Forgetting. Forgetting your address; your spouse; your children; your friends; your life. It is something that none of us want to think about, but it hangs over some of us like a specter. Can’t remember if you fed the cat? Where you put your car keys? Did you forget to pack your lunch or return a phone call? Maybe you are trying to do too many things at once, or maybe you are tired. There are lots of perfectly normal reasons why we all forget things from time to time, but every time I forget something there is a nagging voice in my head saying, “Maybe it is something else.”
Alzheimers disease; there is a history of it in my family. My Father’s Grandmother didn’t recognize anyone in her family when she died. Likewise, her sister and brother both were living in a different reality when they passed away. Now we worry that my uncle seems to be sliding away, but there is nothing we can do to hold him here with us. Every time my Father forgets something I know that secret fear is with him, and as I grow older it is with me as well.
There is lots of research going on right now centered on the aging mind and all that goes with it, but to date there are more questions than answers. There are a few drugs that can help with age-related memory loss. There are none that prevent the slow, sure cognitive decline of neurodegenerative diseases like Alzheimers. There have been some studies, such as the Nun Study that offer glimmers of hope. Pathologically speaking, some of the women involved in the study should have shown the affects of Alzheimers, but they didn’t. Clearly there is a lifestyle component to an individual’s susceptibility to the disease. The problem is that most of us don’t live in a convent, and good, bad or indifferent, we do not have the lifestyle of a nun.
Overwhelmingly, research in the area of Alzheimers disease has focused on the amyloid beta peptide and its pathway. Mutations in genes that control amyloid beta formation have been associated with Familial Alzheimers disease (FAD), and the development of amyloid plaques, dense deposits of the amyloid beta protein, is characteristic of Alzheimers disease. While focusing on amyloid beta pathways makes sense, all amyloid-based drugs so far have failed clinical trials.
A group of researchers from the Salk Institute for Biological Studies took a different tact. Pointing out that over 95% of all Alzheimers cases are not FAD and aging is by far the greatest risk factor for developing Alzheimers, they targeted age related pathologies rather than just amyloid metabolism (1). They isolated a compound using multiple distinct cell culture models of neurodegeneration. The approach resulted in a drug that targets several pathways that decline with Alzheimers. When tested in mice, the drug enhanced memory in normal and Alzheimers transgenic mice, as well as protected the rodents’ brains from the loss of synaptic connections (1). Simply put, the drug shows promise of slowing Alzheimers disease progression as well as offering immediate cognitive benefits.
Before everyone emails me asking the name of the drug (it isn’t commercially available anyway), please remember that we are not mice. Personally I would like to think that my brain differs at least somewhat from that of a rodent. In other words, this might look promising, even exciting, but there have been a lot of drugs that looked as good before they went to clinical trials.
We have to wait, as there is still a lot of science to be done before they know if this drug will live up to it’s promising beginning. And if it doesn’t we can still look to these researchers for hope. Why? Because they thought outside the narrow confines that so many others had built around themselves. They recognized that it was likely that the numerous pathological components of old age (i.e., oxidative stress, loss of trophic factors, reduced energy metabolism, and inflammation) could all lower the threshold for amyloid beta toxicity. They used these broader criteria to screen for a compound, and they found one. Time will tell if it is the right one.
- Chen, Q. et al. (2011) A novel neurotrophic drug for cognitive enhancement and Alzheimers disease. PLoS ONE, 6(12). doi:10.1371/journal.pone.0027865 Accessed December 15, 2011.
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