Cognitive Issues in Parkinson's Disease

Jennifer G. Goldman, MD, MS

It is now recognized that Parkinson’s disease (PD) is much more than a motor disorder. Tremor, slowness, stiffness, and walking trouble are only part of the picture. Non-motor symptoms in PD are common and affect cognition, behavior, sleep, autonomic function, and sensory function. Studies
of PD patients followed over many years reveal that non-motor symptoms become even more important as PD advances. Increased recognition and improved treatments for these non-motor symptoms are greatly needed.

Cognition

First, what is cognition? Cognition is a general term that refers to the mental abilities that we use to process information and apply knowledge. These mental processes allow us to perform daily functions such as paying attention, solving problems, and remembering where items are and how to do certain tasks.When people typically talk about cognition, they often focus on “memory,” but “memory” is only one aspect of cognition. Rather, in the study of cognition, we talk about “cognitive domains” which reflect different types of cognitive processes and are described in detail below.

1. Attention and working memory:

Attention is the ability to selectively focus on a particular aspect of one’s environment, often while ignoring competing stimuli. In PD, people may find it difficult to concentrate on a conversation or reading a book. It may be challenging to talk to someone while walking and maintaining balance.  Working memory refers to the memory process of temporarily storing information in one’s mind and manipulating it over a short period. Mental arithmetic is one example of working memory function. These cognitive processes are often linked to alertness. Sleepiness and sedating medications can impair attention and working memory function. These cognitive processes involve the frontal and parietal lobes in the brain. Working memory also involves the basal ganglia and dorsolateral prefrontal cortex, regions affected in PD.

2. Executive function:

Executive function includes the ability to plan, organize, initiate, and regulate goal directed behavior. One can think of the “CEO” (chief executive officer)
of a company and the many tasks involved in directing the organization. These activities may include multitasking, solving problems, starting new tasks, and switching tasks. Executive function involves the prefrontal cortex of the brain and the dopamine system, which are affected in PD. Executive dysfunction is one of the most common cognitive changes reported in PD.

3. Memory:

In general, the concept of memory invokes learning and remembering information. Memory, however, can be classified into different processes and types. For instance, there is immediate (seconds-minutes), short-term (minutes-days), and long-term memory (days-years). There also is memory for facts, concepts, or events (called declarative memory) and memory for how to do certain tasks like tie our shoes or ride a bicycle (called procedural memory) as well as working memory (described earlier). Declarative memory typically involves the hippocampus or temporal lobe of the brain, whereas
procedural memory often involves the frontal areas and basal ganglia.

People with PD may have trouble recalling information, but in general, memory is less impaired in PD compared to Alzheimer’s disease. In PD, people frequently recall information more readily when given cues or choices. This helps the person to retrieve information from the brain’s memory storage. Long-term memory function typically remains intact in PD.

4. Language:

Language abilities include naming objects, generating words, comprehension, and verbal concepts. The most common language problem in PD is finding the “right” words. People with PD also tend to speak less overall (in addition to softer voice) and use simpler speech. This can be an area of frustration for both the patient and caregiver because verbal communication is such an important part of human behavior.

5.Visuospatial function:

These abilities tell us where things are around us in space, give us a spatial map of our environment, and involve our sense of direction. Visuospatial functions allow us to estimate distance and depth perception, use mental imagery, copy drawings, or construct objects or shapes. Examples include being able to give someone directions to your house by tracing the route in your mind, avoiding obstacles in one’s path, and putting together a puzzle. These abilities rely on the parietal lobe of the brain. 

Cognitive Evaluation

There are several ways to assess cognition in the clinical or in the research setting. Reports from the patient and the patient’s caregiver, spouse, or friend
are important sources of information. The physician may ask questions about cognitive function, whether the cognitive problems represent a change from
prior functioning, and how it impacts activities of daily living or work. The physician may perform short tests of thinking and memory, but generally the
“gold standard” is more comprehensive, formal testing by a neuropsychologist. These evaluations include multiple tests to assess different cognitive domains. Some of the tests require oral answers, while others use a pencil and paper. This evaluation may range from about 45 minutes to several hours.

Cognitive changes in PD

Cognitive symptoms in PD are common, though not every person experiences them. In some people with PD, the cognitive changes are mild. In others, however, cognitive deficits may become more severe and impact daily functioning. Similar to slowness of movement (or bradykinesia), people with PD often report slower thinking and information processing (termed “bradyphrenia”). Attention and working memory, executive function, and visuospatial function are the most frequently affected cognitive domains in PD.

Cognitive deficits that are mild and do not impair one’s ability to carry out activities of daily living have been termed “mild cognitive impairment.” Studies estimate that mild cognitive impairment occurs in about 20-50% of patients with PD. We now recognize that mild cognitive changes may be present
at the time of PD diagnosis or even early in the course of PD. They may or may not be noticeable to the person. They may or may not affect work or activities, depending on the demands of specific tasks and work situations.

Dementia refers to a syndrome in which patients have problems in more than one cognitive domain, and the cognitive problems significantly  impair everyday life functioning. About 40% of PD patients develop dementia. Dementia in PD typically develops many years after the initial onset of PD and is more common with advanced disease. When dementia develops before or at the same time as the PD motor symptoms, patients are often given the
diagnosis of dementia with Lewy bodies. Many physicians and researchers, however, consider PD dementia and dementia with Lewy bodies to represent related disorders and fall under an umbrella term of “Lewy body disorders.”

