14.4 Neurocognitive Disorders

The patterns of cognitive aging challenge another assumption: that older people always lose the ability to think and remember. That is not true. Many older people are less sharp than they were, but are still quite capable of intellectual activity. Others experience serious decline.

The Ageism of Words

It is undeniable that the rate of neurocognitive disorders increases with every decade after age 70. To understand that and prevent the worst of it, caution is needed in using words. Formerly, senility was used to mean severe mental impairment, which implied that old age always brings intellectual failure—an ageist myth; senile simply means “old.” Dementia was a more precise term than senility for irreversible, pathological loss of brain functioning, but dementia also has inaccurate connotations. The DSM-5 now describes neurocognitive disorder (NCD), either major neurocognitive disorder or mild neurocognitive disorder, depending on the severity of symptoms.

Memory impairment is common in every cognitive disorder, although symptoms of neurocognitive disorders include many more problems, especially in learning new material, using language, moving the body, and responding to people. Practical challenges include getting lost, becoming confused about using common objects like a telephone or toothbrush, or having extreme emotional reactions.

The lines between normal age-related problems, mild disorder, and major disorder are not clearly defined, and the symptoms vary depending on the specifics of brain loss and context. Variation is evident in origin as well: More than 70 diseases can cause neurocognitive disorder, each with particular symptoms, sequence, and severity. Making distinctions more difficult is that the former word—dementia—is still often used in research, and the inaccurate word—senility—is used in common speech.

The problem of ageist terminology has been recognized internationally. In Japanese, the traditional word for neurocognitive disorder was chihou, translated as “foolish” or “stupid.” As more people reached old age, the Japanese decided on a new word, ninchihou, which means “cognitive syndrome” (George & Whitehouse, 2010). That is similar to the changes in English terminology over the past decades, from senility to dementia to neurocognitive disorder.

Mild and Major Impairment

Many instances of memory loss are not necessarily ominous signs of severe loss to come. Older adults who have significant problems with memory, but who still function well at work and home, might be diagnosed with mild NCD, formerly called mild cognitive impairment (MCI). Although some of these adults will develop major disorders, about half will be mildly impaired for decades or will regain cognitive abilities (Lopez et al., 2007; Salthouse, 2010).

Many tests are designed to measure mild loss, including one that takes less than 10 minutes—the quick MCI (Qmci) (O’Caoimh et al., 2013). The problem with every test is that scores are affected by many factors, with no universally accepted cut-off between normal, mild, and major impairment.

Many scientists seek biological indicators (called “biomarkers”), such as substances in the blood or cerebrospinal fluid, or brain indicators (as found in brain scans) that predict major memory loss. However, although abnormal scores on many tests (biological, neurological, or psychological) indicate possible problems, an examination of 24 such measures found no single test, and no combination of tests, to be 100 percent accurate (Ewers et al., 2012).

The final determinant of neurocognitive disorders is the clinical judgment of a professional who considers all the symptoms and markers—everything from uncontrolled impulses to memory lapses. Any diagnosis may focus too much on losses and not enough on individual strengths. As the previous sections on brain aging and information processing explain, no very old person is as intellectually sharp as they once were, so almost everyone could be considered mildly impaired. Opinions are always subjective; objective data can be discounted or overemphasized by both professionals and patients. That obviously complicates diagnosis.

Prevalence of NCD

According to the Alzheimer Society of Canada, in 2011, 747 000 Canadians were living with some form of cognitive impairment, including NCD, which accounted for about 14.9 percent of Canadians aged 65 and older (Alzheimer Society of Canada, 2012). (Figure 14.5 shows the predicted number of new cases of NCD in Canada each year until 2038.) Rates of NCD vary by nation, from about 2 to 25 percent of elders, with an estimated 35 million people affected worldwide (Kalaria et al., 2008; WHO, 2012). Developing nations have lower rates, but that may be because millions of people in the early stages are not counted or because health care overall is poor.

FIGURE 14.5 Projected Prevalence The number of new cases of neuro-cognitive disorder in 2038 among Canadians 65 years and older is expected to be about 2.2 times that of the number of cases in 2013, with a much higher prevalence rate in females than in males.

How would poor health care lead to less, not more, impairment? Because many people die before any neurocognitive problems are apparent. People with diabetes, Parkinson’s disease, strokes, and heart surgery are more likely to lose intellectual capacity in old age, but in poor nations many people with those conditions die before age 70.

