Cognitive Impairments and Frontotemporal Dementia in Patients with Amyotrophic Lateral Sclerosis

Bailey Baumann

Webpaper #3

Professor Grobstein

Cognitive Impairmentsand Frontotemporal Dementia in Patients with Amyotrophic Lateral Sclerosis

            Amyotrophiclateral sclerosis is a progressive neurodegenerative disease that ischaracterized by the progressive loss of both upper and lower motor neurons inthe brain and the spinal cord. Motor neurons control the movement of voluntarymuscles and when these neurons are destroyed, individuals will experience anincrease in muscle weakness and eventually a complete loss of control overvoluntary movement, leading to a state of paralysis. The course of ALS isextremely variable, but, on average, an individual will survive an average of3-5 years following diagnosis (1).Although ALS is considered a rare disorder, it is one of the most common adultonset neurodegenerative disorders, with an incidence of 1-2 per 100,000individuals (2). There iscurrently no cure or treatment for ALS that can prevent or halt the weakeningand destruction of motor neurons.

            InMay of 2006, my best friend’s father died after a year and a half long battlewith ALS. Until this point I have vehemently avoided even thinking about, letalone researching, the disorder. I knew very little of what was happening andit always seemed easier that way. The one piece of information that I didunderstand was that ALS is unique in that the only aspect of the body affectedby the disorder is movement, leaving all cognitive function intact. After ourclass discussions throughout the semester I found it increasingly difficult tobelieve that there was a neurological disorder that exclusively affected oneaspect of the nervous system, leaving all other aspects essentially untouched.Motor neurons and the parts of the brain that control movement do not work in abubble, and so massive neuron death needs to have consequences outside ofisolated parts of the brain.

            Throughmy research on the causes, treatments and etiology of ALS, I came across somenew studies that are providing evidence for the presence of cognitivedysfunction in a minority of ALS patients. Although current ALS research isfocused on finding new treatments to halt the loss of motor control, I believethat it is also important to continue to learn about the role that cognitionplays in the development of ALS, research that may lead to more efficient andmore compassionate care for sufferers.

            Popularviews of ALS paint the disorder as a purely motor disorder, where cognitivefunction stays intact. This aspect of ALS has been considered both a blessingand a curse for patients and their families (3). Some believe that the benefitof being ‘present’ throughout the process allows patients to spend valuabletime with their families and to prepare for death. While others find theprospect of being fully conscious throughout the process to be too painful tobear. In fact, ALS has been irreversibly linked with the debate over assistedsuicide. Of the 39 patients who died with assistance by Dr. Kevorkian, 8 wereALS patients (3). In one study, researchersinterviewed ALS patients and discovered that the majority of the patients wouldconsider assisted suicide in the future (4). Despite varied opinions on the topic, it is suffice to say that ALSshould be considered a unique disorder, which requires specialized care to meetthe individual needs of each patient. 

            AlthoughALS was first thought of as simply a neuromuscular disorder, new evidencesuggests that in some patients, there is a change in cognitive function. Thesestudies have found that cognitive disabilities in ALS patients are found on acontinuum from very mild cognitive disturbances to frontotemporal dementia(FTD). Frontotemporal dementia is characterized by the degeneration of frontalor anterior temporal lobe neurons, which will result in deficits in reasoning,the ability to make realistic judgments or behave appropriately, and gradualchanges in an individual’s personality (5). FTD is one of the most common typesof dementia, with 250,000 Americans affected each year, and is the most commoncause of early-onset dementia (5). InALS patients, the presence of full FTD is rare, 3-5% of patients (6), but more mild disabilities are more common thanpreviously thought. In fact, in one large group study, approximately 60% of ALSshowed some type of neuropsychological deficits (7).

