Copyright © 2007-2017 Russ Dewey
In ancient times, people were fortunate to live past their 50s. Now, people hope to reach their 90s, so old people must take better care of their bodies and minds, if they want to enjoy their later years.
Scientists have known for a long time that nerves grow more slowly in older animals. Scheff, Bernard, and Cotman (1978) noted a decrease in axon sprouting after injury in old rats. Buell and Coleman (1979) found the same thing in humans. However, not all neurons are equally affected. Buell and Coleman wrote:
...There are two populations of neurons in normal aging cortex, one a group of dying neurons with shrinking dendritic trees, the other a group of surviving neurons with expanding dendritic trees. In normal aging the latter population prevails. (Buell & Coleman, 1979, p.856)
What two populations of neurons did Buell & Coleman discover?
As noted in Chapter 2, the human nervous system undergoes a natural selection process from childhood onward. Neurons that contribute positively to the organism grow, and others are eliminated through apoptosis (programmed cell death). This is normal and results in improved neural functioning.
Up until the ninth decade of life in humans, continual growth of the remaining neurons compensates for the loss of other neurons. Dendritic trees (and axonal arborizations) make up 95 percent of the surface of nerve cells in the cortex, so if individual dendritic trees grow, the brain as a whole stays the same size, although the number of cells decreases with age.
Marian Diamond of the University of California at Berkeley found that continued stimulation was necessary to retain large dendritic trees in the brains of aging rats. When rats were kept in standard barren metal laboratory cages, instead of enriched environments, their brains decreased in size with age.
The decrease in brain size was not due to nerve death. It was due to the dendritic trees on existing neurons getting smaller. Diamond commented:
When I lecture, I show my hand–my palm is the cell body and my fingers are the dendrites. With use, you can keep those dendrites out there, extended, but without stimulation, they shrink down. It's quite simple: You use it or lose it. (Hopson, 1984)
How does the phrase "use it or lose it" relate to the findings of Diamond and Scheibel?
Dr. Arnold Scheibel of UCLA, Diamond's husband and co-researcher, added, "The dendritic projections are like muscle tissue. They grow more the more they're used." (Goleman, 1985) This helps explain why continuing an active lifestyle after retirement helps older people delay negative effects of old age. In the 2010s this phenomenon is referred to as cognitive reserve (below).
Attempts to analyze nerve health in old age have often centered on Nerve Growth Factor (NGF). The assumption has been that (a) growing neurons is good, and (b) NGF helps neurons grow, therefore (c) NGF might reduce cognitive decline in old age. Studies in mice have suggested that older mice might be rejuvenated by NGF, for example, in blood infusions from younger mice.
Why has so much research centered on nerve growth factor (NGF)?
In China NGF has been legal to use in human therapies since 2005. Zhao, Li, and Zou (2015) surveyed all the research on NGF therapies in humans and provided a meta-analysis of 64 randomized control trials involving 6,297 patients.
In these studies, NGF was used for treatment of peripheral nerve injuries, central nervous system injuries, and nervous system infections. Most studies reported improvements after treatment with NGF. There were few adverse reactions.
However, no behavioral or cognitive measures were included in the research, only "speed of nerve conduction" (which increased with NGF). Few of the studies used double-blind methodology (only 3 of 62 in China). The main encouraging result was a lack of serious side effects.
NGF was also studied as a possible treatment for Alzheimer's Disease (AD). 10 patients with AD were followed the University of California, San Diego, Medical Center from 2001 to 2012 after receiving gene therapy to stimulate NGF production. As patients died they were autopsied and their brains examined.
NGF gene therapy did increase "axonal sprouting toward the NGF source" in all patients. Three patients received the gene therapy on one side of the brain only, and they showed hypertrophy (increased growth) on that side only.
The growth persisted ten years after treatment. There was no improvement in the Alzheimer's Disease, but like the Chinese researchers, the California research team concluded that, "Growth factor therapy appears safe over extended periods and merits continued testing" (Tuszynski, Yang, Barba, et al., 2015).
What are the results of NGF research in humans?
There is a crucial difference between regenerating neurons (replacing those that have been injured) and continuing the growth process in healthy neurons. In the peripheral nervous system, neurons can re-grow. In the central nervous system, with the exception of areas near the hippocampus, neurons cannot regrow.
The best tactic for aging humans is not to let nerve cells shrink or die from neglect in the first place. This was known in the 1980s when the Diamonds did their research, and their slogan "Use it or lose it" is a good way to express it.
News stories tell of extraordinary old people who remain productive into their 90s or even over the age of 100. The common element in their stories is continuity. They practice their skills in their 90s as they did in their 70s or 80s.
Participation in activity is what maintains healthy neurons. "Use it or lose it" could be rephrased as: "Anything you continue to do, you can continue to do."
Musicians provide many examples of individuals who maintained exceptional skills into old age. Lionel Hampton, the jazz vibraphonist, lived to age 94. He had to cut back on performances after a stroke at age 84, but he continued to play brilliantly and performed at the Smithsonian National Museum of American History in 2001 shortly before his death from heart failure.
Arthur Rubinstein was a classical pianist who played well up to his death at 95, although he stopped performing publicly after he lost his sight around age 85. Les Paul, inventor of the famous solid-body electric guitar that bears his name, played until shortly before his death in 2009 at age 94.
The concept of cognitive reserve may be key to the continuing abilities of some people in their 90s. The concept came from research on Alzheimer's Disease (AD), the most common cause of senility. Researchers noticed that people with more years of education were less likely to suffer from AD, even if their brains showed AD-like damage.
