“Dementia caregivers: Learning to live in your loved one’s reality” (Philadelphia Inquirer)

This Philadelphia Inquirer article is a report on an Alzheimer’s caregiver conference in Valley Forge.  The keynote speaker was Tam Cummings, a gerontologist from Texas.  Ms. Cummings and other speakers made several points:

* “Cummings urged family members to ask their doctors more questions — as many questions as they might ask if the diagnosis were cancer.  Knowing more, she said, may help them understand and cope with the memory lapses, confusion, delusions, falls, depression, and stubbornness that often accompany dementia.”

* “A recurring theme: People with dementia have brain damage that limits what they can do and how they can think.  It’s those around them who have to change. … If people with dementia are being obstinate or aggressive, it’s up to caregivers to try to figure out whether there is an explanation that their loved one can no longer communicate: Are they in pain? Are they afraid? Were the instructions too complicated? Have perceptual changes made the environment look dangerous to them?”

* “Cummings told the crowd that ‘your loved one’s reality is your reality.'”

This short article is worth reading.  Here’s a link to it:

www.philly.com/philly/health/Dementia-caregivers-Learning-to-live-in-your-loved-ones-reality-alzheimers-association.html

Dementia caregivers: Learning to live in your loved one’s reality
Updated: April 26, 2017 — 3:01 am EDT
by Stacey Burling, Staff Writer
Philadelphia Inquirer

Robin

Supporting, and getting support, from loved ones after a diagnosis

Though this newspaper article is about dementia, I think most of the concepts apply to everyone with a neurological diagnosis.

In Monday’s article in The Sacramento Bee, retired journalist Kent Pollock writes about his dementia diagnosis and how many with a dementia diagnosis struggle to receive support from their loved ones.

The article is here:

www.sacbee.com/news/local/health-and-medicine/article144682519.html

HEALTH & MEDICINE
APRIL 17, 2017 8:00 AM
Supporting, and getting support, from loved ones after a dementia diagnosis
By Kent Pollock
Special to The Bee

Robin

 

“Next-Generation Tau PET Tracers Strut Their Stuff” – differentiating PSP from AD

This is a report by Alzforum from the Alzheimer’s/Parkinson’s 2017 conference in Vienna at the end of March.  The focus of the report is on next-generation tau PET tracers.  Tau is the protein involved in Alzheimer’s Disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick’s disease, and chronic traumatic encephalopathy.

There are five new PET tracers under development.  The report says:

“[The] new tracers…appear at first glance to be able to overcome the limitations of the earlier compounds. In general, the newcomers boast higher brain uptake and more specific binding, yielding cleaner-looking scans with sharper distinction between positive and negative findings. While the older tracers work only in AD, some of the new ones appear to light up other tauopathies, as well. Researchers at Piramal Imaging wowed the crowd with scans showing a distinct, specific pattern of binding of their tracer in progressive supranuclear palsy (PSP) compared to AD.”  (Check out the online version of the article for AD vs. PSP images.)

The first-generation tau PET tracers described in the report are:  Lilly/Avid’s AV-1451 (flortaucipir) and THK5351, discovered at Tohoku University in Sendai, Japan, and licensed by GE Healthcare for commercial distribution.  The report indicates that both tracers have lots of problems.

As a result, many researchers are “now eyeing Merck’s and Piramal’s [tracers]. … Merck reported on their tau PET tracer, MK-6240, at the Human Amyloid Imaging (HAI) meeting held January.”  Other companies working on tau ligands include Genentech, Roche, and Janssen.

“Piramal started a Phase 1 trial on four people with AD, three with PSP, and two healthy controls. … Notably, AD and PSP scans revealed distinct patterns. In PSP, only a few discrete regions, mainly the pallidum and substantia nigra, lit up. In contrast, AD patients took up tracer in broader areas known to accumulate tau tangles, such as the lateral temporal lobe, hippocampus, entorhinal cortex, and precuneus.  Curiously, one of the AD patients had a negative tau scan. Stephens noted this patient had mild AD, with an MMSE of 26, and may not have accumulated much pathological tau yet. Incidentally, other PET experts, too, noted that as more research groups image both amyloid and tau pathology in the same cognitively impaired people, they are finding a few whose scans are amyloid-positive but tau-negative.”

