Frontotemporal Disorder: Corticobasal Syndrome

Corticobasal syndrome (CBS) is a progressive neurological disorder that may involve the motor system, cognition or both. Classically, it begins as a movement disorder, with affected individuals showing a unilateral (one sided) paucity of movement and muscle rigidity with a tremor. This may result in the patient first being diagnosed as having Parkinson’s disease. Strength remains normal but the limb becomes progressively less useful because of the problems with tone, slowness, tremor and praxis. A sign called “apraxia,” or loss of praxis, describes a disconnection between the thought and the action despite adequate strength to complete that action.

Patients with CBS are easier to diagnose if they are showing apraxia, such as no longer being able to use the remote control for the television set, or not being able to retrieve mail from the mailbox. Initial symptoms of CBS often begin around age 60 (although there is variability in the age of onset) and become bilateral as the disease progresses. A patient with CBS may first present with a language disorder and develop the motor symptoms over time.

Corticobasal degeneration (CBD) is applied to cases which have a particular type of tauopathy at autopsy (detailed below). Some cases of CBS prove to have Alzheimer’s pathology instead.

Key Clinical Features

Motor symptoms of CBD are similar to those found in Parkinson disease, such as:

  • Akinesia/bradykinesia – an absence or slowness of movements; lack of spontaneous movements
  • Rigidity -a resistance to imposed movement
  • Tremor, often complex
  • Limb dystonia – abnormal posture of the extremities

These cognitive symptoms may be associated with CBD (though not all are seen in all patients):

  • Alien hand syndrome in which the patient does not recognize the actions of his hand and can’t control movement of the hand or arm;
  • Apraxia – the loss of the ability to make familiar, purposeful movements, manifested as difficulty using familiar objects or doing familiar things. Examples include using utensils, combing one’s hair, and dressing;
  • Acalculia – difficulty carrying out simple calculations, such as adding and subtracting.
  • Visual-spatial impairment – an individual with corticobasal degeneration may have difficulty orienting objects in space.

Language symptoms including hesitant and halting speech (progressive aphasia), are seen in some patients.

A CBS patient may begin with any of the three types of signs above: cognitive, motor or language. Development of a second and/or third category of signs makes it easier for the physician to recognize the illness as CBS.

Key Pathologic Features

Upon autopsy, the brain tissue of corticobasal degeneration (CBD) patients is characterized by nerve cell loss, gliosis and atrophy (shrinkage) of the deeper layers in the posterior frontal and/or parietal lobes, and the substantia nigra. Swollen (ballooned) nerve cells containing tau and phosphorylated neurofilament epitopes, similar to those seen in Pick’s disease, are a hallmark feature.

Scientists have recently determined that affected CBD brain cells contain deposits of abnormal forms of the protein tau. Tau is present in all neurons, and it plays important roles in the structure and function (metabolism) of neurons. But in CBD, tau is abnormally phosphorylated, and this biochemical change keeps it from functioning properly.

Genetics

CBD is almost always sporadic, developing by chance rather than being inherited. Some research has found associations with CBD and a specific form (variant) of the tau gene. However, this information is not useful for the diagnosis of specific individuals because the tau forms are neither sensitive nor specific for this degeneration.

Treatment /Management

There is no treatment available to slow the course of corticobasal degeneration, and the symptoms of the disease are generally resistant to therapy. Drugs used to treat Parkinson disease-type symptoms are sometimes tried, but often do not produce significant or sustained improvement for motor symptoms.

Some CBD patients benefit from the selective serotonin reuptake inhibitors (SSRIs) used in treating depression and/or the acetylcholinesterase inhibitors used in Alzheimer disease, which enhance the activity of neurotransmitters in the brain. Clinicians may also employ antioxidants, such as vitamin E or coenzyme Q10, which are known to slow the progression of damage to brain cells in general. Medications may also be prescribed to diminish the tremor.

Maintaining a healthy lifestyle with physical and mental activity is generally recommended for patients with central nervous system degenerative diseases, as is a “heart healthy” diet.

Although there is no treatment for CBD, therapy does help to manage the symptoms, and hopefully one day we will be able to delay their progression. Occupational and physical therapies provide passive range of motion in affected muscles, and help prevent contractures (paralysis of a muscle in the tense state) in rigid limbs. Speech therapy may help delay the progression of language symptoms.

