Alzheimer’s: Its causes, current treatment, and potentially promising research

Alzheimer’s Disease is the most common cause of dementia.

While it usually strikes older people, it can be seen in younger age groups as well.

Alzheimer’s causes several problems with cerebral functioning: memory loss, difficulty storing new memories, problems with language functions, depression, hallucinations, and problems with using mathematical functions, among others.

Alzheimer’s is progressive and leads to death about 5-10 years after diagnosis. Death usually occurs from disease-related causes (like pneumonia, cachexia, vascular diseases, etc.). Alzheimer’s may be the 5th or 6th leading cause of death in the US today.

Patients with Alzheimer’s develop an excessive amount of β-amyloid and tau protein in their brains. β-Amyloid forms the plaques that interfere with nerve signal transmission, among other things, and can be toxic to the nearby neurons. Tau protein acts to cause neurons to form neurofibrillary tangles and it too, is toxic to nerve cells. The areas of the brain most affected cause the results that are seen in the disease: memory loss, computational problems, etc.

What causes Alzheimer’s?

There IS a genetic component. The gene that contributes to the production of the plaques is found on chromosome 21. People with Down’s syndrome (Trisomy 21) have three copies of chromosome 21 and they produce about 2 times as much of this precursor that leads to the plaques which are a part of AD. They develop Alzheimer’s at an early age.

There are other genes on other chromosomes involved in the pathogenesis of AD, too. But genetics seems to only be part of the cause. Immune mechanisms seem to have a part to play, as do free radicals, diabetes, homocysteine, trauma to the brain and possibly other factors.

Alzheimer’s treatment

Treatment includes any of several drugs that may somewhat slow the progression of Alzheimer’s for a brief time but are unable to stop it.

Elderly Patient via Shutterstock

Elderly Patient via Shutterstock

One class of drugs are cholinesterase inhibitors. These inhibit the enzyme that breaks down acetylcholine (ACh), and allows more ACh to remain available to the neurons. As Alzheimer’s progresses, the amount of acetylcholine produced by the brain decreases. And ACh is important for proper memory function. As the enzyme that breaks down ACh gets blocked, ACh levels rise.

A different type of medication is also available, this one is an N-methyl D-aspartate (NMDA) antagonist. NMDA works by decreasing the amount of available glutamate in the brain. Higher than normal levels of glutamate can cause brain cell death.

Regrettably, these drugs, even when used in combination, only delay the inevitable. Perhaps they will allow the patient to be able to continue to be able to use the bathroom on his own for several more months. It makes things a little easier on the patient and family, and helps the patient maintain some dignity.

New Alzheimer’s treatments on the horizon

However, there is some interesting information available, including a new treatment in clinical trials.

First is a vaccine. Researchers found several years ago that in mice models of Alzheimer’s, immunologically stimulating the mice by using fragments of proteins found in Alzheimer’s caused improvements in memory, reduced inflammation, may have healed and/or caused new neurons to form and helped clear away plaque deposits.

Glatiramer, a drug that is given to patients with multiple sclerosis, seemed to produce similar results. Glatiramer is now just starting human trials in patients with Alzheimer’s. So the possibility exists that this immunomodulatory drug may do more than just slow the inevitable course of the disease. Groups of patients are now starting to receive the drug via injection, and they will be carefully observed to see if cognitive function improves and if plaques diminish.

A vaccine was also developed and clinical trials were begun. But there were side effects from the vaccine that caused the trial to be ended. Research continues on how to make a vaccine that would avoid those complications. But that did, indirectly, lead to another therapy under study. Researchers intravenously infused pre-made anti-amyloid antibodies into Alzheimer’s patients. Research with this technique is continuing.

In a paper just published this month, a research team has found that the areas of the brain most compromised by beta amyloid and tau protein also have a much higher level of iron in those areas. Alzheimer’s preferentially attacks certain areas of the brain, like the hippocampus early in the disease and spares others, like the thalamus, until later.

In the brains studied, the hippocampus’ iron levels were substantially higher that iron levels in the thalamus. This will lead to further research and may provide some additional potential treatment for Alzheimer’s. Though that would be years away.

So, while current therapy for Alzheimer’s Disease is only able to temporarily slow its progression, there are some drug studies in progress of therapies that may be able to do much more.


Mark Thoma, MD, is a physician who did his residency in internal medicine. Mark has a long history of social activism, and was an early technogeek, and science junkie, after evolving through his nerd phase. Favorite quote: “The most exciting phrase to hear in science... is not 'Eureka!' (I found it!) but 'That's funny.'” - Isaac Asimov

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  • Djena

    Thank you for this informative article on a disease that is growing rapidly in America. We should all be very concerned about Alzheimer’s Disease as the cost of caring for those it will impact over the next 20-30 years has the potential to bankrupt Medicare. We really need to find a cure. Support research by donating to the Alzheimer’s Association.

  • http://adgitadiaries.com/ karmanot

    Totally on topic. The stories we carry forth and share can be healing many wounds.

