More testing

Tomorrow, we travel to Seattle for the quarterly cognitive and physical testing required for the insulin study.  I plan to get a good night's sleep tomorrow, and be fresh Wednesday morning for the testing.  In February I stayed up late the night before and did less than optimally during the test.  Last November, I slept well the night before and did very well.

They won't give me the test results, but I will share with you my impressions a few days after I'm done.

More on physical exercise worsening dementia

This week's issue of ALZ Forum included an article about the study published in The BMJ that found physical exercise seemed to "slightly" worsen dementia.  The article pointed out that this was a big surprise, but there were some facts in the article I hadn't seen before.  Most important was that the study subjects were not living in institutions, but they had nevertheless advanced to the stage of their disease where they required the service of a caregiver.  Recall that dementia is defined based on an individual's inability to perform their daily activities.

A few statistics:  There were 494 test subjects with an average age of 77.  The population was about 60% male, 40% female.  329 followed an exercise program, while 165 did not.  Exercise consisted of a mix of 30 minutes of aerobic exercise + some weight training.  There were two supervised sessions per week.  

The article quoted Laura Baker of Wake Forest School of Medicine, who contrasted these results with her success with treating mild cognitive impairment with exercise.  She also wondered about the design of the research.  She said, "In my work with patients with mild cognitive impairment, it takes at least six months of moderate to high-intensity aerobic exercise, with weekly trainer support and accountability, to see improvements in executive function.  To get similar improvements in people with dementia, they might need to exercise for a longer period of time.”

My conclusion:  Physical exercise clearly improves cognition in people with MCI, at least if it's due to AD.  Physical exercise may not improve cognition in people with actual dementia, but it still improves their overall health.  Most importantly, it helps prevent falls in older adults.

Uh oh ... Physical Exerice Actually Worsens Dementia?

This week, a team of British medical researchers published a report of their research that found "a moderate to high intensity aerobic and strength exercise training programme does not slow cognitive impairment in people with mild to moderate dementia."  In fact, physical exercise may have worsened cognitive impairment in some subjects.  The authors speculated that reoxygenation of cortical areas may have been slowed.  Inflammation induced by higher levels of exercise might also be implicated.  The research was published in theBMJ, which is a top-tier medical journal.

So what does this mean?  Does it contradict all of the existing research that associates physical exercise with improved cognition -- a premise of Beating the Dementia Monster?

No, it doesn't.  Quoting Dr Elizabeth Coulthard, Consultant Senior Lecturer in Dementia Neurology at the University of Bristol, the London Telegraph notes that these results are relevant to people with mild to moderate dementia, but they are not relevant to people with mild cognitive impairment.  People with MCI have cognitive challenges, but they have not advanced to dementia.

What occurs to me here is that once someone has advanced to true dementia, brain function may have deteriorated in a manner that reoxygenation of cortical areas is impaired.  If so, this would explain why physical exercise may contribute to deterioration of cognition in people with even mild dementia, even though it actually improves cognitive function in people with MCI.

As noted in my April 30 post, the medical community has redefined the term "Alzheimer's disease" and differentiated Alzheimer's disease and Alzheimer's dementia.  Alzheimer's disease may begin years or a decade before symptoms of cognitive impairment appear.  Alzheimer's dementia appears much later.  A person is considered to have advanced from mild cognitive impairment to dementia when the disease begins to interfere with daily activities. 

More on Mild Traumatic Brain Injuries , and a Clue Regarding Higher Rates of AD in Women

I read an article in this weeks ALZ Forum about several recent studies correlating brain injury with dementia.  The article made reference to the studies I discussed in my April 30 post, but the study that was the centerpiece of the new article addressed brain injuries that did not involve loss of consciousness.  Again, the study did not attempt to explicitly associate the dementias with AD.  What was interesting here was the way the study addressed increased rates of dementia even when the brain injury was not sufficient to cause unconsciousness.

In the same issue of ALZ Forum was an article suggesting why women are more likely to get AD than men.  This has been a mystery, and it can't be simply attributed to women living longer than men.  The idea in the article focuses on the ApoE4 gene, which is the most prominent genetic risk factor for AD.  Other variants of the ApoE gene are ApoE2 and ApoE3.  Each of us carries two copies of the gene, but they may not all be the same variant.

Apparently estrogen affects expression of the ApoE gene, but estrogen levels decrease after menopause and vary the influence of the different gene variants.  The protein synthesized from the ApoE4 gene is implicated in higher levels of inflammation in the brain, which plays a role in the development of AD.  Apparently, changes in estrogen levels can vary the how much of the protein originates from the different variants of the gene.  More protein from ApoE4 means more inflammation, hence a higher likelihood of AD.  Or that's what I got from the article.     

Why do we sleep? And does it matter for AD?

I recall that in the 1970s science was drawing a complete blank on why we sleep. The traditional explanation was that it was an opportunity for the body to repair itself, but no one could find any repairs in progress. The best explanation seemed to be that diurnal animals should be rolled up somewhere safe at night, and nocturnal animals should be doing the same during the day. An imperative for sleep would force this behavior. So it all seemed to hinge on the geometry of the eye. Eyes were designed for either diurnal or nocturnal animals, and there was no design to accommodate both.

But researchers are now going back to the repair concept, and it seems to have implications for our understanding of AD.  In Beating the Dementia Monster, I cited research correlating interrupted and inadequate sleep with increases in beta amyloids in cerebral-spinal fluids.  This strongly suggests a connection between sleep problems and AD.

A recent understanding is that deep sleep (as opposed to “raid eye movement” (REM) sleep) facilitates the removal of waste products from between brain cells. (REM sleep is lighter sleep, and it’s when you dream.) As cells function, they create wastes that are expelled from the cells through their membranes and into the space between them. During deep sleep, the space between the cells expands and allows a fluid system to flush the wastes out of the brain. Here is one study analyzing this. There is a hypothesis that when the wastes build up between the cells and are not flushed out, the presence of the wastes promotes AD.

Another thing to understand about sleep relates to what’s called “plasticity.” Neurons are constantly disconnecting and reconnecting to other neurons as a part of the memory retention process. This process occurs primarily during sleep (including REM sleep), and is important to memory. In AD, sleep patterns are disrupted, complicating the brain’s challenges with respect to memory consolidation and retention.