It is important for caregivers and families to think about long-term management issues and identify a team of experts who can help with difficult medical, financial and emotional challenges. It is imperative to have a physician who is knowledgeable about frontotemporal degeneration and CBD. Other medical specialists who may be helpful include: speech therapists, occupational and physical therapists, neuropsychologists, nurses (especially home-care nursing), and genetic counselors.

Prognosis

Corticobasal degeneration usually progresses slowly over the course of 6 to 8 years. During this time, the patient’s ability to live and function independently is diminished, leaving them dependent on others for activities of daily living.

Death in CBD is generally caused by pneumonia or other complications, such as sepsis (an infection throughout the body) or pulmonary embolism (a blood clot that blocks a major blood vessel in the lung).

For additional information and support:

The Association for Frontotemporal Degeneration
Radnor Station Building #2, Suite 320
290 King of Prussia Rd.
Radnor, PA 19087
Toll free: 866-507-7222
E-mail: info@theaftd.org
www.theaftd.org

CurePSP (Foundation for PSP, CBD and Related Disorders)
30 E. Padonia Road, Suite 201
Timonium, MD 21093
Toll free: 800-457-4777
E-mail: info@curepsp.org
www.psp.org

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Memory Formation Triggered by Stem Cell Development

Researchers at the RIKEN-MIT Center for Neural Circuit Genetics have discovered an answer to the long-standing mystery of how brain cells can both remember new memories while also maintaining older ones. They found that specific neurons in a brain region called the dentate gyrus serve distinct roles in memory formation depending on whether the neural stem cells that produced them were of old versus young age.

The study will appear in the March 30 issue of Cell and links the cellular basis of memory formation to the birth of new neurons — a finding that could unlock a new class of drug targets to treat memory disorders.

The findings also suggest that an imbalance between young and old neurons in the brain could disrupt normal memory formation during post-traumatic stress disorder (PTSD) and aging. “In animals, traumatic experiences and aging often lead to decline of the birth of new neurons in the dentate gyrus. In humans, recent studies found dentate gyrus dysfunction and related memory impairments during normal aging,” said the study’s senior author Susumu Tonegawa, 1987 Nobel Laureate and Director of the RIKEN-MIT Center.

Other authors include Toshiaki Nakashiba and researchers from the RIKEN-MIT Center and Picower Institute at MIT; the laboratory of Michael S. Fanselow at the University of California at Los Angeles; and the laboratory of Chris J. McBain at the National Institute of Child Health and Human Development.

In the study, the authors tested mice in two types of memory processes. Pattern separation is the process by which the brain distinguishes differences between similar events, like remembering two Madeleine cookies with different tastes. In contrast, pattern completion is used to recall detailed content of memories based on limited clues, like recalling who one was with when remembering the taste of the Madeleine cookies.

Pattern separation forms distinct new memories based on differences between experiences; pattern completion retrieves memories by detecting similarities. Individuals with brain injury or trauma may be unable to recall people they see every day. Others with PTSD are unable to forget terrible events. “Impaired pattern separation due to the loss of young neurons may shift the balance in favor of pattern completion, which may underlie recurrent traumatic memory recall observed in PTSD patients,” Tonegawa said.

Neuroscientists have long thought these two opposing and potentially competing processes occur in different neural circuits. The dentate gyrus, a structure with remarkable plasticity within the nervous system and its role in conditions from depression to epilepsy to traumatic brain injury — was thought to be engaged in pattern separation and the CA3 region in pattern completion. Instead, the MIT researchers found that dentate gyrus neurons may perform pattern separation or completion depending on the age of their cells.

The MIT researchers assessed pattern separation in mice who learned to distinguish between two similar but distinct chambers: one safe and the other associated with an unpleasant foot shock. To test their pattern completion abilities, the mice were given limited cues to escape a maze they had previously learned to negotiate. Normal mice were compared with mice lacking either young neurons or old neurons. The mice exhibited defects in pattern completion or separation depending on which set of neurons was removed.