  • http://adgitadiaries.com/ karmanot

    OMG, imagine the horror of rooming with a demented former assassin of the Special Forces.

  • Hue-Man

    Alzheimers patients present many very difficult care issues: my grandmother was very angry and physically violent as she realized that her mental health was deteriorating. Once the disease had progressed, she was docile but incapable of caring for herself. Her brief periods of lucidity were, in some ways, more difficult because she’d decide to move back into her own home and get away from all those old sick people!

    Then this story from this past weekend: “After the death of an elderly man [at the hands of his 95-year old roommate] at a Vernon [British Columbia] care home on Sunday, a woman, whose husband died after he was attacked at a care home in Kamloops, says the province needs to do a better job of protecting seniors with dementia from violence at the hands of other patients.” http://www.cbc.ca/news/canada/british-columbia/story/2013/08/20/bc-widow-wants-improved-care-home-safety.html

    Postscript (I’ve deliberately left out his name): The 95 year old charged with murder “…was a platoon sergeant in world war 2 in an elite commando unit known as the Devil’s Brigade. He was shot twice in Italy and went on to fight in France. In 2007 [he] was awarded a Bronze Star from the US Army.” http://www.cbc.ca/kamloops/index.html

  • HolyMoly

    A couple of links to elaborate.

    (1) Regarding the removal of diacetyl by popcorn manufacturers (the reason is for the compound’s link to some sort of respiratory disease, but it still goes to show that adding something artificially to a food product, though it may occur naturally in other food products, can lead to health issues):

    http://www.nytimes.com/2007/09/06/business/06popcorn.html?_r=0

    (2) The reason behind removal of diacetyl from store-bought popcorn:

    http://www.huffingtonpost.com/2012/09/20/wayne-watson-popcorn-lung-lawsuit_n_1898769.html

    Most likely the guy ate popcorn quite frequently (thanks to the invention of home entertainment centers — maybe he should sue them too ).

  • HolyMoly

    No, not “scary” or “evil, evil, evil,” as you say (I do enjoy the occasional strawman). I did say to exercise caution (i.e., use moderation or cut it out, especially if your family has a history of Alzheimer’s).

    Though it does occur naturally in butter, when it is added to a product to create a butter-like flavor, it is likely added in larger amounts than what is normal, to make up for the fact that there’s not any actual butter in the product (1). Scary? No. Evil? No. Dangerous? In a manner of speaking, everything becomes a poison when taken in excess (2).

    (1) Popcorn manufacturers such as Orville Redenbacher (spelling?) and Pop Weaver (the kind I eat), after having been advised to reduce diacetyl, have removed the chemical altogether.

    (2) Paracelsus: “Everything is poison; there is poison in everything. Only the dose makes a thing not a poison.” Take, for example, wine. Drinking a glass of wine every day is beneficial to your health, but drinking a bottle of wine every day will kill your liver — and you — in the long run.

  • docsterx

    That’s a cool story and fairly typical. Some memories/functions seem to be preserved well nto late dementia, while others go early on.

  • docsterx

    There are a couple of articles that aren’t as positive about metformin, but several say it does have some promise. Here’s an abstract of an article about to be published that shows several medications that might act to inhibit AD. It’s written in slightly advanced Layman.

    Diabetes Metab Res Rev. 2013 Jul 18. doi: 10.1002/dmrr.2442. [Epub ahead of print]

    Type 2 Diabetes Mellitus and Alzheimer’s Disease: from physiopathology to treatment implications.

    Moreira RO, Campos SC, Soldera AL.

    Source

    Instituto
    Estadual de Diabetes e Endocrinologia (IEDE) e Pontifícia Universidade
    Católica do Rio de Janeiro (PUC-RJ), Rio de Janeiro, Brasil.

    Abstract

    Alzheimer’s
    Disease (AD) is the most common cause of dementia worldwide. Type 2
    Diabetes Mellitus (T2DM) is a disease characterized by insulin
    resistance (IR) and progressive β cell failure, and affected individuals
    are at increased risk to develop several forms of cognitive
    dysfunction, including AD. Different mechanisms have already been
    identified linking visceral obesity, IR and AD. Insulin resistance is
    associated with a decrease in glucose uptake by neurons, an increase in
    Amyloid β production and secretion, in the formation of senile plaques,
    and also in tau protein phosphorylation. Other mechanisms also include a
    decrease in Insulin Degrading Enzyme (IDE) activity and an increase in
    oxidative stress secondary to hyperglycemia. Taken together, these
    mechanisms suggest that drugs used to ameliorate hyperglycemia and IR
    may also have beneficial effects in diabetic patients with AD. Indeed,
    manuscripts investigating the effects of metformin, thiazolinediones,
    leptin, GLP-1 therapies, insulin and bariatric surgery in cognition and
    AD have been published with very promising results, and may indicate an
    alternative approach for these patients. This article is protected by
    copyright. All rights reserved.

    This article is protected by copyright. All rights reserved.

