One of the most significant medical advancements of the last few decades has been the use of cholesterol-lowering medications called statins.  These drugs, when used properly, have been shown over and over to lower the risk of heart attacks, strokes, and death.  But like all drugs, they have many effects, both those we like (preventing heart attacks) and those we don’t (in this case, rare liver and muscle problems); the latter we call “side-effects”.  Studies done on drugs before they hit the market can identify common side-effects, but it’s not until many more people are exposed for a long period of time that rare side-effects show up.

A recent Scientific American article wondered if one of these rare side-effects could be memory problems.  At first glance, the idea seems pretty improbable, but the SI article takes some sketchy anecdotes and runs with the idea, managing to cobble together an interesting hypothesis:

It is not crazy to connect cholesterol-modifying drugs with cognition; after all, one quarter of the body’s cholesterol is found in the brain. Cholesterol is a waxy substance that, among other things, provides structure to the body’s cell membranes. High levels of cholesterol in the blood create a risk for heart disease, because the molecules that transport cholesterol can damage arteries and cause blockages. In the brain, however, cholesterol plays a crucial role in the formation of neuronal connections—the vital links that underlie memory and learning. Quick thinking and rapid reaction times depend on cholesterol, too, because the waxy molecules are the building blocks of the sheaths that insulate neurons and speed up electrical transmissions.

It’s not crazy to connect cholesterol-modifying drugs with cognition, but it’s quite a stretch.  We do know that statins affect the central nervous system.  They’ve been proven to reduce the risk of stroke, a devastating central nervous system disease.  If they can prevent brain disease, might they also cause it?  We have some ideas about why statins prevent strokes: they lower cholesterol and stabilize arterial plaques, perhaps by reducing inflammation in these plaques.  They can even cause plaques in some arteries to shrink.  Is there a plausible hypothesis as to why statins might cause memory problems?  What is being posited is that statins actually reduce cholesterol levels so much that cell membranes are damaged and neuronal saltatory conduction* is impaired.  If this were the case, we might also expect to find cognitive differences  when comparing people with high and low cholesterol levels, or to see cognition affected by cholesterol-lowering diets.  This is not the case.

Still, dementia—the most common and severe form of memory loss— is a devastating disease, so if there is even a chance, maybe we should ask the question.   A large  cohort study published in Archives of Neurology in 2005 looked into whether statins might actually help prevent dementia.  They groups of elderly patient who took statins, and those who did not and compared the incidence of dementia in each group. There found neither a protective effect nor a harmful effect.

The idea that lipids (fat molecules) can affect brain function has been supported by certain epidemiologic studies and some animal models.  Omega-3-fatty acids have been touted for possible use in preventing and treating dementia.  Last week, a randomized controlled trial of a particular omega-3-fatty acid was published in JAMA.  The study design was strong, and the study found no evidence that this particular molecule helped dementia patients.

The two most common types of dementia are vascular dementia and Alzheimer’s disease.  The cause of Alzheimer’s disease isn’t known, making prevention difficult.  Vascular dementia, however,  is to a certain extent preventable.  It is caused by a variety of factors that affect blood vessels such as hypertension, and studies have shown that many of the same interventions that prevent stroke can help prevent vascular dementia.  One of the most potent risks for vascular disease is cigarette smoking, so it would make sense that smoking would be a risk factor for vascular dementia.  A surprising result of a study recently published in Archives of Internal Medicine was that smoking is a risk factor not only for vascular dementia but also for Alzheimer’s dementia.

The story of dementia risk is complex, and there is a rich vein of literature to mine.   I was disappointed that the SI article presented anecdotes rather than data, case-reports rather than good studies, and highlighted “experts” who presented fear-mongering testimony rather than the measured caution that we can expect from real experts.

___________________________________

*“Saltatory conduction” describes a way that nerve signals travel quickly.  Nerve cells can function as a sort of wire for electrical signals, and the myelin sheath allows electrical signals to jump from node to node, increasing the speed of conduction when compared to an un-myelinated neuron.  Certain diseases, such as multiple sclerosis, involve destruction of the myelin sheath, decreasing nerve conduction velocity, leading to weakness and other symptoms.    Myelin contains cholesterol, among other things.

References

Rusanen, M., Kivipelto, M., Quesenberry, C., Zhou, J., & Whitmer, R. (2010). Heavy Smoking in Midlife and Long-term Risk of Alzheimer Disease and Vascular Dementia Archives of Internal Medicine DOI: 10.1001/archinternmed.2010.393

Quinn, J., Raman, R., Thomas, R., Yurko-Mauro, K., Nelson, E., Van Dyck, C., Galvin, J., Emond, J., Jack, C., Weiner, M., Shinto, L., & Aisen, P. (2010). Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease: A Randomized Trial JAMA: The Journal of the American Medical Association, 304 (17), 1903-1911 DOI: 10.1001/jama.2010.1510

Rea, T. (2005). Statin Use and the Risk of Incident Dementia: The Cardiovascular Health Study Archives of Neurology, 62 (7), 1047-1051 DOI: 10.1001/archneur.62.7.1047

Forette F, Seux ML, Staessen JA, Thijs L, Birkenhäger WH, Babarskiene MR, Babeanu S, Bossini A, Gil-Extremera B, Girerd X, Laks T, Lilov E, Moisseyev V, Tuomilehto J, Vanhanen H, Webster J, Yodfat Y, & Fagard R (1998). Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet, 352 (9137), 1347-51 PMID: 9802273