“By studying mice genetically modified to block neuronal communication from old neurons — or by wiping out their adult-born young neurons — we found that old neurons were dispensable for pattern separation, whereas young neurons were required for it,” co-author Toshiaki Nakashiba said. “Our data also demonstrated that mice devoid of old neurons were defective in pattern completion, suggesting that the balance between pattern separation and completion may be altered as a result of loss of old neurons.”

The work was supported by the RIKEN-MIT Center for Neural Circuit Genetics, Howard Hughes Medical Institute, Otsuka Maryland Research Institute, Picower Foundation and the National Institutes of Health.

T

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Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer’s Disease

N Engl J Med. 2002 Feb 14;346(7):476-83.

Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease.

Source

Department of Neurology, Boston University School of Medicine, MA 02118-2526, USA.

Abstract

BACKGROUND:

In cross-sectional studies, elevated plasma homocysteine levels have been associated with poor cognition and dementia. Studies of newly diagnosed dementia are required in order to establish whether the elevated homocysteine levels precede the onset of dementia or result from dementia-related nutritional and vitamin deficiencies.

METHODS:

A total of 1092 subjects without dementia (667 women and 425 men; mean age, 76 years) from the Framingham Study constituted our study sample. We examined the relation of the plasma total homocysteine level measured at base line and that measured eight years earlier to the risk of newly diagnosed dementia on follow-up. We used multivariable proportional-hazards regression to adjust for age, sex, apolipoprotein E genotype, vascular risk factors other than homocysteine, and plasma levels of folate and vitamins B12 and B6.

RESULTS:

Over a median follow-up period of eight years, dementia developed in 111 subjects, including 83 given a diagnosis of Alzheimer’s disease. The multivariable-adjusted relative risk of dementia was 1.4 (95 percent confidence interval, 1.1 to 1.9) for each increase of 1 SD in the log-transformed homocysteine value either at base line or eight years earlier. The relative risk of Alzheimer’s disease was 1.8 (95 percent confidence interval, 1.3 to 2.5) per increase of 1 SD at base line and 1.6 (95 percent confidence interval, 1.2 to 2.1) per increase of 1 SD eight years before base line. With a plasma homocysteine level greater than 14 micromol per liter, the risk of Alzheimer’s disease nearly doubled.

CONCLUSIONS:

An increased plasma homocysteine level is a strong, independent risk factor for the development of dementia and Alzheimer’s disease.

Citation

Researchers Develop An Algorithm To Predict How And When Proteins Misfold

Several neurodegenerative diseases – including Alzheimer’s and ALS (Lou Gehrig’s disease) – are caused when the body’s own proteins fold incorrectly, recruit and convert healthy proteins to the misfolded form, and aggregate in large clumps that gum up the works of the nervous system. “For Star Trek fans, this is like the Borg, [a fictional race of cyborgs that abduct and assimilate humans and other species],” says Steven Plotkin, a biophysicist at the University of British Columbia in Vancouver who studies the process of protein misfolding.

Plotkin’s team has developed an algorithm that can predict which regions of a protein are prone to exposure upon misfolding, and how mutations in the protein and changes in the cellular environment might affect the stability of these vulnerable regions. These predictions help scientists gain a better understanding of protein dynamics, and may one day help in developing treatments to effectively combat currently incurable neurodegenerative diseases. The team will present its findings at the 56th Annual Meeting of the Biophysical Society (BPS), held Feb. 25-29 in San Diego, Calif.

The algorithm developed by Plotkin’s group uses the energy equations of thermodynamics to calculate the likelihood that certain stretches of protein will be displayed when the protein misfolds. Since the exposed regions are specific to the misfolded version of the protein, researchers can use these regions as targets for diagnostic and therapeutic treatments. The algorithm can be adapted for different proteins and predicts several potential target regions for each protein. The group has used it to study neurodegenerative disease-causing proteins as well as misfolded proteins that have been implicated in some cancers.

More recently, the research group used computer simulations to manipulate proteins in a virtual environment, testing out how easy it is for mutated proteins to misfold and propagate. Using this tool has helped the team predict the progression of hereditary ALS disease.
“The fact that we can predict the lifetime of an individual diagnosed with hereditary ALS from simulations of a protein’s mechanical properties is something that is both satisfying and that gives one pause,” says Plotkin. “We hope that such information might give some clues as to how to develop effective therapies for this disease.”

