15.4 Brain Disorders in Late Adulthood

Vascular Dementia

Vascular dementia is the second most common form of dementia. (Alzheimer’s disease, the most common, is discussed later.) Vascular dementia’s cognitive symptoms and declines are associated with blocked blood flow to the brain, typically the result of a stroke, that results in cell damage or death in the affected part of the brain. There are two major types of stroke.

• An ischemic stroke occurs when a blood clot prevents an area of the brain from receiving enough blood or oxygen. While ischemic strokes can be fatal, they can also occur as less severe mini-strokes that disrupt blood flow for only a short time, resulting in less severe symptoms that can sometimes go undetected.
• A hemorrhagic stroke tends to be more severe, often with a sudden onset, and is much more likely to be fatal. A blood vessel in the brain ruptures, resulting in bleeding that deprives an area of the brain of sufficient blood flow and oxygen.

All types of strokes are associated with a high risk of vascular dementia; however, not all stroke victims experience it (Kalaria et al., 2016). The cognitive problems associated with vascular dementia can occur suddenly or slowly worsen over time. Their nature varies widely, depending on the area of the brain that was affected; for example, a left-hemisphere stroke is more likely to produce difficulty with speech, because the left hemisphere typically contains the parts of the brain important for language use. Strokes often produce other symptoms, such as problems with balance and motor control and paralysis on one side of the body.

Insufficient flow of blood related to heart conditions including heart failure can result in hypoxia, which occurs when lack of oxygen damages body tissues. When this occurs in brain tissue, it can also contribute to vascular dementia (Calabrese et al., 2016). Risk factors for strokes, heart disease, and vascular dementia are all similar and include lack of exercise, an unhealthy diet, smoking, high alcohol consumption, high blood pressure, and high cholesterol. Like the symptoms of stroke, cognitive problems associated with vascular dementia can improve over time if the underlying cause of the stroke or heart condition is addressed and no further damage to the brain occurs. If disruptions in blood flow continue, the dementia will also likely worsen (Alzheimer’s Association, n.d.-a).

Lewy Body Dementia and Parkinson’s Disease

Lewy body dementia is the third most common type of dementia. It’s caused by deposits of a specific protein found in the cortex of the brain (Figure 15.19). These protein deposits, called Lewy bodies, have been linked to loss of the neurons responsible for producing neurochemicals, such as acetylcholine (which plays a role in attention, learning, and memory) and dopamine (related to experiencing pleasure, motivation, sleep, and cognition). The most common symptoms of Lewy body dementia are visual hallucinations, difficulty paying attention, and difficulty with thinking and judgment. These tend to change drastically over short periods of time, going from nearly nonexistent to severe and back again without any apparent reason. Other symptoms are related to motor skills and include stiffness, slow movement, and shaking (Orad & Shiner, 2022).

Figure 15.19 (a) This image shows a healthy brain with the hippocampus outlined in red. (b) In this image of a brain afflicted with Lewy body dementia, notice that the hippocampus (inside the red box) is smaller, indicating that brain tissue has died. (credit a and b: modification of work “MRI Alzheimer Disease and Dementia with Lewy Bodies” by McKeith IG, Boeve BF, Dickson DW, et al./Wikimedia Commons, CC BY 4.0)

Lewy body dementia is difficult to predict because its cause is unclear. Though the risk increases with age, research has not identified any behavioral or lifestyle risk factors. The condition is progressive and fatal, with no effective treatment or cure.

Parkinson’s disease is also characterized by damage to the neurons responsible for dopamine production and shares many of the physical symptoms of Lewy body dementia, such as stiffness, shaking/trembling, and slow movement. Many patients with Parkinson’s disease never develop dementia, however, and others do so only in the disease’s later stages. Research indicates there is a connection and overlap between Lewy body dementia and Parkinson’s disease dementia, as they both involve the same Lewy body proteins, however, work is still being done to understand this relationship (Haider et al., 2023; Huang, 2023; National Institute on Aging, 2021).

