1.3 Brain Development and Aging

The brain is a continuously developing organ, from a few weeks after conception to early adulthood in the mid to late twenties. There are various factors that directly affect the development of the brain. Prenatally, this process is driven by genetics but can also be affected by environmental factors such as nutrition and teratogens (factors to which pregnant women are exposed to that can result in fetal abnormalities). Postnatally, brain development is driven by experience in addition to the genetic makeup of each individual.

During embryonic development, about three weeks after conception, is when gastrulation occurs and three germ layers are created: ectoderm, mesoderm, and endoderm. These layers develop into different layers of the human body such as muscles. which originate from the mesoderm layer and the respiratory tract which originates from the endoderm layer. The ectoderm layer is where the human nervous system originates from, specifically the neuroectodermal stem cells that act as neural progenitor cells. Complex genetic signaling occurs to prepare these stem cells to transform into nervous tissue. Initially, the nervous system is characterized by the formation of a neural plate, which wraps around itself to form the neural tube. The cells on the inside of the neural tube give rise to the brain and spinal cord, while the cells on the outside of the neural tube give rise to the surrounding nerves outside of the CNS. Upon closure of the neural tube during three to four week of embryonic development, three primary vesicles are formed: (1) the prosencephalon which forms the forebrain, (2) the mesencephalon which forms the midbrain, and (3) the rhombencephalon which forms the hindbrain (Figure 19). After five-weeks of embryonic development, these vesicles further develop into five secondary vesicles: (1) the telencephalon and (2) the diencephalon both of which originate from the forebrain, (3) the mesencephalon, which is a continuation of the midbrain, and finally (4) the metencephalon and (5) the myelencephalon both of which originate from the hindbrain (Figure 19). Each of these five vesicles ultimately give rise to a myriad of subcortical structures that are key for proper brain function and human behavior.

The neural cells in each of the regions will undergo proliferation, migration, and differentiation to form the neurons and glial cells mentioned in previous sections. The formation of synapses, otherwise known as synaptogenesis, is first seen around the twenty-third week of gestation, however, this process will peak in the first year after birth. Early development during childhood is characterized by synaptogenesis and synapse pruning, which is how our brains learn during this period. Synapse pruning is the process by which the brain removes unnecessary synapses, as they are produced in excess, and this process is guided by experience. As the brain learns which synapses are important, it will strengthen those connections while weakening others that are not being used. Synapse production is connected to plasticity, and this differs among different regions of the brain in terms of when it occurs and for how long. The prefrontal cortex, for example, does not reach its synapse production peak until about fifteen months after birth. This is important because this region of the brain will remain plastic due to its late peak onset compared to other regions. Similarly, synapse pruning also differs among different brain regions depending on when and how long it occurs. For example, synapse pruning in regions relating to higher cognitive function will continue even through the adolescent years into early adulthood and is characteristic of brain maturation. This is also the case for myelination of the brain which is important for its development. Once again, myelination will differ in time and length based on the region of the brain, but like synapse pruning, myelination of the prefrontal cortex will complete in early adulthood, also contributing to maturation.

After the brain has developed and matured, it will start to change both physically and cognitively, as we age. After the age of forty, the brain will lose 5% of its volume each decade thereafter, and with this volume loss, the brain will shrink as a result. This is part of normal aging, not to be confused with pathological changes which may present similarly but are a result of a disease rather than the aging process. Gray matter and white matter both decrease with age, with lesions developing in the white matter in some individuals, and the vasculature in the brain ages and weakens, which in conjunction with higher blood pressures can increase the risk for strokes. Cortical thickness will also begin to decrease with age while ventricle volume will increase with age. Other physical changes include the degradation of myelin sheaths as well as a reduction in dendritic synapses and therefore plasticity as a result. As we age, the brain’s ability to change will steadily decrease, and in turn, this means the effort required for that change to occur will expectedly increase with age. As is the case in the development of the brain, changes due to aging affect brain regions differently as well. The prefrontal cortex is the most affected region by normal aging, while the occipital cortex is the least affected by normal aging. This leads to the symptomology often observed with normal aging which can affect memory and executive function for example. Aging also affects the hippocampus which results in problems with memory, which is the most common cognitive change seen with increasing age. Two of the four types of memory are the most affected by age and these are episodic and semantic memory.

There are also age-related brain changes seen on a molecular level. Neurotransmitters such as dopamine and serotonin are the most affected as they both decline with age. Sex hormones and growth hormones also decrease with age which can have a negative effect on cognition. There is also an increase in the production of monoamine oxidase and reactive oxygen species with age and these can be especially destructive to the brain and neurotransmitters if left unchecked. As the brain reduces in volume, this is referred to as atrophy, and this can result in a reduction of glucose metabolism which is needed for the brain to function properly.

Genetic factors and environmental factors can both affect normal aging. There are health risk factors which can promote the effects of aging on the brain, and these include diabetes, high cholesterol, and high blood pressure. However, there are also protective factors which can slow the effects of normal brain aging. These include having a healthy diet and regular exercise, low to moderate alcohol consumption, as well as obtaining a higher level of education.