Improvements in health care can reduce cognitive impairment. The three ideal goals of public health are said to be better physical health, less mental disorder, and longer lives. That is becoming a reality in some nations. In England and Wales, the rate of NCD for people over age 65 was 8.3 percent in 1991 but only 6.5 percent in 2011 (Matthews et al., 2013). Sweden had a similar decline (Qiu et al., 2013). In China, rates were much higher in rural areas than in urban ones, probably because rural Chinese had less education (Jia et al., 2014) and, thus, less understanding about how to stay healthy. A comparable survey has not been done in North America, but some signs suggest improvement.

Of course, reduction in rate does not necessarily mean reduction in number, since more people live to old age. In England over the past 20 years, the number of people with NCD has stayed about the same (Matthews et al., 2013) even while the rate has declined.

Genetics and social context affect rates, but it is not known by how much (Bondi et al., 2009). For example, more older women than older men are diagnosed with neurocognitive disorders, which may be genetic, educational, or stress-related. Or it may be simply that women live longer than men (Alzheimer’s Association, 2012).

Now consider some specific types of age-related neurocognitive disorders.

Alzheimer’s DiseaseIn 1906, a physician named Dr. Alois Alzheimer performed an autopsy on a patient who had lost her memory. He found unusual material in her brain, but he was uncertain whether it specified a distinct disease (George & Whitehouse, 2010). Others, convinced that he had discovered a disease, named it after him. In the past century, millions of people in every large nation have been diagnosed with Alzheimer’s disease (AD), now formally referred to as major or mild NCD due to Alzheimer’s disease. (See TABLE 14.2 for the stages of Alzheimer’s disease.) In China, for example, 5.7 million people have Alzheimer’s disease (K.Y. Chan et al., 2013).

As Dr. Alzheimer discovered, autopsies reveal that some aging brains have many plaques and tangles in the cerebral cortex. These abnormalities destroy the ability of neurons to communicate with one another, causing severe cognitive loss. Plaques are clumps of a protein called beta-amyloid, found in tissues surrounding the neurons; tangles are twisted masses of threads made of a protein called tau within the neurons. A normal brain contains some beta-amyloid and some tau, but in brains with AD these plaques and tangles proliferate, especially in the hippocampus, the brain structure crucial for memory. Forgetfulness is the dominant symptom; working memory disappears first.

Although finding massive brain plaques and tangles at autopsy proves that a person diagnosed with NCD had Alzheimer’s disease, between 20 and 30 percent of cognitively normal elders have, at autopsy, the same level of plaques in their brains as people who had been diagnosed with AD (Jack et al., 2009). Possibly the elders who had not been diagnosed with NCD had compensated by using other parts of their brains; possibly they were in the early stages, not yet suspected of having AD; possibly plaques are a symptom, not a cause.

Alzheimer’s disease is partly genetic. If it develops in middle age, the affected person either has trisomy-21 (Down syndrome) or has inherited one of three genes: amyloid precursor protein (APP), presenilin 1, or presenilin 2. For these people, the disease progresses quickly, reaching the last phase within three to five years.

The Alzheimer’s Brain This computer graphic shows a vertical slice through a brain ravaged by Alzheimer’s disease (left) compared with a similar slice of a normal brain (right). The diseased brain is shrunken as a result of the degeneration of neurons.

ALFRED PASIEKA/SCIENCE PHOTO LIBRARY/SCIENCE SOURCE

Most cases begin much later, at age 75 or so. Many genes have some impact, including SORL1 and ApoE4 (allele 4 of the ApoE gene). People who inherit one copy of ApoE4 have about a 50/50 chance of developing AD. Those who inherit two copies almost always develop the disorder if they live long enough.

Vascular NCDThe second most common cause of neurocognitive disorder is a stroke (a temporary obstruction of a blood vessel in the brain) or a series of strokes, called transient ischemic attacks (TIAs, or ministrokes). The interruption in blood flow reduces oxygen, destroying part of the brain. Symptoms (blurred vision, weak or paralyzed limbs, slurred speech, and mental confusion) suddenly appear.