Here’s a link to the full report:

www.alzforum.org/news/conference-coverage/next-generation-tau-pet-tracers-strut-their-stuff

Next-Generation Tau PET Tracers Strut Their Stuff
Series – AD/PD 2107 Draws Record Number of Scientists To Vienna
14 Apr 2017
by Alzforum

Robin

 

“Before you send your spit to 23andMe, what you need to know” (STAT News)

Here’s a very helpful article from today’s STAT News (statnews.com) about what 23andMe’s genetic reports can and cannot show.

www.statnews.com/2017/04/07/genetic-analysis-need-to-know/

Health
Before you send your spit to 23andMe, what you need to know
By Sharon Begley
STAT News
April 7, 2017

Robin

 

FDA allows 23andMe to sell genetic tests again (NYT article)

The FDA is now allowing 23andMe to sell genetic tests again.  I don’t believe the test looks for any alpha-synuclein, MAPT, or other tau-related genetic mutations so any genetic test from 23andMe won’t have any bearing on the disorders with the Brain Support Network community.  However, this is still big news for the genetic testing world.  According to the article, customers have to specifically ask to be tested for Alzheimer’s and Parkinson’s risk.

Here’s a link to today’s New York Times article on the development:
www.nytimes.com/2017/04/06/health/fda-genetic-tests-23andme.html Health
F.D.A. Will Allow 23andMe to Sell Genetic Tests for Disease Risk to Consumers
By Gina Kolata
New York Times
April 6, 2017Robin

5 common dementias, including Lewy Body Dementia

A post today on a Canadian newspaper website, Castanet (castanet.net), is about five common dementias.  The five include:  Alzheimer’s, vascular dementia, Lewy body dementia, frontotemporal dementia, and Wernicke-Korsakoff’s syndrome (caused by prolonged alcohol consumption).  Here’s a link to the post:

www.castanet.net/news/Dementia-Aware/191198/5-common-dementias

Here’s how Lewy body dementia (LBD) is described:

Lewy body dementia:
Often mistaken for other dementias, e.g. Parkinson’s dementia
* Presence of Lewy bodies: tiny spherical protein deposits that develop inside nerve cells in the areas of thinking, memory and movement
* Fluctuating cognitive impairment: periods of increased confusion & windows of lucidity
* Hallucinations or delusions occur frequently and can be quite detailed
* Spatial disorientation e.g. falls, fainting
* Tremor, rigidity and slowness of movement
* Highly sensitive to neuroleptic drugs: Risperidone

This is OK except for two problems.  First, the author says that LBD is mistaken for other dementias such as Parkinson’s dementia.  Well, by definition Parkinson’s (Disease) Dementia is ONE of the disorders on the Lewy Body Dementia spectrum.

Second, I’m not sure how “fainting” is an example of “spatial disorientation.”  Fainting is an example of autonomic dysfunction.

Definitely not by favorite short LBD overview….

Robin

Multimodal Imaging Ties Tau to Neurodegeneration, and Symptoms

This is an Alzforum (alzforum.org) article about important researcher into tauopathies by researchers at Mass General.  The article was posted last week to Alzforum; the research study was published online in JAMA Neurology a couple of weeks ago.

What the researchers confirmed is that there is a “tight correlation between tau neurofibrillary tangles and neurodegeneration in individual patients in early clinical stages of various forms of Alzheimer’s disease.”  Three patients with typical Alzheimer’s Disease (AD) were studies, and three patients with atypical AD were studied.  One of the “atypical AD” cases was a person with corticobasal syndrome (CBS)

In this study, all patients were given a tau PET scan, an amyloid PET scan, and an MRI.  Researchers found that “tau predicts atrophy [which] predicts symptoms.”  It is not the protein amyloid in the brain that predicts atrophy or predicts symptoms.

In fact, we have known this from brain donation for a long time but now researchers have confirmed this in living patients.

Perhaps one reason that a CBS patient was studied rather than a PSP (progressive supranuclear palsy) patient is that the tau load in CBD is greater than in PSP.

Here’s a link to the article:

www.alzforum.org/news/research-news/multimodal-imaging-ties-tau-neurodegeneration-and-symptoms

Multimodal Imaging Ties Tau to Neurodegeneration, and Symptoms
Alzforum
07 Mar 2017

It is challenging reading.  Check it out online for cool images of the patient with corticobasal syndrome.

