"Give with a free hand, but give only your own."
 -- J.R.R. Tolkien The Children of Hurin

Parkinsonian Syndromes
(associated with increased brain iron content)

I have nothing to sell you.

The purpose of this web site is to provide you with information for when you meet with a physician to discuss what can be done for someone suffering from brain failure:  Alzheimer's disease (AD), Vascular Dementia (VD), Normal Pressure Hydrocephalus (NPH), or any of the Parkinsonian Syndromes.  You will have a list of questions to ask, and sources to read so that you can ask them intelligently.  I want to share some of the information I've accumulated in my search to help my mother.


 Parkinsonian syndromes associated with brain iron accumulation:
    Parkinson's disease
    Diffuse Lewy body disease (DLB)
    Parkinsonian type of multiple system atrophy (PMSA)
    Progressive supranuclear palsy (PSP)
    Corticobasal ganglionic degeneration (CBD/CBGD)
    Westphal variant of Huntington's disease

Parkinson's disease:

Diffuse Lewy body disease (DLB):
[Not sure if this is the same as dementia with Lewy bodies (DLB)]

Parkinsonian type of multiple system atrophy(P-MSA):

Progressive supranuclear palsy (PSP):



See also CBD

[Here is a bunch of stuff I've found out about CBD. I edited together
notes I've sent, etc. Probably more than you will have time to read, but here it is anyway.]


Here is a brief description of corticobasal ganglionic degeneration (CBGD):
from Dr. Bradly F. Boeve, MD

"Corticobasal degeneration (CBD), also known as corticobasal ganglionic
degeneration (CBGD), was first described in the late 1960’s by Drs.
Rebeiz, Kolodny, and Richardson. Following a lengthy period with no
additional reports, several more patients were identified and their
symptoms and autopsy findings were described in the 1980’s and 1990’s.
Patients typically have symptoms reflecting dysfunction in the cerebral
cortex (thus the term “cortical” or “cortico-”) and basal ganglia (thus
the terms “basal” or “basal ganglionic”), and symptoms are usually worse
on one side of the body. Specifically, cortical dysfunction is
manifested as poor coordination of the arms or legs (apraxia), tendency
for the arm “to act as if it has a mind of its own” (alien limb
phenomenon), numbness or odd sensations (cortical sensory loss), poor
comprehension and/or expression of language (aphasia), and quick jerks
(myoclonus). Slowness of movement (bradykinesia), stiffness in a limb
(rigidity), fixed muscle contractions such as when the fingers curl into
a fist (dystonia), and tremor are presumed to reflect basal ganglia
dysfunction. Some patients develop memory impairment and/or
personality/behavioral changes. Problems with walking eventually occur
in almost all. In our studies the duration of illness from onset of
symptoms to death has ranged from 3-13 years. The vast majority of
patients do not appear to have any family history of dementia or
parkinsonism, although there are rare cases in whom a hereditary process
may be at play. The cause of CBD is not yet known.

"This illness is frustrating to patients, their families, and the
physicians who care for them. Since insight and memory tends to be
preserved throughout most of their illness, depression is common and
should be treated when it evolves. Physical, occupational, and speech
therapy can be helpful although as the illness progresses third party
payers tend to not reimburse for these services, unfortunately.
Medications provide little benefit, but agents such as Sinemet are worth
trying. All sleep disorders such as sleep apnea and restless legs
syndrome should be evaluated and treated as improvement in quality of
life for patients and their loved ones can occur."


Here is the link to a paper about using MRI imaging to distinguish CBD
from other types of brain atrophy, especially Alzheimer's disease. The
article about the use of infrared imaging is near the end of this note.

"Corticobasal Degeneration: Evaluation of Cortical Atrophy by Means of
Hemispheric Surface Display Generated with MR Images"

"RESULTS: The extent and magnitude of cortical atrophy were larger in
the group with corticobasal degeneration than in the group with
Alzheimer disease. The parasagittal and paracentral regions were
significantly more atrophic in patients with corticobasal degeneration
than in patients with Alzheimer disease (P < .05). The mean
hemispheric-to-total intracranial volume ratios were significantly
smaller in the patients with corticobasal degeneration (61%) and those
with Alzheimer disease (64%) than in control subjects (69%). Asymmetry
of hemispheric volume was significantly larger in the group with
corticobasal degeneration than in the control group.

"CONCLUSION: The extent of cortical atrophy in corticobasal degeneration
is more widespread than was previously thought. Parasagittal and
paracentral atrophy is a distinctive feature of corticobasal
degeneration and distinguishes it from Alzheimer disease."

Also ran across this:
"Innovative 3D-imaging Technique Captures Brain Damage Linked To
Alzheimer's Disease"

"ScienceDaily (Oct. 29, 2007) — Using an advanced three-dimensional
mapping technique developed by UCLA researchers, the team analyzed
magnetic resonance imaging data from 24 patients with amnestic mild
cognitive impairment (MCI) and 25 others with mild Alzheimer’s disease.

