Exercise and dementia (research updates from Alzforum)

This post may be of general interest since many of us are dealing with dementia or will be dealing with dementia at some point in our lives.

At the recent Alzheimer’s Association International Conference in Washington DC (mid-July), a lot of research was presented on exercise.  The Alzforum has two good summaries of the research.

The first summary is here:


The first summary examines research into whether Alzheimer’s disease can be tempered by aerobic exercise and whether dementia can be avoided through exercise:

“Speakers…presented new evidence that regular aerobic exercise can help people in prodromal disease stages maintain their cognition, while for those with full-blown dementia it relieves neuropsychiatric symptoms. Some studies provided hints that exercise can also hone thinking at the dementia stage, but only if the participants reach moderate intensity heart rates during their workout. Exactly how exercise helps the brain is still not known, but several talks reported better cerebral blood flow and improved structural and functional connectivity in exercisers, and even some signs that six months or more of physical activity can slow pathology.  Researchers agreed that the duration and intensity of an exercise intervention are crucial to determining its effects. For aerobic exercise in particular, the field is standardizing methods and narrowing in on the appropriate dose to prescribe. Some believe supervised exercise classes could become part of the standard of care for people with cognitive problems. … Researchers have few doubts now that exercise protects normal older adults against brain decline.”

(prodromal = before symptoms appear)

The second summary is here:


The second summary explores research into whether exercise can slow the progression of a neurodegenerative process:

“Overall, the findings indicated that working out enhances vascular brain health and connectivity, implying a direct benefit to brain structure and function. Data were mixed on whether exercise slows the progression of underlying Alzheimer’s pathology, however. One six-month study of moderate aerobic exercise reported a drop in cerebrospinal fluid tau in cognitively impaired people, but a shorter intervention failed to budge brain amyloid in people with AD. In general, speakers agreed that the cognitive boost from exercise likely comes from diverse benefits on several different aspects of brain function, something that would be hard to match pharmacologically.”

Both summaries are worth reading if exercise research is of interest.

While this may be a good day to go to the gym, this is probably not a good day to exercise outdoors.

Stay cool,

Tau imaging research and how tau may spread (Alzforum update)

This post may be of interest to those in the PSP and CBD community who are interested in what’s happening in research, particularly imaging of tau, as well as a hypothesis of how tau spreads in the spread.

Alzheimer’s is a disorder of two kinds of proteins — tau and amyloid (or beta amyloid, Aβ).  PSP and CBD are disorders of one kind of protein — tau.

At the recent Alzheimer’s Association International Conference in Washington DC (mid-July), scientists reported on data from tau PET imaging.  Three ligands or chemical tracers from La Roche are being studied, with one seeing superior results.  The data also provide clues as to how tau may spread in the brain.

The Alzforum has a good summary of the tau imaging research presented at the conference:

“…tau imaging data bolstered the idea that tau sits tight in the medial temporal lobe until Aβ builds up, then it spreads, wreaking havoc on cognition. New imaging data suggests that once it breaks loose, tau spreads through functional networks and impairs brain metabolism. What’s more, unlike Aβ, which appears diffusely throughout the brain, tau deposits seem to map closely onto regions where atrophy occurs and cognitive deficits originate. ‘Unlike amyloid imaging, tau PET seems to strongly correlate with cognition and clinical states,’ said Gil Rabinovici, University of California, San Francisco. Researchers were also excited by a new tau ligand that appears to have better specificity and kinetics than its predecessors.”

Here’s a bit more on tau building up in certain brain regions, as in corticobasal syndrome (CBS), and the relevance of tau as a target:

“Disaster Strikes Wherever Tau Lands
Once outside the medial temporal lobe, tau seems to cause trouble wherever it lands. At AAIC, Daniel Schonhaut, who works with Rabinovici, expanded on the notion that tau builds up in brain regions thought to underlie clinical symptoms in patients with atypical forms of AD. He compared performance on a variety of cognitive tests with T807/AV1451 scans from 19 patients with typical and atypical forms of AD, including posterior cortical atrophy, primary progressive aphasia, and corticobasal syndrome.  Schonhaut reported that people with typical AD who performed more poorly on memory tasks had more tau in the hippocampus and surrounding medial temporal areas, while patients with worse visual function indicative of posterior cortical atrophy had more tau in occipital regions. A third group — those with language difficulties typical of primary progressive aphasia — had more tau in the left temporoparietal region. ‘The distribution patterns of tau we’re seeing with this PET tracer seem to underlie the clinical phenotype of our patients,’ Schonhaut told Alzforum.  ‘These data show nicely that there’s a relationship between where the tau is clinical symptomatology,’ said Jagust. ‘We haven’t seen that with amyloid.’ Rabinovici noted that these results corroborate findings from classic postmortem studies demonstrating that cognitive state correlates much more strongly with tangle than amyloid pathology. They also support tau as a therapeutic target, particularly in the symptomatic phase of AD, he told Alzforum.”

