIs were obtained in 72 patients with PD, 32 patients with PSP, 15 patients with MSA-P, and in 46 control subjects. Subcortical volume was measured automatically by FreeSurfer. Multivariate analysis of covariance, adjusted for intracranial volume (ICV), sex and age, was used to explore group differences.

RESULTS: No volumetric differences were found between PD and controls group; otherwise the volumes of the cerebellum, the thalamus, the putamen, the pallidum, the hippocampus, and the brainstem were significantly reduced in PSP and MSA-P compared to patients with PD and control subjects. PSP and MSA-P patients only differed in thalamus volume which was smaller in PSP group (p < 0.001). Moreover, patients with PSP and MSA-P showed a ventricular system (including lateral, third and fourth ventricles) larger than that detected in PD and controls (p < 0.001).

CONCLUSIONS: Volumetric data obtained with automated segmentation of cerebral regions show a significant atrophy of different brain structures in parkinsonisms rather than in PD. Our study also demonstrates that the atrophy of the thalamus only occurs in PSP while the enlargement of the whole ventricular system characterizes both PSP and MSA-P.

Copyright 2010 Elsevier Ltd. All rights reserved.

PubMed ID#: 21236720 (see for this abstract only)

PSP: “new concepts” – summary article

This nice summary article, “Progressive supranuclear palsy: new concepts,” is available online at no charge. It reviews the all of the clinical subtypes of PSP, including the two most common types (Richardson’s Syndrome and PSP-Parkinsonism). A photo of a PSP patient with retrocollis is shown.

Given my advocacy for brain donation, I found these points interesting: “[L]ess than a half of patients with pathologically-proven PSP will have received the diagnosis of PSP at presentation. The National Institute of Neurological Disorders and Stroke/ Society for PSP (NINDS/SPSP) criteria detect only 50-70% of patients within 3 years of disease onset.”

Let me know if anything caught your eye.

Here’s a link to the full article: … so&tlng=en

If this link doesn’t work for you, then go to and type 21243256 into the search box. Then an abstract will appear along with a logo. Click on the logo to get the article.


Arquivos de Neuro-Psiquiatria. 2010 Dec;68(6):938-46.

Progressive supranuclear palsy: new concepts.

Barsottini OG, Felício AC, Aquino CC, Pedroso JL.
Department of Neurology and Neurosurgery, Federal University of São Paulo, São Paulo, SP, Brazil.

Progressive supranuclear palsy (PSP) is a distinctive form of neurodegenerative disease which affects the brainstem and basal ganglia. Patients present supranuclear ophthalmoplegia, postural instability and mild dementia. PSP is defined neuropathologically by the accumulation of neurofibrillary tangles in the subthalamic nucleus, pallidum, red nucleus, substantia nigra, striatum, pontine tegmentum, oculomotor nucleus, medulla and dentate nucleus. Over the last decade many lines of investigations have helped refine PSP in many aspects and it is the purpose of this review to help neurologists identify PSP, to better understand its pathophysiology and to provide a more focused, symptom-based treatment approach.

PubMed ID#: 21243256

‘Bicycle Sign’ May Distinguish PD From Atypical Parkinsonism

This is a news article based upon some new research published in the latest issue of The Lancet. “New research suggests the preserved ability to ride a bicycle after onset of symptoms may accurately differentiate between Parkinson’s disease (PD) and atypical parkinsonism,” such as PSP, CBD, MSA, LBD, and vascular parkinsonism.

“Making the differential diagnosis … is important clinically for counseling patients and accurate inclusion of suitable patients into trials but remains challenging,” the researchers note. “Here, we suggest that the answer to 1 simple question — ‘Can you still ride a bicycle?” — offers good diagnostic value for separating Parkinson’s disease from atypical parkinsonism.”

Could it be this easy?

The short, two-page article in The Lancet is available at present at no charge online. See: … 40-6736(11)60018-4/fulltext

The table is worth a quick look.

Here’s a link to the news article in Medscape and the full text.


‘Bicycle Sign’ May Distinguish Parkinson’s From Atypical Parkinsonism
Susan Jeffrey
From Medscape Medical News > Neurology

January 7, 2011 — New research suggests the preserved ability to ride a bicycle after onset of symptoms may accurately differentiate between Parkinson’s disease (PD) and atypical parkinsonism.

The investigators, with senior study author Bastiaan R. Bloem, MD, PhD, medical director of the Parkinson Center Nijmegen at Radboud University Nijmegen Medical Center, the Netherlands, had previously reported a case study of a patient with advanced PD who showed an astonishing residual ability to ride a bicycle.

Now they have found in a new series of patients that preserved cycling ability is limited to patients with PD but is lost after disease onset among those with atypical parkinsonism.

“Simply asking about cycling abilities could be added to the list of red flags that can assist clinicians in their early differential diagnosis of parkinsonism,” the study authors conclude.

They report their findings as correspondence in the January 8 issue of The Lancet.