"Patients in both categories exhibit progressive brain atrophy, with
most MCI patients showing the pathologic changes characteristic of
Alzheimer’s. MCI patients slip into dementia at a rate of 10 to 15
percent each year. The research team found that patients with mild
Alzheimer’s had 10 to 20 percent more atrophy in most cortical areas
than did MCI patients.

"The research showed the striking differences in cortical damage between
amnestic MCI and mild Alzheimer’s, and demonstrated that this innovative
three-dimensional mapping technique greatly outperforms other popular 3D
imaging techniques such as voxel based morphometry "

See Patricia's Protcol


I also found out that iron metabolism seems to play a role in
"Parkinsonian Syndromes", of which CBGD is classified

"Iron metabolism in Parkinsonian syndromes"
Mov Disord. 2006 Sep;21(9):1299-310.

Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2052-7. Epub 2008 Feb 4


In the paper, an extract of the the curry spice turmeric, curcumin, was
mentioned as a possible iron chelator.

It's on page 8 of the the PDF document. Here's an excerpt...

"In an attempt to overcome the problem of brain impermeability of
desferrioxamine, development is under way of brain-permeable iron
chelators, such as VK-28 (5-[4-(2hydroxyl)
piperazine-1-ymethyl]-quinoline-8-ol); bifunctional iron chelators
combining iron chelating, monoamino oxidase A- and B-selective
inhibitory and neuroprotective antiapoptotic properties like HLA-20,
M30, and M30A160; and the copper–iron chelator iodochlorhydroxyquin.
Although animal experiments are promising, the use of these iron
chelators must be carefully controlled to avoid toxic side effects. 176
EGCG ((-)-epigallocatechin-3-gallate; the major polyphenol of green tea)
and curcurium (a constituent of turmeric) are discussed as nontoxic
metal chelators. Also antioxidant–radical scavengers, such as vitamin
E,lipoic acid, ebselen, melatonin, and glutathione, can be considered."

"However, it has to be kept in mind that, in comparison with
monogenetically determined causes of brain iron accumulation, iron
overload in PD and atypical parkinsonian syndromes is small. Different
possibly additive neurotoxic mechanisms have to be considered.
Therefore, iron chelation can be only one of several mechanisms to try
to ameliorate neurodegeneration in these disorders."

The text uses the word "curcurium" but I think it is misspelled. The
associated note, #178 reads: 178. Baum L, Ng A. Curcumin interaction
with copper and iron suggests one possible mechanism of action in
Alzheimer's disease animal models. J Alzheimers Dis 2004;6:367–377.

The last paragraph seems reasonable in that excess iron is probably just
one of several necessary targets.

Desferrioxamine, I think, must be injected. There is an oral iron
chelator, Exjade (deferaserox?). Desferrioxamine is also known as
desferal or desferral. In the article "Inhibition of iron-catalysed
hydroxyl radical formation by inositol polyphosphates: a possible
physiological function for myo-inositol hexakisphosphate",
(http://www.biochemj.org/bj/294/0929/2940929.pdf) the authors found that
IP6 (a.k.a. InsP6) was a strong chelator of iron, arguably with a
stronger affinity for iron than desferal.

"The data (Figure 2) show that InsP6, EDTA and Desferral all fall into
this category; the greater potency of InsP6 compared with the other two
chelators [InsP6 and EDTA] is presumably because InsPJ has multiple
phosphates which are capable of chelating Fe3+ with high affinity (i.e.
more than one Fe3+ can be bound per InsP6"

A good question is, is IP6 able to cross the blood-brain barrier? I
don't remember reading that it does or does not, and I can't find
anything that says either way. I searched for reference quickly, but
didn't come up with anything. I'll keep searching.

However, curcumin is itself a good iron chelator:

"Curcumin interaction with copper and iron suggests one possible
mechanism of action in Alzheimer's disease animal models."
J Alzheimers Dis. 2004 Aug;6(4):367-77; discussion 443-9. Baum L, Ng A.