Citation

Researchers Discover Possible Key To Degenerative Nerve Diseases

Researchers at the University of Wisconsin-Madison and collaborators have discovered a new protein in the eye of the fruit fly that may shed light on disorders in humans, such as Alzheimer’s disease, age-related macular degeneration, Huntington’s, Parkinson’s and other diseases related to nerve degeneration. All of these disorders may be linked to the malfunction of similar but yet-to-be-identified proteins in the human eye and brain.

In the fruit fly the new protein, which the scientists have named XPORT, is a molecular  “chaperone” for two other important proteins that are key to sensory  activities in the eye.

Rhodopsin is a protein that is responsible for absorbing light. The  other protein, TRP, is a channel that plays a role in calcium influx  into cells. XPORT guides these two proteins from the place where they  are manufactured in the cell to the location where they do their jobs.

This intricate process of chaperoning includes synthesis,  folding, assembly, quality control, transport and targeting of proteins  to their appropriate locations, says senior author Dr. Nansi Jo  Colley, a professor in the Department of Ophthalmology and Visual Sciences at the University of Wisconsin School of Medicine and Public Health. The complex process is prone to error, and a malfunction in any of the steps can have dire consequences in tissues.

“Accumulation of misfolded proteins often leads to severe pathology  and cell death, producing blinding diseases and other neurodegenerative  diseases,” says Colley, “Molecular chaperones are one of the first lines of defense in these fundamental processes.”

The team of researchers discovered XPORT while studying fruit flies with damaged retinas. Those with malfunctions in the function of XPORT  displayed retinal degeneration and defects in rhodopsin and TRP, they  found.

According to the researchers, XPORT forms a complex with rhodopsin and  TRP and is required to successfully transport the two proteins to a  specific location on the cell surface. Colley and the team of  researchers also determined that XPORT is essential for cell survival. Mutations in XPORT prevented the two proteins from  moving through the trafficking pathway and this ended in retinal  degeneration and blindness in the fly.

TRP channels play a vital role as biological sensors, Colley said. They  regulate calcium entering cells that are involved in vision, taste,  olfaction, hearing and touch. “Defective TRP channels can cause night  blindness in certain people,” Colley said.

XPORT was also found to interact closely with heat shock proteins, another family of molecular chaperones. “Heat shock proteins have also been implicated as agents that  protect nerve cells from degeneration,” Colley says, “so XPORT or  XPORT-like proteins might have therapeutic potential as well.”

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What is Senior Housing?

Seniors with low vision, especially if they have other health problems, may want to think about long-term living arrangements that offer assistance. Some of the options are listed below. When planning for the future, consider the possibility that vision loss may progress. Take into account the current and future levels of care that may be needed, as well as location and budget constraints. Although the cost will fluctuate depending on real estate market trends, location and the level of services or amenities, long-term care is expensive. The entire financial situation needs to be carefully evaluated to determine available resources.

Types of Housing

  • Independent Living or Retirement Communities are for seniors who are generally healthy and able to care for themselves. They offer housing with recreational, educational and social activities geared specifically to older people. Meals, housekeeping, transportation and planned activities may also be available. Different communities can have a wide variety of amenities, including golf, tennis, pools and fitness centers. The average cost of these communities ranges from $1300-2500/month, depending on the size of housing, location, services and amenities. Most communities accept only private methods of payment, but there may be some subsidies for low-income individuals.
  • Assisted Living Facilities offer private apartments with in-house care and social activities for older people. They can offer a home-like setting, 24-hour staff coverage, housekeeping and meal assistance, therapeutic activities and in-house medical services if needed. Depending on the size and location of housing and the level of care, the cost of assisted living facilities can range from $1,000-6,000/month, with a national average of $2,500-3,000/month.
  • Life Care Communities or Continuing Care Retirement Communities require a lifetime commitment. They begin as independent living facilities, but offer continued care to residents as they age and their needs change. The person must be able to live independently at first and can then be transferred from an apartment to an affiliated nursing home. Normally, there is an entrance fee of between $20,000-400,000, as well as monthly maintenance fees ranging from $400-2,500.
  • Nursing Homes or Skilled Nursing Facilities offer long-term 24-hour care. They provide rooms, meals, supervised activities and necessary therapy to residents. Nursing homes must be licensed by the state and certified by Medicare and Medicaid, thus they are subject to strict standards, inspections and evaluations. Medicare does not cover long-term care, so private funds and insurance must cover the cost. Eligibility for Medicaid payment varies from state to state, but is available for those with low income and limited assets, or when resources are exhausted. The average cost of a nursing home falls between $3,000-6,000/month.

