“Depression, Delirium & Dementia” – lecture notes

Stanford University (stanford.edu) sponsored a 3-part series on geriatric health in May.  The first evening, May 11, 2006, included this lecture:

“Depression, Delirium & Dementia: What Should We Be Doing?”
Speaker:  Barbara Sommer, MD, Asst Prof of Psychiatry and Behavioral Sciences, Stanford Univ

Local support group member Karen D. gave me her notes on the lecture.  This post attempts to summarize some of the key points in that lecture.

Robin


Dr. Sommer stated that life expectancy increases are not due to doctors but to infrastructure changes, such as indoor plumbing.

She stated that 27% of people older than 60 living in a community have some degree of depression.  Depressed people have two times the number of doctors’ appointments than others.  75% of elderly suicides have seen their doctors in the last month.  The rate of elderly white males is increasing.  Elderly women’s suicide rates drop to zero after they stop caregiving for their elderly spouses!

Of those with dementia, 64% have AD, 25% have Vascular Dementia, and 12-15% have Frontotemporal Dementia (FTD).

She mentioned that there are several drugs on the market to treat AD:  three acetylcholinesterase inhibitors (including Aricept) and Namenda.  The standard treatment is to prescribe one of the acetylcholinesterase inhibitors and add Namenda.  Glutamate is essential to the brain.  Namenda restores the glutamate levels to normal.

Dr. Sommer said that memory can be optimized through mental gymnastics, dance and tai-chi, avoiding medication that affects the brain, diet, avoiding obesity, avoiding stress, and optimizing near vision.

Medication that affects the brain includes some anticholinergics, benzodiazepams or sleeping pills, antihistamines, etc.

Those with a higher BMI (body mass index) have a higher risk of dementia. She pointed out that when you lose near vision, you lose stimulation and the ability to participate in activities.  Bottom line – lose weight and see your optometrist!

Dr. Sommer repeatedly noted the negative effects of stress.

Dr. Sommer said that delirium is reversible.  She distributed an article on “Preventing delirium in older people,” published 7/15/05 in the British Medical Bulletin.  You can find an abstract of the article online at no charge:

bmb.oxfordjournals.org/cgi/content/abstract/73-74/1/25

The article states that:

“Up to 50% of delirium affecting older people develops after admission to (the) hospital.  These cases often result from hospital-related complications or inadequate care.” 

The paper focuses on how to prevent the delirium that is acquired in the hospital and is preventable.

 

“Cognitive Changes w/Aging” and “Maintaining Health” – lecture notes

Stanford sponsored a 3-part series on geriatric health in May. The second evening, May 18, 2006, included two lectures:

“Cognitive Changes With Aging: How Much Is Too Much?”
Speaker: Michael Greicius, MD, MPH, Dept of Neurology, Memory Disorders, Stanford Univ

“The Big Picture of Maintaining Health — Medications, Tests and Safety At Home”
Speaker: Yusra Hussain, MD, Dept of Internal Med, Geriatrician, Stanford Hospital & Clinics

This email attempts to summarize some of the key points in those lectures and provide a web link to the handout.

Dr. Greicius said that one-tenth of people over 65 have Alzheimer’s Disease. One-third of people over 85 have AD. 70% of the dementia cases are AD. The most common non-AD dementias are Vascular Dementia, FTD, and LBD. According to the “nun study,” the more education you have, the less impaired you are than someone with less education for the same degree of AD.

There is a disorder known as Mild Cognitive Impairment (MCI). Half of those with MCI convert to AD every four years. Scientists are looking into who will convert and how this can be prevented. Neither Vitamin E nor Aricept helped treat MCI.

There are many reversible causes of memory loss including B12 deficiency, low thyroid, medication (anticholinergics including some medications for urinary incontinence, beta-blockers, enzodiazepines, opiates, anti-epileptics, some medications for neuropathy), depression, alcohol, and retirement.

In general, people in their 50s and 60s can handle less than half the alcohol they could handle in their 30s.

There are some cognitive IMPROVEMENTS with normal aging: emotionality, semantic knowledge (knowledge of the world), and vocabulary.