Department of Medicine and Therapeutics, Chinese University of Hong
Kong, Shatin. lwbaum@cuhk.edu.hk

"Curcumin is a polyphenolic diketone from turmeric. Because of its
anti-oxidant and anti-inflammatory effects, it was tested in animal
models of Alzheimer's disease, reducing levels of amyloid and oxidized
proteins and preventing cognitive deficits. An alternative mechanism of
these effects is metal chelation, which may reduce amyloid aggregation
or oxidative neurotoxicity. Metals can induce Abeta aggregation and
toxicity, and are concentrated in AD brain. Chelators desferrioxamine
and clioquinol have exhibited anti-AD effects. Using spectrophotometry,
we quantified curcumin affinity for copper, zinc, and iron ions. Zn2+
showed little binding, but each Cu2+ or Fe2+ ion appeared to bind at
least two curcumin molecules. The interaction of curcumin with copper
reached half-maximum at approximately 3-12 microM copper and exhibited
positive cooperativity, with Kd1 approximately 10-60 microM and Kd2
approximately 1.3 microM (for binding of the first and second curcumin
molecules, respectively). Curcumin-iron interaction reached half-maximum
at approximately 2.5-5 microM iron and exhibited negative cooperativity,
with Kd1 approximately 0.5-1.6 microM and Kd2 approximately 50-100
microM. Curcumin and its metabolites can attain these levels in vivo,
suggesting physiological relevance. Since curcumin more readily binds
the redox-active metals iron and copper than redox-inactive zinc,
curcumin might exert a net protective effect against Abeta toxicity or
might suppress inflammatory damage by preventing metal induction of

PMID: 15345806 [PubMed]

And, curcumin has been found to be beneficial for other ailments:

"Ingredient In Yellow Curry Can Reduce Heart Enlargement And May Prevent
Heart Failure"

Here's the link to the full article.

Here's an excerpt: "ScienceDaily (Feb. 22, 2008) — Eating curcumin, a
natural ingredient in the spice turmeric, may dramatically reduce the
chance of developing heart failure, researchers at the Peter Munk
Cardiac Centre of the Toronto General Hospital have discovered."

"In a study entitled, “Curcumin prevents and reverses murine cardiac
hypertrophy,” published in the February edition of the Journal of
Clinical Investigation, researchers found when the herb is given orally
to a variety of mouse models with enlarged hearts (hypertrophy), it can
prevent and reverse hypertrophy, restore heart function and reduce scar

Also this one...

"Curry-derived Molecules Might Be Too Spicy For Colorectal Cancers"

Here's the link to the full article:

Here's an excerpt from the article:

ScienceDaily (Nov. 6, 2007) — "Curcumin, the yellowish component of
turmeric that gives curry its flavor, has long been noted for its
potential anti-cancer properties. Researchers from Tohoku University in
Sendai, Japan, report on an apparent improvement upon nature: two
molecular analogues of curcumin that demonstrate even greater tumor
suppressive properties. The team presented their findings from the first
test of these molecules in a mouse model of colorectal cancer November 5
at the American Association for Cancer Research Centennial Conference on
Translational Cancer Medicine."

Curcumin Inhibits Formation of Amyloid {beta} Oligomers and Fibrils,
Binds Plaques, and Reduces Amyloid in Vivo
J. Biol. Chem., Vol. 280, Issue 7, 5892-5901, February 18, 2005

"Alzheimer's disease (AD) involves amyloid {beta} (A{beta})
accumulation, oxidative damage, and inflammation, and risk is reduced
with increased antioxidant and anti-inflammatory consumption. The
phenolic yellow curry pigment curcumin has potent anti-inflammatory and
antioxidant activities and can suppress oxidative damage, inflammation,
cognitive deficits, and amyloid accumulation. Since the molecular
structure of curcumin suggested potential A{beta} binding, we
investigated whether its efficacy in AD models could be explained by
effects on A{beta} aggregation... When fed to aged Tg2576 mice with
advanced amyloid accumulation, curcumin labeled plaques and reduced
amyloid levels and plaque burden. Hence, curcumin directly binds small
{beta}-amyloid species to block aggregation and fibril formation in
vitro and in vivo. These data suggest that low dose curcumin effectively
disaggregates A{beta} as well as prevents fibril and oligomer formation,
supporting the rationale for curcumin use in clinical trials preventing
or treating AD."


I'm not sure what the link between lithium and CBD is, but some
neurologists at the Mayo Clinic in Rochester, MN seem to think that Lithium
may help protect neurons.

 From the CBGD_support discussion site on Yahoo:

"Best as I can tell, the connection with tau is this:
1) ALS is another tauopathy.
2) Hi levels of GSK3 beta have been linked to phosphorylated tau (in
both CDB
and ALS as well as AD, PSP, etc.)
3) Lithium is known to be a GSK3 beta inhibitor (among other things).
4) While this study was not looking directly at tau proteins, the fact
the lithium patients had a much higher survival rate, and very slow rate
of progression suggest that it successfully mitigate the GSK3 beta's
effect on tau."

"They do mention lithium's "inhibitory activity on GSK3 beta" in the
Discussion on Page 5. You can see in the discussion that there is much
more going on than GSK3 beta and tau, and that they don't understand yet
how it all is functioning. Still, this study seems to move things
forward quite a bit by getting such a good result from a human trial. So
far, it's been all about mice."