The entire Alzforum research summary is worth reading, if research is of interest:


Stay cool,

Learning to communicate and enjoy time with someone with dementia

This is a very sweet article from The New York Times about a son who learns to communicate and enjoy time with his mother with Alzheimer’s.

Here are the key excerpts:

My oldest brother [Mark] … talks to my mom by phone every day. He enjoys trading gibberish with her in their incomprehensible conversations. “She’s completely unplugged from reality and disoriented to time and space,” Mark says. “It doesn’t make any sense, so why not have a good time?” At first, I worried Mark’s antics were making fun of my mom — laughing at her, rather than with her. Then I tried it. I stopped concentrating on the content of her words and, instead, went along with every twist. Once she said she wanted to go somewhere for a picnic. “Why, Mom?” I asked. She said: “So we can boil the chicken.” Rather than grilling her about what she meant, I asked what kind of chicken we should boil and where we should hold this picnic.

Mom’s private caregiver, Ellen Knapp, … taught me how to talk to Mom in this new phase of her life. The technique is called validation, and Ellen learned it from a veteran author and psychologist, Naomi Feil. As Ms. Feil explains it to me in a phone interview, this translates to “accepting whatever behavior the person has and trying to become a part of it.” For example, a carpenter with Alzheimer’s might pound his fist against a wall. The wrong way to talk to him would be to say, “Why are you pounding the wall? Stop it!” The right way would be to ask, “Is that wood made out of oak or pine?”

I’m not exactly a Jedi knight of this technique, but I find it relaxes Mom and makes her more easygoing and less frustrated. The key, for me, is to stop judging or trying to analyze or change her behavior. That means fewer questions about her past, even if that subject is difficult for me to avoid — in the past, she was my mom! That’s what I really want to talk to her about, not chickens and picnics. Occasionally I can’t resist and I ask whether she remembers Dad, her husband of 54 years. Sometimes she says yes. Sometimes she says no. It’s a dead end either way.

Here’s a link to the article:


SundayReview | Opinion
New York Times
My Mother, Lost and Found
By Steve Knopper
July 11, 2015

Well worth reading…


Methylene blue update

This post may only interest those of you following experimental drug therapies for PSP and CBD, both tauopathies (disorders of the protein tau).

In a review article from 2011, three tau-directed compounds were listed — methylene blue, tideglusib, and Davunetide.  Both the tideglusib and Davunetide trials in PSP were failures from a drug perspective.  (The great thing is that the worldwide PSP clinical treatment community and patient community showed that a worldwide PSP trial could be conducted.)

Now comes news that methylene blue stopped cognitive decline in tau-transgenic mice but only if the compound was given at the earliest stages.  This implies that if the compound were given in pre-symptomatic people with PSP or people in the early stages of CBD, that the compound might prevent them from getting worse.  Unfortunately we don’t now when someone is pre-symptomatic or in the early stages of PSP or CBD.

Some of you might remember there was an experimental drug called Rember, based on methylene blue.  The latest version of Rember is called LMT-X.  There are clinical trials going on now of LMT-X in Alzheimer’s and frontotemporal dementia.  LMT-X is made by TauRx Therapeutics.  One of the researchers there is Claude Wischik.  On the website Alzforum, Dr. Wischik argues that the data for LMT-X in humans is more positive.  And he’s still hopeful.

If you want all the nitty gritty details, check out this article on the Alzforum:



Alzheimer’s – mitochondrial cascade hypothesis

This post is for the science-oriented people among us!  Thanks to science-oriented Angie for sharing the article.

I thought this was a worthwhile article on a competing theory of Alzheimer’s — that AD is caused because gene variants “inhibit mitochondria from supplying energy to neurons, causing them to die.”  (Energy is in the form of oxygen and glucose.)  One researcher has called this the “Alzheimer’s disease mitochondrial cascade hypothesis.”

The prevailing theory for the last few decades is the “amyloid hypothesis” — that AD is caused by amyloid plaques.  One other competing theory is that the cause of AD is the protein tau.  (UCSF is conducting a lot of clinical research brought to light by the tau hypothesis.)

Continue reading if mitochondrial function of neurons is of interest!


Science, Tech & Environment
Do we all have Alzheimer’s completely wrong? This man says yes
Science Friday, PRI
May 03, 2015 · 9:30 AM EDT
By Turna Ray

Mayo Clinic study of thousands of brains reveals tau as driver of AD

This post is about Alzheimer’s though it’s likely of interest to those dealing with PSP and CBD, and of some interest to those dealing with LBD.  Both PSP and CBD are tauopathies, or disorders of the protein tau.  LBD is not a tauopathy but it commonly co-occurs with the largest tauopathy – Alzheimer’s Disease.

