Seeing Alzheimer's Through Art

William Utermohlen is an artist who died in 2007, twelve years after being diagnosed with Alzheimer's dementia in 1995. His story is discussed in this article in Urban Times. The art that he created during his descent into dementia very graphically tells the tale of his disease.

1996

1997

1998

1999

2000

'All right,' said the Cat; and this time it vanished quite slowly, beginning with the end of the tail, and ending with the grin, which remained some time after the rest of it had gone.

'Well! I've often seen a cat without a grin,' thought Alice; 'but a grin without a cat! It's the most curious thing I ever saw in my life!' 

~Lewis Carroll, from Alice's Adventures in Wonderland


[sorry, accidentally had Comments turned off... fixed it]

Conscientious Nuns Less Likely to Get Alzheimer's Disease

First I got an email about this from Medscape. Then I saw it in the Wall Street Journal's Health Blog. Then I clicked through to the abstract from the Archives of General Psychiatry.


So there's this prospective study of Catholic clergy--priest, nuns, and brother-- called The Religious Orders Study at Rush University, where the participants have yearly physical and psychological exams and agree to donate their brains for autopsy at the appropriate time. Wow. The Religious Orders Study has been going since 1993 and is funded by the National Institute on Aging.

Okay, so Jacob Goldstein at the WSJ blog tells us:

A high conscientiousness score — which the authors describe as reflecting a “tendency to control impulses and be goal directed” — was associated with an 89% reduction in the risk of disease compared with a low score, even after accounting for age, sex and education.

By 'sex' I think he means gender.

At any rate, this study made me think of my dear friend ClinkShrink, pictured above, who a) is often mistaken for a nun and b) is very conscientious.

I'm hoping this bodes well for her brain. If not, I'll still be her friend.

FDA Drugs: November 2006

2007: Mar | Feb | Jan . . . 2006: Dec | Nov | Oct | Sep

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Just a quick list of psychiatry-relevant FDA and related notices...

• More Ambien (zolpidem) generics (and here) get tentative approval. Sanofi's patent expired on Oct 21, 2006, but they triggered an automatic 6-month extension by applying for pediatric use. We should start hearing about generic Ambien around April or May. The first approved generic manufacturer gets an automatic 6-month exclusivity before the flood gates open up, and other manufacturers can get into the game. There are about a dozen manufacturers all lined up for tentative approval.


• Phase I results promising for NGX426. NGX424 gets coverted in the body to tezampanel, an AMPA/kainate receptor antagonist, which makes it a non-narcotic pain medicine. The company, TorreyPines, seems to be looking at indications for migraines and neuropathic pain, though this class of drug may be useful on epilepsy and anxiety, as well.


• Drugs to turn on specific genes. This is one of the new holy grails. As described in the linked PNAS article, using RNA interference techniques, you make a little piece of double-stranded RNA (dsRNA) that is designed to bind to a specific gene, say, the gene that contains the instructions for making amyloid precursor protein (APP), which is involved in causing Alzheimer's dementia, or maybe the gene that codes for a particular variant of the CETP protein, which has been associated with increased longevity. According the article, sometimes this technique will silence a gene, and sometimes it will crank up the volume. Drugs of the future would be used to selectively turn on, off, up, down genes, like fiddling with 100,000 dials on a huge mixing board, trying to get just the right mix. A fascinating, but scary, proposition.


• Mirapex (pramipexole) approved (label .pdf) for Restless Legs Syndrome. This is old news now, thanks to the marketing blitz on this indication.


• Generic Zyprexa (olanzapine) gets tentative approval. There are now 5 companies with approved versions of generic Zyprexa, waiting to launch when either Lilly's patent expires (2011) or someone successfully challenges their patent application (now in process).


• Rimonabant (brands Acomplia or Zimulti) approved in Mexico. The sexy new diet drug is already approved in Europe, and is now on our shores. Rimonabant is a CB1 cannibinoid receptor antagonist, so it will also block the munchies from smoking marijuana. Sanofi Aventis has already submitted a new drug application to the U.S. FDA, followed by a resubmission in October.


• Seroquel marketing warning letter. AstraZeneca received an FDA letter warning that they violated the rules by underemphasizing the risk of diabetes with Seroquel in a piece of marketing material. They also failed to note some other risks.