"Not being a neurologist, I can't spell out the connection with tau, but
the Mayo docs were saying that this study does relate to CDB because of
GSK3's function on tau and lithium's ability to block GSK3. This is
probably an oversimplification, but that's the gist I got. I believe tau
does play some role in ALS, even if it's not classified as a tauopathy."

I don't know the names of the "Mayo docs".  Probably Bradly Boeve, MD

Here's a link to the paper:
"Lithium delays progression of amyotrophic lateral sclerosis."


"ALS is a devastating neurodegenerative disorder with no effective
treatment. In the present study, we found that daily doses of lithium,
leading to plasma levels ranging from 0.4 to 0.8 mEq/liter, delay
disease progression in human patients affected by ALS. None of the
patients treated with lithium died during the 15 months of the
follow-up, and disease progression was markedly attenuated when compared
with age-, disease duration-, and sex-matched control patients treated
with riluzole for the same amount of time. In a parallel study on a
genetic ALS animal model, the G93A mouse, we found a marked
neuroprotection by lithium, which delayed disease onset and duration and
augmented the life span. These effects were concomitant with activation
of autophagy and an increase in the number of the mitochondria in motor
neurons and suppressed reactive astrogliosis. Again, lithium reduced the
slow necrosis characterized by mitochondrial vacuolization and increased
the number of neurons counted in lamina VII that were severely affected
in saline-treated G93A mice. After lithium administration in G93A mice,
the number of these neurons was higher even when compared with
saline-treated WT. All these mechanisms may contribute to the effects of
lithium, and these results offer a promising perspective for the
treatment of human patients affected by ALS."

Another paper that seems to relate:

"Lithium at 50: have the neuroprotective effects of this unique cation been overlooked?"
Biological Psychiatry. 1999 Oct 1;46(7):929-40. PMID: 10509176 [PubMed]

Manji HK, Moore GJ, Chen G.

Department of Psychiatry and Behavioral Neurosciences,
Wayne State University School of Medicine, Detroit, Michigan 48201, USA.

"Recent advances in cellular and molecular biology have resulted in the identification of two novel, hitherto completely unexpected targets of lithium's actions, discoveries that may have a major impact on the future use of this unique cation in biology and medicine. Chronic lithium treatment has been demonstrated to markedly increase the levels of the major neuroprotective protein, bcl-2 in rat frontal cortex, hippocampus, and striatum. Similar lithium-induced increases in bcl-2 are also observed in cells of human neuronal origin, and are observed in rat frontal cortex at lithium levels as low as approximately 0.3 mmol/L. Bcl-2 is widely regarded as a major neuroprotective protein, and genetic strategies that increase bcl-2 levels have demonstrated not only robust protection of neurons against diverse insults, but have also demonstrated an increase the regeneration of mammalian CNS axons. Lithium has also been demonstrated to inhibit glycogen synthase kinase 3 beta (GSK-3 beta), an enzyme known to regulate the levels of phosphorylated tau and beta-catenin (both of which may play a role in the neurodegeneration observed in Alzheimer's disease). Consistent with the increases in bcl-2 levels and inhibition of GSK-3 beta, lithium has been demonstrated to exert robust protective effects against diverse insults both in vitro and in vivo. These findings suggest that lithium may exert some of its long term beneficial effects in the treatment of mood disorders via underappreciated neuroprotective effects. To date, lithium remains the only medication demonstrated to markedly increase bcl-2 levels in several brain areas; in the absence of other adequate treatments, the potential efficacy of lithium in the long term treatment of certain neurodegenerative disorders may be warranted."


Can inhaled anesthetics initiate a biochemical cascade or domino effect
leading to degenerative neurological diseases?

"The Inhalation Anesthetic Isoflurane Induces a Vicious Cycle of
Apoptosis and Amyloid ß-Protein Accumulation"
The Journal of Neuroscience, February 7, 2007, 27(6):1247-1254;

"... Collectively, these findings suggest that isoflurane can induce
apoptosis, which, in turn, increases BACE and {gamma}-secretase levels
and Aß secretion. Isoflurane also promotes Aß aggregation. Accumulation
of aggregated Aß in the media can then promote apoptosis. The result is
a vicious cycle of isoflurane-induced apoptosis, Aß generation and
aggregation, and additional rounds of apoptosis, leading to cell death."

"Molecular mechanism behind aggregation of amyloid beta peptide due to
Medical Research News Published: Sunday, 28-Jan-2007

"Previous studies by the Pittsburgh researchers found that the inhaled
anesthetics halothane and isoflurane and the intravenous anesthetic
propofol encouraged the growth and clumping of Abeta in a test tube

"Anesthesia Leads to Tau Hyperphosphorylation through Inhibition of
Phosphatase Activity by Hypothermia"
The Journal of Neuroscience, March 21, 2007, 27(12):3090-3097;

"...We found that, regardless of the anesthetic used, anesthesia induced
rapid and massive hyperphosphorylation of tau, rapid and prolonged
hypothermia, inhibition of Ser/Thr PP2A (protein phosphatase 2A), but no
changes in APP metabolism or Aß (ß-amyloid peptide) accumulation.
Reestablishing normothermia during anesthesia completely rescued tau
phosphorylation to normal levels. Our results indicate that changes in
tau phosphorylation were not a result of anesthesia per se, but a
consequence of anesthesia-induced hypothermia, which led to inhibition
of phosphatase activity and subsequent hyperphosphorylation of tau..."

