Does early long term use of statins decrease progenitors cells and result in dementia at an earlier age than normal?
Statins are the most widely prescribed drug to lower cholesterol – are there potentially any long term side effects on the brain in kids taking them for all or most of their lives? Interestingly, statins are also being studied for their potentially positive effects on the brain including Parkinson’s disease and dementia. In general the researchers find positive effects of statins on these two brain diseases (though not conclusive), so why then would we be worried about their long term negative effects on brain health?
A new in vitro paper (Sim et al., 2008) studying statins found that in a dose dependent manner this drug at equivalent doses used by humans increased the differentiation of glia progenitor cells into oligodendrocytes (via Rochester University). What does that really mean? Progenitor cells (in this case glial) are similar to stem cells, but just a little further down the commitment line and in general have less potential to form all types of cells. Glial progenitor cells can become astroyctes and oligodendrocytes. Throughout our lifetime there is an overturn of these cells and we get the new cells to replace the old ones from these glial progenitor cells (there is still a limited supply of these cells). Oligodendrocytes myelinate our axons and a decrease of oligodendrocytes is involved in diseases such as multiple sclerosis (MS an autoimmune disorder). Interestingly, researchers are exploring the potential use of statins to treat MS.
Sim et al., found that statins resulted in 5 times more oligodendrocytes in culture of human brain tissue compared to samples not treated with statins. Conversely, the statin treated brain tissue had 1/6 the number of glial progenitor cells. Therefore, it appears that statins increase the differentiation of glial progenitor cells into oligodendrocytes. The end result being statins results in more oligodendrycytes, which can be good when treating condition when there has been a loss of these cells(MS, brain injury, spinal cord injury, or other condition which cause damage to oligodendrocytes). However, what about the long term use of statins?
Early I pointed out that researchers have found some positive results of statin treatment on reducing dementia. But in a more recent paper the authors pointed out that in randomized controlled trails that statins prescribed later in life (older people) there is no effect on dementia. I wonder if does the age related decrease in glial progenitor cells play a role in the lack of effect of statins in older people. Statins can not significantly increase the number of oligodendrocytes cells if there are too few glial progenitor cells.
There is growing research (reviewed here) that suggest that the loss of white matter (oligodendrocytes) possibly plays a larger role in age related dementia than gray matter loss (neurons). Part of the reason there would be a loss of oligodendrocytes would be the age related loss of the glial progenitor cells. Therefore, is it possible that statins used in middle age individuals protects them from dementia because they increase the differentiation of glial progenitors cells into oligodendrocytes, which protects these individuals from the natural age related loss of these cells. However, this same treatment may have no effect on older individuals (as reported above) because the number of glial progenitor cells are too low for statins to have its biological effect?
So what do you would think would happen if an individual starts taking statin treatment at a young age? Is it possible that the higher rate of differentiation of glial progenitor cells into oligodendrocytes could deplete these important cells. Would kids taking statins from a young age end up with very early dementia because of the depletion of glial progenitor cells which would result in an eventual depletion of oligodendrocytes? I do not know the answer, but with the recent results by Sims et al., if confirmed in vivo we might need to rethink the long term use of statins (possibly including 20 and 30 years olds that start taking these drugs). Of course one needs to balance the danger of cardiovascular disease (CVD) from high cholesterol (and the other various cholesterol measurements) and future dementia.
One potential solution might be using non-drug treatments that lower bad cholesterol and increases good cholesterol (exercise and appropriate nutrition).
Update: I wrote about some new research which suggest that statin use may inhibit myelination, which may be detrimental for your long term brain health.
Update II: Though we have to be cautious about the possible long term effects of statins on brain health – specifically myelin – new research points to postive effects on statins reducing the risk of dying from all causes of death
Update III: Reanalysis of the paper in update II suggest that maybe statins do not decrease mortality rate.