Alzheimer's I Want You to Know What I Know

Sometimes I write about how my mother went down hill fast, or did she? At 85 she was still walking long distances with me in New York. At 87 she couldn't walk a block. I found out later that she had stopped walking to the pool, she was bascially reduced to sitting around most of the day. Didn't know it. Nobody saw a problem.

I was living in New York and Reston, Va working away. The sound of my mother's feet and the way she complained constantly on the phone were already bothering me. These were new and different behaviors.

I thought something was wrong, but everyone seemed to think she was just "getting old". It seemed like a reasonable explanation, and I guess I was eager to accept this conclusion. I didn't have a clue about what was happening, so why not "old". It might have stayed that way if my stomach wasn't bothering me, and if I wasn't worried every time I thought about mom.

I know more now then I did back in those days. I now realize that my mother was deteriorating slowly over a long period of time. There were plenty of signs. Hindsight 20/20.

I continue to wonder about how things might have been. I wonder what if I had gotten my mother's memory tested the minute I felt concerned. I wonder if she had gotten on the combination of Aricept and Namenda early, what effect would they have had on my mother. Where would she be today?

I am never going to know the answers to those questions.

Now I spend time wondering how I can get the word out about mild cognitive impairment -- often the precursor to Alzheimer's dementia. The point at which a person starts to lose their memory faster than a person that is just getting "old".

The finding of the study below suggest that the memory and thinking abilities of person suffering from mild cognitive impairment declined two times as fast every year as the abilities of those without any cognitive problems. Thinking ability and memory in subjects with Alzheimer's disease declined four times as fast as in those without any cognitive problems.

"There persists the idea that some decline in memory is typical" with age. -- Robert Wilson

No doubt, memory does decline with age.

Here is my advice. If you have a parent or grandparent that starts to evidence new and different behaviors like meanness, worries about money, forgetfulness, gets lost while driving, or starts scrapping their feet on the ground -- get their memory checked.

If your stomach starts bothering you and you think there could be someone wrong with a parent or grandparent, don't assume they are getting old. Stomach bothering you? Pay attention. It is trying to tell you something -- get their memory checked.

If you have a parent or grandparent over 70 years of age -- get their memory checked every two years. People get physicals don't they? How about a brain physical? A memory test.

Alzheimer's dementia is ugly. You probably agree with that statement. But, if you haven't experienced Alzheimer's personally -- from the front row -- you can't imagine how ugly. No -- possible -- way.

There are treatments, not cures, available for Alzheimer's disease. They work very well for some people. We have people on this list that swear that the combination of Aricept and Namenda made a big difference in quality of life.

If you get worried about someone you love -- take action.

If its Alzheimer's, someone is going to have to assume the caregiver responsibility. The sooner you act the better the quality of life for the patient and the caregiver. The caregiver could be you.

Trust me, I know.

By Bob DeMarco, Alzheimer's Reading Room

Long-Term Efficacy Of Xenazine® (Tetrabenazine) For The Treatment Of Chorea Associated With Huntington's Disease

Lundbeck Inc. has announced the presentation of results from an open-label extension study of Xenazine® (tetrabenazine) for the treatment of chorea associated with Huntington's disease (HD). Data from this study demonstrated that after an 80-week treatment period, subjects treated with Xenazine experienced a statistically significant reduction in chorea score (p<0.0001) as measured using the Unified Huntington's Disease Rating Scale (UHDRS) compared with baseline.1


These results are consistent with the reduction in chorea score observed in a pivotal Phase 3 randomized, double-blind, placebo-controlled multi-center clinical study in which subjects were treated with Xenazine for 12 weeks.2 Data from the open-label study were presented at the 12th Annual American Society of Experimental NeuroTherapeutics (ASENT) meeting in Bethesda, Maryland (Poster No. 0029). Results of this study are published in BMC Neurology, an online open access journal at http://www.biomedcentral.com/bmcneurol. Xenazine carries a boxed warning for increased risk of depression and suicidality.

The jerky, sporadic movements commonly seen with chorea associated with Huntington's disease may make it difficult for affected individuals to do tasks such as holding on to objects or even walking," said Dr. Samuel Frank, MD, assistant professor of neurology at the Boston University School of Medicine and lead investigator in this study. "Prolonged reduction of chorea associated with HD in some patients, as seen in this open-label study of Xenazine, is highly encouraging and suggests that Xenazine could be an important treatment option for those seeking to lessen chorea."