I haven't looked into what the consequences of having
"hyperphosphorylized tau" is.



Light Waves Can Detect Alzheimer's Disease Early On, Study Suggests

ScienceDaily (Mar. 17, 2008) — "A team of researchers in Bedford, Mass.
has developed a way of examining brain tissue with near-infrared light
to detect signs of Alzheimer's disease.

"The new technique developed by Hanlon and his collaborators at Harvard
Medical School/Beth Israel Deaconess Medical Center and Boston
University can detect alterations to the optical properties of the brain
that occur as the tissue undergoes microscopic changes due to
Alzheimer's--sometimes far in advance of clinical symptoms. The
technique is now being tested for its effectiveness at diagnosing
Alzheimer's disease in living people.

"For several years, Hanlon and his colleagues have looked at the
possibility of analyzing the brain with near-infrared light, which has
the advantage of being able to safely penetrate the skull and pass
harmlessly through the brain. Inside the head, some of the infrared
light scatters, however, and how the light scatters can tell researchers
about the condition of the brain.

"In their paper, the team reports observing an optical effect due to the
presence of microscopic features of Alzheimer's. Amyloid plaques, one of
the telltale signs of Alzheimer's disease, scatter light differently
from normal brain tissue. What Hanlon and his colleagues showed was that
as the microscopic plaques accumulate, the optical properties of the
brain change. The team found that this change is detectable and that
their technique could quantify differences between in-vitro samples and
correctly identify signs of Alzheimer's.

"This technique will be a boon to medicine if it is able to detect
microscopic changes that can be related to disease progression. While
techniques like MRI are good at identifying the gross anatomical
features associated with Alzheimer's, they cannot detect more
microscopic changes."

And then on the less believable side, there are these researchers in
England who claim that treating AD patients with 1072nm near-infrared
light for 10 minutes per day could stimulate the neurons to re-generate.
("Emotional responses and memory performance of middle-aged CD1 mice in
a 3D maze: Effects of low infrared light" by S. Michalikovaa, A.
Ennaceura, Author, R. van Rensburgb and P.L. Chazot
) The researchers / inventors made a helmet lined with light emitting
diodes (LEDs) that emit a light spectrum centered around the 1072nm
wavelength. It is believed that water is transparent to infrared light
at 1072nm, opaque to the rest of the infrared (IR) spectrum. In the
absence of 1070nm LED's (which are hard to get, and expensive when you
can find them), I think that one could use a broad-spectrum IR heat lamp
with a layer of water (glass aquarium? ziplock bag filled with distilled
water?) between the person's head and the lamp so that the heating IR
light wouldn't reach them. Since treatments are supposed to take only 10
minutes per day, I don't think it would hurt to try, even if it IS all a
bunch of hooey. (See also "New Research Could Help Reverse The
Biological Clock For Dementia Patients" ScienceDaily (Jan. 26, 2008)
http://www.sciencedaily.com/releases/2008/01/080124104917.htm )


This was posted on the CBGD_support discussion group on Yahoo last year:

Mayo Notes
Three postings by "mindyourbreath" (mylegisonfire@...)
February 2nd, 2007


As promised, here are my first set of notes from our visit to Mayo
this week. This first posting contains some general info and the
following postings will be about medicines and therapies. The more
practical stuff will be in the later postings while this one will
answer questions some of you had about Mayo itself.

This week they held a special clinic focusing on their CBD patients
that included testing, talks, doctor appointments and a luncheon. At
the end of the week, the Mayo team was going to meet (including the
researchers from Florida) and compare notes about their findings.
They plan on doing these special clinics twice a year. Their work on
CBD is partially funded by a larger grant given to their Alzheimer's
Disease Research Program in their Department of Neurology. Many of
the tests and doctor visits for my mother were covered by the research
money. They cannot yet pay for travel, but testing as part of the
study (including MRIs) are covered.

Dr. Bradley Boeve is their resident guru on CBD, and is the doc
coordinating my mother's care at Mayo. (She will be taking his
recommendations to her PCP back home, who is willing try anything he
suggests.) Most of this information came from Dr. Boeve and Dr.
Daniel Druback, the other doctor who met with my mother. She also met
with a speech pathologist named Joseph Duffy. I've tried to reproduce
their ideas as best I can, but not being a medical professional, I'm
bound to make some mistakes. Let me know of anything here appears to
be incorrect.

