Jul 21 2011

Preventing Alzheimer’s Disease

In the latest incarnation of Planet of the Apes, Mark Wahlberg plays Captain Leo Davidson, a researcher on a space station. The movie is set in 2029 and typically presents technology far in advance of anything we can reasonably hope to have by that date (the station depicted could not be built even if we started it today). Future fiction tends to overestimate short term technological advance and underestimate long term advance.

In the film Davidson is researching a cure for Alzheimer’s disease (AD). Apparently the writers think our space technology is advancing much faster than neuroscience, which is the opposite of my impression. But it is true that today we do not have a thorough understanding of what causes AD nor are we on the heels of a cure. We are far enough away from a cure, in fact, that we cannot predict when such a breakthrough will occur.

Also, it is probably misleading to think in terms of “cure.” While a complete cure would be nice, it is more likely that we will develop partial treatments that reduce the risk of developing AD and slow its progression. We may even slow progression to the point where it is inconsequential – not exactly a cure, but pretty close. We already have a few drugs that are considered symptomatic treatment – they improve memory function mildly in AD patients, enough to keep them out of nursing homes for a few more months on average, but overall a modest effect.

Researchers have possibly made a new advance in understanding and treating AD. Johns Hopkins researchers have presented a paper in which they demonstrate reduced risk of progressing from amnestic minimal cognitive impairment (aMCI) to AD. MCI is considered to be a transition between the healthy state and AD. Patients with MCI, as the name implies, have mild memory difficulty but not severe enough to meet the diagnostic criteria for AD. Between 8-15% of patients with MCI progress to AD each year, which is higher than the age-matched background rate and so is considered an independent risk factor.

The researchers were following up on the discovery that patients with MCI have increased activity in certain parts of the brain – specifically the medial temporal lobe, which is involved with memory. Meanwhile other parts of the brain, specifically what is called the default mode network (DMN) shows decreased activity. The DMN displays activity when not engaged in a task – so it’s the default activity when the brain is not engaged in other specific activity. One hypothesis was that the increased activity in the temporal lobe was compensatory to the memory impairment of MCI, and perhaps the decreased activity in the DMN. In other words – the memory parts of the brain are working overtime in order to compensate for the deficits of MCI and perhaps also AD.

The alternate hypothesis is that the increased activity is actually causing the brain damage that leads to MCI and AD. The Hopkins researchers were basing their approach on this hypothesis. They used an approve anti-seizure drug, levetiracetam, to treat adults with aMCI (amnestic MCI is a subtype of MCI) and found a slowing of the progression of memory difficulty. This is a preliminary study, and needs rigorous follow up. If the results hold up, this could mean that the increased activity in the temporal lobe is not merely compensatory, but actually contributes to progression of MCI to AD.

This could become a significant tool in the management and prevention of AD (again – not a cure, but still very useful). Combined with improved techniques to make earlier diagnosis of MCI or early AD this treatment could slow progression and add months or even years of high function to patients with these types of dementia.

At this point we cannot tell what the state of the neuroscience will be in 2029, but there is a great deal of research and progress into the causes of dementia with implications for treatment. We have relatively new tools, such as fMRI scan, to image brain function and see what is going, and our picture of how the healthy brain functions and what goes wrong in various disease states is also rapidly increasing.

Research like this gives great reason for hope. I certainly think it is much more likely that we will have a significant treatment, if not a cure, for AD by 2029 than that we will have advanced research labs orbiting other planets.

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