This open-label, multi-center extension study was designed to assess the long-term use of Xenazine as a treatment for chorea associated with Huntington's disease.1 The study enrolled 75 subjects, all of whom had previously completed 12 weeks of treatment with Xenazine in the pivotal Phase 3 trial, followed by a one week washout period. Xenazine was titrated over a maximum 12 weeks every three to seven days to the best individual dose, up to a maximum of 200 mg/day of Xenazine. Titration was permitted only during the first 11 weeks of the study.1 Patients who appear to require doses of greater than 50 mg/day should be genotyped for CYP2D6. Doses above 100 mg/day are not recommended for any patient in the Xenazine full prescribing information.3

Of the 75 subjects enrolled in the study, 45 subjects completed the 80-week treatment period, of which 42 subjects continued on to complete a one-week washout period.1 Thirty subjects withdrew from the study, of which, three subjects withdrew due to adverse events associated with Xenazine, including depression, delusions associated with previous suicidal behavior and vocal tics, and 26 subjects withdrew for various other reasons. One subject died due to metastatic breast cancer.

The primary efficacy endpoint in this study was the Total Maximal Chorea (TMC) score from the UHDRS at week 80 compared with baseline TMC score.1 TMC score at week 80 was also compared to TMC score at week 81 following the washout period.1 The UHDRS is a validated rating system used to measure the severity of Huntington's disease.2 The rating system ranges from 0 units (absent chorea symptoms) to 28 units (marked/prolonged chorea).

Data from this study demonstrate a statistically significant reduction in chorea in patients compared to baseline who completed 80 weeks of Xenazine treatment, with a mean reduction in the TMC score of 4.6 UHDRS units.1 At week 81, following a one week washout period, the mean TMC score increased 5.3 UHDRS units compared to week 80 (p<0.001), suggesting that continued use of Xenazine at an individualized dose maintains reduction of chorea associated with HD for up to 80 weeks and confirming results from the pivotal study where discontinuation of Xenazine treatment was associated with the return of chorea, but without significant worsening compared to baseline.1

When mild and unrelated adverse events (AEs) were excluded, the most common AEs in this study reported in >5% of subjects (three or more) were sedation/somnolence, depressed mood, anxiety, insomnia, akathisia, fatigue, agitation, fall, dysphagia and dystonia.1 Thirty-nine patients reported at least one AE during the titration phase compared to 20 patients during the maintenance period. Insomnia, somnolence and diarrhea emerged during titration and resolved during the maintenance period. Twelve serious AEs were reported including two falls, two cancer diagnoses, a single suicide attempt, pneumonia, elective hip replacement with post-op agitation, agitation, anxiety, akathisia, and one abnormal CA 27-29 titer in a patient who later died due to metastatic breast cancer.

About Xenazine


Xenazine is the only FDA-approved therapy for the treatment of chorea associated with Huntington's disease. Xenazine was approved by the U.S. Food and Drug Administration (FDA) in August 2008 and was launched by Lundbeck Inc. in November 2008. To learn more about Xenazine, visit http://www.xenazineusa.com.

Xenazine Important Safety Information and Boxed Warning

Xenazine can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington's disease. Anyone considering the use of Xenazine must balance the risks of depression and suicidality with the clinical need for control of choreiform movements. Close observation of patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior should accompany therapy. Patients, their caregivers, and families should be informed of the risk of depression and suicidality and should be instructed to report behaviors of concern promptly to the treating physician.

Particular caution should be exercised in treating patients with a history of depression or prior suicide attempts or ideation, which are increased in frequency in Huntington's disease. Xenazine is contraindicated in patients who are actively suicidal, and in patients with untreated or inadequately treated depression.

Xenazine is also contraindicated in patients with impaired hepatic function, and in patients taking monoamine oxidase inhibitors or reserpine.3 At least 20 days should elapse after stopping reserpine before starting Xenazine. Although Xenazine has been shown to decrease the chorea associated with HD, it was also shown to cause slight worsening in mood, cognition, rigidity and functional capacity and prescribers should periodically re-evaluate the need for therapy. Some adverse effects such as depression, fatigue, insomnia, sedation/somnolence, parkinsonism, akathisia, QTc prolongation and interactions with CYP2D6 inhibitors may be dose dependent, and resolve or lessen with dose adjustment. The most frequent adverse events (over 10% and at least 5% greater than placebo) reported with Xenazine compared to placebo in a randomized, 12-week, placebo controlled clinical trial of HD subjects include sedation/somnolence (31% vs. 3%), fatigue (22% vs. 13%), insomnia (22% vs. 0%), depression (19% vs. 0%), akathisia (19% vs. 0%), anxiety (15% vs. 3%) and nausea (13% vs. 7%). For more information, please see full prescribing information including Boxed Warning or go to http://www.xenazineusa.com.

