Bladder Problems

Urinary problems occur with normal aging. In women they often relate to the changes in female anatomy due to the delivering of babies. With superimposed age-related changes in soft tissues, laxity may result in incontinence (loss of urinary control), especially with coughing, laughing, or straining. In men the opposite symptom tends to occur: urinary hesitancy (inability to evacuate the bladder). This is due to constriction of the bladder outlet by an enlarging prostate; the prostate normally surrounds the urethra, through which urine passes. DLB and PDD are often associated with additional bladder problems. Recall that the autonomic nervous system regulates bladder function and that this system tends to malfunction in Lewy disorders. Hence, reduced bladder control is frequent among those with DLB, PDD, and Parkinson’s disease. This condition is termed neurogenic bladder, which implies that the autonomic nervous system control of bladder reflexes is not working properly. This may manifest as urgency with incontinence or hesitancy. Neurogenic bladder problems require different strategies than those used for treating the simple age-related problems that develop in mid-life and beyond. Moreover, there are certain caveats to treatment once a neurogenic bladder is recognized. The bladder is simply a reservoir that holds urine. It is located in the lower pelvis and is distant from the kidneys. The kidneys essentially filter the circulating blood and make the urine. The urine flows down from the kidneys into the bladder, as shown in Figure 14.1. Normally, as the bladder slowly fills with urine, a reflex is triggered when it is nearly full. This results in conscious awareness of the need to urinate, plus it primes the reflexive tendency of the bladder to contract in order to expel the urinary contents. The bladder is able to contract because of muscles in the bladder walls. Normally, nerves activate these muscles at the appropriate time, which forcefully squeeze the bladder, expelling the urine. Nerve sensors in the bladder wall are activated by bladder filling and transmit this information to the central nervous system, ramping up bladder wall muscle activity.

Blood Pressure and Orthostatic Hypotension: Faints, Near-Faints, and Lightheadedness

Case example: Mrs. H. feels lightheaded intermittently during the day. This happens exclusively when she is up and about. Sometimes she notes graying of vision with these episodes. The feeling is not spinning (i.e., not vertigo). She has fainted twice when standing in line at the grocery store. If she sits, she feels much better. It is worse in the morning but may recur any time of the day. She feels fine while lying in bed at night. Older adults often worry about high blood pressure (BP), yet the opposite problem, low BP, is common among those with DLB or PDD. This is because the Lewy neurodegenerative process impairs the autonomic nervous system. The specific condition that may afflict those with DLB or PDD is orthostatic hypotension. The term orthostatic implies the upright position (i.e., standing); hypotension translates into low BP. Thus, the low BP occurring in these Lewy disorders develops in the upright position; conversely, it is normal or even high when lying down. When standing or walking, the BP may drop so low that fainting occurs. Among people with orthostatic hypotension, the BP is normal when sitting, although in severe cases, even the sitting BP is low. Whereas most people with DLB or PDD do not experience symptoms of orthostatic hypotension, it is sufficiently frequent to deserve attention. It often goes undiagnosed, even when fainting occurs. Unrecognized orthostatic hypotension may limit activities and impair the person’s quality of life. The first half of this chapter provides further background, with focus on BP measurement and recognition of orthostatic hypotension. The last half addresses treatment. The normal autonomic nervous system senses the position of our body with respect to the pull of gravity. It is able to reflexively counter gravity’s downward pull on the blood volume when standing (gravity tends to draw blood toward our feet when standing). An important mechanism for countering gravity’s pull is the constriction of blood vessel diameter in the lower half of the body. These vessels reflexively constrict during standing, in effect forcing blood up to the brain. The autonomic nervous system mediates these and other reflexive changes to stabilize BP.

