Cognitive Problems in Multiple Sclerosis

Problems with thinking or performing normal daily cognitive tasks are a hallmark of Multiple Sclerosis and often grouped with fatigue and depression (as well as anxiety) as the main hidden symptoms of the disease. In fact this constellation of symptoms, reported in over 50 % of newly diagnosed patients, often dominates the lives of people with MS early in the course of the disease when physical manifestations are less apparent and the amount of involvement of the nervous system is relatively limited.

It should therefore come as no surprise that there is often little relationship between the extent of visible white matter involvement on MRI scans and the presence of these hidden symptoms. Given the interrelationship between fatigue, depression (often with sleep disruption) and mild cognitive impairment it has been hypothesized that all three symptoms may be intricately linked early in the course of the disease through some common mechanism or pathway.

In fact successful management of perceived cognitive impairment early in the disease requires a multidisciplinary approach directed at the impact of mood disorders, sleep disruption and fatigue with or without compensatory strategies to help with specific cognitive tasks. Treating only one aspect of this triad is less likely to be successful, as researchers have discovered in clinical trials of drugs to treat fatigue, where patients reported improved fatigue but no change in cognitive performance.

But what are these cognitive problems reported by patients with MS and why are they so difficult for others to recognize? In its mildest form people with MS report forgetfulness and slowing of thought processes often with word finding difficulty and easy distractibility.

These symptoms are identical to those reported by people with isolated chronic fatigue syndrome and depression, thus supporting the connection discussed previously. It is very rare for MS to create obvious problems with language, the ability to carry out common learned tasks (combing one’s hair or knowing how to use eating utensils), or limit awareness of one’s environment to the extent that is typical of dementing illnesses like Alzheimer’s disease.  Some people with MS become even more gregarious and outspoken with time (think, “no filter”), again leading those around them to often fail to recognize the worsening problems with cognition and incorrectly attribute the actions of the patient to willful misbehavior or a personality problem.  The intrusion of crying spells, difficulty controlling smiling or laughing or emotional fluctuations can further lead people to believe that the problem is solely a reflection of depression or another mood disorder, even though there is no other evidence to support a diagnosis of mood disorder and the behavior is not linked to any particular environment clue or stimulus.

Thankfully, these problems with emotional lability do not typically occur early in the course of the disease, if at all. But even early in the course of the disease, learning new information (visually or verbally or both) can be enough of a problem to interfere with school activities or learning a new job task, whereas old well learned tasks remain relatively unaffected.  Once a patient loses the ability to sort and manipulate information, inhibit incorrect responses and develop a cognitive plan to an degree that impairs their ability to execute multistep tasks (this is reason it is called executive dysfunction), it is often very difficult for people with MS to remain employed even with compensatory strategies. 

This often happens well before an individual has lost enough physical function to require disability solely on the basis of their physical problems, and is the main reason that cognitive impairment is the main cause of loss of employment in MS.  The lack of supporting documentation of their cognitive impairment in the form of specific cognitive testing, and the failure of families, employers and physicians to recognize the impact of these deficits on everyday behavior and the ability to perform work related tasks is the main reason for divorce, job terminations and failure to obtain disability. This in turn creates greater stress on patients, caregivers and other family members in a vicious cycle that is very hard to halt or reverse.

But are all people with MS destined to decline in such a dismal manner or do certain features or characteristic of one’s environment or one’s disease predict worse outcomes and possibly offer an opportunity to intervene to improve outcomes?  This is a topic that I have discussed in several previous blogs and is very pertinent to any discussion of cognitive impairment and it’s treatment. First, there are certain individual characteristics that unfortunately are not amendable to modification. Foremost among these are the susceptibility genes we inherit that may affect disease severity, and early childhood enrichment, nurturing and education, collectively referred to as, “passive cognitive reserve”.

Many studies in MS and other degenerative disorders suggest that greater childhood enrichment and education is protective against cognitive decline from a number of diseases later in life. Thankfully, many studies also suggest that “active cognitive reserve”, or ongoing learning and development of new skills in adult life is also protective and the reason so many experts advocate memory games and the acquisition of new skills in older adults. This should form of the core of any treatment strategy to prevent cognitive decline.