Hopeful Brains Even the brain without symptoms (a) might eventually develop Alzheimer’s disease, but people with a certain dominant gene definitely will. They have no symptoms (b) in early adulthood, some symptoms (c) in middle adulthood, and stage five Alzheimer’s disease (d) before old age. Research has led to the discovery of early markers (such as those shown here) that predict the disease. As scientists detect early signs, they hope to determine a treatment to halt brain destruction before it starts.

TAMMIE BENZINGER, MD, PHD, TYLER BLAZEY, WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS

In a TIA, symptoms may vanish quickly, unnoticed. However, unless it is recognized and preventive action is taken, another is likely. Repeated TIAs produce a type of NCD sometimes called vascular neurocognitive disorder. The progression of vascular NCD differs from Alzheimer’s disease, but the final result is similar (see Figure 14.6).

FIGURE 14.6 The Progression of Alzheimer’s Disease and Vascular Neurocognitive Disorder Cognitive decline is apparent in both Alzheimer’s disease (AD) and vascular neurocognitive disorder. However, the pattern of decline for each disease is different. People with AD show steady, gradual decline, while those who suffer from vascular NCD get suddenly much worse, improve somewhat, and then experience another serious loss.

Neurocognitive disorders caused by vascular disease are apparent in many of the oldest-old worldwide. Vascular NCD is more common than Alzheimer’s disease for those over age 90 but not for the young-old. Vascular NCD correlates with the ApoE4 allele (Cramer & Procaccio, 2012), and for some of the elderly it is caused by surgery that requires general anaesthesia. They may suffer a ministroke, which, added to reduced cognitive reserve, damages the brain (Stern, 2013).

Frontal Lobe DisordersSeveral types of neurocognitive disorders are called frontal lobe disorders, or frontotemporal lobar degeneration. (Pick’s disease is the most common form). These disorders are particularly likely to occur at relatively young ages (under age 70), unlike Alzheimer’s disease and vascular NCD, which typically begin later (Seelaar et al., 2011).

In frontal lobe disorders, parts of the brain that regulate emotions and social behaviour (especially the amygdala and prefrontal cortex) deteriorate. Emotional and personality changes are the main symptoms (Seelaar et al., 2011). A loving father with frontal lobe degeneration might reject his children, or a formerly astute businesswoman might invest in a hare-brained scheme.

Frontal lobe problems may be worse than more obvious types of neurocognitive disease in that compassion, self-awareness, and judgment fade in a person who otherwise seems typical. One wife, Ruth French, was furious because her husband

Finally, he was diagnosed with frontal lobe disorder. Ruth asked him to forgive her fury. It is not clear that he understood either her anger or her apology.

Although there are many forms and causes of frontal lobe disorders—including a dozen or so alleles—they usually progress rapidly, leading to death in about five years.

Healing Doll This Japanese robotic doll, Yumel, is purchased not only for children but also for the elderly, for social and therapeutic purposes. Owners cuddle with and talk to these dolls, which have a vocabulary of 1200 phrases, sing lullabies, and can even be programmed to sleep or wake up at the same time as their owners, saying “good morning” or inviting the elderly to go to sleep, as the doll’s eyes close. Interacting with dolls such as these may affect an owner’s brain chemistry and slow down neurocognitive disorder.

KURITA KAKU/GAMMA-RAPHO VIA GETTY IMAGES

Other DisordersMany other brain diseases begin with impaired motor control (shaking when picking up a coffee cup, falling when trying to walk), not with impaired thinking. The most common of these is Parkinson’s disease, the cause of about 3 percent of all cases of NCD (Aarsland et al., 2005).

Parkinson’s disease starts with rigidity or tremor of the muscles as dopamine-producing neurons degenerate, affecting movement long before cognition. Younger adults with Parkinson’s disease usually have sufficient cognitive reserve to avoid major intellectual loss, although about one-third have mild impairment (Gao et al., 2013). Older people with Parkinson’s develop cognitive problems sooner (Pfeiffer, 2012). If people with Parkinson’s live 10 years or more, major neurocognitive impairment almost always occurs (Pahwa & Lyons, 2013).

Another 5 to 15 percent of Canadians with NCD suffer from an excess of Lewy bodies: deposits of a particular kind of protein in their brains. Lewy bodies are also present in Parkinson’s disease, but in Lewy body disease they are more numerous and dispersed throughout the brain, interfering with communication between neurons. As a result, movement and cognition are both impacted, although motor effects are less severe than in Parkinson’s disease and memory loss is not as dramatic as in Alzheimer’s disease (Bondi et al., 2009). The main symptom is loss of inhibition: A person might gamble or become hypersexual.