First of all, we were very impressed with the Mayo facility and the
care they are able to provide. The doctors we met took their time (an
hour or longer), were very open to ideas, and clearly were looking for
anything they could do both to help my mother and find better ways to
treat CBD. The docs at Mayo are paid by salary rather than number or
patients they crank through, and are mandated to work as a team with
their other colleagues. This was quite evident during our visit.

The neurology department currently sees around 40 active CBD patients,
and has seen over 200 cases overall (a lot for CBD). That alone was
helpful because they were able to tell us what symptoms were typical
CBD and which ones may not be a part of the illness. For instance: my
mother's right hand (the one she's having difficulty with) has been
feeling cold, prickly, and turning blue for several years. All the
other docs she showed it to just shrugged. Boeve said that it was not
common for CBD--only a couple of his patients had the symptom. He
suggested other possibilities and wanted to see if it was something
that was treatable.

Boeve describes their treatment approach as "aggressive." By that he
means that he does not wait for a treatment to be officially proven
before trying it. If it is safe and there is a chance it could help,
he suggests using it. He knows that we are running against the clock
and waiting for something to be proven is more of a luxury than a
requirement in this situation.

Dr. Boeve himself acknowledged that most of the information available
on CBD has been poorly written. (I'm sure you can relate.) Much of
it sounds overly discouraging to him, and is often not up to date.
Some info is not publicly available at all.

They describe CBD as a syndrome (or call it CBS--corticobasal
syndrome) because it can express different symptoms and have different
underlying causes, all of which attack the corticobasal region. For
instance, it can start in either the left or right side of the brain
and the symptoms will correspond with the functions that side of the
brain specializes in. If it hits the left side of the brain, the
right hand will be affected as well as speech production. The right
side of the brain controls the left hand, handles depth perception and
monitors the space around you. Also, the further back in the brain
degeneration begins the slower it appears to progress. (They're not
sure why.) The bottom line is that there are number of ways it can
appear and progress, hence the difference in symptoms from patient to

My next posting will be about medications -- what they suggest right
now and what they are working on.


In this second installment of my notes from Mayo, I will cover what
they said about medications and supplements. Much of this information
may be familiar to many of you, but I think there is some new stuff in
here, too. My next installment will cover non-medicinal therapies.
As before, please note that I'm not a medical professional and I'm
just trying to relate this info as best I can. If you see any
inaccuracies, do let me know.

The best treatments, they say, combine both meds and non-med
therapies. In many cases, the meds are used to stimulate use of the
affected areas so the patient can be as active as possible and
continue the therapy. Since apathy is part of the syndrome, low
motivation is another symptom they try to treat. Quality of life is
the bottom line for any combination of approaches.

They have identified two underlying diseases causing CBD: tauopathies
and ubiquitinopathies. Either one or both could be present.

Tauopathy has been known for some time, but a newer discovery is the
role of the GSK-3B enzyme in making the hyperphosphorylated (bad) tau.
From this discovery, one class of drugs called "GSK-3B" inhibitors
are being developed. By targeting the GSK-3B enzyme they hope to
attack the underlying disorder by preventing the enzyme from
destroying tau proteins. The current GSK-3B inhibitors are:

Cysteamine (Cystagon) -- Has been somewhat effective, shown to be safe
and easy to take. Obviously not fully effective, but the limited
clinical data they have shows that it does appear to slow the
progression of CBD. The common dose of 15mg/day was based on it's use
in children for kidney disease, so that part is pure guesswork.

Lithium -- They had high hopes for lithium because it so effectively
blocked GSK-3B in the lab, but it blocks a number of other things as
well. Mayo had ten patients on lithium and they all elected to cease
treatment because the side effects were so bad.

AR-A014418 -- This is NEW and not yet on the market. It is a potent
GSK-3B inhibitor that can stop and even somewhat reverse tauopathy in
tau mice. (Those are the mice in Mayo's research lab that are given a
tauopathy, then a drug, and then a brain biopsy to see if the drug
worked.) Safety studies are underway and they hope to have it to try
humans within the year. Because it narrowly targets GSK-3B, and
appears to have a high potency, they think there is a chance this may
treat the underlying disorder directly. Here's to hoping! I'll let
you know when they start testing the drug on Mayo patients (i.e. my mom).

There are other classes of meds as well, but not as far along in
research for CBD. HSP-70, HSP-90, and CDK-5 inhibitors were mentioned
as possibilities.

Ubiquitinopathy (if I understand this correctly) involves proteins
getting "clumped" together and failing to degrade when they should
after being tagged with ubiquitin. Progranulin is suspected to
facilitate the normal process of protein deconstruction, so one area
of research is focusing on finding a drug that can boost progranulin.
They have medications that are working in lab models and are starting
to be tried on mice. Multivitamins MAY affect this system as well as
cholesterol-lowering drugs. As is the case for many neurological
meds, they're not sure why. Not everyone with CBD has
ubinquitinopathy as the cause.