Other Levodopa-Responsive Problems: Anxiety, Insomnia, and Pain

Carbidopa/levodopa is well recognized to effectively treat movement (“motor”) problems in DLB and PDD, as well as in typical Parkinson’s disease. However, symptoms responding to levodopa also include anxiety and insomnia. Moreover, pain control may improve with optimized levodopa dosages. The role for carbidopa/levodopa in treating these symptoms cannot be overemphasized; quality of life may markedly improve with optimized dosage. Anxiety is a normal part of the human existence. It is normal to become nervous before a school test or speaking before a large audience. In fact, some of us are especially nervous or anxious as part of our normal makeup. However, newly developing anxiety is a frequent component of DLB, PDD, and Parkinson’s disease. In the context of these disorders, anxiety may occasionally be the most troublesome symptom, even bordering on panic. The good news is that this is often treatable with carbidopa/ levodopa. The usual anxiety everyone experiences, or the excessive anxiety of nervous people, does not respond to levodopa. Certain anxiety is normal, such as during family crises and arguments. If a person has been nervous all of their life, levodopa will not be the solution; such anxiety is not due to brain dopamine deficiency. However, anxiety that develops after, or a little before the onset of DLB, PDD, or Parkinson’s disease is different. If recently, small issues have provoked panic and this is not a lifelong pattern, levodopa therapy may prove helpful. The anxiety experienced by those with DLB or PDD may occasionally reach crisis proportions. Emergency room physicians are familiar with older adults being brought in by concerned family members because “mom is in a panic.” Sometimes a Valium-like drug is prescribed to establish a quick response. Medications from the Valium class are termed benzodiazepines and include such agents as alprazolam (Xanax), lorazepam (Ativan), clonazepam (Klonopin), as well as Valium itself (diazepam). Benzodiazepines are very sedating, which is beneficial in the emergency room to relax the nervous person; however, ongoing sedation is not acceptable on a long-term basis. Moreover, these drugs contribute to imbalance (fall risk) and tend to impair thinking.

Symptoms, Related Brain Regions, and Diagnosis

As a prelude to the treatment chapters that follow, we need to define and describe the types of problems and symptoms encountered in DLB and PDD. The clinical picture can be quite varied: problems encountered by one person may be quite different from those encountered by another person, and symptoms that are problematic in one individual may be minimal in another. In these disorders, the Lewy neurodegenerative process potentially affects certain nervous system regions but spares others. Affected areas include thinking and memory circuits, as well as movement (motor) function and the autonomic nervous system, which regulates primary functions such as bladder, bowel, and blood pressure control. Many other brain regions, by contrast, are spared or minimally involved, such as vision and sensation. The brain and spinal cord constitute the central nervous system. The interface between the brain and spinal cord is by way of the brain stem, as shown in Figure 4.1. Thought, memory, and reasoning are primarily organized in the thick layers of cortex overlying lower brain levels. Volitional movements, such as writing, throwing, or kicking, also emanate from the cortex and integrate with circuits just below, including those in the basal ganglia, shown in Figure 4.2. The basal ganglia includes the striatum, globus pallidus, subthalamic nucleus, and substantia nigra, as illustrated in Figure 4.2. Movement information is integrated and modulated in these basal ganglia nuclei and then transmitted down the brain stem to the spinal cord. At spinal cord levels the correct sequence of muscle activation that has been programmed is accomplished. Activated nerves from appropriate regions of the spinal cord relay the signals to the proper muscles. Sensory information from the periphery (limbs) travels in the opposite direction. How are these signals transmitted? Brain cells called neurons have long, wire-like extensions that interface with other neurons, effectively making up circuits that are slightly similar to computer circuits; this is illustrated in Figure 4.3. At the end of these wire-like extensions are tiny enlargements (terminals) that contain specific biological chemicals called neurotransmitters. Neurotransmitters are released when the electrical signal travels down that neuron to the end of that wire-like process.

