Antidepressants, Alzheimer’s and Brain Injuries: making bad worse


What we knew:lights-1088141__340

  • Use of antidepressants with Alzheimer’s patients increases the risk for falls and hip fractures
  • There is a protein found in the brain cells of persons with dementia and brain injuries that causes the Axon in the cell (electronic message transmitter) to swell and shut down. This protein is absent from normal cells. Elimination of the protein can cause the axon to start functioning again. (References are in previous blog.)

What the University of Eastern Finland has added to what we know:

  • Use of antidepressants with Alzheimer’s patients results in an increased incidence of traumatic brain injuries among these patients

The mechanism for the injury is probably falling. With slower mental processing and thus slower reflexes, these patients are less able to protect themselves when falling. That means a higher rate of concussions.

This ties back to another previous post on this blog — “deprescribing”. Drugs may have a value in one stage of a person’s life and be counterproductive at another stage. Doctors know how to prescribe drugs, but there are few protocols (apart for drug interactions) regarding when to stop taking a drug.  There is a group in Canada developing guidelines for deprescription, and while NIH has published articles on the topic, I’m not aware of any similar projects to develop guidelines in the US. Some US physicians appear to be doing this on an ad hoc basis.

I suspect deprescription is not a popular topic among pharmaceutical executives, but it needs to be addressed. Continuation of unnecessary medication is just one of many factors that bloats medical costs in the US — and why spending level no longer indicates quality of care. Unnecessary medication poses risks to some patients.


  1. Heidi Taipale, Marjaana Koponen, Antti Tanskanen, Piia Lavikainen, Reijo Sund, Jari Tiihonen, Sirpa Hartikainen, Anna-Maija Tolppanen. Risk of head and traumatic brain injuries associated with antidepressant use among community-dwelling persons with Alzheimer’s disease: a nationwide matched cohort study. Alzheimer’s Research & Therapy, 2017; 9 (1) DOI: 10.1186/s13195-017-0285-3
  2. University of Eastern Finland. “Antidepressant use increases risk of head injuries among persons with Alzheimer’s disease.” ScienceDaily. ScienceDaily, 9 August 2017. <>.
  3. Gurusamy Sivagnanam, “Deprescription: The prescription metabolism,”
    J Pharmacol Pharmacother. 2016 Jul-Sep; 7(3): 133–137.
    doi:  10.4103/0976-500X.189680
  6. Joaquín Hortal Carmon, IvánAguilar Cruz, FranciscoParrilla Ruiz, “A prudent deprescription model,” Science Direct, Medicina Clínica, Volume 144, Issue 8, 20 April 2015, Pages 362-369.


Restoring Brain Function


I don’t usually write about early or animal-phase research, but this is potentially quite important for those dealing with dementia, related illnesses, and brain injury.

The protein amyloid beta is believed to be the major cause of Alzheimer’s disease. This protein basically clogs cells and causes neurotransmitters in cells to become hyperactive, generating noise that interferes with thinking and memory.

That leaves three interesting questions:

  • What triggers the production of this protein?
  • Is there a way to shut production of the protein down?
  • What happens if we do?

A team of researchers at the University of Munich (Germany) have identified one such substance, of a category known as BACE inhibitors, that is effective in reducing the amount of amyloid beta in brain cells. Tested in mice, with the inhibitor included in their food for eight weeks, the result when beyond what the researchers expected:

As expected, the mice had less amyloid beta in their brain after this period, since its production was inhibited. However, the effect of the substance was much more far-reaching: the animals’ brain functions actually normalized. There were fewer hyperactive nerve cells, and the slow-wave brain patterns once again resembled those in healthy mice. A key finding for the scientists was the observation that the animals’ memory also improved.
(1 is the original journal article; 2 is the report in Science Daily for non-technical readers.)

Basically, functioning was restored to a level comparable to healthy animals who had never had the disease.

These researchers are planning a human clinical trial.

What makes this a really big deal is that amyloid beta is also a factor in traumatic brain injury (TBI). This presents a possible and quick route to restoration of brain function for both dementia and TBI victims. It is not a “cure” for either, but for the victim and their family, the potential is life-changing.

It’s amazing what you can find buried in a list of breaking scientific news.


  1. A. D. Keskin, M. Kekuš, H. Adelsberger, U. Neumann, D. R. Shimshek, B. Song, B. Zott, T. Peng, H. Förstl, M. Staufenbiel, I. Nelken, B. Sakmann, A. Konnerth, and M. A. Busche. BACE inhibition-dependent repair of Alzheimer’s pathophysiology. Proceedings of the National Academy of Sciences, 2017 DOI: 10.1073/pnas.1708106114
  2. Technical University of Munich (TUM). “Dementia: BACE inhibitor improves brain function: BACE inhibitor successfully tested in Alzheimer’s animal model.” ScienceDaily. ScienceDaily, 28 July 2017. <>
  3. . Amyloid imaging with carbon 11-labeled Pittsburgh compound B for traumatic brain injury. JAMA Neurol. 2014 Jan;71(1):23-31. PubMed.
  4. ALZFORUM, “Imaging Reveals Amyloid Up To a Year After Traumatic Brain Injury,” 16 November 2013.
  5. VE Johnson et. al., “Traumatic brain injury and amyloid-β pathology: a link to Alzheimer’s disease?” Nat Rev Neurosci. 2010 May;11(5):361-70. doi: 10.1038/nrn2808.
  6. Rebekah C. Mannix and Michael J. Whalen, “Traumatic Brain Injury, Microglia, and Beta Amyloid,” International Journal of Alzheimer’s Disease, Volume 2012 (2012), Article ID 608732, 5 pages.