Dr. Greicius spoke about cognitive decline with normal aging. Related to that topic, he distributed an article from the journal Nature Review Neuroscience, Feb ’04, titled “Insights into the Ageing Mind: A View from Cognitive Neuroscience.” He said this was an excellent review of the topic. An abstract of the article can be found at: (The full article costs $30.)
http://www.nature.com/nrn/journal/v5/n2/abs/nrn1323_fs.html

What can be done to minimize cognitive decline? His guesses include living healthy, moderate alcohol consumption, and no cigarettes. He explored the possible role of NSAIDs and cognitive training in minimizing decline.

His recommendations include: all things in moderation; minimize cardiovascular risk factors; sell your TV; read, dance, exercise; spend more time with friends and family; participate in medical research. Two journals did a review of ginkgo biloba studies. They showed no benefit. He doesn’t recommend taking extra Vitamin E.

Dr. Greicius said that there is a GRAIN of truth only to the layperson’s notion that for the clock test (part of the 4-hours of neuropsychological testing) those with AD can draw the clock and those with LBD cannot. He said that generally speaking those with LBD have visuospatial impairment early on, which is why they can’t draw the clock. But not all those with LBD have visuospatial impairment at the time of diagnosis. Another point: those with late stages AD can’t draw the clock either.

Dr. Hussain said that most people get a serious chronic condition at the age of 55. These can include geriatric syndromes, which are urinary incontinence, MCI, and depression.

If you think your health is excellent, you will live longer. If you think your health is merely good, your lifespan is normal/average.

About half of all deaths are attributable to preventable factors.

A healthy lifestyle includes: maintaining social life; being active each day; eating well; avoiding tobacco and excessive alcohol intake; following up on periodic health examinations and screening tests.

The best diet is rich in fruits, vegetables, whole grains, and nuts. One should have moderate consumption of polyunsatured fatty acids, omega 3 fatty acids, protein and dairy. One should have low consumption of carbs and animal fats. She does not recommend taking a multi-vitamin with antioxidants as a supplement. She says that antioxidants should be part of the diet.

In order to maintain cognitive function, she said that the “nun study” shows that it’s important to have a purpose in life and to stay busy with family and friends.

Frailty cannot be reversed.

That’s it! I didn’t attend the third lecture nor was I very interested in it so I won’t be emailing out notes from that one.

Regards,
Robin

Caregiving for those with Dementia – Class Notes

This post will be of interest to those who are caring for people with dementia…

I attended the 4-week class on caregiving for those with dementia at Avenidas in Palo Alto this month (May ’06). The class, called “It Takes Two: Dealing with Dementia-related Behavior,” was run by the Family Caregiver Alliance (caregiver.org), an SF-based organization that offers classes, resources, and counseling to those throughout the SF Bay Area and nationally.

A Dementia Fact Sheet was handed out. It states:

“[The] term ‘dementia’ is used by the medical community to describe patients with impaired intellectual capacity… Signs of dementia include short-term memory loss, inability to think problems through or complete complex tasks without step-by-step instructions, confusion, difficulty concentrating and paranoid, inappropriate or bizarre behavior. Clinical depression also may accompany early signs of dementia.”

In the first class, we discussed dementia. I think I wrote these statistics down correctly:
* 10% of people older than 65 have AD or dementia
* over the age of 85, almost 50% of the people have AD or dementia

There are reversible dementias and irreversible ones. The importance of getting a diagnosis was made clear by the fact that some dementias are reversible. In the first class, different diseases with dementia components were discussed, beginning with AD. LBD and PSP were both discussed.

Though it was not distributed, I think this publication summarizes the information presented the first day of class:

www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=569

Lots of FCA-authored materials were handed out at the first class, including:

1. Dementia – Fact Sheet: I can’t find this on their website. It lists possible causes of dementia (deteriorating intellectual capacity) including reactions to medications, emotional distress, metabolic disturbances, nutritional deficiencies, etc.

2. Alzheimer’s Disease – Fact Sheet: this is available on their website at:

www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=567

The fact sheet breaks AD into three stages and describes the dementia-related behaviors of each stage.

