Category Archives: Alzheimer’s

Argyrophilic grain disease – Brazilian Aging Brain Study Group description

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This interesting review of argyrophilic grain disease (AGD) was recently published by the Brazilian Aging Brain Study Group.  (One of the leaders of the Brazilian study is now at UCSF.)  The full article is available at no charge here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618985/

The abstract notes:

Argyrophilic grain disease (AGD) is an under-recognized, distinct, highly frequent sporadic tauopathy, with a prevalence reaching 31.3% in centenarians. The most common AGD manifestation is slowly progressive amnestic mild cognitive impairment, accompanied by a high prevalence of neuropsychiatric symptoms. … AGD is frequently seen together with Alzheimer’s disease-type pathology or in association with other neurodegenerative diseases. 

Generally, clinical symptoms of AGD are memory impairment (like Alzheimer’s) and neuropsychiatric symptoms.  The mild cognitive impairment progresses very slowly, in most cases.  Common neuropsychiatric symptoms include personality changes (rudeness, stubbornnes, egocentric behavior, disinhibition, obsession, apathy) and depression.  The neuropsychiatric symptoms may pre-date the memory impairment.  Given these symptoms, common clinical diagnoses are Alzheimer’s, frontotemporal dementia, and progressive supranuclear palsy.

The article notes:

A study comparing Parkinson’s disease patients with and without AGD, and studies showing a high prevalence of AGD in individuals with late-onset schizophrenia and delusional disorders, corroborate the association of AGD with psychiatric symptoms.  Asaoka et al. reported an AGD case exhibiting delusions and hallucinations at clinical presentation.  A few reports implicate AGD as the underlying condition in patients featuring clinical frontotemporal dementia. In such cases, AGD pathology is widespread in the brain, as opposed to the majority of AGD cases where involvement is restricted to limbic structures.

There are no clinical diagnostic criteria for diagnosing someone with AGD during life.  The article addresses this by noting, “At any rate, AGD is virtually unknown to the clinical community because most cases do not present any known distinctive clinical symptoms.”  Confusingly for clinicians, AGD can be present in those with cognitive impairment or neuropsychiatric symptoms.  It is a postmortem diagnosis.

Pathologically, we at Brain Support Network see AGD co-occurring with other neurodegenerative diseases, especially other tauopathies such as progressive supranuclear palsy (PSP).

AGD commonly occurs in older people. But AGD can be seen in younger people.  The article states,  “In the series of the Brain Bank of the Brazilian Aging Brain Study Group, 6.7% of individuals aged between 50 and 60 had AGD.”

There is some thought that the presence of AGD may ward of the development of other pathologies, such as Alzheimer’s Disease.  The authors note:

The reasons why AGD does not develop with prominent clinical features have yet to be clarified. Recent evidence of lack of tau acetylation in AGD suggest a protective role of this entity against spread of other neurodegenerative conditions, particularly Alzheimer’s disease and is a hypothesis currently being investigated.

This review article adds greatly to our understanding of AGD.

Robin

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

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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!

newsnetwork.mayoclinic.org/discussion/mayo-clinic-study-of-thousands-of-brains-reveals-tau-as-driver-of-alzheimers-disease/

MAYO CLINIC PRESS RELEASE
24-MAR-2015
Mayo Clinic study of thousands of brains reveals tau as driver of Alzheimer’s disease

Robin

 

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

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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:

www.neurologyadvisor.com/neurodegenerative-diseases/diagnosing-and-treating-rapidly-progressive-dementias/article/382447/

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

Robin

Are PET scans helpful in diagnosing dementia?

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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:

thegeriatrician.blogspot.com/2014/11/are-pet-scans-good-enough-to-diagnose.html

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

Robin

 

Posterior cortical atrophy – short overview

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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:

www.alz.org/dementia/posterior-cortical-atrophy.asp

I’ve copied a short excerpt below.

Robin
________________________

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.