A big recent discovery happened last April when they identified the
ubiquitin gene. They discovered the tau gene as well about ten years
ago. The most promising hope for a cure lies in a gene therapy using
the DNA sequence for tau or ubiquitin. This is expected to take
several years, however.

They cannot yet test accurately for the presence of tau or
ubiquitinopathy. A test is also in the works, and will make the
doctor's job much easier for obvious reasons.

The other use of medicine is to manage the symptoms of motor
dysfunction and cognitive dysfunction. This is not only to help
quality of life, but to increase use which also helps to slow the
progression (see my next post).

For motor dysfunction, meds now in use are:
--Carbidopa/levodopa (Sinemet)
--dopamine agonists (Mirapex)
--Clonazepam (Klonopin)
--valproic acid (Depakote)
--gabspentin (Neurotonin)

For cognitive disfunction:
--Cholinesterase inhibitors (Aricept)
(They have not been too impressed with this for CBD.)
--NMDA receptor antagonist (Namenda)
(Also not impressive, costly.)
--Psychostimulants (Provigil)

Other neuroprotective agents that can help and probably won't hurt:
--Coenzyme Q10 (recommended 1200mg/day, but any amount may help. Only
downside appears to be cost--$200/mo for the highest dose.)
--Fish oil (1000mg-2000mg/day)

Less recommended:
--Vitamin E -- has been questioned recently for it's effectiveness and
safety at higher dosages.
--Ginko Biloba -- could be causing some problems. A safety study is
underway and they are waiting for the results before recommending it
--St. John's Wort -- avoid if also using a serotonin drug such as

Also notable: We told Dr. Boeve that our neurologist recommended that
my mother try Cerefolin with NAC (http://www.cerefolin.com/). He had
heard of
it, but not seen it in use for CBD. My mother had been on it for just
over a month before visiting Mayo and we are certain that her speech
has improved. Her hand was unaffected. Boeve took note of this and
said he would bring it up with the rest of the team when they met at
the end of the week. Later, he got back to us and said his team gives
Cerefolin a thumbs-up. Has anyone else tried Cerefolin? It is more of
a supplement than a drug, but it has had no side-effects and we're
pretty sure has helped her speech.

Note: this is not an exhaustive list, but I believe this is everything
that Doctors Boeve and Druback emphasized in their talks, and in our
meeting with him.

When I get time to type up the rest of my notes, I'll cover what they
had to say about physical therapy and brain plasticity.


This installment of my notes from my mom's Mayo visit in early
February will focus on non-medicinal therapies. Look to my previous
posts on Mayo for notes about medicines and about Mayo in general.
Sorry it took me so long to get this installment out. I wanted to
make sure I got this down as correctly and simply as I could and have
not had much time to work out it.

Correction from last time: In the previous notes I mispelled Dr.
Drubach's name as "Druback."

Once again, please note that I'm not a medical professional and am
just trying to relate this info as best I can. If you see any
inaccuracies, please let me know. Okay, without further ado...


The Mayo docs are strongly recommending occupational therapy (OT) and
speech therapy to their CBD patients. Although I expected this, I did
not know much about how therapy is supposed to help with CBD until I
saw the talks by Dr. Drubach and Dr. Boeve.

Dr. Drubach focused his talk on brain "plasticity." Plasticity is
your brain's ability to change and adapt. This can happen on all
levels--from a single cell to the large groups of neurons that work
together to create actions. They have known for some time how young,
developing brains are capable of compensating and recovering from
trauma in miraculous ways. More recently, they have discovered that
older brains are changing as well, just not as quickly.

Each neuron in our brain can execute any number of different tasks,
work with different groups of neurons, and be re-purposed for
different uses.

One example is the brain of someone practicing and learning and
instrument. With practice, the neural pathways form to execute
complex movements more quickly and efficiently. The repetition
improves the efficiency of that brain pattern, and essentially changes
the brain in the process. When you stop practicing, those neurons
and brain cells move on and are reclaimed by the brain to execute
other activities. There is a circular relationship between doing a
thing, and the brain activity required to do the thing: the activity
of doing changes the brain which changes your ability to do that thing
which changes the activity and on and on. The idea of "use it or lose
it" definitely applies because the brain wants to be efficient and
repurposes unused cells for use on other tasks.

After neurological injury (such as a stroke) brain cells around the
dead ones reorganize to compensate. Sometimes they compensate for the
better, sometimes for the worse. Why it gets better or worse is
unknown and a current focus of research.

The independent variables (ones you can't change) for plasticity are:
--Age (younger is better)
--Gender (females do better)
--Type of injuries
--What parts of the brain are effected.