Note that the Dementia with Lewy Bodies – Fact Sheet on their website is woefully out of date. I’d suggest getting the latest info from the LBDA website. In particular, this brochure is excellent for caregivers, MDs, etc:

www.lewybodydementia.org/docs/brochure/3_brochure.pdf

3. Tips for Interacting with a Person with Dementia: I can’t find this on their website. The tips are:
* Reassure, reassure, reassure
* Try to remain calm
* Do not disagree with made up stories
* Give compliments often
* Respond to the person’s feelings, not their words
* Use distractions
* Do not try to reason with the person
* Give yourself permission to alter the truth
* Avoid asking questions that rely on short term memory
* Break down all tasks into simple steps
* Respond calmly to anger, don’t contradict or argue

4. Tips on Interacting with Persons with Alzheimer’s Disease or other Dementias (pages 1-3) and Qualities of Friendship in Relation to Someone with Dementia (page 4). I can’t find this on their website.

5. Principles for Understanding and Communicating with a Person with Dementia. I can’t find this on their website. The five principles are:
* Knowing and accepting the cognitive limitations of the person will help you set realistic expectations of the person’s behavior.
* Understand that OUR thoughts, attitude, and actions significantly impact on the behavior of the person with dementia.
* Recognize that behavior, even in a confused person, more likely results from a cause. It is triggered.
* Learn that to enhance communication with a person with dementia requires a commitment to remain “connected” regardless of the content of the conversation.
* Understand that changing behavior takes time, effort, and patience. Reward yourself often for working towards change.

6. A Reference List for Families and Professionals – Caring for Individuals with Dementia: I can’t find this on their website. It’s a list of books on family caregiving and dementia care.

7. Caring for Adults with Cognitive and Memory Impairments – Fact Sheet: this is available on their website at:

www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=392

The other three classes are hard to summarize. Basically we discussed and role-played communication strategies based on the tips and principles listed above.

This class will certainly be taught again in the Bay Area. It was taught in April in SF, I believe. And then the May class was in Palo Alto. My guess is that it will be taught again in the fall. You can check in periodically with the FCA’s website listing of classes to learn what’s available:

www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=1001

Regards,
Robin

Namenda (memantine) and PSP

A group member with progressive supranuclear palsy asked me recently what I knew about two Alzheimer’s drugs — Aricept and Namenda — in treating PSP. I posted a few days ago about Aricept, which is an acetylcholinesterase inhibitor.

Here is a link to that post:

https://www.brainsupportnetwork.org/aricept-and-psp-2001-study

This post is about Namenda, which is a chemical receptor agonist that appears to work by regulating the activity of glutamate, a messenger chemical in the brain. Glutamate plays an essential role in learning and memory.

I found an interesting fact sheet on Namenda from the Alzheimer’s Association:

http://search.alz.org/Resources/FactSheets/FSmemantine.pdf

According to this Alzheimer’s Association publication, Namenda is approved for moderate to severe AD, which is defined as initial scores ranging from 3 to 14 on the Mini-Mental State Exam or MMSE. The FDA’s approval was based on the evidence provided by two drug-company studies. In one study, those taking Namenda showed a small but statistically significant benefit in a test of their ability to perform daily activities and on the Severe Impairment Battery when compared to those taking a placebo. In another study of people who had previously taken Aricept for 6 months, those taking Namenda showed a statistical benefit in performing daily activities and on the Severe Impairment Battery when compared to those taking a placebo and Aricept.

From this publication I learned that Namenda is NOT approved for mild Alzheimer’s. I will take this information to my father’s neurologist next month. My dad has mild to moderate dementia, I would say, yet he’s been on Namenda for 2 years.

Robin

“Health Challenges & Recommendations for the Older Adult”

Stanford University (stanford.edu) sponsored a 3-part series on geriatric health in May. The first evening, May 11, 2006, included this lecture:

“Health Challenges & Recommendations for the Older Adult”
Speaker: Peter Pompei, MD, Assoc Prof of Geriatric Medicine, Stanford Univ

Local support group member Karen D. gave me her notes on the lecture. This post attempts to summarize some of the key points in that lecture.

