CHAPTER8

Adult & Aging Brain

The previous chapter described how your brain changes as you grow — in overall size, number of cells, myelination, and synapse formation — even continuing to develop well beyond your teenage years. In fact, recent research suggests that maturation is still occurring in the third decade of your life. So when does a human brain finally reach maturity? What is the structure of a fully-formed adult brain? And what can it do that a developing brain cannot?

THE ADULT BRAIN

An adult brain differs from an adolescent brain in many ways. Between childhood and adulthood, a human brain loses gray matter as excess neurons and synapses are pruned away, although the rate of loss slows down by a person’s late 20s. At the same time, some brain regions strengthen their connections with each other, and the major nerve tracts become wrapped in insulating myelin, which increases the brain’s white matter. Around age 40, the white matter in the human brain has reached its peak volume.

Much of the added white matter represents increased connections between widely separated brain areas. During childhood and adolescence, most brain networks are locally organized, with areas near each other working together to accomplish a cognitive task. In adulthood, the brain’s organization is more widely distributed, with distant areas connected and working together.

The most important brain area to become fully “wired up” in adulthood is the prefrontal cortex (PFC) — the front (anterior) portion of the frontal lobe. This area handles many of our higher-level cognitive abilities such as planning, solving problems, and making decisions. It is also important for cognitive control — the ability to suppress impulses in favor of more appropriate responses. Adult brains are better “wired up” for cognitive control than are adolescent brains, in which decision-making is more highly influenced by emotions, rewards, and social influences.

Desmazieres, et al. Journal of Neuroscience, 2014

As the brain matures, a fatty substance called myelin wraps around axons to speed up electrical transmission. This image shows axons wrapped in myelin, with exposed areas in the middle called nodes of Ranvier.

Intelligence also peaks during early to middle adulthood, roughly ages 25 to 60. However, different cognitive abilities have distinctive patterns of maturation. Fluid intelligence, which includes abilities like solving problems and identifying patterns, peaks around age 30. By contrast, crystallized intelligence, which deals with vocabulary and knowledge of facts, increases until about age 50. Some scientists speculate that there is no single age at which all (or even most) of our cognitive functions are at their peak.

WHAT IS AGING?

Normal vs. Pathological Aging

Aging is a dynamic, gradual process. While it can be characterized by resilience in both physical and neurological health, too often aging increases the risk of injury and disease. One such risk is dementia, a decline in cognitive ability that interferes with a person’s day-to-day functioning. While aging is inevitable, dementia and disability are not. In fact, neuroscientists believe our brains can remain relatively healthy as we age. Pronounced decline in memory and cognitive ability, once thought to be part of normal aging, are now recognized as separate disease processes in the aging brain. Although the brain loses some neurons as we age, a widespread and profound loss of neurons is not part of normal aging.

Nonetheless, some mental decline is normal. The continuous process of aging involves subtle changes in brain structure, chemistry, and function that commonly begin in midlife. Some studies suggest that cognition starts declining as early as the 20s and 30s, while other studies indicate that cognition improves into the 50s or 60s, before declining. A growing area of neuroscientific research focuses on understanding “healthy aging,” which includes lifestyle choices, such as diet and exercise, which support cognitive health throughout life.

HOW THE BRAIN CHANGES

Cognitive Changes

Subtle changes in cognition are a normal part of the aging process, with memory decline being the most common. However, not all types of memory are affected; declarative memory declines with age, but nondeclarative memory remains largely intact.

As you learned in Chapter 4, declarative memory includes autobiographical memory of life events, called episodic memory, and memory of learned knowledge, or semantic memory. Nondeclarative memory includes procedural memory like remembering how to ride a bike or tie a shoe.

Working memory — the ability to hold a piece of information in mind and manipulate it (for example, looking up a phone number and reciting it as you dial) — also declines with age. Some studies suggest that a slow decline starts as early as age 30. Working memory, an example of the fluid intelligence mentioned above, is a set of cognitive skills that depend on rapid processing of new information rather than on stored knowledge. Other aspects of fluid intelligence, such as processing speed and problem-solving, also decrease with age.

Certain aspects of attention can also become more difficult as our brains age. For example, it might be harder to focus on what friends are saying when we’re in a noisy restaurant. The ability to focus on a particular stimulus and filter out distractions is called selective attention. Another type of attention, divided attention, refers to the ability to focus on two tasks at the same time. Activities that require this type of split focus — such as holding a conversation while driving — also become more challenging with age.

Structural Changes

All of these alterations in cognitive ability reflect changes in the brain’s structure and chemistry. As we enter midlife, our brains change in subtle but measurable ways. Studies using brain imaging techniques have revealed that total brain volume begins to decline when people are in their 30s or 40s, and starts declining at a greater rate around age 60. However, studies of individual brain regions suggest that the volume loss is not uniform throughout the brain. Some areas appear to shrink more, and faster, than other areas. The prefrontal cortex, cerebellum, and hippocampus show the biggest losses, which worsen in advanced age.