Robin

“Jumping Genes Suspected in Alzheimer’s” – mitochondria cascade hypothesis

This article from Duke Today (today.duke.edu) describes the “Alu neurodegeneration hypothesis,” also known as the “mitochondrial cascade hypothesis.”

Here’s an excerpt:

“The dominant idea guiding Alzheimer’s research for 25 years has been that the disease results from the abnormal buildup of hard, waxy amyloid plaques in the parts of the brain that control memory. But drug trials using anti-amyloid drugs have failed, leading some researchers to theorize that amyloid buildup is a byproduct of the disease, not a cause.  The Duke study builds on an alternative hypothesis. First proposed in 2004, the ‘mitochondrial cascade hypothesis’ posits that changes in the cellular powerhouses, not amyloid buildup, are what cause neurons to die.”

The full article is below.

Robin

———————-

today.duke.edu/2017/03/jumping-genes-suspected-alzheimers

Jumping Genes Suspected in Alzheimer’s
Mechanism might explain initial stages of neurodegenerative disease
Duke Today|Research
By Robin A. Smith, Duke Research
Published March 8, 2017

DURHAM, N.C. — The latest round of failed drug trials for Alzheimer’s has researchers questioning the reigning approach to battling the disease, which focuses on preventing a sticky protein called amyloid from building up in the brain.

Duke University scientists have identified a mechanism in the molecular machinery of the cell that could help explain how neurons begin to falter in the initial stages of Alzheimer’s, even before amyloid clumps appear.

This rethinking of the Alzheimer’s process centers on human genes critical for the healthy functioning of mitochondria, the energy factories of the cell, which are riddled with mobile chunks of DNA called Alu elements.

If these “jumping genes” lose their normal controls as a person ages, they could start to wreak havoc on the machinery that supplies energy to brain cells — leading to a loss of neurons and ultimately dementia, the researchers say.

And if this “Alu neurodegeneration hypothesis” holds up, it could help identify people at risk sooner, before they develop symptoms, or point to new ways to delay onset or slow progression of the disease, said study co-author Peter Larsen, senior research scientist in biology professor Anne Yoder’s lab at Duke.

The dominant idea guiding Alzheimer’s research for 25 years has been that the disease results from the abnormal buildup of hard, waxy amyloid plaques in the parts of the brain that control memory. But drug trials using anti-amyloid drugs have failed, leading some researchers to theorize that amyloid buildup is a byproduct of the disease, not a cause.

The Duke study builds on an alternative hypothesis. First proposed in 2004, the “mitochondrial cascade hypothesis” posits that changes in the cellular powerhouses, not amyloid buildup, are what cause neurons to die.

Like most human cells, neurons rely on mitochondria to stay healthy. But unlike other cells, most neurons stop dividing after birth, so they can’t be replaced if they’re damaged.

In Alzheimer’s patients, the thinking goes, the mitochondria in neurons stop working properly. As a result they are unable to generate as much energy for neurons, which starve and die with no way to replenish them. But how mitochondria in neurons decline with age is largely unknown.

Most mitochondrial proteins are encoded by genes in the cell nucleus before reaching their final destination in mitochondria. In 2009, Duke neurologist and study co-author Allen Roses (now deceased) identified a non-coding region in a gene called TOMM40 that varies in length. Roses and his team found that the length of this region can help predict a person’s Alzheimer’s risk and age of onset.

Larsen wondered if the length variation in TOMM40 was only part of the equation. He analyzed the corresponding gene region in gray mouse lemurs, teacup-sized primates known to develop amyloid brain plaques and other Alzheimer’s-like symptoms with age. He found that in mouse lemurs alone, but not other lemur species, the region is loaded with short stretches of DNA called Alus.

Found only in primates, Alus belong to a family of retrotransposons or “jumping genes,” which copy and paste themselves in new spots in the genome. If the Alu copies present within the TOMM40 gene somehow interfere with the path from gene to protein, Larsen reasoned, they could help explain why mitochondria in nerve cells stop working.