Freezing of Gait

In April 2010, Dr. Bloem and colleague Anke Snijder, MD, reported the case of a 58-year-old man with advanced PD and severe freezing of gait who could nonetheless ride his bicycle for up to 15 miles per day. After meeting this patient, Professor Bloem reported having found an additional 20 PD patients in his outpatient clinic, where he specializes in gait and balance disorders, all of whom could still ride a bicycle (N Engl J Med. 2010;362:13).

“In hindsight, it’s not a unique observation, and we’ve just missed out, maybe because we failed to ask about it or patients fail to volunteer this, but it’s certainly not a unique observation,” he told Medscape Medical News at that time.

Making the differential diagnosis between PD and atypical parkinsonism disorders, such as progressive supranuclear palsy, multiple system atrophy, or Lewy body dementia, is important clinically for counseling patients and accurate inclusion of suitable patients into trials but remains challenging, they note.

“Here, we suggest that the answer to 1 simple question — ‘Can you still ride a bicycle?” — offers good diagnostic value for separating Parkinson’s disease from atypical parkinsonism,” they write.

To look at this prospectively, investigators performed an observational study of 156 consecutive patients who presented with parkinsonism but did not yet have a definitive diagnosis. All had a structured interview, comprehensive neurological assessment, and cerebral magnetic resonance imaging (MRI) at baseline. Standard questions in the interview asked “whether, when, and why” cycling had become impossible for them.

The gold standard for diagnosis was at 3 years of follow-up, based on clinical examination, response to treatment, and MRI.

Of these patients, 111 had ridden a bicycle before first manifestation of their disease; 45 developed PD and 64 some form of atypical parkinsonism, mostly multiple system atrophy (n = 35, 31.5%) or vascular parkinsonism (n = 17, 15.3%).

At the time of inclusion in the study, occurring at a median disease duration of about 30 months, 34 of 64 patients ultimately diagnosed as having atypical parkinsonism had stopped cycling compared with only 2 of the 45 PD patients, yielding a sensitivity of 52%, and a specificity of 96% (area under the curve, 0.74; 95% confidence interval, 0.64 – 0.83).

The loss of cycling ability was seen with all atypical parkinsonism conditions, they note, and regression analysis showed no significant effect of age, parkinsonism, or ataxia on this ability, “suggesting this was an independent marker of atypical parkinsonism,” they write.

Cycling requires a highly coordinated interplay among balance, coordination, and rhythmic pedaling of the legs, Dr. Bloem and colleagues point out. “This skilled task is probably sensitive to subtle problems with balance or coordination, caused by the more extensive extranigral pathology in atypical parkinsonism,” they speculate.

“We suggest that loss of the ability to cycle after disease onset might serve as a new red flag, signaling the presence of atypical parkinsonism,” the study authors conclude. “The diagnostic value of the ‘bicycle sign’ was good: its presence was highly specific for the diagnosis of atypical parkinsonism.”

The study was supported by a research grant from the Internationaal Parkinson Fonds. The study authors have disclosed no relevant financial relationships.

Sinemet shortage in early 2011?

Those of you who take Sinemet may be interested in this news relayed by the National Parkinson’s Foundation…

The “issue” with taking the generic form of Sinemet is that the FDA requires the bioequivalence of any generic product to be between 80% and 125% of that of the innovator product. This is a rather large range.

Email from National Parkinson’s Foundation

Merck & Co. Inc. has informed the Parkinson’s disease community that in early 2011, there may be a potential temporary supply shortage in the U.S. for SINEMET® (carbidopa-levodopa) and SINEMET CR® (carbidopa-levodopa controlled release tablets).

While there is currently no shortage, it is advisable to speak with your health care provider about appropriate steps should a shortage occur. Your health care provider can give you relevant information about potential short-term alternative therapies, including the availability of alternative generic equivalents.

The FDA has shown generic SINEMET® to be effective against the symptoms of Parkinson’s disease, but dosing may need to be slightly adjusted due to differences in manufacturing and formulation. Should you need to temporarily switch to a generic version of SINEMET®, be aware that some people may experience a change in how the medication works. If you do experience a change, contact your health care provider who may prescribe a different dose or timing regimen.

Patients, caregivers and health care professionals in the U.S. who have more questions about the availability of SINEMET® can contact the Merck National Service Center at 1-800-NSC-MERCK.

NPF is committed to keeping you informed of developments on this issue. We will alert you if we get any more information about either a shortage developing or the crisis being averted. If you are informed by your doctor or pharmacist that SINEMET® is not available in your area, please contact us at 1-800-4PD-INFO (473-4636) or [email protected]. If you have any questions, Dr. Okun is prepared to address issues about the shortage and generic substitution on our Ask the Doc online discussion forum.

In vivo comparison of the two most common PSP types

This looks like a carefully-done study for 23 PSP patients though I don’t think there’s pathological confirmation of the diagnosis. Of the 23, 14 had the Richardson’s syndrome (RS) type of PSP, called “classic PSP.” Nine had PSP-parkinsonism, the second most common type of PSP.