Brain Injury and Football — No Place to Run


The latest evidence is pretty hard to ignore.

The research leader is Dr. Ann McKee, chief of neuropathology at the VA Boston Healthcare System and director of the CTE Center at Boston University. She examined the brains of 111 deceased NFL players. Of these, 110 had CTE, the degenerative disease caused by repeated blows to the head.

The marker for CTE is a protein found in damaged cells. Because it involves microscopic examination of brain cells, it can only be done after death.

However, families often don’t need that proof. While the victim is alive, they deal with issues such as early on-set dementia and suicide attempts.

The argument in the current report is that even if no one else in the NFL had CTE, the 110 proven cases would prove a statistically higher incidence of CTE among NFL players than in the general population. The bodies examined were a non-random sample of NFL players; families donated them because of concerns. However, the sheer number of cases makes the results statistically meaningful. There simply aren’t millions of NFL players.

And it seems likely that other players do have it. The skulls examined come from all playing positions on the American football field:

  • Linemen
  • Running backs
  • Defensive backs
  • Linebackers
  • Quaterbacks
  • Wide receivers
  • Tight ends
  • Place kickers
  • Punters

Everyone who plays is at risk.

More generally everyone is at risk. The major causes of brain injuries are car accidents and slip-and-falls. The difference between civilians and sports players is repetition. People don’t collect (hopefully) 5 or 10 concussions driving, but then can in football, soccer, auto racing, bike racing and other activities.

Even a single concussion can be devastating.

Like the cigarette debate of the 1970s, it’s time for fans and owners to move from denial to action. What do we do to care for the injured? Deal with suicide risks? Cover the costs of dementia c are?

There’s also the ethical question of whether people have the right to do things that will shorten their life. There is still an active debate on the ethics of assisted suicide in the US; doesn’t this fall into that discussion? If you opt to do something that you know can kill you, does it matter what the method is?


  1. “110 NFL Brains,” The New York Times, 25 July 2017.
  2. Gil D. Rabinovici, MD, “Advances and Gaps in Understanding Chronic Traumatic Encephalopathy,” JAMA, 25 July 2017.

How Long Concussion Effects Last


A new study from researchers at the University of Washington Medical School 20150317_CDC_Concussionestablishes that even mild concussions can have effects on mental functioning and quality of live as long as five years after the injury.

The study looked at soldiers who had received mild concussions from explosions during tours in Iraq and Afghanistan.

“This is one of the first studies to connect the dots from injury to longer-term outcomes and it shows that even mild concussions can lead to long-term impairment and continued decline in satisfaction with life,” said lead author Christine L. Mac Donald, Ph.D., an associate professor in the Department of Neurological Surgery at the University of Washington School of Medicine in Seattle. “Most physicians believe that patients will stabilize 6-12 months post-injury, but this study challenges that, showing progression of post-concussive symptoms well after this time frame.”

It’s important to understand the length of impairment in terms of providing adequate services for veterans. That’s why NIH and DoD funded this work.

However, it’s also important to remember that civilians, athletes and First Responders suffer concussions — sometimes quite similar to what soldiers experience.

Forcing people to return to work before they are recovered can have unintended and unfortunate consequences. In fact, that was the explanation for a police shooting of an unarmed civilian in Seattle last year, discussed in an earlier post, and the deaths of high school and college football players as recently as 2016.

Arguably, the current health insurance system isn’t set up to meet the needs of people who may require care for 3-5 years as they recover from TBI. The US healthcare and health insurance system was designed long before we understood the nature of the problem and the length of recovery. The system hasn’t changed with the growth of knowledge.


  1. Mac Donald CL et al. “Early clinical predictors of 5-year outcome following concussive blast traumatic brain injury.” JAMA Neurology. May 1, 2017.
  2. Alan Neuhauser, “Sudden Death,” US News, 11 August 2016.
  3. “Brain-injury deaths in high school football players rising,” Fox News Health, 6 January 2017.

Brain Injury: New Developments


imagesA brain protein, tau, may be an indicator of the length of time required for recovery from a concussion.

A research team from the National Institutes of Health and the University of Rochester Medical Center conducted a study of college athletes (NCAA Div. I and III) from a mix of sports.  Tau levels were measured preseason and within six hours following a concussion.

Tau was already a suspect in brain illnesses, having been identified as a factor in the development of chronic traumatic encephalopathy or CTE, frontotemporal dementia and Alzheimer’s disease.

Tau levels jump after concussion, and higher levels are linked statistically to longer recovery time requirements.

The research focused strictly on athletes and on defining an objective measure of when a player should be allowed to go back into play.  The report calls for follow-on studies including the capture of blood samples on the sidelines of games to assess how quickly tau levels change and whether that could be used as an immediate indicator.

However there are potential applications of tau to other situations and occupations, for example, people involved in traffic accidents and in law enforcement.  Is tau a potential measure of long term injury?  Could the metric be used to assess how long a worker should be out after a work-related injury?  Frankly, if tau works for athletes, it’s hard to see why it wouldn‘t work in these other situations.


  • Jessica Gill, Kian Merchant-Borna, Andreas Jeromin, Whitney Livingston, Jeffrey Bazarian. Acute plasma tau relates to prolonged return to play after concussion. Neurology, 2017; 10.1212/WNL.0000000000003587 DOI: 10.1212/WNL.0000000000003587
  • University of Rochester Medical Center. “Brain protein predicts recovery time following concussion.” ScienceDaily. ScienceDaily, 6 January 2017. <>.