A new study published in the journal Neurology has found that high and high-normal thyroid levels are linked to greater risk of developing dementia, but not vascular brain disease.
This is a very interesting finding because (as this previous post illustrates) cognitive decline has been linked with hypothyroidism and high TSH.
Low TSH May Also Be a Risk Factor? Wait…What?
This study shows that having too low TSH can also be risk factor (we’ll explore why this might be in a moment). What this also shows us is just how important balance is. There may be a “Goldilocks” zone of TSH and free T4 that’s “just right”.
In this study, researchers led by Layal Chaker, MD, MSc, of Erasmus University Rotterdam, the Netherlands investigated the role of thyroid function in dementia, cognitive decline, and vascular brain disease.
They examined a subgroup of 9446 people (mean age 65) enrolled into this Rotterdam Study. Researchers looked into the link between thyroid-stimulating hormone (TSH) and free thyroxine (free T4) and incidents of dementia.
Here’s what they found: Over the course of follow-up (mean 8 years), 601 patients developed dementia (Alzheimer’s dementia n=487). Higher levels of TSH were found to be associated with lower dementia risk for both the full and normal ranges of thyroid function, independent of cardiovascular risk factors (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.83–0.98; and HR 0.76, 95% CI 0.64–0.91, respectively).
Higher Levels of Free T4 Too?
Participants with higher levels of free thyroxine were found to have greater dementia risk (HR 1.04, 95% CI 1.01–1.07).
Higher levels of TSH were associated with better cognitive scores (P =.021), and in older women, a 5% decrease in absolute 10-year dementia risk. Notably, thyroid function was not found to be associated with subclinical vascular brain disease.
The results, the authors concluded, suggest that thyroid hormone impacts dementia risk through nonvascular pathways.
How Can This Be?
The researchers offered a couple of other ideas about why this might be including the possibility that excess free thyroxine may affect the way that genes are expressed in important pathways in the brain or that destruction to nerves my be caused by oxidative stress which can cause destruction of brain tissue (which, frankly, makes a lot of sense to me – more on this in a moment).
Also, participants with early signs of dementia may have changes in behavior, like diet, which may alter thyroid function. (As we know diet and behavior are extremely important for maintaining a healthy brain).
“In other words, we may not be observing a true effect of thyroid hormone on dementia risk but rather the opposite,” the authors concluded.
Here’s My Take on This
This is one of those instances when looking at research can make you crazy. Too high TSH and hypothyroidism is clearly a potential problem and too low TSH may also be a potential problem.
Age is another factor to consider when trying to wind yourself through this maze. Thyroid hormone is absolutely essential for the developing brain, so if your are pregnant or if you are an infant or young child, it may be more important to have your TSH a little lower (In fact, the American Endocrine Society has recommendations for TSH in each trimester and they can be found in this post.)
As we age, the brain becomes becomes more vulnerable to certain processes and, I think, the chief concern here may be the role of oxidative stress on the mitochondria in the brain.
In thyrotoxicosis (excessively low TSH or a hyperthyroid state), glucose uptake and utilization by muscle is increased as is the breakdown of glycogen (glycogenolysis) and glycogen (a substance that stores carbohydrates) depletion is seen in muscle biopsy samples.
Also, mitochondrial oxidation is increased and lipid oxidation, protein and purine breakdown all occur and this results in lower ATP (our cells energy sources).
And being naturally a little hypothyroid might actually protect your brain from this (but, it can also cause it’s own problems – damned if you do and damned if you don’t!)
Mitochondrial Problems Lead to Destruction of Brain Tissue
And mitochondria are smack dab in the middle of this whole process because they are involved in both energy production and cell death.
Mitochondria are unique in that they both produce energy and make free radicals. They do this in order to monitor cellular health and to make a rapid decision (if necessary) to initiate programmed cell death.
When this process goes haywire in the brain, it can have devastating impacts on nerve cells. And too much free T4 can be one of the factors that drives this.
Ironically, mitochondria in the brain are really of victims of their own amazing abilities.
If the amount of free radical species produced by them overwhelms the neurons in the brain’s ability to neutralize them, oxidative stress occurs, followed by mitochondrial dysfunction and neuronal damage.
Reactive species generated by mitochondria have several cellular targets including mitochondrial components themselves (lipids, proteins, and DNA). The lack of histones in mitochondrial DNA (mtDNA) and the diminished capacity for DNA repair render the mitochondria an easy target to oxidative stress events.
So, they are especially vulnerable to their own attacks. (There has to be a lesson there. 🙂 )
All of this can translate into destruction of brain tissue due to this oxidation which produces free radicals. (In fact, many symptoms of aging are due to these free radicals).
Basically, this all comes down to electrons. These reactive oxygen species are untethered electrons flying around breaking up cells, and wreaking havoc (think bullet in a tin can).
And really, at the end of the day, this mitochondrial dysfunction is a causal link between neurodegeneration caused by both hypo and hyperthyroidism.
So, obviously, this begs the question, How do we preserve and heal the mitochondria in our brains (and the rest of our bodies?)
Stay tuned. We’ll be exploring this in a future post in considerable depth.
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923401/ Endocrine Risk factors for Cognitive Impairment
https://www.ncbi.nlm.nih.gov/pubmed/17353866 Hypothyroidism and reversible cognitive decline
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496329/ Review of 23 studies on subclinical hyperthyroidism and cognitive decline
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3872098/ Role of Thyroid Hormone in Oxidative Stress and Neurodegeneration
http://joe.endocrinology-journals.org/content/176/3/321.full.pdf Hypothyroidism alters mitochondria
http://www.sciencedirect.com/science/article/pii/S0925443909002427 Mitochondria Dysfunction and Alzheimer’s