The modifiable variables (what you can change) for plasticity are:
--Rehab strategies
--Environmental enrichment
--Tissue Transplantation (I have no other notes on this. I'm sure
it's not being used for CBD and he did not go into it much.)
--Genetic modification (not yet available)

In order to maintain brain function and/or regain function, there
always needs to be a little bit of stress. (Of course, you do not
want too much stress, but a little is always good.) Drubach stressed
the need to "keep an edge" in your daily activities and keep your
brain learning new things.

One type of therapy that helps create that edge is Constraint-Induced
Movement Therapy (CIMT). This involves constraining the less affected
limb to force the use of the problem area. For instance, one would
place an oven mitt over their good hand to force use of their problem
hand. The theory is that this will drive the brain plasticity and
reorganize the brain to send better signals to that hand. (This is a
prominent theory in stroke rehab, has been shown to be true in rats in
1996, and is showing strong data in humans as well.) The extent to
which we can change our brains late in life is still unknown. However, they are confident that you can dramatically slow the progress of CBD and even regain some function with regular practice. It is hard, frustrating work, and motivation is key to success.

The goal of this therapy is to turn "explicit" actions in to
"implicit" ones. Explicit action is when you want to pick up a glass
but you have to think about how your hand will go about doing that,
try a few things, and eventually get your hand to execute the action.
An implicit action is when you can go from wanting to pick up the
glass to just picking it up without all the thought in between. This
can require the same kind of practice one would use when learning how
to do something for the first time. This sort of learning also drives
brain plasticity and helps retain function.

To successfully exercise the brain, the focus of the therapy should be
around doing things, rather than simply exercising the effected limbs.
Likewise with speech, the emphasis should be on talking rather than
tongue and mouth exercises. Even if you do not succeed with the
action you are attempting, you are exercising that part of the brain
and reorganizing those brain cells.

The doctors made a useful distinction between impairment and
disability. An impairment is the loss of function, such as in the
hand. This part is the same for similar patients. Disability is how
that impairment affects the level of function and quality of life.
This is different between patients with similar impairments.

The level of disability is determined largely by the patient's
motivation and attitude towards challenge. This is where the doctors
encourage the patient to take on a "fighting stance." Humorously, Dr.
Drubach stated that "poor patients" tend to fare better with
disability. What he meant was that patients that do not listen to
their doctor's orders (what they call "poor" patients) and stubbornly
continue to live as fully as possible tend to fare better. A lack of
motivation has been seen as a common aspect of the syndrome and
sometimes medications are used to boost motivation by helping with the
physical dysfunction or emotional difficulties.

It can be difficult to find therapists enthused about treating a
degenerative disorder, and for insurance companies to fund treatment,
because they are always hitting a moving target. Unlike stroke, where
there is an event in time after which you can recover and even be
"cured," CBD continues to progress and it is difficult to measure what
effect the therapy is having. While it is possible to regain some
functions, the main goal is to slow the progression, which is
different from the process of rehabilitation that therapies are
typically used for. The therapy may be helping even if the patient is
getting worse over time. With that in mind, these are the stages
typical for someone who discovers they have a neurological disease and
decides to battle it:

Mourn --> Stop Mourning --> Take Inventory of Abilities --> Maximize
Function of Existing Abilities --> Keep an Edge to Retain Abilities


In the four months since the Mayo visit, my father located an OT who
in neurodegenerative disorders. She has been very optimistic about
helping mom regain some of her abilities and so far her predictions
have been correct. One exercise has my mother flipping over dominoes.
The first day my mother tried it, she could barely get over one. But the
very next day she was able to turn over all ten. The OT also has her
pushing around marbles and carrying out certain tasks like preparing a pizza (with just a little help).

My dad is having my mother doing her OT exercises every day, in addition
to speaking and reading aloud a little every day. She also has had a
speech therapist working with her who has also helped her maintain her
speaking ability.

Mom also started taking Sinemet and Cystagon. The Sinemet seemed to help
her with her hand somewhat. It is hard to tell if the Cystagon is
doing anything.

In March, my mother fell and broke both of her ankles. It was clearly a setback, mainly because they had to deal with her immediate needs and struggle to stay positive rather than focus on the CBD therapies. She lost some ability during this time but the ankles healed quickly and she is back on the therapy. Once again, she is gaining back function she has lost. It is still very frustrating for her, but my father is not letting her give up and she seems determined to keep working on it. Needless to say we are big believers in the therapy approach. Now, the game has been to set a schedule of therapy and meds for her to stick to every day. So far, it seem to be working.

Westphal variant of Huntington's disease:

Home Preface Brain Failure Notes References pg. 1 References pg. 2
Nutritional Alternatives


You can reach me by mai|ing to perpetualcommotion.com, at gmail.

Updated September 7, 2010
Inception Aprill 1, 2008