Several changes at the level of individual neurons can also contribute to the decreased volume seen in aging brains. The changes in aging are due to shrinking neurons, retraction and decreased complexity of dendrites, and loss of myelin. In contrast, the volume loss in adolescence is primarily driven by synaptic pruning and the death of excess cells.

Our cerebral cortex, the wrinkled outer layer of the brain containing neuron cell bodies, also thins as we age. Cortical thinning follows a pattern similar to volume loss, with some regions of the brain affected more than others. Thinning is especially pronounced in the frontal lobes and parts of the temporal lobes.

The temporal and frontal lobes are among the areas that demonstrate the most pronounced declines in both volume and cortical thickness. These are the areas that took longest to reach maturity. This finding has led to a “last in, first out” theory of brain aging, which holds that the last parts of the brain to develop are the first to deteriorate. Interestingly, studies of age-related changes in white matter support this hypothesis. The first of the brain’s long-distance fibers to develop are the projection fibers that connect the cortex to lower parts of the brain and spinal cord. Fibers connecting diffuse areas within a single hemisphere — association fibers — are the last to reach maturity, and show the steepest functional declines with age.

Neuronal Changes

The aging brain also undergoes numerous changes at synapses. Although the synaptic changes are selective and subtle, their effect on cognitive decline is believed to be greater than the effects of structural and chemical changes. In the prefrontal cortex and hippocampus, scientists have observed alterations in dendrites, the branching processes that receive signals from other neurons. With increasing age, the dendrites shrink, their branches become less complex, and they lose dendritic spines, the tiny protuberances that receive chemical signals.

A study in rhesus monkeys observed that the aging process targets a certain class of spines called thin spines. These small, slender protuberances are also highly plastic structures, extending and retracting much more rapidly than the larger “mushroom” class of spines. This has led scientists to speculate that thin spines might be involved in working memory, which requires a high degree of synaptic plasticity. The loss of thin dendritic spines could impair neuronal communication and contribute to cognitive decline. So far, direct evidence of their role in cognitive decline is lacking, and more studies are needed.

Finally, the formation of new neurons also declines with age. Although neurogenesis was once believed to halt after birth, we now know of two brain regions that continue to add new neurons throughout life: the olfactory bulbs and the dentate gyrus of the hippocampus. Studies suggest that the rate of neurogenesis plummets with age in mice, but recent human studies suggest a more modest decline. It is not yet clear whether neurogenesis appreciably affects cognition in the aging human brain, but mouse studies indicate that strategies that boost neurogenesis can enhance cognitive function.

Many different theories have been advanced to explain why neurons, and cells in general, age.

Chemical Changes

The amount of neurotransmitters and the number of their receptors might also decline with age. Several studies have reported that less dopamine is synthesized in the aged brain, and there are fewer receptors to bind the neurotransmitter. Less robust evidence indicates that the amount of serotonin might also decline with age.

WHY DOES THE BRAIN AGE?

From cortical thinning to the loss of dendritic spines, you’ve seen how the brain ages. But what causes these changes? Many different theories have been advanced to explain why neurons, and cells in general, age. One possibility is that changes in gene expression play a role. Researchers have found that genes important for synaptic plasticity are expressed less in the brains of older people than in the brains of younger adults. The underexpressed genes also showed more signs of damage.

Oxidative Stress and DNA Damage

DNA damage that accumulates over a lifetime could contribute to aging processes throughout the brain and body, and DNA damage due to oxidative stress has received a great deal of attention. Every cell in your body contains organelles called mitochondria, which function a bit like cellular power plants, carrying out chemical reactions that provide energy for cell use. Some of these metabolic reactions produce harmful byproducts called free radicals, highly reactive molecules which, if left unchecked, can destroy fats and proteins vital to normal cell function and can damage DNA as well.

Your body has natural defense mechanisms to neutralize free radicals. Unfortunately, these mechanisms decline with age, leaving aging tissues more vulnerable to oxidative damage by the free radicals. Studies of brain cells have shown that damage to their mitochondrial DNA accumulates with age. In addition, the brains of people with mild cognitive impairment and Alzheimer’s disease show more signs of oxidative damage than the brains of healthy people. Studies in rodents also link increased oxidative damage to memory impairments.

Your brain is one of the most metabolically active organs, demanding around 20 percent of the body’s fuel. Its enormous energy requirements might make the brain even more vulnerable than other tissues to the metabolic changes that occur in aging. While the brain’s energy demands remain high, its energy supply can no longer keep pace; the brain’s ability to take up and use glucose diminishes and mitochondrial metabolism declines.

