Maintaining Your Cognitive Edge

Mini-Medical School #4         August 6, 2016
Stephanie Taylor MD PhD

“I have reached an age when, if someone tells me to wear socks, I don’t have to.” Albert Einstein (1879-1955).

Healthy aging is the most popular topic in the Mini-Medical School Series, and for good reasons. The average lifespan has increased dramatically in the last 100 years, and nothing in our social structure has kept pace with that fact.
In 1900, the average lifespan for women was 48 years (men 46), in 1950 it was 71 years (men 66) and in 2000 it was 80 (men 74). Social Security was enacted in 1935 and was intended to support the aging population for the few years before their natural death. We have moved from a time when an elder could look forward to a few years of rest before a quiet death by infectious disease or multi-organ failure to a prolonged maturity of three decades. This is an international crisis, especially in the developed world.
Popular interest in maintaining vitality is exploding. Fortunately, the science is keeping pace.

“Those who think they have no time for bodily exercise will sooner or later have to find time for illness.” Edward Stanley (1826-1893)

The first principle of healthy aging is to not break the equipment before you wear it out. There is robust scientific evidence for these assertions:
Stress and social isolation accelerates aging possibly by shortening telomeres.
Environmental toxins accelerate aging, often by direct damage to DNA.
Excess calories accelerate aging, possibly through hormonal signaling by fat cells.
Vascular disease and diabetes accelerate aging.
Exercise and meditation slow aging. The most physically active were 40% less likely to decline, and 50% less likely to develop Alzheimer’s. Scans show an increase in hippocampal size and in tests of memory. Animal studies show that physical activity increased blood vessels, and increased hormones that support nerve growth.
A diet rich in phytonutrients shows aging, probably through its antioxidant effects. Mediterranean Diet.

“Grow old along with me! The best is yet to be.” Robert Browning (1812-1889)

What healthy brains do as they age: they adapt. Let me show you!
First meet the players-The major brain regions in aging research are the frontal cortex (proactive planning and working memory), the hippocampus (episodic memory). The structure of the brain is composed of nerve cells and their supporting glial cells. These cells are very high fat and high water, and this will become important later.
The fMRI studies show there is a difference in young and old brains, but what that means is very open to interpretation. The good news is that the older brain recruits new regions when there is a slowdown in a prior processing area. The brain may recruit another region, but the most fascinating fact about the older brain is that this recruitment crosses into the opposite hemisphere. This does not happen in younger people.

“He who is of a calm and happy nature will hardly feel the pressure of age, but to him who is of an opposite disposition, youth and age are equally a burden.” Plato (427-346 B.C.)

The aging brain responds best to active management. This has many layers of meaning, and here are some from the researchers:
Enhancing memory-repetition is less effective than investing the memory with meaning, especially if it is surprising or funny.
We are hard wired to remember visual and spatial information much better than words.
We remember things better if they are associated with something else that we already know.
Recalling information (self-testing) enhances memory much better than repetition.

“Because I could not stop for death – He kindly stopped for me.” Emily Dickinson (1830-1886)

As a society, we are developing a more mature attitude toward dying. This is most welcome, but we have not solved the crisis of losing your mind long before the death of the body. Alzheimer’s disease is the third leading cause of death, and affects 5.2 million Americans. The lifetime risk is 15%, which means that 45 million Americans will be affected as the population ages. This is a national emergency.

There are several types of dementia, but the most common is called Alzheimer’s disease. Alzheimer’s disease is defines by the presence of amyloid plaque and tau protein. These “scars” in the brain are thought to cause Alzheimer’s disease and have been the target of therapy. Unfortunately, all the pharmaceutical therapies to date have failed. Here is the reason:

There is more than one kind of Alzheimer’s disease, and they have different causes. All three types are beta-amyloid positive and tau positive, and are currently diagnosed as Alzheimer’s disease.

Type 1-Inflammatory-Multiple inflammatory associated genes; inability of the innate immune system to remove amyloid, persistent “wound-like” micro-pockets; systemic inflammation affecting the brain, and ApoE4 associated. Symptoms are focused on memory loss, and MRI shows hippocampal atrophy, with no cortical atrophy.

Type 2-Non-inflammatory-Insulin resistance, low Vitamin D, elevated homocysteine, steroid hormonal  loss. Systemic markers of inflammation are usually normal. Also associated with ApoE4.

Type 3-Cortical-non-amnestic.  A fundamentally different process than Types 1 &2. Typically early onset (with preceding stress or toxic exposure), with loss of long-term memory, no family history, ApoE4 negative, MRI shows general cortical atrophy rather than hippocampal loss, and a reduction in glucose utilization. Zinc levels are low. The six patients reviewed by Bredesen MD all had a history of toxic exposures, including mycotoxins. This subtype is also called “Inhalational Alzheimer’s disease.”

Treatment depends on the type and by metabolic characterization. This work is being done at the Easton Lab for Neurodegenerative Disease, UCLA and the Buck Institute for Research on Aging in Novato.  The protocol (MEND) is in development, and I think we can expect some news stories in the coming year. In the meantime, don’t break the equipment and keep yourself well fed, exercised, safe and happy.

Bredesen, Dale E. “Reversal of cognitive decline: A novel therapeutic approach.” Aging. September 2014.
Bredesen, Dale E. et al. “Reversal of Cognitive Decline in Alzheimer’s disease.” Aging, June 2016.