About Chorea Associated with Huntington's Disease

Chorea is the most common symptom of Huntington's disease (HD), a rare neurodegenerative disease that results in uncontrolled movements, emotional disturbances, and mental deterioration. HD affects approximately 30,000 people in the United States.4 Chorea associated with HD is characterized by irregular, abrupt movements of the face, fingers, arms, legs, or body that can appear as constant jerky, twisting, and uncontrollable, dance-like motions.5,6 As the disease progresses, it may interfere with many voluntary movements, making it more difficult to walk, talk or hold things.7 Currently, there is no known cure for HD and the disease and prognosis is poor.3,8,9 To learn more about chorea associated with Huntington's disease, please visit http://www.xenazineusa.com.

Sources

Frank S. Tetrabenazine as anti-chorea therapy in Huntington disease: an open-label continuation study. BMC Neurol. 2009 Dec 18;9:62.

Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. 2006 Feb 14;66(3):366-72.

Xenazine® Full Prescribing Information. Deerfield, IL: Lundbeck Inc. September 2009.

What is Huntington's Disease (HD)? Huntington's Disease Society of America. http://www.hdsa.org/about/our-mission/what-is-hd.html. Last accessed 2/22/10.

Huntington Study Group. Unified Huntington's Disease Rating Scale: Reliability and Consistency. Movement Disorders. 1996;2(2):136-142.

Chorea, Huntington's Disease. The Movement Disorder Society. http://www.movementdisorders.org/disorders/chorea.php. Last accessed 02/22/10.

Kirkwood SC, Su JL, Conneally PM, Foroud T. Progression of symptoms in the early and middle stages of Huntington disease. Archives of Neurology 2001;58:273-278.

Huntington's Disease: Hope Through Research. National Institute of Neurological Disorders and Stroke. http://www.ninds.nih.gov/disorders/huntington/detail_huntington.htm. Last accessed 02/22/10.

Huntington's disease. Mayo Clinic. http://www.mayoclinic.com/health/huntingtons-disease/DS00401/METHOD=print. Last accessed 2/22/10.

Source:

Nikki Kidd

Edelman Public Relations

View drug information on Xenazine

The Social Security Administration added early-onset/younger onset Alzheimer's!

Social Security Disability - Breaking News

The Social Security Administration (SSA) has added early-onset/younger onset Alzheimer's to the list of conditions under its Compassionate Allowance Initiative, giving those with the disease expedited access to Social Security Disability Insurance (SSDI) and Supplemental Security Income (SSI). The Alzheimer's Association, a longtime advocate for those with early-onset Alzheimer's, has played an integral role in this movement to reduce the length of disability decision process.

Complete statement from Alzheimer's Association

Washington, DC February 11, 2010 – In its effort to improve and expedite the disability
determination process, the Social Security Administration (SSA) has announced that it
will add early-onset Alzheimer’s disease to its Compassionate Allowances Initiative. The
initiative identifies debilitating diseases and medical conditions that meet the SSA’s
disability standards for Social Security Disability Income (SSDI) or Supplemental
Security Income (SSI). Inclusion in the initiative allows for faster payment of Social
Security benefits to individuals with Alzheimer’s disease. The Alzheimer’s Association
applauds Social Security Commissioner Michael Astrue and the SSA for understanding
that the cognitive impairment caused by Alzheimer’s disease leaves individuals unable
to maintain gainful employment and deserving of an expedited disability determination.

“As the leading research, advocacy, and support organization for Alzheimer’s disease,
the Alzheimer’s Association has actively sought the inclusion of early-onset Alzheimer’s
in the Social Security Administration’s Compassionate Allowances Initiative,” says Harry
Johns, President and CEO of the Alzheimer’s Association. “Now, individuals who are
dealing with the enormous challenges of Alzheimer’s won’t also have to endure the
financial and emotional toll of a long disability decision process.”

Since 2003, the Alzheimer’s Association has been advocating on behalf of individuals
with early-onset Alzheimer’s as they navigate the Social Security disability
determinations process and welcomes the SSA’s decision. Until now, individuals with
early-onset Alzheimer’s disease have faced a myriad of challenges when applying for
SSDI or SSI, including a long decision process, initial denials, and multiple appeals.
Today’s decision will simplify and streamline the SSDI/SSI application process and
decrease the wait time for benefits, which for some has lasted as long as three years.
There are currently an estimated 5.3 million Americans with Alzheimer’s disease.
Although the majority of Alzheimer cases are individuals age 65 and older, a significant
number of people under age 65 are also affected by this fatal disease and have few
financial options other than the Social Security disability program.