This Mayo Clinic press release from last Tuesday is focused on Alzheimer’s Disease (AD).  AD is a disorder of two proteins – tau and amyloid.  There has long been a dispute in the researcher community as to which tau or amyloid is the “culprit” in AD.  (The two camps are called the tauists and the baptists.  bap = beta amyloid protein.)

In this major study of 3600 donated brains at the Mayo Clinic in Jacksonville, Mayo researchers conclude that tau is the primary culprit.  And efforts should focus on halting tau.

This is great news for the PSP and CBD communities because if researchers can solve the problem of tau building up, then they may be able to treat PSP and CBD.

At the link, there’s a one-minute video with Dr. Melissa Murray explaining the findings.  I usually find such videos worthwhile but this one was too short and too much of a summary to be of interest to me.  Your opinion may be different!


Mayo Clinic study of thousands of brains reveals tau as driver of Alzheimer’s disease



“Diagnosing and Treating Rapidly Progressive Dementias” (dementia within one year)

Rapidly progressive dementias (RPDs) “include prion diseases such as CJD [Creutzfeldt-Jakob Disease], autoimmune dementias, paraneoplastic conditions, infections that can mimic prion diseases, and fungal infections as well as some viral and toxic metabolic conditions, such as Wernicke’s encephalopathy (a condition that stems from thiamine deficiency often due to malnutrition) and even conditions stemming from complications from an overdose of Pepto-Bismol.”

Here’s a short overview of RPDs. I don’t think it’s necessary to read the entire article, though it is short. For our purposes, here are the key excerpts:

* “Dementia may result from as many as 40 different diseases and conditions ranging from dietary deficiencies to inherited diseases, according to the Encyclopedia of Mental Disorders. With that, the definition of dementia has broadened over time from a focus on memory loss to a focus on impairment in one or more cognitive domains — particularly memory, language, frontal executive function, organizing, planning, and multitasking — that is severe enough to interfere with a person’s daily function. Typically, chronic degenerative dementias are characterized by damage or wasting away of brain tissue usually progressing over seven to 10 years. These include Alzheimer’s disease, frontal lobe dementia, and Pick’s disease. Dementias associated with progression of other diseases or conditions include Huntington’s disease, Lewy body dementia, and other parkinsonian dementias, such as corticobasal degeneration.”

* “Michael Geschwind, MD, PhD, associate professor of neurology at the Memory and Aging Center at the University of California, San Francisco said that although there is no defined time frame for rapidly progressing dementias (RPDs), he uses the term to describe patients that go from normal cognition to dementia within a year or less. However, he has seen some patients with Creutzfeldt-Jakob Disease (CJD) take as long as two years to develop dementia. Although there can be overlap with some typical degenerative dementias presenting in a rapid fashion, in general, patients who may have an RPD need clinicians to consider a different set of disorders, because these conditions can be both treatable and quickly fatal in some cases, Geschwind explained. … In a 2007 monograph on RPD published in Neurology Clinic, Geschwind’s team observed that 15% to 20% of the 825 patients referred to UCSF with rapidly progressing dementia presumed to be CJD turned out to have other non-prion conditions.”

* “Steven Vernino, MD, professor of neurology and neurotherapeutics at the University of Texas Southwestern Medical Center in Dallas, specializes in autoimmune encephalopathies. As a referral center, he said they see a fair number of treatable autoimmune RPDs each year. These include anti-N-methyl D-aspartate (anti-NMDA) receptor antibody encephalitis, paraneoplastic limbic encephalitis (PLE), and autoimmune limbic encephalitis associated with potassium channel-related antibodies, such as leucine-rich, glioma-inactivated 1 (LGI-1) antibody.”

Here’s a link to the full article for those who want to know more:


Diagnosing and Treating Rapidly Progressive Dementias
Michael O’Leary
Neurology Advisor
November 10, 2014


Are PET scans helpful in diagnosing dementia?

This is a good post in The Geriatrician, a blog (thegeriatrician.blogspot.com).  The post provides an overview of how a geriatrician thinks about the value of PET scans in diagnosing dementia. Apparently there is very little value so this geriatrician has sent only one to get a PET scan, despite the fact that half of his patients have dementia.

When the author says “PET scans,” he is referring to “FDG PET scans.”  I rather doubt his bottom-line would be any different if he were talking about amyloid PET scans.

The crux of the argument has to do with sensitivity , specificity, positive predictive value, and negative predictive value – statistical terms.  He refers people to Google and Wikipedia to look up definitions of these terms.  He also points to a “handy dandy calculator,” found at vassarstats.net/clin2.html.