Comorbidity is common with all these disorders. For instance, most people with Alzheimer’s disease also show signs of vascular impairment (Doraiswamy, 2012). Parkinson’s disease, Alzheimer’s disease, and Lewy body disease can occur together: People who have all three experience more rapid and severe cognitive loss (Compta et al., 2011).

Some other types of NCD begin in middle age or even earlier, caused by Huntington disease, multiple sclerosis, a severe head injury, or the last stages of syphilis, AIDS, or bovine spongiform encephalitis (BSE, or mad cow disease). Repeated blows to the head, even without concussions, can cause chronic traumatic encephalopathy (CTE), which first causes memory loss and emotional changes, and eventually further cognitive loss (Voosen, 2013). Although the rate of systemic brain disease increases dramatically with every decade after age 60, brain disease can occur at any age, as revealed by the autopsies of a number of young professional athletes. For athletes, prevention includes better helmets and fewer body blows.

Preventing Impairment

Since aging increases the rate of cognitive impairment, slowing down senescence may postpone major neurocognitive disorders, and ameliorating mild losses may prevent worse ones. That may have occurred in the decreasing rates of major NCD documented in England (Matthews et al., 2013).

Epigenetic research is particularly likely to lead to better prevention, because “the brain contains an epigenetic ‘hotspot’ with a unique potential to not only better understand its most complex functions, but also to treat its most vicious diseases” (Gräff et al., 2011). Genes are always influential. Some are expressed, affecting development, and some are latent unless circumstances change. The reasons are epi-genetic: Factors beyond the genes are crucial (Issa, 2011; Skipper, 2011).

The most important non-genetic factor is exercise. Because brain plasticity continues throughout life, exercise that improves blood circulation not only prevents cognitive loss but also builds capacity and repairs damage. The benefits of exercise have been repeatedly cited in this text. Now we simply emphasize that physical exercise—even more than good nutrition and mental exercise—prevents, postpones, and slows cognitive loss of all kinds (Erickson et al., 2012; Gregory et al., 2012; Lövdén et al., 2013).

Medication to prevent stroke also protects against neuro-cognitive disorders. In a Finnish study, half of a large group of older Finns were given drugs to reduce lipids (primarily cholesterol) in their system. Years later, fewer of them had developed NCD than did a comparable group who were not given the drug (Solomon et al., 2010).

Avoiding specific pathogens is critical. For example, beef can be tested to ensure that it does not have BSE, condoms can protect against AIDS, and syphilis can be cured with antibiotics. For most neurocognitive disorders, however, despite the efforts of thousands of scientists and millions of older people, no foolproof prevention or cure has been found. Avoiding toxic substances (lead, aluminum, copper, and pesticides) and adding supplements (hormones, aspirin, coffee, insulin, anti-oxidants, red wine, blueberries, and statins) have been tried as preventative measures but have not proven effective in controlled, scientific research.

Lost Memories This man, who is in the last stage of Alzheimer’s disease, no longer remembers his daughter and is often unresponsive when she visits.

ALAN ODDIE/PHOTOEDIT, INC.

Thousands of scientists have sought to halt the production of beta-amyloid and have had some success in mice but not yet in humans. One current goal is to diagnose Alzheimer’s disease 10 or 15 years before the first outward signs appear in order to prevent brain damage. That is one reason for the interest in mild neurocognitive disorders: They often (though not always) progress to major problems. If it were known why some mild losses do not lead to major ones, a means of prevention might be found.

Among professionals, hope is replacing despair. Earlier diagnosis seems possible; many drug and lifestyle treatments are under review (Hampel et al., 2012; Lane et al., 2011). The first step, however, in prevention and treatment of NCD is to improve overall health. High blood pressure, diabetes, arteriosclerosis, and emphysema all impair cognition, because they disrupt the flow of oxygen to the brain. Each type of neurocognitive disorder, each slowdown, and every chronic disease interact, so progress in one area may reduce incidence and severity in another. A healthy diet, social interaction, and, especially, exercise decrease cognitive impairment of every kind, affecting brain chemicals and encouraging improvement in other health habits.