Immune Dysfunction

Immune dysfunction often occurs in conjunction with the metabolic changes seen in aging. Microglia, the brain’s resident immune cells, perform many important jobs: defending against pathogens, cleaning up cellular debris, and helping maintain and remodel synapses. These inflammatory responses are protective, but a prolonged inflammatory state is harmful to brain health. Microglia become more reactive with age, increasing the inflammatory response in the brain while also damping production of helpful anti-inflammatory molecules. Mouse studies suggest that excessive microglial activity also contributes to cognitive impairments.

Synapses begin to weaken as a person ages, which can contribute to normal cognitive decline.

Impaired Protein Recycling

We know that excessive buildup of abnormal proteins in the brain contributes to age-related neurodegenerative diseases like Alzheimer’s and Parkinson’s. Buildup of proteins and other cell components can also contribute to cellular degeneration in the healthy brain. Cells normally break down and recycle damaged proteins and molecules, using a process that is usually efficient but not perfect. Over time, damaged molecules can build up in cells and prevent them from functioning normally. Because neurons in the brain are not replaced as often as cells in other parts of the body (for example, bone marrow, intestinal lining, hair follicles), brain cells might be even more vulnerable to this buildup of damaged molecules. Also, the cellular machinery involved in breakdown and recycling processes degrades with age, reducing the efficiency of the “waste removal” systems.

Finally, remember that changes in the aging brain occur within the context of other changes throughout the body. Researchers speculate that worsening cardiovascular health, for example, could contribute to, or even drive, many changes seen in the aging brain.

HEALTHY AGING

We have learned how the brain changes with age and why these changes can occur. Now let’s turn our attention to a growing field in neuroscience that explores ways to slow these changes and preserve healthy brain function.

Diet and Exercise

Strong evidence now suggests that habits and choices that keep your body healthy also benefit your mind. Poor cardiovascular health puts a person at increased risk of age-related cognitive impairment. Diets rich in vegetables, fruits, and whole grains, and low in meat and dairy products, can reduce cardiovascular risk factors linked to cognitive impairment, such as high blood pressure and high levels of LDL cholesterol. Indeed, observational studies have found that people who follow plant-rich diets such as the Mediterranean diet or Dietary Approaches to Stop Hypertension (DASH) are less likely to develop cognitive decline and dementia.

Specific nutrients have been linked to improved cognitive performance and lower rates of dementia. Antioxidants, such as vitamins C and E, flavonoids, and omega-3 fatty acids have received considerable attention, with observational studies showing that high dietary intake of these compounds is beneficial. However, the results of lifestyle intervention studies using supplements have been more mixed. Finally, caloric restriction — substantially reducing the number of calories eaten without leading to malnutrition — has been linked to improved cognitive health as well as a longer lifespan.

iStock.com/artyme83.

Exercise has been shown to increase neurogenesis in the adult brain, and can slow the cognitive decline associated with aging.

Growing evidence shows that aerobic exercise can improve cognitive function and offset some of the declines seen in aging. Numerous studies have found that people who engage in regular physical activity show improved learning, improved memory, and a reduced risk of developing dementia. Physical activity might even slow the progression of Alzheimer’s disease and dementia, and higher levels of physical activity have been linked to improvements in some markers of structural brain health, such as reduced cortical thinning and less shrinkage in the hippocampus.

Exercise exerts its neuroprotective effects in the brain by improving neuroplasticity — the brain’s ability to form and reorganize connections between neurons in response to changes in behavior and environment. Scientists also believe that exercise increases neurogenesis (the formation of new nerve cells) which, in turn, enhances neuroplasticity. Evidence from rodent studies confirms that exercise increases neurogenesis: Older mice allowed to run on a wheel have higher rates of neurogenesis in the hippocampus than sedentary mice, and they perform better on learning and memory tests. Exercise can also improve blood flow and increase production of neurotrophic factors that support new neurons and synapses. For humans, starting exercise later in life can be beneficial, but the studies suggest that adopting an exercise program earlier in life could yield even more neuroprotective benefits.

Mental Stimulation and Social Networks

Mental stimulation and large social networks can also improve cognitive function in aging. In lab studies, mice housed in cognitively stimulating environments with many opportunities for social interaction perform better on learning and memory tests as they age compared to mice housed in standard cages. Much like physical exercise, cognitive stimulation appears to enhance neuroplasticity by increasing neurogenesis and boosting levels of important neurotrophic factors.

People who perform cognitively-demanding work or engage in stimulating activities such as reading, solving puzzles, or playing a musical instrument have lower rates of cognitive decline with aging. An active social life has also been shown to be beneficial for cognition as we age.

Neuroscientists have learned a lot about the aging brain — how it changes, why it changes, and how to maintain healthy cognitive functioning as we age. Even so, many questions remain. Answers to those questions could identify new strategies for protecting the brain, not only in our later years, but throughout our lives.