What about specific disease characteristics associated with a more rapid decline in the physical function of MS patients? Remember, cognitive impairment is like any other manifestation of MS; features associated with a more aggressive disease course and rapid physical decline tend to be associated with more rapid and significant declines in cognition. Since men and African Americans tend to have more severe problems with MS, it stands to reason and is supported by data that they also tend to have more problems with cognition as the disease worsens. Similarly, greater MRI white matter involvement at onset of the disease or developing within the first few years of the disease tends to be associated with greater development of cognitive impairment over time. An even better predictor of cognitive impairment is the degree of brain atrophy or the rate at which brain volume declines over time.

Therefore, treatments that are more effective at preventing the disease from getting worse, as defined by MRI and physical examination, should have a similar benefit on preventing or slowing the development of cognitive impairment over time. This in fact has been demonstrated in clinical trials of disease modifying therapies beginning with the seminal study of Avonex for relapsing MS.  There is every reason to suspect that disease-modifying therapies that significantly affect the course of the disease should lessen cognitive impairment, although not all clinical trials include adequate assessments of cognition to test this hypothesis.  Therefore, the most important treatment for cognitive impairment, and the treatment supported the most by clinical research, is prevention of further worsening with effective disease modifying therapies. What is not known is whether the benefits of disease modifying therapies accrue to patients in both early and later stages of the disease or whether the benefits are enhanced in either group by cognitive enrichment and learning programs although there it is probably a good bet that both treatment strategies are required.

What other features should be considered in the assessment and management of cognitive impairment? As noted previously, the assessment and management of mood disorders and fatigue are essential if one is to have a significant impact on the manifestations of cognitive impairment.  This is true at all stages of the disease. Equally important is the discontinuation of potentially offending medications that are not required and contribute to cognitive complaints. The list of medications that may worsen cognition is almost endless but is dominated by narcotics (eg Percocet, vicodin etc), sleep aides, benzodiazepines (eg include valium, lorazepam), alcohol and marijuana. To be sure, many people require these medications but there are many with no need for them or with a different need that requires a less harmful treatment.

Lastly, it is exceedingly important to eliminate other potential disorders that may worsen cognitive impairment in people with MS. These conditions, many of which are more common in people with MS than the general population, include thyroid disorders, sleep disorders, (sleep apnea and other primary or secondary sleep disorders) and Vitamin deficiency, particularly B12 deficiency. Periodic worsening of cognitive is common later in the disease and frequently associated with undetected infections (UTI) or the development of new medical problems (heart disease, COPD).

What about specific pharmacologic treatment of cognitive impairment?  Unfortunately, specific treatment of cognitive dysfunction in MS patients with drugs used to treatment other memory disorders like Alzheimer’s disease has not been beneficial; these treatments include Donepezil, Rivastigmine and Memantine. Furthermore, all of these treatments may create unacceptable side effects. Ginko Biloba has a long history of use for this symptom but controlled studies suggest no significant benefits in MS or significant side effects. As mentioned previously, treatments meant to ameliorate fatigue, such as amantadine and modafinil, may benefit fatigue and excessive daytime sleepiness, but alone will not generally improve cognition. This does not mean the drugs used for fatigue do not play an important role in multidisciplinary management of cognitive impairment.

What is the best approach to cognitive impairment in MS at this point in time?

1. Assessment of the severity and impact of cognitive dysfunction on daily activities: this may occur in the clinic during a visit with a neurologist or with more specific neuropsychological testing, depending on the circumstances
2. Evaluation and management of additional factors or MS symptoms that may be contributing; this is an extensive category requiring considerable expertise and experience for both evaluation and treatment. It includes assessing the impact of depression and anxiety, adjusting medications and managing sleep disorders.
3. Education of patients and families: this is extremely important to build support and understanding
4. Early and effective use of disease modifying therapies to eliminate or limit disease activity and halt the development of further brain atrophy
5. Exercise program and increased overall physical activity: There is significant evidence to support a role of enhanced physical and social activity in the management of cognitive impairment associated with many diseases including MS. This includes the use of Yoga programs
6. Cognitive enrichment and learning: This may include specific cognitive rehabilitation problems, although the evidence in support of these programs for MS is limited at this time
7. Compensatory strategies: This includes minimizing distractions, doing tasks one at a time, taking and rewriting notes, taking adequate breaks and limiting the duration of a work day to minimize the effects of fatigue or working from home. 
8. Ongoing assessment and education over the disease course
   

-Rip Kinkel, MD

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