Robin
——————

Karen’s Notes from

“Health Challenges & Recommendations for the Older Adult”
Speaker: Peter Pompei, MD, Assoc Prof of Geriatric Medicine, Stanford University
May 11, 2006

Dr. Pompei distributed a document on “Aging parents: Five warning signs of health problems.” You can find a copy of this online at:

mayoclinic.com/health/aging-parents/HA00082

The five warning signs are:
* unintended weight loss
* difficulties maintaining their home (so that the home becomes unsafe)
* failure to keep up with daily routines and personal appearance
* poor mood (down or depressed)
* difficulty getting around (which means that they have difficulty caring for themselves)

Dr. Pompei introduced the concept of homeostenosis. When we were young, we could adapt to stressful environments. But when we’re older, we can’t bounce back.

Dr. Pompei also distributed an article in the April 2006 issue of Geriatrics magazine, titled “Health promotion in older adults: Promoting successful aging in primary care settings.” You can find a copy of this online at:

www.geri.com/geriatrics/data/articlestandard/geriatrics/152006/318873/article.pdf

The article states that:

“Although achieving and maintaining health is influenced by many factors,
one of those is within the grasp of almost everyone: Making wise health
choices… (These) choices…can be summarized by an easy to remember
phrase: eat right, eat less, and exercise more.”

(That particular issue of Geriatrics magazine has a number of interesting articles, including one on exercises for the frail and home bound:
www.geri.com/geriatrics/data/articlestandard/geriatrics/202006/327139/article.pdf.)

Dr. Pompei recommended two websites with health information:

American Geriatrics Association
www.healthandage.com

Merck Foundation
www.merckmedicus.com

The lead article on the American Geriatrics Association website is how
physical fitness can fight off dementia.

During the Q&A period, someone asked how a patient should be told he/she is losing it. Dr. Pompei’s answer was: be forthright but show that the patient may not understand.

“Foiling Chemical Event May Combat Brain Breakdown”

This post is about an interesting article on preventing misfolded protein accumulations (which occurs in AD, PD, and many related diseases), protecting an enzyme (called called protein disulphide isomerase), and stopping a chemical (nitric oxide) from wreaking havoc in the brain.

The Bloomberg News article talks about a study just published in the journal Nature. The aarticle notes:

“While previous studies showed that nitric oxide can be involved in the degeneration of brain cells through a variety of mechanisms, the new study shows a previously unrecognized relationship between the chemical and protein misfolding.”

Here’s a link to the article:

www.bloomberg.com/apps/news?pid=10000082&sid=avdCh4_MT55U

Foiling Chemical Event May Combat Brain Breakdown, Study Says
Bloomberg.com
May 24, 2006

Aricept and PSP (2001 study)

A group member with progressive supranuclear palsy (PSP) asked me recently what I knew about two Alzheimer’s drugs — Aricept and Namenda — in treating PSP.

I’ve done a little bit of digging on the subject today and found a randomized, double-blind, placebo-controlled study funded by NIH done in 2001. The abstract follows.

Bottom line — these MDs do not recommend that those with PSP take Aricept (donepezil) because although the “Double Memory Test” scores will improve, status of activities of daily living (ADL) and mobility scores will worsen significantly.

I will search a bit on Namenda over the next few days. Since Namenda is NOT an acetylcholinesterase inhibit (Aricept is), this study will not apply.

Robin

———————–
www.neurology.org/cgi/content/abstract/57/3/467
Randomized placebo-controlled trial of donepezil in patients with progressive supranuclear palsy

I. Litvan, MD; M. Phipps, BA;, V. L. Pharr, MA; M. Hallett, MD; J. Grafman, PhD; and A. Salazar, MD

From the Cognitive Neuropharmacology Unit (Dr. Litvan, M. Phipps, and V.L. Pharr) and the Defense and Veteran Head Injury Program (Dr. Salazar), Henry M. Jackson Foundation; and the Medical Neurology Branch (Dr. Hallett) and the Cognitive Neuroscience Section (Dr. Grafman), National Institute of Neurological Disorders and Stroke, National Institutes of Health. (Robin’s note: Dr. I. Litvan is now at the University of Louisville in KY.)