Other reasons for cognitive symptoms

Besides PD, there are other important causes of cognitive dysfunction to keep in mind. Medical illnesses such as thyroid disease or vitamin B12deficiency can cause cognitive symptoms. Urinary tract infections or pneumonia can acutely cause confusion or hallucinations. In these settings, the cognitive symptoms are generally reversible after the infection or medical condition is treated. One should be aware that some medications for pain or bladder problems may cause sedation/sleepiness or confusion, and, thereby, impair cognitive function.

Overall, there are variable effects of dopaminergic medications (levodopa, dopamine agonists, MAO-B inhibitors) on PD cognition. Some studies report
improved alertness, working memory, and planning abilities. Other studies find no effect of dopaminergic medications on PD cognition, and some report
increased cognitive symptoms or increased sleepiness. Elderly patients do not tolerate dopamine agonists and anticholinergics as well as younger people
and are more susceptible to confusion or hallucinations. It is important to check with one’s physician regarding potential drug interactions or side effects. In addition, hearing loss or vision impairment can be a cause of cognitive problems. If one cannot adequately see or hear the information well enough to process it, it can be difficult to learn, remember, and retrieve it. Cognitive function also can be affected by poor nighttime sleep and excessive daytime sleepiness. Depression and anxiety may mimic cognitive symptoms. Lastly, head trauma, seizures, strokes, or “mini-strokes” may be other reasons for cognitive deficits.

Causes of cognitive impairment in PD

The exact causes of cognitive impairment or dementia in PD are not fully understood. There may be changes in the neurochemical signals that the brain
uses to pass along information to different regions of the brain. Besides dopamine, the neurochemical signals (or neurotransmitters) - acetylcholine, serotonin, and norepinephrine - are especially important for cognition, memory, attention, and mood. In autopsy studies, Lewy bodies, abnormal protein accumulations, have been found in neurons in brain regions responsible for cognitive processes. Other causes include co-existing strokes or “mini-strokes” or Alzheimer’s disease pathology.

Management strategies

Management of cognitive impairment in PD depends on the timing and degree of cognitive dysfunction. For example, if cognitive problems develop
abruptly, the physician may first search for an infection, new neurological problem (such as a stroke), or newly prescribed medication. If the cognitive
problems gradually develop, the evaluation may be different, and examination by a neurologist, neuropsychologist, or specialist in cognition may be helpful.

Medications used to treat dementia in PD have been based on FDA-approved treatments for Alzheimer’s disease, even though these are different diseases. The medications work on the cholinergic system in the brain (a neurochemical involved in attention and memory). Medications
in this group include donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne). To date, only rivastigmine (Exelon) is FDA-approved
for the treatment of dementia in PD. The cognitive effects of these medications in clinical research studies have been modest, but should be discussed on
an individual basis with one’s physician. Side effects include nausea, diarrhea, and in some, worsened tremor. Memantine (Namenda) is another medication that has FDA-approval for Alzheimer’s disease but requires further study in PD dementia. At present, these medications have not been studied in PD patients with mild cognitive impairment.

There are also non-medication strategies for treating PD cognitive impairment. The goals of these strategies are to help patients with cognitive tasks, communication, and daily activities; improve quality of life, and address safety concerns. Pill reminders, clock alarms, and timers are useful ways to help patients remember to take their medications. Executive function strategies use step-by-step approaches to break down activities into simple steps, tools such as making “to do” checklists and daily planners and alarms to keep track of events and time. Maintaining a regular routine for daily activities and exercise is important. Household items such as utensils, glasses, and keys should be kept in the same place all the time, and drawers can be labeled. Patients may respond better when given choices, cues, or yes-no answers, particularly if wordfinding difficulties or slowed thinking is
present.

Just like physical exercise, mental “exercise” is important for cognition in PD as well as successful aging. Although the exact mechanism is unknown, scientific studies suggest that rats housed in “enriched environments” that have toys and interesting objects show increased brain growth and better capacity for learning than those kept in “boring” environments. This leads to the concept of “use it or lose it” for cognition. Mental activities can include doing puzzles, playing cards or other games, reading a book, going to lectures or concerts, or learning a new activity. These can be coupled with physical exercise such as learning new dance steps or yoga positions. Just like with physical exercise, there is no single “right” mental exercise. Social interactions are an important piece of mental stimulation. Many of these activities can be done with friends or family members. It is important for patients and caregivers alike not to get frustrated when cognitive problems, decreased initiation of activities, or communication problems are present. Patience is key.

While it is not always an easy decision to stop driving, this is an important safety issue to address. Driving involves many different cognitive processes including attention, executive function, visuospatial abilities, and processing speed plus motor demands. Some occupational therapy departments offer
simulated driving tests or on-the-road tests that can help physicians and families make decisions about driving abilities. For patients with more advanced
dementia, adult day care programs and group activities in the nursing home can enhance social interaction. Social workers can be a valuable asset to help the patient and caregiver deal with stressors and frustrations.

Dr. Goldman is Assistant Professor, Section of Parkinson Disease and Movement Disorders, Department of Neurological Sciences at Rush University Medical Center, Chicago, IL. In this article, Dr. Goldman will focuses on cognitive issues in PD. This article was prompted by her Parkinson Education Program on April 29, 2011 in St. Louis, Missouri and it was printed in the August, 2011 issue of the APDA St. Louis Newsletter. 

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