What Is Known about the Cause

Most of the research into the cause of Lewy disorders has focused on Parkinson’s disease, since that is the best defined of these conditions and, therefore, the most straightforward to study. Dementia with Lewy bodies (DLB) is more difficult to diagnose with certainty, especially in the early years of the disease. What we collectively learn about Parkinson’s disease will likely be very relevant to our understanding of DLB. Multiple investigations have linked Parkinson’s disease to both environmental exposures and genetic factors. However, these associations have all been modest, and none of them accounts for more than a few percent of the contribution to the cause of sporadic Parkinson’s disease (i.e., the attributable risks are low). These investigations are ongoing and hopefully will soon provide a more complete understanding of the cause(s). Perhaps the most important clue to all Lewy conditions is located in the brain: the Lewy body itself. A recent sophisticated analysis of Lewy bodies revealed approximately 300 different component proteins. However, we already knew that Lewy bodies contain high concentrations of a normal protein called alpha synuclein. In fact, Lewy bodies are conventionally identified under the microscope with antibody stains that specifically bind to alpha synuclein. Could this be the crucial protein among the nearly 300? While the alpha synuclein story is focused on Parkinson’s disease, it may be just as relevant to DLB, as we shall see. The story starts with a large Italian-American family with Parkinson’s disease, studied by Dr. Lawrence Golbe and colleagues at the Robert Wood Johnson Medical Center in New Brunswick, New Jersey. In this rare family, many members of multiple generations had been affected by Parkinson’s disease (with Lewy bodies), consistent with a single gene passed on with dominant inheritance. It took a number of years to identify that abnormal gene, which ultimately was proven to be the gene coding for alpha synuclein. It was quickly discovered that this genetic error is not present in usual cases of Parkinson’s disease.

Bowels and Constipation

Constipation is common among older adults, in general. However, it is very common among people with Lewy body disorders, and the reason is dysautonomia. Lewy body disorders tend to impair control of gut motility by the autonomic nervous system. At the stomach level, bloating may develop when the stomach fails to empty into the upper small intestine. At the other end, constipation is the consequence of Lewy processes affecting motility in the colon. Colon motility (peristalsis) is what moves the remnants of digested food (stool) to the rectum for expulsion. These regions are shown in Figure 15.1. Drugs that block the neurotransmitter acetylcholine are notorious for worsening constipation; these include medications used to treat urinary urgency (overactive bladder). All of the anticholinergic drugs for bladder overactivity that were listed in Table 12.1 cause constipation, as does another bladder drug, trospium (Sanctura). The tricyclic drugs for depression shown in Table 12.1 have variable anticholinergic properties and also tend to be constipating. One needs to balance benefits against the side effect of constipation if considering these medications. In the setting of DLB or PDD, constipation is typically due to autonomic nervous system dysfunction, often exacerbated by medication side effects. However, there are exceptions and the primary care clinician or internist should consider whether colonoscopy is appropriate. This procedure involves inserting a scope into the anus and then advancing the instrument to visualize the entire colon. In this way hidden colon cancers are detected before they become deadly. It is common knowledge that several natural remedies help prevent constipation: fruits, vegetables, fluids, and fiber. Individuals with constipation should make sure that their diet includes adequate fruits, which make a good snack. Meals should include vegetables, such as green beans, peas, and squash; catsup and potatoes do not count as vegetables. Intake of six to eight tall glasses of water, juice, or other fluids may help maintain moisture in the stool, making it easier to pass. Finally, fiber needs to be included in the diet in order to give the stool bulk. These strategies are often insufficient for persons with Lewy disorders, and additional measures are often necessary.

Dementia: Impaired Thinking and Judgment; Confusion

Dementia implies problems with cognition (thinking), and this is a fundamental component of DLB and PDD. Dementia also implies that the cognitive problems are sufficiently troublesome to affect activities of daily living. Less severe impairment of memory or thinking that does not interfere with daily activities is classified as mild cognitive impairment (MCI). MCI may be a prelude to dementia. If MCI accompanies parkinsonism, then the treatment strategies outlined in this text are appropriate. Dementia does not necessarily mean that a rapid progression to an advanced state is inevitable. Dementia may be relatively mild and well compensated, especially with the help of the spouse and family; it may remain that way for years. The cognitive profile of DLB and PDD was described in Chapter 4. To review, this impairment affects several major components of intellect. This includes executive function, localized to the frontal lobes of the brain. Visuospatial conceptualization is similarly affected, which reflects problems in the posterior brain (i.e., parietal and occipital lobes). Memory declines in DLB and PDD, but less than in Alzheimer’s disease. Fluctuations in mental clarity are often noted in these Lewy disorders, where near-normal thinking may be followed hours later by confusion. In Chapter 4, the process of diagnosing DLB and PDD was also discussed. Before clinicians consider such a diagnosis, however, they must be certain that they have not overlooked any other treatable causes or contributors. Sometimes the DLB or PDD diagnosis is correct but the dementia is exacerbated by some other factor. In this chapter, those factors and the appropriate workup are considered. One should not arrive at the final diagnosis of a neurodegenerative dementia before considering treatable factors, including medical conditions, brain lesions (e.g., bleeds), and medication effects. This is especially relevant if there has been a rapid decline or recent onset. Prescription drugs are a common cause of cognitive impairment. Before ordering tests, it is appropriate to go over all medications that the patient is taking. Commonly prescribed drugs that can impair cognition include those shown in Table 12.1. This is not an exhaustive list. The primary clinician should decide what, if any, medication should be eliminated.