In addition to Alzheimer’s disease, mixed-dementia and Primary Progressive Aphasia
were also added to the Compassionate Allowances Initiative under the SSA’s recent
decision. To determine which diseases and conditions to include, SSA has held several
public outreach hearings throughout the country that have included testimony from
medical and scientific experts, as well as those directly affected by these diseases and
conditions. The July 2009 Compassionate Allowance Hearing on Early-Onset
Alzheimer’s Disease and Related Dementias, held in Chicago, included testimony from
Johns, several of the nation’s top Alzheimer researchers, and caregivers and individuals
with early-onset Alzheimer’s who discussed the challenges they faced during the
disability application process. During the day-long hearing, SSA officials heard about the
terminal nature of Alzheimer’s, the disabilities that often prohibit work in even the earliest
stages of the disease, and the lack of effective treatments to modify or halt the
progression of Alzheimer’s.

In addition to participation in the hearing, as many as 600 people with Alzheimer’s and
other dementias and their caregivers responded to the Association’s request to submit
written comments to SSA about their experiences applying for disability benefits. A
sample of these comments are posted on SSA’s Compassionate Allowances website:
http://www.socialsecurity.gov/compassionateallowances/statements.htm

The Social Security Administration’s proactive efforts to “fast track” certain conditions will
help to reduce the backlog of disability claims and, more importantly, ensure those
claims that fall under this initiative will be decided within days instead of months or
years.

“The diagnosis of Alzheimer’s indicates significant enough cognitive impairment to
interfere with daily living activities, including the ability to work. This decision will help a
significant number of Alzheimer families. It will also help the Social Security
Administration, since long delays and appeals in the disability determination process are
costly for the agency,” says Johns. “The Alzheimer’s Association praises SSA for this
decision and remains committed to continue to work with Commissioner Astrue and his
colleagues at the Social Security Administration in support of its implementation
nationwide.”

Researchers find new risk factor for early-onset dementia

Examining brain tissue from over 500 individuals in 11 countries, researchers from the University of Pennsylvania School of Medicine and the Children's Hospital of Philadelphia, and colleagues found a new risk factor for the second-most-common cause of early-onset dementia after Alzheimer's disease.

"Using a genome-wide scan for genetic variation in post-mortem brain tissue, we were able to pinpoint variations common to patients with a specific subtype of frontotemporal lobar degeneration, FTLD," says co-first author Vivianna Van Deerlin, MD, PhD, associate professor of Pathology and Laboratory Medicine at Penn. "This gives us more information on what proteins may underlie the molecular events leading to FTLD, and eventually, new drug targets." The findings were published online this week in Nature Genetics.

"By identifying gene variants that may play a role in the development and progression of one type of FTLD, this research, if replicated, will take us one step closer to an understanding of the complex biologic pathways involved in this devastating disease," said Marcelle Morrison-Bogorad, PhD, director of the National Institutes of Health Division of Neuroscience.

The findings build on a 2006 discovery by co-senior authors Virginia Lee, PhD, director of the Center for Neurodegenerative Disease Research, and John Q. Trojanowski, MD, PhD, director of the Institute of Aging at Penn. They led an international team that found that a protein called TDP-43 accumulates abnormally in brain tissue from individuals with one type of heritable FTLD. TDP-43 is a known protein widely expressed throughout the body, with multiple functions, including regulating transcription of the genetic code and as scaffolding for nuclear and motor neuron proteins.

FTLD cases that are characterized by TDP-43 inclusions can be passed from one generation to the next, as a result of mutations in another protein called progranulin (GRN). Using post-mortem brain tissue from 515 patients with TDP-associated FTLD, the team found that these patients had multiple genetic variations called SNPs in common in a region on chromosome 7 containing the protein TMEM106B, compared to over 2,500 disease-free controls.

From this, the team concluded that the TMEM106B gene variants confer a higher genetic risk for all FTLD-TDP patients, as well as in the subset of patients with GRN mutations. What's more, alterations in levels of TMEM106B protein in the brain may be directly or indirectly involved in causing FTLD.

How TDP-43, GRN, and TMEM106B proteins might normally interact in brain cells and be disrupted in FTLD remains to be deciphered. Nevertheless, the discovery of TMEM106B is an important step toward a better understanding of FTLD. The team plans to sequence the TMEM106B segment of chromosome 7, and in parallel, study the normal functions of TMEM106B.

