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.
9 Responses to “Preventing Alzheimer’s Disease”
Leave a Reply
You must be logged in to post a comment.
Hi Stephen Novella –
Regarding prevention of Alzheimer’s, I’d be interested in your thoughts on the possibility of neuroscience discovering lifestyle changes that might reduce getting Alzheimer’s in the first place, as opposed to phamaceuticals to slow symptoms.
I ran into this paper a while ago and it opened my eyes towards a programming train of thought on Alzheimer’s, and lots of things.
http://www.jneurosci.org/content/28/1/3.full
Thanks.
- pD
As a side note, did you ever notice how nearly all movies set several decades in the future assume everyone will be driving new cars in the future?
You rarely (if ever) see any old, beat up versions of cars that were current when the movie was made shown in a movie set in the future even though you see plenty of older cars from the 80′s and earlier driving around today in real life.
@Karl: Children of Men seemed to pay special attention to that fact.
One of the more ‘out-there’ ideas about the relationship between the default network over-activity & Alzheimer’s is that spending a lot much time in different forms of personal reflection might increase risk. I saw Randy Buckner talk about this, and read a few bits here and there – maybe I’ll have time to link them later.
The idea is that he MTL (and much of the default) is engaged not only during episodic memory, but when we think prospectively as well. Any type of day-dreaming one does – from fantasizing to reminiscing – engages MTL and the default network. This leads to overactivity of the default, and increases risk.
This makes the prediction that certain personality types (e.g., people often lost in personal reflection) would have a greater risk than those who are more task-oriented. It would also account for data showing that people who “use their brain” (as apocryphal as this phrase is) might be at lower risk, as engaging the active task network leads to reduction in default activity.
All of this seems far from solid, but it’s a novel and interesting idea.
Can you provide a link to the Johns Hopkins study? I thought this might have been a press release from the ICAD meeting in Paris, but couldn’t find anything about a levetiracetam/MCI study there or on PubMed.
This sounds interesting, but the road to effective treatment for AD is littered with failed compounds. If true, it might also have implications for some forms of epilepsy. I wonder if the increased medial temporal activity is a “kindling” phenomenon that past a certain point becomes a self-perpetuating process refractory to intervention? If this abnormal physiology somehow incites the neurodegeneration of AD, could it also imply something about epileptogenesis, which is often associated with medial temporal structures?
If there is a window of intervention related to this hypermetabolism seen on imaging, it is imperative that the timing be clarified. Such functional imaging studies are very costly.
The physical health of the elderly is variable such that continued administration of seizure medication with other enhancing drugs like Namenda create heavy sedation. Psychiatric decisions change with the patient’s health.
@steve12
That is interesting. As an avid day dreamer, its a bit depressing. I hope it proves unfounded.
I think spending a lot of time in “personal reflection” is a trait of depression as well. I wonder if there is a correlation there as well.
I had hoped they would have AD all fixed by the time I hit an at risk age, but it doesn’t look too hopeful. sigh.
@Karl – I have commented on that a lot. They also don’t seem old homes or buildings either. Apparently at some point in our future we lose all interest in preserving old architecture.
“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.”
This NOT the way to prevent a disease like Alzheimer’s. This kind of reductionist approach never goes very far. You try to slow the progression by focusing on individual aspects of the disease, without ever trying to put it all together and determine the actual cause of the systemic imbalance. You don’t try to see how lifestyle factors may be involved.
The materialist/reductionist approach starts from the premise that nature is mindless, and the body evolved haphazardly and is poorly designed. The system as a whole is seldom considered, because you don’t see the system as having intelligence. You don’t see the body as something that can heal itself if given a chance.
This approach to Alzheimer’s is like the mainstream reductionist approach to cancer, which focuses on prolonging life by months or at most a few years.
Cancer, heart disease and Alzheimer’s are probably often caused by decades of the typical American lifestyle, which can result in an overly stressed and out-of-balance immune system.
Cancer and heart disease are probably often related to long term chronic inflammation, and that may also sometimes be the case with Alzheimer’s.
Novella thinks delaying onset of symptoms leads to incremental improvements and eventually a cure or near cure. But that is the same philosophy behind the cancer research which has mostly failed.
There are some exceptions, but overall progress in treating or curing the major chronic diseases has been minimal.
Yet Novella has unfailing faith in the reductionist approach.
Hello Steven,
Just wanted to let you know that I appreciate you a lot for letting people know about this terrible disease. I also wanted to present you a software we’ve developed and let me know what you, as a professional, think about it. It’s http://www.dementialife.com/
Thanks a lot!