Objective:­ There is no effective treatment for progressive supranuclear palsy (PSP). Because results of immunochemical and pharmacologic studies suggest that the cholinergic system may play a role in the cognitive and motor features of PSP, the authors investigated the effects of donepezil (10 mg/day), an acetylcholinesterase inhibitor, in 21 patients with PSP (mean age ± SD; 65.7 ± 4.7 years) by a randomized, double-blind, placebo-controlled crossover trial.

Methods:­ Donepezil and placebo were administered for 6 weeks each with a 1-month washout period. Patients were evaluated before and at the end of each treatment phase. Outcome measures evaluated neuropsychiatric, global cognitive, frontal, memory, motor, and activities of daily living (ADL) status.

Results:­ Two patients withdrew during the washout phase because of unrelated medical problems. Donepezil-induced systemic side effects were transient and generally mild. Because of worsening of motor function, three patients received 5 mg/day of donepezil. All patients achieved blood and CSF therapeutic levels of donepezil. While the patients were taking donepezil, their Double Memory Test scores improved, whereas their ADL/mobility scores significantly worsened.

Conclusion:­ The findings suggest that acetylcholinesterase inhibitors such as donepezil have at best selective, modest effects on cognition in patients with PSP. In light of its deleterious effects on ADL/mobility, donepezil is not recommended for this patient population.

“A Surprising Clue to Parkinson’s” (MIT Technology Review)

I saw an article in the May/June ’06 issue of Technology Review, an MIT publication, related to protein aggregations in those with PD and other diseases. What I found interesting was the fact that there is not scientific agreement over whether abnormal protein aggregations in the brain are a bad thing. The author says that the MIT biotechnology study demonstrates “that increased protein aggregation can improve the health of cells modeling neurodegenerative disease.”

That led to a related article published on the Technology Review’s website on 3/7/06. Excerpts from that March article:

“It’s easy to distinguish a healthy person from a person with advanced Parkinson’s: the Parkinson’s sufferer has large clumps of proteins in his or her brain cells. Scientists disagree, however, about the nature of these clumps. Some contend that they lead to the massive neuronal cell death and resulting movement disorders in Parkinson’s, others that the clumps are merely a byproduct of the disease — and some scientists contend that the clumps are actually protective, sequestering toxic proteins so they can’t hurt the cell. Mounting evidence points to the last possibility.”

“Existing research already suggests that the biggest clumps, known as inclusions, are helpful. Cells that form clumps of the mutant Huntington protein, for example, survive longer than clump-free cells. Now MIT scientists have discovered a compound that increases clumps in cell models of Huntington’s and Parkinson’s disease and makes the cells healthier. Scientists aren’t sure how the compound works, but they think it might be helping cells get rid of toxic forms of the proteins floating around in the cell by isolating them into clumps.”

Here’s a link to the older article:

www.technologyreview.com/read_article.aspx?id=16517&ch=biotech

A Surprising Clue to Parkinson’s
Drugs that boost the protein clumping that occurs during neurodegenerative disease could provide a new route to treatment.
Technology Review (MIT)
By Emily Singer
March 7, 2006

And a link to the newer article:

www.technologyreview.com/read_article.aspx?ch=biotech&sc=&id=16825&pg=2

A Curious Clue to Parkinson’s
Drugs that boost protein aggregation could provide a new route to treatment
Technology Review (MIT)
May/June 2006

PSP Research Study- NIH-Funded and Parkinson’s Institute is a Site

I just received this email from the Society for PSP (in Maryland) about an important NIH grant given to Dr. Irene Litvan, one of the top researchers in the US on progressive supranuclear palsy. One of the eight sites is The Parkinson’s Institute (thepi.org) in Sunnyvale. The site coordinator there is our friend Dr. James Tetrud, a neurologist with wide knowledge of PSP. (He spoke at the Society’s recent PSP Family Conference. He mentioned the arctic ground squirrel. Most of you received an email from me about that.)

If you are interested in participating in this PSP research study, please contact Whitney Rogers, the Clinical Coordinator for the main study and for the University of Louisville site in particular. Her contact info is: 502-852-4612 or [email protected]

I have just spoken with Whitney to get some general info; she is very nice. She explained that every person with PSP who wants to be involved in the study needs to bring with them two controls. The controls should: not have PSP, not be a blood relative, and be similar in age to the person with PSP (plus or minus 5 years). One control must be the same gender as the person with PSP; this is usually an in-law. The other control can be a different gender as the person with PSP; this is usually the spouse.

