After 22 posts about dementia in which I repeatedly inveigh against the all-too prevalent hype about how the cure for Alzheimer’s disease is just around the corner, I finally have some encouraging news. A piece in the “Medical News and Perspectives” section of the Journal of the American Medical Association highlights a radically new approach to preventing dementia.
At the heart of the approach is the recognition, as the JAMA article leads off by saying, that “pathology is not destiny.” We know that this is true in large part because of the nun study, an ingenious epidemiological study that’s been ongoing since 1986. In this study, 678 of the School Sisters of Notre Dame agreed to annual assessments of their cognitive and physical function as well as to blood tests for genetic studies. They also agreed to donate their brains to the researchers upon their deaths. Taken together, these tests allow researchers to uncover the relationship between cognitive function during life (the presence, absence or degree of dementia), biochemical markers in the blood, and pathologic changes in the brain.
The study population is particularly useful because the nuns tend to stay within their order—they don’t move around the way many Americans do—simplifying longitudinal follow-up. Moreover, because they all live in the same order, where they have a similar diet and participate in many of the same activities, they exhibit a degree of environmental homogeneity seldom found in other groups. One of the many things we have learned from the nun study is that there are people with evidence of advanced Alzheimer’s disease at autopsy who clinically had very mild disease and conversely, there are people whose brain pathology is consistent with early Alzheimer’s disease who were clinically quite severely affected. This observation strongly suggests that factors other than the brain plaques and tangles that are the hallmarks of Alzheimer’s can mediate the severity of a person’s symptoms.
One of these mediators is other brain pathology, such as vascular disease, which causes strokes. It turns out that vascular changes plus plaques and tangles are far more devastating than would be expected by simply summing the expected effects of each alone. The implication is that preventing atherosclerosis (what once upon a time was known as hardening of the arteries), which involves smoking cessation and treatment or prevention of high blood pressure, diabetes, and elevated cholesterol, is an effective means of attenuating dementia, even dementia due to Alzheimer’s disease. But another mediator is entirely new and different: recent results from the longitudinal Framingham Heart study point to special proteins that the brain manufactures to protect itself. Remarkably, a stimulus for the body to make more of these magic molecules is social engagement.
One such brain protein has the awkward name of brain-derived neurotrophic factor, abbreviated BDNF. This substance appears to reduce the risk of both dementia and stroke, probably by promoting the growth of new neurons and of synapses, the connections between neurons, as well as by protecting neurons from dying. Another protein, with the equally euphonious name of vascular endothelial growth factor, abbreviated VEGF, may also play a protective role. VEGF promotes the growth of new blood vessels, which may counteract the damage to the brain resulting from amyloid, a principal factor in the development of Alzheimer’s dementia. Just as social networks seem to boost BDNF, exercise seems to increase the levels of VEGF.
So far, no one has found a drug that either mimics the effects of BDNF or VEGF or stimulates the brain to make more of these substances. Or at least, the one such drug that has been studied, davunetide, failed to show any benefit in a clinical trial. It’s conceivable that a combination of pharmacology and life style interventions will be needed to make a clinical difference. But the idea of harnessing the body’s own repair mechanisms is promising; it seems much better than trying to remove amyloid deposits after they’ve formed (by which time the damage has already been done) or to boost levels of the neurotransmitters needed for neuron to neuron communication (which doesn’t work if the neurons that are supposed to communicate are already dead).
If one way to coax the brain into producing more protective protein is by exercising and remaining socially engaged, both of which have other benefits and almost no side effects, that would be welcome news indeed.