The geriatrician says:

“[According] to the Alzheimer’s Association, PET scans to make the diagnosis of dementia are 95% sensitive and 75% specific.  Sensitivity means that if someone has dementia, the test will pick it up. Specificity means that the test doesn’t pick up other things like depression.  … While the sensitivity seems great, the specificity is the achilles heel.”

In the blog post, the geriatrician goes through the math.  In summary, he says:

“I would say that the test is useful as a rule out type of test for those who have an intermediate or low suspicion.  Not so much to make the diagnosis.  I wouldn’t be comfortable telling someone they have a fatal neurodegenerative disease when I have a 20% chance of being wrong.  Or even 8% chance.  The second point is that the test is only useful in the setting of a clinical suspicion.  You can see how the characteristics of the test change depending on clinical suspicion.  However when people talk about PET scans, they imply that maybe it would be useful BEFORE a person has clinical symptoms.  It’s not there yet. Maybe the new Amyloid PET scans but not the tagged glucose pet scans.  After going through the math, this is why I don’t use PET scans.  I think it’s more useful to hone my clinical skills than use a test to compensate for poor clinical skills.”

Read the full blog post here:


Are pet scans good enough to diagnose dementia?
The Geriatrician
Sunday, November 16, 2014



Posterior cortical atrophy – short overview

One of Brain Support Network’s missions is to assist families with brain donation.  In the 200 or so brain donations we’ve helped with thus far, we’ve seen a few cases where the donor during life was diagnosed with Lewy Body Dementia but, upon brain donation, the confirmed diagnosis is posterior cortical atrophy (PCA).  Most people with PCA suffer from visual hallucinations or severe visual disturbances.

There is some dispute in the dementia community if PCA is a variant of Alzheimer’s Disease (AD) or whether it’s a separate disease.  The brain pathology is very similar; both typical AD and PCA have neurofibrillary tangles and amyloid plaques.  But the distribution of this pathology differs in the brain between PCA and AD.  In PCA, the pathology is in the back part of the cortex, where visual processing takes place.

The Alzheimer’s Association website has a good, short overview of PCA.  See:


I’ve copied a short excerpt below.


From Alzheimer’s Association website

About Posterior Cortical Atrophy
Posterior cortical atrophy (PCA) refers to gradual and progressive degeneration of the outer layer of the brain (the cortex) in the part of the brain located in the back of the head (posterior). It is not known whether PCA is a unique disease or a possible variant form of Alzheimer’s disease. In many people with PCA, the affected part of the brain shows amyloid plaques and neurofibrillary tangles, similar to the changes that occur in Alzheimer’s disease but in a different part of the brain. In other people with PCA, however, the brain changes resemble other diseases such as Lewy body dementia or a form of Creutzfeld-Jacob disease. Most cases of Alzheimer’s disease occur in people age 65 or older, whereas the onset of PCA commonly occurs between ages 50 and 65.


Tau Therapies in the Pipeline (one to be studied in PSP in late 2015)

As you may know, Alzheimer’s is a disorder involving two proteins — tau and amyloid.  Tau gets misfolded into tangles in Alzheimer’s.  These tau tangles are also part of PSP and CBD.  There has been a push over the last few years — largely led by Adam Boxer, MD, at UCSF (well, that’s my view of things) — that Alzheimer’s drugs targeting tau are best studied in PSP.  More precisely, they are best studied in the Richardson’s Syndrome form of PSP (PSP-RS).

There are several reasons for this.  One is that atrophy occurs in the PSP-RS brain at a faster rate than in an AD brain.  Another is that PSP is a disorder of tau only so it’s ideal to study a tau-busting drug in PSP.  Another the diagnostic accuracy for PSP-RS is quite high.  Also, it is easier to get a PSP drug trial approved by the FDA since PSP is considered a rare disorder.

The Alzheimer’s Association held at International Conference in mid-July in Denmark.  Alzforum, a website for Alzheimer’s researchers, posted a write-up in mid-August of the tau-related research reported at the conference:


The write-up summarizes the research this way:

“Potential therapies included two active vaccines, an antibody, an inhibitor of the enzyme that removes sugar molecules from tau, and an anti-aggregating compound. Most scientists are planning, or have already started, tests in humans.”

Other than those sentences and a few other general sentences, the tau therapies write-up is pretty hard to understand.  Of course I tried harder to understand when “PSP” was mentioned.

One research group plans for human studies in late 2015 in PSP with a compound that it hopes will disrupt the aggregation of tau.

Remember that there is currently a safety study going on at UCSF in both PSP and CBS with intravenous infusions of an experimental drug aimed at tau.  There are four infusions over a nine week period.  See:


Hopefully one of these efforts will pan out for PSP, CBD, and AD!