• Warning: Tamiflu side effects - delirium, self-injury. Roche and FDA sent out notification letters warning of reports about self-injury and delirium occurring in people, especially children, who have the flu and take Tamiflu. They note that these reactions may also occur from the flu itself.


• Warning: Methadone side effects - cardiac, breathing, death. FDA put out a public health advisory warning of "reports of death and life-threatening adverse events such as respiratory depression and cardiac arrhythmias in patients receiving methadone. These adverse events are the possible result of unintentional methadone overdoses, drug interactions, and methadone's cardiac toxicities (QT prolongation and Torsades de Pointes)."

Search the FDA's "Orange Book" for more drug data.

technorati tags:ambien, NGX426, FDA, iRNA, insomnia, mirapex, pramipexole, zolpidem, RLS, zyprexa, olanzapine, rimonabant, acomplia, zimulti, seroquel, quetiapine, tamiflu, methadone, methadon, psychiatry, psychology, medications

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Methuselah's Genes

Two interesting new research pieces came out this past week or so on aging and dementia.

First, this piece about a gene which is found more often in folks who live 100 years, suggesting that people with the val-val variant of the CETP gene (cholesteryl ester transfer protein) may have a better shot at living a longer life. Centenarians with this genetic variant were also five times less likely to have dementia. The gene, found on Chromosome 16 (OMIM), produces a protein involved in lipid metabolism which results in larger, less sticky, cholesterol particles. The article came out in today's Neurology.

I looked in PubMed for similar articles from this author (Barzilai) and found this April 2006 article in PLoS Biology looking at several longevity-related genes in this same population. This article describes two genes which are more prevelant in really old people: the val/val (also known as I405V) variant of CETP and the -641C variant of the APOC3 gene (another one that deals with lipids).

Here's what's really cool. This guy has gathered this big group of centenarians and is doing genome-wide scans to determine which genes may be associated with longer (and healthier) lives. This work comes out of Albert Einstein's Institute for Aging Research.

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The second item is the NEJM article, from Gary Small at the UCLA Center on Aging, which showed that a molecule (FDDNP) binds to the amyloid plaques and tau protein tangles which are characteristic for Alzheimer's disease. After an injection of this experimental tracer chemical, a PET scan can then show where this stuff is in the brain. If there's enough of it, and in the right places, chances are good that you have (or are developing) Alzheimer's dementia.

This is just a research tool, at the moment. Neither this imaging tool, nor the above genetic tests, can be used clinically in the assessment of dementia risk or diagnosis. Maybe one day.

technorati tags:aging, longevity, brain, dementia, Alzheimer's, genes, FDDNP, APOC3, CETP, PET, UCLA, Einstein, psychiatry

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FDA Drugs: October 2006

2007: Mar | Feb | Jan . . . 2006: Dec | Nov | Oct | Sep

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Just a quick list of relevant FDA and related notices...

Europe approves Chantix: FDA approved this drug in May, but I have yet to see ONE patient on it. This is a unique, anti-smoking drug, so I figure it would be going like gang-busters by now. What's up with that?

Generic Zyprexa: Generic-maker Roxane has received "tentative approval" to make generic olanzapine. This Lilly drug is usually one of the top 3 most costly line-items in each state Medicaid pharmacy budget. The problem with "tentative" approvals is that there remain many hoops for Roxane to jump through, including patent battles, before they can get this to market. Lilly's patent expires in 2011, so it may be a long battle.

Johnson&Johnson has received an approvable letter for their new schizophrenia drug, paliperidone. Unfortunately, it's not much of a new drug. Risperdal (risperidone) get converted to paliperidone in the liver, so the new drug is pretty much the same as the old one. But since Risperdal comes off patent soon, this new drug provides more shelf-life on this product. I figure most will stick with the older, cheaper drug. For more on this, and a great blog I just discovered, go to David E. Williams' Health Business Blog.

First Autism Drug: Janssen (a J&J subsidiary) received a new indication for "irritability associated with autistic disorder" for Risperdal (there are some concerns). That's two firsts. First drug for autism. First drug for "irritability". This really opens up a whole new horizon. It will now be a race to get a drug approved for "agitation associated with dementia". This would be a block-buster!

Severe Alzheimer's Dementia indication approved for Eisai's Aricept (donepezil). It used to be just mild to moderate dementia.

Seroquel for Bipolar Depression: AstraZeneca has received a new indication for "treatment of major depressive episodes associated with bipolar disorder." I think Lamictal is the only other one with this indication (correct me if not).