SOURCE University of Pennsylvania School of Medicine

Early-stage and younger-onset Alzheimer's Disease Defined

Early-stage is the early part of Alzheimer’s disease when problems with memory, thinking and concentration may begin to appear in a doctor’s interview or medical tests. Individuals in the early-stage typically need minimal assistance with simple daily routines. At the time of a diagnosis, an individual is not necessarily in the early stage of the disease; he or she may have progressed beyond the early stage.
The term younger-onset refers to Alzheimer's that occurs in a person under age 65. Younger-onset individuals may be employed or have children still living at home. Issues facing families include ensuring financial security, obtaining benefits and helping children cope with the disease. People who have younger-onset dementia may be in any stage of dementia – early, middle or late. Experts estimate that some 500,000 people in their 30s, 40s and 50s have Alzheimer's disease or a related dementia.

By Alzheimer's Association

Early-onset Alzheimer's: When symptoms begin before 65

Early-onset Alzheimer's is an uncommon form of dementia that strikes people younger than age 65. Glenn E. Smith, Ph.D., a neuropsychologist at Mayo Clinic, Rochester, Minn., answers questions about this condition.

How common is early-onset Alzheimer's?

Of all the people with Alzheimer's disease, only 5 to 10 percent develop symptoms before age 65. So if 4 million Americans have Alzheimer's, at least 200,000 people have the early-onset form of the disease. Early-onset Alzheimer's has been known to develop between ages 30 and 40, but that's very uncommon. It is more common to see someone in his or her 50s who has the disease.

What causes it?

It often runs in families. Many people with early-onset Alzheimer's have a parent or grandparent who also developed Alzheimer's at a younger age. A significant proportion of early-onset Alzheimer's is linked to three genes.

These three genes are different from the APOE gene — the gene that can increase your risk of Alzheimer's in general. But you can have the APOE gene and never develop Alzheimer's. Conversely, you can have Alzheimer's and not have the APOE gene. The genetic path of inheritance is much stronger in early-onset Alzheimer's. If you have one of those three genes, it would be very unusual for you not to develop Alzheimer's before age 65.

If early-onset Alzheimer's runs in my family, should I get tested for it?

That's a personal decision that only you can make. There are pros and cons to genetic testing. Anyone who's considering it should never proceed without genetic counseling — to examine these pros and cons beforehand.

Does early-onset Alzheimer's progress at a faster rate?

There's a perception that it does, but it's not backed up by hard data. It depends on what endpoint you're using in your measurement. If you use admission to a nursing home, that may occur earlier for the early-onset group — but only because their spouses have so many other things on their plates.

For example, people who have early-onset Alzheimer's often still have children at home. They or their spouses may have elderly parents that need care, too. That generation often is sandwiched between caring for their ailing parents and caring for their teenage children at the same time. Adding in a spouse with Alzheimer's can simply be too much to handle.

What types of problems occur more often in early-onset Alzheimer's?

Alzheimer's disease has a tremendous impact at any age. But we don't expect to see dementia at a young age, so problems emerging at work or home may be mistakenly ascribed to lack of motivation or diligence, or possible psychiatric problems. People with early-onset Alzheimer's may lose relationships or be fired instead of being identified as medically ill or disabled.

The loss of intimacy is something that comes up a lot with early-onset Alzheimer's. Many people who develop late-onset Alzheimer's have already been widowed. But couples in their 40s or 50s are often in the middle of their married lives. Spouses face the possibility of spending many years of their lives without an active partner. Losing the romantic component and changing to a caregiver status complicates the relationship.

Are there financial issues as well?

People with early-onset Alzheimer's often have to quit work, and this loss of income is a serious concern. Finances get even tighter if their spouses also quit their jobs to become full-time caregivers. Some medical benefits and many social-support programs won't provide assistance unless the person with Alzheimer's is over age 65. Younger people may need special waivers to get into such programs.

How important is it to obtain an accurate diagnosis?

Accurate diagnosis is critical so that you can explain your condition to your employer and perhaps arrange a lighter workload or more convenient schedule. For family reasons it is even more crucial. The diagnosis is fundamental in helping the family react with appropriate understanding and compassion. In addition, a complete evaluation will rule out reversible forms of dementia that might improve with treatment.

What advice do you have for those with early-onset Alzheimer's and their families?

The key treatments in Alzheimer's are education and support. This is especially true given the unique social challenges of early-onset Alzheimer's. Getting connected to services such as support groups can help you identify resources, gain a deeper understanding and learn ways to adapt to the situation.

By Mayo Clinic Staff