Characteristics and Diagnosis of Alzheimer’s Disease

Currently, the diagnosis of Alzheimer’s disease relies on a combination of clinical observations and medical testing. Professionals can distinguish between a clinical diagnosis based on symptoms and performance on cognitive tests, and a biological diagnosis based on the presence of certain pathological elements in brain tissue. You’ll learn about the latter approach first.

The amyloid plaques characteristic of the disease are believed to form in the brain due to elevated levels of a naturally occurring protein called amyloid precursor protein. As levels of this protein increase, fragments of it gather between neurons, forming plaques that have been linked to cell death and are also believed to interfere with the functioning of neurons. Within the neurons of people with Alzheimer’s disease, threads of the naturally occurring protein tau become twisted, forming neurofibrillary tangles that can interfere with cellular functioning and also contribute to cell death (Alzheimer’s Association, 2024; National Institute on Aging, 2017) (Figure 15.20). Death of brain tissue in certain areas, especially the hippocampus (Jack et al., 2018), also occurs.

Figure 15.20 (a) Plaques are clusters of protein fragments that form between neurons. (b) Neurofibrillary tangles are twisted strands of protein. Micrographs show (c) plaques and (d) tangles in the brain of an individual with Alzheimer’s. (credit a and b: ©2023 Alzheimer’s Association. www.alz.org. All rights reserved. Illustrations by Stacy Jannis. Used with permission; credit c: modification of work “Histopathology of amyloid plaque in Alzheimer’s disease – annotated” by Mikael Häggström/Wikimedia Commons, CC0 1.0; credit d: modification of work “Histopathology of neurofibrillary tangles in Alzheimer’s disease – annotated” by Mikael Häggström/Wikimedia Commons, CC0 1.0)

These changes appear with increasing frequency in most individuals as they get older. They may be an aspect of primary aging and typically do not interfere with functioning. However, as they increase beyond what’s considered normative, they may produce MCI and eventually Alzheimer’s disease (Ganz et al., 2018; Guillozet et al., 2003; Tahami Monfared et al., 2022), an example of secondary aging. Changes in the body’s insulin response may also be a factor. The risk of type 2 diabetes increases with age, and people with type 2 diabetes consistently show cognitive declines. Some research has thus proposed the existence of “type 3 diabetes” caused by neurons in the brain becoming insulin resistant. However, this is not currently an official medical diagnosis, and it’s unclear whether the association between insulin resistance and dementia is caused by diabetes damaging neurons or whether a variant of the APOE4 gene, sometimes called the “Alzheimer’s gene,” interferes with the way the brain processes insulin (Janoutová et al., 2022; Zhao et al., 2017).

An issue with the biological diagnosis of Alzheimer’s disease is that traditionally, detecting the presence of plaques and tangles required examining the patient’s brain tissue under a microscope, which could be done only at autopsy. Dead brain tissue can be detected on living patients’ brain scans but can be caused by several different factors, so this imaging isn’t specific enough to indicate Alzheimer’s disease (Jack et al., 2024). This is why many cases of Alzheimer’s disease are diagnosed through clinical means. The clinical diagnosis rules out other potential causes like stroke, looks for the presence or absence of certain symptoms like visual hallucinations, and compiles a medical history to check for factors like previous head injuries, chronic alcoholism, or untreated infections, all of which can produce dementia symptoms. This strategy typically leads to a diagnosis of “probable” or “possible” Alzheimer’s disease, but it isn’t always accurate. Up to 30 percent of people with a clinical diagnosis of Alzheimer’s disease don’t have signs of plaques and tangles, and a similar percentage of people with plaques and tangles never develop symptoms of Alzheimer’s disease (Jack et al., 2018). It’s estimated that Alzheimer’s disease may go undiagnosed as much as 50 percent of the time (Alzheimer’s Association, 2024; Tahami Monfared et al., 2022).

