If you ask older adults to describe their experience of changes in their central nervous system, it’s likely that they will be hard pressed to do so. This is because the age-related changes in the brain that we will consider begin very subtly; they are often difficult to notice in the beginning and to document because they are microscopic and are hard to tie to specific behaviors. Changes in the brain occur mainly at the level of individual brain cells, called neurons. Much of what we have learned about age-related brain changes has come from highly sophisticated computer-enhanced imaging techniques and from careful research in neuroscience (described in Chapter 2). In this discussion we consider primarily changes that are currently
viewed as normative. Abnormal brain aging, such as that which occurs in Alzheimer’s disease, is considered in more detail in Chapter 4.
As you can see in Figure 3.6, neurons have several parts that play specialized roles in receiving, conducting, and transmitting information. At the left end of the neuron in the figure are the dendrites, which pick up the chemical signals coming in from other nearby neurons much as TV antennae pick up signals from nearby stations. The signal is brought into the cell body, where it is converted into an electrochemical impulse and sent down the axon to the terminal branches. The terminal branches, shown at the right end of the drawing, act like transmitter stations. Chemicals called neurotransmitters are released at the terminal branches and carry the information signal to the next neuron’s dendrites. The neurotransmitters are necessary for communication between neurons because neurons do not physically touch one another. The gap between the terminal branches of one neuron and the dendrites of another, across which neurotransmitters travel, is called the synapse.
We are born with roughly 1 trillion neurons of different sizes and shapes, which constitute all the neurons we will ever have. The good news is that neurons can grow in size and complexity
across the life span; the bad news is that, like heart muscle cells, neurons cannot regenerate (Green & Ostrander, 2008). Once a neuron dies, it is lost forever. But we will also see that there is a line of exciting research that indicates the brain may be able to resist negative changes and provide alternative ways to process information.
Individual neurons undergo a wide variety of normative age-related changes. In most people, these changes produce little noticeable difference in behavior until very old age. However, when the changes are widespread and occur more rapidly, disease typically is present. One problem in differentiating between normal and abnormal brain aging is that many of the same changes underlie both; for example, the defining characteristics of brain changes in Alzheimer’s disease also are normative. So in order to differentiate normative and abnormal brain aging, repeated assessment using sophisticated brain-imaging techniques is usually necessary (Carlson et al., 2008).
A second problem is that although we have documented many neuronal changes, we understand the implications of only a few. Tying specific brain changes to specific behaviors is very difficult. However, significant advances have been made using sophisticated brain-imaging techniques.
Structural Changes in Neurons. How does the structure of neurons change with age? The most important change in the cell body and axon involves changes in the fibers contained there. Sometimes, for reasons we do not understand, neurons in certain parts of the brain develop neurofibrillary tangles, in which fibers in the axon become twisted together to form paired helical, or spiral, filaments (Green & Ostrander, 2008). Large concentrations of neurofibrillary tangles are associated with behavioral abnormalities and are one defining structural brain change characteristic of Alzheimer’s disease (Wippold, 2008). However, researchers do not yet understand what causes neurofibrillary tangles or why the rate of change differs across people. To complicate matters even more, some degree of neurofibrillary tangling occurs normally as we age. This is an example of why it is sometimes difficult to tell the difference between normal and abnormal aging.
Changes in the dendrites are complex. As some neurons deteriorate and die, there is a compensatory lengthening and increase in the number of dendrites of the remaining neurons (Matus, 2005). There is ample evidence, though, that the organization of the brain’s circuitry is constantly changing as a result of experience (Kolb et al., 2003; Matus,
2005) . This capability of the brain to adapt its functional and structural organization to current requirements is called plasticity (Matus, 2005; Roder & ROsler, 2003).
One promising line of research shows that exercise may be an effective way to enhance brain health and plasticity (Churchill et al., 2002; Cotman & Berchtold, 2002). Voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF) and other brain growth factors, which play a major role in supporting the survival and growth of neurons (Cotman & Berchtold, 2002; Lu, 2003). In addition, these compounds help make synapses work more efficiently and effectively, and foster the creation of alternative pathways to process information. All these effects help keep brain function intact, thereby possibly slowing the rate of change.
The new connections between the dendrites may make up for the loss of neurons, but only to a point. Eventually, the loss of neurons outpaces the ability of remaining neurons to make connections. The rate of this shift may be a difference between normal and abnormal aging, but additional research on this issue is necessary.
Damaged and dying neurons sometimes c ollect around a core of protein and produce amyloid plaques. Brain-imaging techniques show that amyloid plaques can develop in various parts of the brain (Nordberg, 2008). Although the number of neuritic plaques increases with age, large numbers of them are not observed in normal brain aging until late in life. Until then, high concentrations of neuritic plaques are considered characteristic of abnormal aging; for example, they are also indicative of Alzheimer’s disease (Nordberg, 2008).
