BRAIN NEUROANATOMY AND NEUROPATHOLOGY
The normal brain A comprehensive neuroanatomical review is beyond the scope of this course, but a brief refresher on the primary regions and accompanying functions of the brain may facilitate understanding of the pathology of AD. The brain stem (made up of the midbrain, pons, and medulla) is most notable for regulation of vital life functions, such as respiration, cardiac function, some reflex activities (e.g., coughing, vomiting, swallowing), and autonomic functions (e.g., vasomotor tone). The cerebellum plays a large role in motor function via its influence on muscle tone, coordination of movements, and control of posture and balance. The cerebellum does not initiate motor commands, but modulates and adapts movement to situational needs. The left and right cerebral hemispheres communicate via the corpus callosum, a thick bundle of heavily myelinated nerve fibers, allowing for rapid transmission and communication between hemispheres. The cerebral hemispheres are anatomically divided into frontal, temporal, parietal, and occipital lobes. The frontal lobes, the most anterior part of the brain, house our unique personalities and intellects and control executive functions such as thinking, planning, memory, attention, and problem solving. The motor cortex is located at the most posterior aspect of the frontal lobe, and, upon the integration of sensory, cognitive, and memory data, is responsible for goal-directed movement. The lower portion of the left frontal lobe (in the majority of left-brain dominant individuals) contains Broca’s speech area, which is responsible for speech and language production. Positioned posterior to the frontal lobes, the parietal lobes house the somatosensory cortex and interpret sensory information (e.g., pain, touch, taste, and visuospatial cues). The temporal lobes, located along the inferior lateral aspect of the brain, house the primary auditory cortex and Wernicke’s speech area (left side), which allows the individual to interpret sounds and language. Taste and smell capabilities are also located in the temporal lobe. The temporal lobe is home to the hippocampus, a structure that is vital to new learning and the formation, storage, and retrieval of short-term memories, as The brain in Alzheimer’s disease Serious memory loss (that impacts function), confusion, and major changes to executive functioning are not components of normal aging. They may be signs that brain cells are failing. In an effort to facilitate early diagnosis, the Alzheimer’s Association has introduced the Know the 10 Signs campaign (Alzheimer’s Association, 2018b). Ongoing issues with any of the following 10 signs may be of concern: 1. Memory loss that disrupts daily life. 2. Challenges in planning or solving problems. 3. Difficulty completing familiar tasks at home, at work, or at leisure. 4. Confusion with time or place. 5. Trouble understanding visual images and spatial relationships. 6. New problems with words in speaking or writing. 7. Misplacing things and losing the ability to retrace steps. 8. Decreased or poor judgment. 9. Withdrawal from work or social activities. 10. Changes in mood or personality. Often older adults become overly concerned when they acknowledge that they are not as “sharp” or “fast” as they used to be, or if they notice themselves struggle a bit with word finding or multitasking. It is useful to encourage older individuals to compare themselves to their age-matched peers as opposed
well as the conversion of short-term memories into long-term memories; it is implicated early in the course of AD. The predictable pattern of AD pathology and the close proximity of the hippocampus to areas responsible for taste and smell help to explain the degradation of these senses in many individuals with AD. The occipital lobes, on the posterior aspect of the brain, are responsible for interpretation of visual information. The term limbic system describes a functional and anatomical interconnectedness among several brain structures, including the hypothalamus, amygdala, and hippocampus. The hypothalamus monitors bodily activities, such as temperature and appetite, and influences the body’s endocrine functions, including the release of key hormones. The amygdala has a role in the fight-or-flight response and plays a major role in emotional responses and emotional memory. The thalamus, superior to the brain stem in the center of the brain, is a relay station for sensory and limbic information coming into the brain. The ventricular system is a communicated system of CSF with two lateral ventricles and the more centrally located third and fourth ventricles. The human brain is made up of billions of neurons. Each neuron has a cell body with a nucleus that controls the cell’s activities, an axon, and many dendrites. The axon extends out from the cell body and transmits electrical impulses or messages to other neurons. Dendrites branch out from the cell body to receive messages from other nerve cells. Each nerve cell is connected to thousands of other nerve cells through its axon and dendrites. Neurons communicate with one another through the transmission of electrical impulses and the release of neurotransmitters. Typical aging brings structural and functional changes to the brain. There is shrinkage in brain volume and increase in ventricle size. The volume changes in the normal aging brain appear to be less related to neuronal loss and more related to shrinkage of neurons, decrease in synapses, and decreased length of myelinated axons (Fjell & Walhovd, 2010). Cognitive changes with normal, healthy aging include decreased processing speed, slower retrieval, and benign forgetfulness. to their younger selves when they evaluate their own cognitive abilities. This can be reassuring to individuals experiencing typical aging effects. Table 2 represents the contrast between typical and atypical (pathological) cognitive and memory changes. In individuals with AD, the brain undergoes the typical changes of aging, and it also demonstrates pathological changes that impair neuronal activity and eventually destroy brain tissue. The pattern of destruction is somewhat predictable. Initially, neurons in the hippocampus, a key area of the brain involved in memory, are affected. As stated previously, amyloid plaques and neurofibrillary tangles are the pathological hallmarks of AD. Beta-amyloid is an insoluble protein fragment that is also seen to a lesser degree in the normal aging brain. It is not entirely clear whether beta-amyloid is a cause or a by-product of AD. These abnormal clusters of protein fragments build up between cells and create plaques that block cell-to-cell transmission. Neurofibrillary tangles are twisted fibers of abnormal tau protein. Tau protein is present in a normal aging brain, but it is chemically altered and present in abundance in the AD brain. Neurofibrillary tangles are present within the neuron’s microtubule transport system and inhibit the cell’s ability to import and utilize essential nutrients. Figure 2 represents these typical pathological changes in AD.
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