However, the diagnostic approach may be changing. Technology now exists to identify the presence of amyloid and tau proteins in cerebrospinal fluid, and positron emission tomography scans can locate amyloid plaques in the brain (Alzheimer’s Association, 2024). A blood test to detect amyloid protein is also being developed (Barthélemy et al., 2024; Schindler et al., 2019). Genetic testing can identify people at increased risk for Alzheimer’s disease, and professionals can use that information to closely monitor their cognitive health. In the near future, scientists may be able to rely more on biological diagnosis of Alzheimer’s disease and achieve more accurate results (Jack et al., 2018; Scheltens et al., 2021).

Types of Alzheimer’s Disease

Alzheimer’s disease may exist in different forms. Early-onset disease is a very rare form characterized, as its name suggests, by symptoms that occur earlier than typical, before age sixty-five years and sometimes decades earlier. This version has been associated with specific risk factors, such as having Down syndrome. Other cases have been linked to mutations of three different dominant genes and thus appear to be entirely genetic. Having a parent with this type of early-onset Alzheimer’s disease gives you a 50 percent chance of carrying one of the genes and developing the disease at a younger age than typical. These genetic variations also appear to be more common in Black individuals than in White and Indigenous individuals (Alzheimer’s Association, 2024). While routine genetic screening does not test for the genes, people with a strong family history of Alzheimer’s disease at young ages can be tested to see whether they carry them (National Institute on Aging, 2023).

Most cases of Alzheimer’s disease are considered late-onset and occur after age sixty-five years. Risk increases with age, and 80 percent of all Alzheimer’s patients are diagnosed after age eighty years. This form of the disease is more difficult to predict, but it is also associated with a slower progression of symptoms and changes to the brain than early-onset Alzheimer’s disease (Rabinovici, 2019).

Symptoms and Progression of Alzheimer’s Disease

Memory problems are usually the first symptom of Alzheimer’s disease, although it can be hard to distinguish them from the typical memory problems associated with normal aging. In general, forgetting things a person has known for a long time, like the names of loved ones or the route home from the store, or having a noticeable increase in forgetfulness is cause for concern. Some research suggests that problems in word recall (remembering the names of objects and people) and orientation (knowing where you are as well as things like the date and season) are specific early indicators of dementia, coming before impairment of other cognitive functions like attention and executive function (Tahami Monfared et al., 2022).

Several large-scale research studies are currently trying to better grasp all aspects of Alzheimer’s disease. For example, the Dallas Lifespan Brain Study is studying brain development at a wide range of ages, with the goal of better understanding both the risk factors for and the early development of Alzheimer’s (Chan et al., 2014). Two other examples are the Religious Orders Study (which has a sample of nuns and priests) and the Rush Memory and Aging Project. Both examine cognitive ability, brain health, and other variables in differently aged adults over time. All participants also agree to organ donation after death so that irregularities in the brain, such as plaques and tangles, can be studied and associated with brain activity, cognitive functioning, and a variety of other variables (Bennett et al., 2018).

Thanks to these and other efforts, researchers understand a great deal about the symptoms and progression of Alzheimer’s disease. Several studies have identified neurological changes that occur several years before any symptoms. For example, research using PET scans has been able to identify changes in brain activity four years before participants developed any symptoms. These include a pattern of more activity in the frontal cortex of the brain and less in the temporal and parietal cortexes. The declines in the temporal and parietal cortexes are believed to signal some of the earliest damage to the brain in the Alzheimer’s disease process (Figure 15.21). Increased activity in the frontal cortex, in turn, is believed to be evidence of neuroplasticity, occurring as healthier parts of the brain compensate for the damaged area (Beason-Held et al., 2013; Choudhury et al., 2023; Raskin et al., 2015).