The normative loss and growth pattern in neurons may provide insight into abnormal brain aging. It could be that abnormal brain aging occurs when losses greatly outnumber gains before very old
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age. This is clearly the case in conditions such as Alzheimer’s disease and related disorders, in which there is massive progressive loss of neurons in many areas of the brain.
Changes in Communication between Neurons. Because neurons do not physically touch one another, they must communicate by releasing neurotransmitters into the synapse. Are there age-related changes in neurotransmitters? Yes, and the changes help us understand why some older adults experience certain kinds of problems and diseases. Changes in the level of neurotransmitters affect the efficiency of information transmission between neurons. Age — related changes occur along several neurotransmitter pathways, which are groups of neurons that use the same neurotransmitter (Whitbourne, 1996a).
One pathway in the brain that is responsible for controlling motor movements uses the neurotransmitter dopamine. As we age, the level of dopamine decreases; if this decline is extreme due to the loss of dopamine-producing neurons, we develop Parkinson’s disease (National Institute ofNeurological Disorders and Stroke, 2008). Parkinson’s disease is characterized by four key sets of symptoms: tremors of the hands, arms, and legs, which decrease when one is performing voluntary tasks; rigidity or stiffness in the arms, legs, and trunk; difficulty keeping one’s balance; and a shuffling walking style
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Jamie McCarthy/Wirelmage for The Michael J Fox Foundation/Getty Images |
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Parkinson’s disease has become better known because it has struck famous people, such as Michael J. Fox. |
(National Institute of Neurological Disorders and Stroke, 2008). Many famous people, including former boxer Muhammad Ali and actor Michael J. Fox, have Parkinson’s disease.
Recent evidence indicates that Parkinson’s disease may be induced by frequent use of MDMA, more commonly known as “ecstasy” (Kuniyoshi & Jankovic, 2003). The drug’s effects on the dopamine system appear to trigger the symptoms of the disease.
Although there is no cure, medications or surgery can alleviate the symptoms of Parkinson’s disease, and researchers have discovered a gene they believe is responsible for a form of Parkinson’s that may result in future innovative treatments. One drug, L-dopa, is converted into the neurotransmitter dopamine, which helps restore the normal balance of the neurotransmitter (National Institute of Neurological Disorders and Stroke, 2008). Drugs that mimic dopamine’s role in the brain also allow patients to regain some of their lost muscle control.
Additionally, two catechol-O-methyltransferase (COMT) inhibitors (e. g., entacapone and talcapone) are approved for use with L-dopa in the United States (National Institute of Neurological Disorders and Stroke, 2008). COMT inhibitors block a key enzyme responsible for breaking down L-dopa before it reaches the brain, making L-dopa more effective. Surgical interventions include “brain pacemakers,” which consist of a wire surgically implanted deep within the brain and connected to a pulse generator, similar to a cardiac pacemaker, implanted near the collarbone. Whenever a tremor begins, a patient can activate the device by passing a handheld magnet over the generator. Other surgical interventions include destroying certain parts of the brain that are overactive in Parkinson’s disease (National Institute of Neurological Disorders and Stroke, 2008).
Recently, much attention has been focused on transplanting fetal tissue containing dopamine neuron precursors as a potential treatment for Parkinson’s disease; this approach has shown some promise (Svendsen, 2008). Because stem cells are the parent cells of all tissues in the body, researchers believe that one day they may be able to direct the cells to become dopamine-producing neurons that could provide a treatment, but not a cure (Svendsen, 2008).
Despite the range of therapies available to ease the disease’s debilitating symptoms, however, treatments now on the market can neither replace the faulty nerve cells that cause the disease nor stop Parkinson’s from progressing.
Age-related declines in other neurotransmitters are well documented. For example, the age-related declines in the neurotransmitter acetylcholine are linked with both normative memory problems in old age and several diseases (Katz & Peters, in press). Research interest in acetylcholine is spurred by its link to both Alzheimer’s disease and Huntington’s disease. For example, levels are reduced by as much as 90% in Alzheimer’s disease (Giacobini,
2003) . Much of the search for drugs to alleviate the symptoms of Alzheimer’s focuses on this and other enzymes related to acetylcholine.
In a thorough review of the clinical evidence concerning compounds that are thought to affect the brain mechanisms underlying memory, McDaniel, Maier, and Einstein (2002) conclude that very little evidence supports the idea that there may be “brain-specific” nutrients that enhance memory. They point out that early positive results in animal research do not always translate into human benefits, and that the complex brain processes involved in cognitive functioning make it difficult to isolate individual compounds that are effective. Dodge and colleagues (2008) concluded that the use of compounds such as Ginkgo biloba may help prevent mild cognitive decline, but only when participants adhered to the scheduled dosage. But because the experimental group also had more strokes, they concluded that the results were too tentative to draw any firm conclusions.