Cognitive reserve can be defined as extra protection against cognitive decline in people with greater intellectual enrichment earlier in life. "Extra protection" is a theory-neutral label for the effect seen in data.
People with more education (more stimulating jobs, or more active social networks) are less affected by brain damage of all kinds. This includes damage produced by normal aging.
What is cognitive reserve?
Research on cognitive reserve often uses years of formal education as an operational definition of "intellectual enrichment earlier in life." That variable is objective and easy to measure. However, other factors may play the same role, including "a challenging occupation, engaging hobbies and active social networks" (Brynie, 2008).
Two forms of evidence support the cognitive reserve concept. First, more education results in less likelihood of decline or senility. Second, given the same symptoms (the same degree of senility as measured by clinical tests) people with more education have more severe brain damage. More damage is required to bring down their performance scores.
Catherine Roe and colleagues at the Alzheimer's Disease Research Center at the Washington University School of Medicine in St. Louis did a brain-imaging study on 198 people averaging 67 years of age. The sample included 161 people without dementia and 37 with a diagnosis of Alzheimer's.
The researchers used a marker (Pittsburgh Compound B) that binds to beta-amyloid plaques of Alzheimer's Disease and shows up in PET scans. They found no cognitive decline at all in people with no plaques. "However, for people who did have plaques in their brains, the severity of dementia symptoms was related to how much education they had completed." (Brynie, 2008)
Other studies showed that education correlates with physical health and durability in brains. Researchers analyzed cerebrospinal fluid of older adults and found those with at least 16 years of education (enough to complete college in the U.S.) had less evidence of neurodegeneration (Almedia et al., 2015).
Richard and Sacker (2003) did a statistical analysis to trace the origins of the cognitive reserve effect. The researchers found that educational attainment of parents did not matter. Environmental factors predominated over family genetics in explaining cognitive reserve.
Three factors predicted high cognitive reserve late in life. These were: childhood cognitive ability, educational attainment, and adult occupation. Adult occupation had the weakest effect, and childhood cognition the strongest. This suggests cognitive reserve is related to life-long cognitive competence.
To explore the possibility that cognitive reserve might be initiated later in life, a study called the Tasmanian Healthy Brain Project was started in 2011 and is expected to run for 10 to 20 years. Older adults were recruited to go to college late in life, while their brain health was monitored.
An initial group of 359 volunteers aged 50 to 79 received cognitive tests then enrolled for a year of full or part-time study at the University of Tasmania. Early tests showed that 92 percent of the college-studies group already displayed a significant increase in cognitive capacity, compared to 56 percent in a control group.
Exercising the mind might exert a beneficial effect even late in life. The same is apparently true of exercising the body. Even minimal daily exercise has a big effect on aging bodies.
A study published in JAMA (the Journal of the American Medical Association) with 19 authors gathered data from nine studies of 34,485 individuals living in retirement communities. It showed that gait speed–how fast a person walked–
Men aged 75 to 84 who walked fastest had a 92% chance of surviving at least ten more years. Even the slowest walkers showed some benefits, increasing their chances of survival (compared to non-walkers) by 15%. Among women, those with slow gaits enjoyed a 35% increased probability of living ten more years, compared to non-walkers.
A daily walk at a fast pace may be enough to have a protective effect, if it is done on a regular basis. The key is to start this routine at an age when walking is still easy. Establish a habit of walking at a fast gait, then continue it.
Almeida, R. P. et al (14 authors) Cognitive Reserve Modifies Age-Related Alterations in CSF Biomarkers of Alzheimer's Disease. JAMA Neurology. Retrieved from: http://europepmc.org/articles/pmc4639566 . doi:10.1001/
Brynie, F. H. (2008, December 2) New evidence supports the cognitive reserve hypothesis of Alzheimer's Disease. The Dana Foundation. Retrieved from: http://www.dana.org/News/Details.aspx?id=42881
Buell, S. J. & Coleman, P. D. (1979). Dendritic growth in the aged human brain and failure of growth in senile dementia. Science, 206, 854-856.
Goleman, D. (1985, July 30). New evidence points to growth of the brain late. New York Times, pp.Y19-Y24.
Hopson, J. (1984, November) Marian Diamond: Love affair with the brain. Psychology Today, pp.63-73.
Richards, M. & Sacker, A. (2003) Lifetime Antecedents of Cognitive Reserve. Journal Of Clinical And Experimental Neuropsychology. Retrieved from: http://www.tandfonline.
Scheff, S. W., Bernard, L. S., & Cotman, C.W. (1978) Decrease in adrenergic axon sprouting in the senescent rat. Science, 202, 775-778.
Stern, Y. (2012) Cognitive reserve in ageing and Alzheimer's disease. Lancet Neurology, 11, 1006-1012. doi:10.1016/S1474-4422(12)70191-6
Studentski, S. et al. [19 authors] Gait speed and survival in older adults. JAMA, 305, 50-58. doi:10.1001/
Tuszynski, M. H., Yang, J. H., Barba, D., et al. (2015) Nerve Growth Factor Gene Therapy Activation of Neuronal Responses in Alzheimer Disease. JAMA Neurology. Retrieved from: http://jamanetwork.com/
Zhao, M., Li, X., & Zou, L. (2015) Efficacy and safety of nerve growth factor for the treatment of neurological diseases. Neural Regeneration Research, 10, 819-828. doi:10.4103/1673-5374.156989
Write to Dr. Dewey at email@example.com.
Copyright © 2007-2017 Russ Dewey