Reversible Neurocognitive Disorder?

Sometimes memory and other problems are not the result of a neurocognitive disorder. Older people may be thought to be permanently “losing their minds,” when in fact a reversible condition is at fault. This highlights the importance of an accurate diagnosis.

Depression and AnxietyThe most common reversible condition that is mistaken for neurocognitive disorder is depression. Normally, older people tend to be quite happy; frequent sadness or anxiety is not normal. Ongoing, untreated depression increases the risk of NCD (Y. Gao et al., 2013).

Ironically, people with untreated anxiety or depression may exaggerate minor memory losses or refuse to talk. Quite the opposite reaction occurs with early Alzheimer’s disease, when victims are often surprised when they cannot answer questions, or with Lewy body or frontal lobe disorders, when people talk without thinking.

Specifics provide other clues. People with neurocognitive loss might forget what they just said, heard, or did because current brain activity is impaired, but they might repeatedly describe details of something that happened long ago. The opposite may be true for emotional disorders, when memory of the past is impaired but short-term memory is not.

NutritionMalnutrition and dehydration can also cause symptoms that may seem like brain disease. The aging digestive system is less efficient but needs more nutrients and fewer calories. This requires new habits, less fast food, and more grocery money (which many do not have). Some elderly people deliberately drink less because they want to avoid frequent urination, yet adequate liquid in the body is needed for cell health. Since homeostasis slows with age, older people are less likely to recognize and remedy their hunger and thirst, and thus may inadvertently impair their cognition.

Additionally, several specific vitamins, including antioxidants (C, A, E) and vitamin B-12, have been suggested as a means of decreasing the rate of neurocognitive disorders. Conversely, high levels of homocysteine (from animal fat) seem to increase NCD (Perez et al., 2012; Whalley et al., 2013). Obviously, any food that increases the risk of heart disease also increases the risk of stroke and hence vascular disease. In addition, some prescribed drugs destroy certain nutrients, although specifics require more research (Jyrkkä et al., 2012).

Indeed, well-controlled longitudinal research on the relationship between particular aspects of nutrition and NCD has not been done. It is known, however, that people who already suffer from NCD tend to forget to eat or choose unhealthy foods, which hastens their mental deterioration. It is also known that alcohol abuse interferes with nutrition, directly (reducing eating and hydration) and indirectly (by destroying some vitamins).

PolypharmacyAt home as well as in the hospital, most elderly people take numerous drugs—not only prescribed medications, but also over-the-counter preparations and herbal remedies—a situation known as polypharmacy (Hajjar et al., 2007). Excessive reliance on drugs can occur as a result of doctor’s orders as well as a lack of patient knowledge.

Unfortunately, recommended doses of many drugs are determined primarily by clinical trials with younger adults, for whom homeostasis usually eliminates excess medication (Herrera et al., 2010). When homeostasis slows down, excess may linger. In addition, most trials to test the safety of a new drug exclude people who have more than one disease. That means drugs are not tested on many of the elderly who will use them, so recommended dosages may not be appropriate for them.

The average elderly person in Canada sees a doctor several times a year. Typically, each doctor follows “clinical practice guidelines,” which are recommendations for one specific condition. A “prescribing cascade” (when many interacting drugs are prescribed) may occur. In one disturbing case, a doctor prescribed medication to raise his patient’s blood pressure, and another doctor, noting the raised blood pressure, prescribed a drug to lower it (McLendon & Shelton, 2011–2012). Usually, doctors ask patients what medications they are taking and why, which could prevent such an error. However, people who are sick and confused may not give accurate responses.

Another problem is that people of every age forget when to take which drugs (before, during, or after meals? after dinner or at bedtime?), a problem multiplied as more drugs are prescribed (Bosworth & Ayotte, 2009). Short-term memory loss makes this worse. Even when medications are taken as prescribed and the right dose reaches the bloodstream, drug interactions can cause confusion and memory loss. Cognitive side effects can occur with almost any drug, but, in particular, drugs intended to reduce anxiety and depression often affect memory or reasoning.

Finally, following recommendations from the radio, friends, and television ads, many of the elderly try supplements, compounds, and herbal preparations that contain mind-altering toxic substances. Some of the elderly believe that only illegal drugs are harmful to the mind; clearly, this is not the case.