    KEYWORDS:

    Alzheimer’s Disease, Cognition, Diabetes Mellitus

    PMID:23868462 [PubMed - as supplied by publisher]

    When the article gets published, you may be able to get a free copy by contacting your local library. Even if they don’t subscribe to ATHENS or something similar, they may be able to get if for you.

  • cole3244

    i have dealt with alzheimer’s personally with my mother and it is not something you want to experience.
    i wouldn’t wish the disease on my worst enemy and i hope a cure is found eventually.

  • http://www.americablog.com/ Naja pallida

    All forms of age-related dementia are truly scary. My only experience with a family member with such a condition was an amazing one though. I actually met my grandmother’s grandmother in the early 1980s. She was around 100 years old, and came to live with my grandparents because all her previous caregivers had died. She had some form of dementia for many years. I’m not sure if it was Alzheimer’s or something else, but if you left room and came back, you’d have to reintroduce yourself because she wouldn’t remember you. It was especially bad because my father and all his brothers were around at the time, and she was scared to death of strange men in the house. So my grandmother had to spend pretty much every waking moment at her side, explaining things to her over and over, and keeping her calm as we all tried to go about our daily business.

    The amazing thing was, she was a quilter all her life and made the most intricate hand-embroidered quilt squares. I was given a Spirograph as a gift that spring, and was playing with it on the floor while she was quilting nearby in a rocking chair. She pointed down at me doodling designs and said “If you make me a pattern, I’ll quilt it for you.” She didn’t get the quilt done before she died, about three months later, but as someone who doesn’t really have a whole lot of connection with family, it was just one of those little things that has stuck with me. As long as I knew her, she was completely lost in her own mind, but she could always quilt like you wouldn’t believe.

    Sorry for veering off topic, but I just thought I would share. :)

  • Hue-Man

    `A drug to watch is the diabetes medication Metformin. I’ve been following this because Alzheimers appears hereditary and my grandmother had it.

    “Could metformin, the most widely used diabetes drug in the world, be useful for fighting a number of health problems?

    Early research suggests the decades-old drug can slow cancer, reduce heart disease and maybe even limit the ravages of Alzheimer’s. Now, a new study in mice finds that it can extend life by a number of weeks — the human equivalent of 3-4 years.” http://www.usatoday.com/story/news/nation/2013/07/30/diabetes-drug-metformin/2599379/ (I chose this as it’s from last month and written in “layman”)

    The research studies range from “metformin may be a treatment for Alzheimers” to “metformin may cause Alzheimers” and are typically based on non-human test subjects. It’s worth monitoring the research literature because the drug is wisely used, has well-studied side effects (vs. untested brand new drugs) and is inexpensive.

    BTW, did I mention my grandmother had Alzheimers? Just kidding.

  • http://adgitadiaries.com/ karmanot

    Excellent article Doc——well done!

  • docsterx

    Brain slices. Normal brain on the left, severe Alzheimer’s Disease on the right. Not the loss of brain mass and increased size of the ventricles (holes) in the Alzheimer’s brain. There are other, more subtle changes, too, on close inspection.

    http://alzheimers.about.com/library/blbrain.htm

  • docsterx

    Since I wrote the above, some additional news has come out concerning research for another site to attack AD. Most of the anti-Alzheimer’s treatments have focused on the ß amyloid to either prevent its formation or remove it. Research is now starting to look ad doing something similar for tau protein. In animal models, decreasing the concentration of tau causes fewer neurofibrillary tangles and seems to help maintain relatively normal cerebral function better.

    People with diabetes have a higher risk of developing dementia. The increase in risk to develop dementia seems to be directly related to average levels of blood glucose. Roughly, the higher the glucose level the higher the risk of dementia. For diabetics who had average daily blood sugars of 190 mg/dL (normal glucose levels are about 65-105 mg/dL) their risk of developing dementia increased up to 40% higher than people with normal glucose levels. Regular exercise seems to decrease the risk of dementia possibly by acting to normalize blood glucose levels.

  • Monoceros Forth

    The “something called diacetyl” is also, along with the related compound acetoin, what gives natural butter its smell and flavor. Just pointing that out before you play the “scary chemicals with weird names they must be evil evil evil” card again.

  • http://AMERICAblog.com/ John Aravosis

    Oh, actually I’d read something recently about artificial butter flavors. I hadn’t thought of the movie popcorn stuff, though I don’t eat it anyway. Interesting.

  • HolyMoly

    Another possible cause..or maybe something that increases your odds if you’re genetically predisposed:

    Movie theater popcorn butter:

    http://www.webmd.com/alzheimers/news/20120808/popcorn-butter-flavorant-linked-to-alzheimers

    For anyone who doesn’t have the time to read the link, it’s not actual butter that goes on the popcorn, but some sort of butter-flavored chemical concoction that contains something called diacetyl, which in studies has been shown that it affects natural chemical reactions in the brain in the same way as those suffering from Alzheimer’s.

    Forgo the butter when you go to the movies; go plain or add just a little salt if you want a little seasoning.

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