Aging Brain and Neurological Changes
2.2 The Aging Brain: Structural Changes in Normal Aging .1 Basic Anatomy
© Springer International Publishing AG 2018 15
S. Masiero, U. Carraro (eds.), Rehabilitation Medicine for Elderly Patients, Practical Issues in Geriatrics, DOI 10.1007/978-3-319-57406-6_2
H. Ihle-Hansen, MD (*) • H. Ihle-Hansen, MD, PhD
Department of Research, Vestre Viken Hospital Trust, Bærum Hospital, 3004 Drammen, Norway
e-mail: [email protected]; [email protected]
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through synapses, a chemical transmission, in which a signal is transferred to the next cell in the signal path. It is believed that our intelligence, memory, emotions, and behavior are stored and regulated through activity and interplay in these com- plex circuits. A modern conception views the function of the nervous system partly in terms of stimulus-response chains and partly in terms of intrinsically generated activity patterns, meaning spontaneous cell-generated activity.
The neurons are electrically excitable cells consisting of soma and neurites (one axon and dendrites). Neuron geometry is associated with functions: number of syn- apse, signal patterns, location remove and pattern of connection (Fig. 2.1).
Most neurons send signals via their axons, although some of them are capable of dendrite-to-dendrite communication.
2.2.2 Basic Physiology
The cell communicates through the action potential (AP). Prerequisite to develop an action potential are ion channels, a lipid bilayer and a potential across the mem- brane. Action potentials are generated by voltage-gated ion channels embedded in the membrane. These channels are shut when the membrane potential is near the membrane potential of the cell, but they rapidly begin to open if the membrane potential increases to a precisely defined threshold value. The shift in membrane polarity leads aging to inactivity in the ion channels. This is the start of the repolar- ization phase, ending with the cell again assuming its steady-state condition. The AP propagates along the neuron’s axon toward its ends and thereby connects with other neuronal synapses, motor cells or glands.
As the AP reached the axonal end, the electrical potential is transformed into chemical signals. This happens in the synapse. The AP leads to release of neu- rotransmitters, which are stored in presynaptic vesicles, into the synaptic cleft. Then the neurotransmitters diffuse to the postsynaptic membrane (on the dendrite), bind to a receptor, and induce a signal that can be excited or inhibited. In other words, synaptic inputs to a neuron cause the membrane to depolarize or hyperpolarize.
A chemical synaptic transmission provides flexibility and provides the opportu- nity to a wide range of chemical transmitters and receptors in a single synapse.
Anatomic part Function
Soma Cell body of a neuron
Any process extending from the body of a neuron A neurite, that often project to another region.
Specialized to conduct axons potential. A neuron has in general one axon, which again can have a lot of branches
A local neurite. The number of dendrite correlates with the input. Primary function receiving axonal input.
Neurite Axon
Dendrite
Fig. 2.1 Anatomic parts of the neuron and their function
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Formation of the synapses and the plasticity of the synapses changes over time and during the normal aging. Biochemical changes seem to play an important role in the aging brain. Alteration in syntheses and turnover of neurotransmitters has been observed. The reduction of dopamine synthesis and dopamine receptors has been linked to motility disturbance and change in cognitive flexibility. Alterations in calcium regulation, glutamate, and serotonin are also described. Calcium plays an important role in neuronal firing and propagation of AP. Glutamate is an excitatory neurotransmitter, and it is a documented age-related decrease, especially in the pari- etal gray matter and basal ganglia. Interconnections of neuronal network are involved in human cognition and mental life and are thought to represent a cognitive reserve. The neuronal degeneration is part of the normal aging process.
2.2.3 Synaptic Plasticity
Through learning we can build, strengthen, or remodel the circuits. This leads to structural and biochemical changes, as a response to increase or decrease in their activity, with the development of new synapses and up- and downregulations of neurotransmitters, receptors, and ion channels.