Previous studies suggest “that the clinical presentation of the two subtypes differs especially in the first 2 years of disease and then converges.” This German study attempted to confirm that view.

They found that “RS and PSP-P show considerable symptoms overlap during the disease course when using routine assessments, with persisting differences regarding non-motor symptoms.” Those non-motor symptoms include psychological, cognitive, and behavioral deficits.

We can glean two other points from the abstract:

* “RS patients showed shorter time from disease onset to diagnosis…”

This is certainly because RS patients have “classic PSP” so neurologists are better able to recognize it as being PSP.

” Shorter disease duration of the comparably affected RS patients indicates that this subtype has an accelerated disease progression at early disease stages.”

We know from previous studies that those with the RS type of PSP have a shorter survival time than those with the PSP-P type.


Journal of Neural Transmission. 2011 Jan 5. [Epub ahead of print]

In vivo comparison of Richardson’s syndrome and progressive supranuclear palsy-parkinsonism.

Srulijes K, Mallien G, Bauer S, Dietzel E, Gröger A, Ebersbach G, Berg D, Maetzler W.
Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, University of Tuebingen, Tuebingen, Germany

Richardson’s syndrome (RS) and progressive supranuclear palsy-parkinsonism (PSP-P) are the most common subtypes of PSP.

Post-mortem data suggests that the clinical presentation of the two subtypes differs especially in the first 2 years of disease and then converges. This hypothesis has, to our knowledge, never been confirmed in a living cohort.

Medical history was used to define subtypes retrospectively in 23 consecutive PSP patients from our outpatient clinic specialized in movement disorders. 14 patients suffered from RS, and 9 from PSP-P.

Using a prospective cross-sectional approach, clinical, cognitive, behavioral, speech and biochemical (cerebrospinal fluid tau levels) features were compared.

RS patients showed shorter time from disease onset to diagnosis and more neuropsychological and neurobehavioral deficits than PSP-P patients, but differed not significantly with regard to clinical and biochemical features.

RS and PSP-P show considerable symptoms overlap during the disease course when using routine assessments, with persisting differences regarding non-motor symptoms.

Shorter disease duration of the comparably affected RS patients indicates that this subtype has an accelerated disease progression at early disease stages.

PubMed ID#: 21207078

First AD patient with PIB scans

Those of you interested in advances in imaging for neurodegenerative disorders and the correlations between imaging studies (while a patient is alive) and brain pathology (seen on post-mortem autopsy) will LOVE this news.

The PET is a type of brain scan. Currently, nearly all PET scans employ FDG, which picks up on glucose in the brain. For the last several years, the latest in PET scans for Alzheimer’s or other dementia patients employs PIB, Pittsburgh Compound B. PIB picks up on amyloid plaques. (The dye is retained by the insoluble amyloid protein.) Alzheimer’s disease is a disorder of two proteins — amyloid (which forms plaques) and tau (which forms tangles).

Hopefully, one day, we’ll have PET scans that can detect tau tangles (which would help diagnose PSP and CBD). Also, PSP and CBD can co-occur with Alzheimer’s Disease, so this news may be relevant to some in the PSP/CBD community also. (I’ve forgotten the exact percentage but it’s something like 20-30% of the time.)

The Alzheimer Research Forum has a (mostly-understandable) summary of a recently published article in the December 13th issue of the journal Brain about a woman with Alzheimer’s Disease who “volunteered for the first PET-PIB scan ever performed. She received another PIB scan two years later, and over the course of her disease also got an MRI and three PET scans using fluorodeoxyglucose (FDG), a marker for glucose use and therefore brain metabolism.” The woman died at the age of 61. She donated her brain for autopsy.

“Over the eight years she was studied, the woman’s score on the Mini-Mental State Examination declined from a near-normal score of 27 down to five. The FDG data showed that her brain’s glucose metabolism decreased in parallel with her cognitive powers. By contrast, PIB retention, already high at first examination, showed little change over two years during which her cognition declined steeply. The amount of amyloid deposition seen at autopsy three years later also looked similar to PIB estimates…suggesting no further change in amyloid between the second PIB scan and death three years later. This pattern matches the data from numerous previous studies, in which PIB retention increases during mild cognitive impairment, then seems to plateau during AD.”

“Autopsy results confirmed the patient’s diagnosis of pure AD. … The results confirmed that in vivo PIB retention correlates quite well with amyloid deposits, but does not correlate closely with tau and neurofibrillary tangles, as previous studies have found. … In addition, the authors performed detailed studies not done before and turned up intriguing correlations between amyloid accumulation and synaptic receptor density, as well as a surprising lack of correlation with markers of inflammation.”

The summary on the Alzheimer Research Forum discusses four clinical trials with compounds targeting amyloid in Alzheimer’s patients. The trials were all negative. This PET-PIB study gives additional insight as to why that may be the case.

Here’s the summary on ARF about the recently-published study:

Note that some of the comments are well worth reading, though harder to understand than the summary. Some of the comments (posted in 2004) give historical info on PIB.

The recently-published study is available at no charge through the journal Brain. See: (for HTML version)