Hospitalization and Nursing Facilities: Keeping Everyone on the Same Page

Nearly all of us end up in the hospital for something sooner or later. The unique problems of Lewy disorders and medications can challenge hospital care teams. On a related note, some individuals with DLB or PDD may require care in a nursing facility. This may be transient, requiring rehabilitation and stabilization following a hospitalization; in other cases, it is indefinite because of the complex care necessary for DLB and PDD. In this chapter, the focus is on the care teams in these facilities. Although many staff in these settings are familiar with the medications and problems of DLB and PDD, this knowledge is not universal. Little published literature addresses the special needs of those with PDD or DLB admitted to the hospital or living in extended care facilities. It is hoped that this chapter can be an aid in caring for those with PDD or DLB. People with DLB or PDD are, by definition, cognitively impaired. Sometimes this is associated with hallucinations or delusions. Most individuals also have dopamine deficiency states with parkinsonism. Another common component is autonomic nervous system dysfunction. This dysautonomia may be associated with bladder and bowel disorders but, more importantly, with orthostatic hypotension (potential for fainting when ambulating). Some people with PDD or DLB are mildly impaired by these problems, and others are quite compromised. What follows is a summary of crucial knowledge for nursing and paramedical staffs. 1. As with any dementia, novel environments are disorienting. 2. Hallucinations are a frequent component of DLB and PDD. These may be exacerbated by psychoactive medications, including narcotics for pain. 3. Carbidopa/levodopa is the least likely among the potent drugs for parkinsonism to provoke hallucinations. Other Parkinson drugs should generally not be started. 4. People with DLB or PDD commonly experience dream enactment behavior (REM sleep behavior disorder); this should not be misinterpreted as nocturnal hallucinations. 5. Anticholinergic medications for urinary urgency may cross the blood–brain barrier and impair cognition (e.g., oxybutynin). The only drug from this class that cannot get into the brain is trospium (Sanctura).

Benefits of Regular Exercise: Disease-Slowing?

Our culture has seen a generational shift in activity levels. In the 1950s everyone walked. How do I know? I grew up in the 1950s. Cars were typically reserved for day trips or vacations, except for people living in the country. Garages had one stall. Shopping malls had not proliferated and people walked to stores; children did not take buses to school, except for farm kids. Snow was removed with shovels, and grass was cut with push mowers. In a half-century, this scene has changed and we have adopted a sedentary lifestyle. Further contributing to this lifestyle is the proliferation of video games, multichannel TVs with remote controls, and computers. Blue collar work is increasingly done overseas. A sedentary culture should favor those with DLB or PDD, right? Lewy-related parkinsonism is physically challenging. With our cultural change, there is no longer a need to get up from the chair and walk very far. In fact, a lift chair with a motor will make it easy to stand. Ostensibly, this is all good. However, there is a dark side to this scenario, which is the focus of this chapter. As you have probably already surmised, we are going to enlarge on that old adage “if you don’t use it, you lose it.” It turns out that there is much truth in that statement, documented in scientific and medical journals. Exercising is easy when one is young and energetic, but it becomes increasingly difficult in middle age; it is downright hard during senior years, even with no neurologic or orthopedic conditions. Excuses and alternatives can easily sidetrack the best of intentions. Anything this difficult needs a compelling rationale. This chapter will summarize the scientific evidence suggesting that vigorous exercise has a biological effect on the brain that may well counter neurodegeneration and brain aging. The term exercise is used in a variety of ways. In this chapter, the focus is on aerobic exercise, which will also be referred to as vigorous exercise. This is exercise sufficient to induce sweating and raise the heart rate.