Please let me know if you do contact Whitney and run into some issues that the rest of the group should know about. Also, I’d appreciate knowing who eventually signs up to participate in this study!

Thanks,
Robin

PS. The “Mayo Clinic” mentioned below is the one in Jacksonville, FL.

Subject: NIH Grant to Irene Litvan
Date: Mon, 22 May 2006 13:10:25 -0400
From: CurePSP
To: Support Group Leaders

Movement Disorder Program Awarded Novel NIH Clinical Research Grant to Study Rare Neurodegenerative Disease

Dr. Irene Litvan, Raymond Lee Lebby Professor of Neurology and Director of the Movement Disorder Program has been awarded a $3.4 million NIH grant to study the genetic and environmental risk factors for progressive supranuclear palsy. Progressive supranuclear palsy (PSP) is the most common atypical parkinsonian movement disorder. Dr. Litvan will lead a team of movement disorder specialists from 8 sites across the country (Baylor, Case Western, Emory, Mayo Clinic, Parkinson Institute, Massachusetts General Hospital, University of Maryland) and basic science researchers (Duke, Johns Hopkins, Mayo Clinic, Washington University, University of Louisville), in determining the role of genetic, occupational and environmental components in the development of PSP. Specifically, this large case/control study that will involve 500 PSP patients and 1000 controls will seek to determine if there is an association between PSP and specific H1 tau genotypes, alpha-synuclein polymorphisms, parkin gene deficits or other gene-gene interactions. The study will also explore whether there is an association between PSP and occupational and or environmental chemical exposures functionally or structurally similar to known parkinsonian toxicants. This is the first major research award to focus on PSP.

The Movement Disorder Program has begun recruiting patients with PSP for inclusion in the study. Interested parties should contact the Movement Disorder Program at 502-852-4612. It is hoped that this major effort will in turn help find ways to prevent or treat this devastating disease.

Journal article on MRIs to distinguish PSP, MSA, and PD

This article in the Movement Disorder Society magazine (of the UK) is on using MRIs to distinguish between Progressive supranuclear palsy (PSP), Multiple system atrophy (MSA), and Parkinson’s disease (PD). Apparently the technique is most (only?) effective in later stages. This was published online on 4/6/06. The abstract is below.

Robin

——————————–

Regional brain volumes distinguish PSP, MSA-P, and PD: MRI-based clinico-radiological correlations
Dominic C. Paviour, MRCP, Shona L. Price, BSc, Marjan Jahanshahi, PhD , Andrew J. Lees, MD, FRCP , Nick C. Fox, MD, FRCP

Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are neurodegenerative disorders, each with a prevalence of around 5 per 100,000. Regional brain atrophy patterns differ in the two disorders, however, and magnetic resonance imaging is sometimes helpful in distinguishing them in the later stages. We measured whole brain and regional volumes, including cerebellum, pons, midbrain, superior cerebellar peduncle (SCP), and ventricular volumes as well as frontal and posterior-inferior cerebral regions in 18 subjects with PSP, 9 with MSA-P (parkinsonian phenotype), 9 with Parkinson’s disease (PD), and 18 healthy controls. Associations between these volumes, cognitive profiles, and clinical measures of disease severity and motor disability were assessed. Mean midbrain volume was 30% smaller in PSP than in PD or controls (P < 0.001) and 15% smaller than in MSA-P (P = 0.009). The mean SCP volume in PSP was 30% smaller than in MSA-P, PD, or controls (P < 0.001). Mean cerebellar volumes in MSA-P were 20% smaller than in controls and PD and 18% smaller than in PSP (P = 0.01). Mean pontine volume in MSA-P was 30% smaller than in PD or controls (P < 0.001) and 25% smaller than in PSP (P = 0.01). Motor disability was most strongly associated with midbrain volume, and more severe executive dysfunction was associated with reduced frontal volume. These distinct patterns of cortical and subcortical atrophy, when considered together rather than independently, better differentiate PSP and MSA-P from each other and also from healthy controls. © 2006 Movement Disorder Society