Figure 15.21 Scans show the decrease in brain volume in the cortex (outer portions of the brain) and hippocampus (red box) when comparing (a) a healthy brain to (b) a brain with Alzheimer’s disease. (credit a and b: modification of work “MRI Alzheimer Disease and Dementia with Lewy Bodies” by McKeith IG, Boeve BF, Dickson DW, et al./Wikimedia Commons, CC BY 4.0)

More recent research using magnetic resonance imaging has supported this earlier work, indicating that people eventually diagnosed with Alzheimer’s disease show more loss of neurons in the temporal lobe than in other regions of the brain. Other types of dementia are characterized by other patterns of neuron loss; for example, Lewy body dementia appears to disproportionately affect the parietal lobe (Orad & Shiner, 2022).

In other words, before people have any cognitive or behavioral symptoms of Alzheimer’s disease, the brain seems to realize that certain areas are being damaged. As a result, the frontal lobes start working extra hard to pick up the slack, preventing any noticeable changes in cognitive ability. This trend continues until the damage accumulates and the frontal cortex is no longer able to compensate. Eventually, the frontal cortex starts to experience damage from Alzheimer’s disease as well.

Indicators of Alzheimer’s disease have been found outside the brain. Research suggests that declines in the sense of smell can predict the level of Alzheimer’s disease–related pathology in the brain, such as the presence of plaques and tangles (Brai et al., 2020; Mi et al., 2023; Wilson et al., 2009). Amyloid that forms plaques has also been found in the retina of the eye, and its presence positively correlates with the degree of cognitive decline (Koronyo et al., 2023).

While changes in the brain, declines in the sense of smell, and the presence of amyloid in the eyes are potentially important clinical indicators of Alzheimer’s disease, they are not the typical changes that families first notice. In early-stage Alzheimer’s disease, individuals may have increased memory problems, such as difficulty finding the right words, forgetting information they recently learned, and more frequently forgetting where they left objects, but typically they can still function independently. The middle stage of the disease is the longest, typically lasting several years during which individuals require some assistance completing daily tasks. Memory problems are more severe, including difficulty remembering information relevant to their personal history. This stage of Alzheimer’s is also linked to general confusion, wandering, sleep difficulty, difficulty with daily tasks such as bathing and dressing, and personality changes.

Another symptom common in mid-stage Alzheimer’s disease is sundowning, a tendency for dementia symptoms to worsen in the evening. Individuals tend to become increasingly confused or agitated. They may pace or wander, exhibit increased aggression, and experience hallucinations, typically as night approaches but also throughout the night. Sundowning is frequently reported in institutional settings such as nursing homes. It is not completely understood, and there are a variety of theories about its potential causes (Cipriani et al., 2015). Communicating earlier in the day with loved ones who have dementia could increase the likelihood of having meaningful interactions.

The final stage of disease is the most debilitating. People have difficulty communicating or having conversations, they need assistance with ADLs, and they cannot independently care for themselves. Physical abilities also tend to decline, and individuals can lose the ability to walk, sit, or even swallow. Vulnerability to infectious disease such as pneumonia also increases. Due to the severity and scope of these symptoms, end-of-life care such as hospice is often needed (Alzheimer’s Association, n.d.-b).

Treatment and Prevention of Alzheimer’s Disease

A great deal of Alzheimer’s research has focused on developing effective treatments, including medications meant to remove amyloid plaques from the brain (Srivastava et al., 2021), since their accumulation is believed to lead to the development of tangles. While most attempts have so far failed, some medications, such as aducanumab (Aduhelm), decrease amyloid plaques and reduce the rate of cognitive decline. Aducanumab was the first medication to receive FDA approval (in 2021). It did not reverse the disease but may have helped those at the earliest stages by slowing its progression. It had been linked to potentially serious side effects, too, including swelling of the brain (Woloshin & Kesselheim, 2022). This was the first medication to try to treat the disease and not just provide symptom management (Beshir et al., 2022; Karran & Strooper, 2022; Wang, 2023). However, research still has a long way to go in Alzheimer’s treatment, as Aduhelm is being discontinued and will no longer be available by late 2024 (Alzheimer’s Association, n.d.-c).