Senior Housing

  • Commission on Accreditation of Rehabilitation Facilities
    Offers advice on finding an accredited rehabilitation facility.www.carf.org
    1-888-281-6531
  • Helpguide.org
    “Senior Housing and Care” section of website provides information on long-term care and housing options.www.helpguide.org
  • seniorDECISION.com
    Offers a list of home healthcare and senior housing options by state and area with consumer ratings and reviews.www.seniordecision.com
Senior Housing

 

The Growing Alzheimer’s Family

One in eight older Americans, or some 5.4 million people, has Alzheimer’s disease or another form of dementia. And nearly 15 million family members and others are providing unpaid care for them. That means more than 20 million Americans either have Alzheimer’s or provide unpaid care for those with the disease.

Most of those with Alzheimer’s are over 65, including nearly half of those over age 85. Nearly two-thirds of Americans with Alzheimer’s are women, a result of the fact that women tend to live older then men. At any given age, women and men are equally likely to develop the disease, and every 69 seconds someone develops Alzheimer’s.

These are among the findings of a new roundup of facts and figures from the Alzheimer’s Association. The figures reflect the growing burden of Alzheimer’s as our population continues to live longer. In 2000, there were an estimated 411,000 new cases of Alzheimer’s. By 2010, that number had risen to 454,000. It is expected to reach 615,000 by 2030.

Most people with Alzheimer’s live an average of four to eight years, though some can live as long as two decades. Alzheimer’s is the sixth leading cause of death in the United States.

While about two-thirds of those with advanced Alzheimer’s are cared for in nursing homes, millions of people with the disease are cared for at home. Some 80 percent of the 15 million caregivers who provide unpaid care are family members. Last year, they provided unpaid help on average for nearly 22 hours a week, though for many this figure was much greater. Caregiving can also cause problems with keeping a paid job outside the home.

Over half of family caregivers are women, typically spouses or adult children of those with the disease. Over a quarter of unpaid caregivers also have young children to take care of. Help includes everything from shopping for groceries and household cleaning, to help with bathing and dressing, managing finances, and arranging for medical appointments and care.

Not surprisingly, over 60 percent of caregivers say that they have “high” or “very high” levels of stress. Nearly a third have symptoms of depression. The demands of daily home care contribute to stress for caregivers, but putting a loved one in a nursing home, or making end-of-life care decisions, are also major sources of stress.

These figures highlight current and future challenges in dealing with Alzheimer’s. It remains the only leading cause of death that cannot be prevented or even slowed. Drugs for Alzheimer’s may provide some temporary relief from symptoms, but the disease continues its downward course.

Now, more than ever, more effective treatments are needed. The Fisher Center for Alzheimer’s Research Foundation continues to be a leading source of funding for Alzheimer’s research and education. It serves Alzheimer’s patients and their families by seeking to understand the causes of, discover a cure for, and improve the lives of people with Alzheimer’s disease. For more information, visit www.ALZinfo.org.

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Source: Alzheimer’s Association: 2011 Alzheimer’s Disease Facts and Figures. http://www.alz.org/alzheimers_disease_facts_and_figures.asp

Ever Seen a Patent Application? Here is one for a DNA Vaccine for Alzheimer’s Disease

Scientists all over the world are looking for a cure for Alzheimer’s disease.  I found an application for a patent that aims to provide a DNA vaccine for Alzheimer’s disease. You can read the patent inline, or download a copy to review through Adobe Reader.

If you have never seen an application for a patent, I thought you would find this interesting.  Please remember that this is an application for an invention; it does not mean that a vaccine for Alzheimer’s has been found.

~ Jennifer