“Alu elements are a double-edged sword,” Larsen said. Once dismissed as selfish or junk DNA, they are now recognized as contributors to the diversity and complexity of the human brain. “They can provide new and beneficial gene functions,” Larsen said. “They have helped humans evolve higher cognitive function, but perhaps at the cost of neuron vulnerability that increases with age.”

When the researchers looked across the human genome, they found that Alus were more likely to be lurking in and around genes essential to mitochondria than in other protein-coding genes.

Alus are normally held in check by clusters of atoms called methyl groups that stick to the outside of the DNA and shut off their ability to jump or turn genes on or off. But in aging brains, DNA methylation patterns change, which allows some Alu copies to re-awaken, Larsen said.

The TOMM40 gene encodes a barrel-shaped protein in the outer membrane of mitochondria that forms a channel for molecules — including the precursor to amyloid — to enter. Larsen used 3D modeling to show that Alu insertions within the TOMM40 gene could make the channel protein it encodes fold into the wrong shape, causing the mitochondria’s import machinery to clog and stop working.

Such processes likely get underway before amyloid builds up, so they could point to new or repurposed drugs for earlier intervention, said study co-author Michael Lutz, assistant professor of neurology at Duke.

The TOMM40 gene is one example, the researchers say, but if Alus disrupt other mitochondrial genes, the same basic mechanism could help explain the initial stages of other neurodegenerative diseases too, including Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis (ALS).

The researchers describe the Alu neurodegeneration hypothesis in a paper published online by Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

“We need to start thinking outside of the box when it comes to treating neurological diseases like Alzheimer’s,” said Larsen, who has filed a provisional patent that focuses on preserving mitochondrial function by keeping Alus in check.

Other authors include Kelsie Hunnicutt, Mirta Mihovilovic and Ann Saunders of Duke. This research was supported by a seed grant from Allen Roses and Duke funds to Anne Yoder.

CITATION:  The full text of the research article can be found here in DukeSpace, the university’s online repository of open-access research. “The Alu Neurodegeneration Hypothesis: A Primate-Specific Mechanism for Neuronal Transcription Noise, Mitochondrial Dysfunction, and Manifestation of Neurodegenerative Disease,” Peter Larsen, Michael Lutz, Kelsie Hunnicutt, Mirta Mihovilovic, Ann Saunders, Anne Yoder and Allen Roses. Alzheimer’s & Dementia, Mar. 8, 2017 DOI: 10.1016/j.jalz.2017.01.017

“The blessing inside my sister’s Alzheimer’s disease” (Washington Post)

This is a sweet story in today’s Washington Post about the “blessing” of a sister’s Alzheimer’s disease:

www.washingtonpost.com/opinions/the-blessing-inside-my-sisters-alzheimers-disease/2017/03/03/04e80d0a-fec9-11e6-8f41-ea6ed597e4ca_story.html

Opinions
The blessing inside my sister’s Alzheimer’s disease
The Washington Post
By Jennifer Palmieri
March 3 at 7:24 PM

Robin

“Risky drugs: Antipsychotics, dementia can be lethal combination”

This article from the Pittsburgh (PA) Tribune-Review is about a gentleman with Lewy body dementia being given Haldol, an antipsychotic, at a hospital. He was agitated and the nurses wanted to calm him before a CT scan. Within ten minutes of receiving the injection, the gentleman experienced fever and seizures. He died several days later from neuroleptic malignant syndrome.

Here’s an excerpt from the article:

“‘[Antipsychotics] get used a lot in dementia despite the black box warning,’ said Dr. James Leverenz, director of the Cleveland Lou Ruvo Center for Brain Health and chairman of the Lewy Body Dementia Association’s scientific advisory council. Few other drugs are effective in treating psychosis, Leverenz said. He said he reserves the drugs for patients suffering the most acute psychosis. For example, he might prescribe them if a patient is calling police to report hallucinated break-ins at his or her home, he said. Leverenz said he opposes using the drugs to treat agitation except in very severe cases.”

Here’s a link to the full article:


triblive.com/news/healthnow/11908611-74/dementia-drugs-shook

Health Now
Risky drugs: Antipsychotics, dementia can be lethal combination
by Wes Venteicher
Tribune-Review
Saturday, Feb. 11, 2017, 1:24 p.m.

Hopefully everyone in the Brain Support Network knows about the dangers of antipsychotics in those with dementia and in those with parkinsonism!

Robin