Synapses are capable of forming memory traces by means of long-lasting increase in signal transmission between two neurons—a change in synaptic strength. One of the most interesting and studied forms of neural memory is the long-term potentiation, which was first described back in 1973, but is still not fully understood. The phenomenon is characterized by the fact that the neurotransmitter glutamate acts on a special type of receptor known as the NMDA receptor. The NMDA receptor has an “associative” property: if the two cells involved in the syn- apse are both activated at approximately the same time, a channel opens that per- mits calcium to flow into the target cell. A second messenger induces a cascade that ultimately leads to an increase in the number of glutamate receptors on the target cell, thereby increasing the effective strength of the synapse. This change in strength can last for weeks.
2.2.4 Structural Changes
The reason why the brain atrophies or shrinks in size with age is not completely understood.
It is assumed that normal healthy aging is associated with numerous structural, chemical, gene expression and functional changes. Downregulation and genetic and environmental factors are central concepts, and there is a thin line between normal aging and pathology. Over the past decade, the introduction of new radiological modalities has made it possible to measure brain volume and in some part brain activity in healthy aging individuals. Gray matter as well as white matter volume decreases with age. Some regions are especially vulnerable to gray matter loss, such as insula and superior parietal gyri. On the other hand, some regions are spared to
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this decrease in gray matter, such as the occipital cortex surrounding the calcarine sulcus and the cingulate gyrus. The decrease in volume is assumed not to be driven by loss of neurons or cell death, but through a decrease in spine density and synaptic alterations.
Age-related cognitive decline varies among older persons. Factors involved in this variability include genetics, education, occupational engagement, comorbidi- ties and co-medications. In addition, lifestyle factors like nutrition, smoking, alco- hol use, and physical activity and vascular risk factor have an impact on this decline.
Amyloid plaques, which are linked to Alzheimer’s disease (AD), are supposed not to be found in a healthy brain. On the contrary, neurofibrillary tangles may be present in some regions and part of a normal aging process. The number of tangles in a cell is relatively low in a healthy brain and only located in amygdala, entorhinal cortex, the olfactory nucleus and parahippocampal gyrus. Findings of tangles in other specific locations may however indicate pathology.
DNA damage accumulates with age, leading to reduced expression of genes that are involved in learning, memory, and behavioral pattern. DNA damage is partly induced by oxidative stress, also linked to mitochondrial dysfunction. Environmental and lifestyle factors lead to vascular changes with potential disturbance in the cere- bral blood flood and blood-brain barrier.
2.2.5 Neuroplasticity
The brain is a dynamic organ that has a natural ability to adapt and change with time, called brain plasticity or neuroplasticity. Even after a CNS injury, the brain changes by setting up new connections and paths between neurons, building new and strength- ening existing circuits. We now know that the brain can create new neurons in some parts of the brain, although the extent and purpose of this is still uncertain.
Plasticity of the brain occurs at every stage of development throughout the life cycle. Plasticity is more likely to occur when there is stimulation of the neural sys- tem, meaning that the brain must be active to adapt. Development of new neuronal network through exposure to a stimulating environment leads to structural changes and improved skills. These changes do not occur quickly; the recovery goes on for months and sometimes years.
Education, occupation and cognitive activity have been found to be associated with higher cognitive performance and delay of cognitive impairments. A lifetime intellectual enrichment is thought to represent a preventive intervention for cogni- tive decline and dementia. By keeping the cognitive activity constant throughout the lifespan, we may protect the brain and delay the onset of cognitive impairments for 5 years! Specific training is linked to both faster response and general cognitive improvement.
There is a growing body of evidence regarding the benefit of exercise in terms of neuroplasticity and the ability of the brain to self-repair. In particular, goal-based exercises and aerobic exercises increase synaptic strength (increasing neurotrans- mission, receptor density, and dendritic spine formation) and improve brain health
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by increasing trophic factors, blood flow, immune system, neurogenesis, and metab- olism. Therefore, the strengthening of the circuitry of basal ganglia, cortex, thala- mus, cerebellum and brainstem results in improved motor and cognitive behavior, mood and motivation.
2.3 The Aging Brain: Functional Changes