            Studieshave found that the most common type of cognitive impairments in patients withALS deal with deficits in executive function, which indicates frontal lobedysfunction. Typically ALS patients will demonstrate problems with logic,problem solving, planning, and most frequently, verbal fluency and other wordretrieval tasks (7). When tested, ALS patients seem to do the worst of fluencytests, which require them to think of words that begin with a certain letter. Whenvolunteers are asked to complete tasks such as the verbal fluency test,researchers have found that there is impaired activation in specific areas ofthe patient’s brain, all located in either the frontal or temporal lobes of thebrain (6). When ALS patients undergoPET scans, there is also a significant decrease in cerebral glucose metabolismin both the motor cortex and the frontal cortex (8), which is further evidence to support theinvolvement of “…extramotor cortical regions” (8). Besides the frontal and temporal lobes, there isalso evidence to suggest that there is decreased activation in a number ofnonmotor areas of the brain including the anterior cingulated region, theparahippocampal gyrus, and the anterior thalamic nuclear complex (9). 

            Interestingly,there is a positive connection between the number of bulbar symptoms inpatients and the degree of cognitive involvement (9). Bulbar symptoms of ALS include dysarthia, a motorspeech disorder, and dysphagia, swallowing difficulties (10). In one study,only 21% of patients without cognitive deficiencies presented with bulbarsymptoms, while 75% of patients with cognitive deficiencies presented withbulbar symptoms (10). Thesefindings support a “relation between psychological breakdown and bulbarinvolvement in MND [ALS]” (10).Although cognitive deficits are widespread in executive functions, there islittle evidence to support the idea of memory deficits in ALS patient. Indeed,patients, even in the late stages of the disorder, consistently demonstratefully intact short-term and long-term memory.

            Thepresence of FTD is some ALS patients is raising important questions concerningdefinitions of the disorder. Because the majority of patients with ALS nevershow any evidence of cognitive disorders, let alone frontotemporal dementia,should patients who have FTD still be considered ALS patients, or does thepresence of FTD put these patients into another category altogether? Thiscontroversy is more than a discussion of semantics, as ALS patients with FTDrequire different care than other ALS patients. If separating the disorders canhelp create more efficient and directed treatments, I believe that it may benecessary to at least make ALS with FTD a separate category of ALS disorder.

            Thepossibility of a connection between ALS and cognition was first proposed backin the 1800’s, but even today, the cognitive involvement in ALS is a relativelyunknown phenomenon. One of the reasons that the cognitive underpinnings of ALShave not been investigated until recently is the inability of researchers toreliability and accurately test patients because of their physical handicaps.In fact, there has been no assessment of cognitive function in patients withlate stage ALS because of the demands of the testing, which may require writtenor vocal responses. Although there have been no tests done on late stage ALSpatients, post- mortem studies do confirm damage to certain areas of the brainthat control cognitive function. Communication becomes hard when the individualenters the “locked in” state, although there have been attempts made to assessthese patients using specialized instruments and tests such as an EEG (11).

            Becausethe cognitive deficits that are present in ALS patients most often deal withsmall nuisances such as word generation or word fluency, it is often easy tooverlook the disabilities especially because they usually don’t affect more‘important’ functions such as memory. As a caregiver, it may be difficult tocare about small changes in personality or cognition when the sick individualis having problems performing everyday activities such as eating andswallowing. But, these small changes are important,in fact, they may lead to better diagnostic assessment, better treatment, and abetter understanding of the causes and emergence of ALS.

            Forobvious reasons, the current studies of cognition in ALS patients have occurredlong after the diagnosis, but evidence collected from patients and caregiversindicates that executive dysfunction may precede the diagnosis of ALS (9,10). This new evidence is extremely importantconsidering the many issues involved in diagnosis. Currently, it may take overa year for patients to receive a full diagnosis and there is no definitive testthat can establish the presence of ALS (1). An individual needs to go through amyriad of tests before they can get a diagnosis and start receiving treatment.For some individuals, this waiting time is unbearable and frustrating as theysee their loved one getting progressively worse. This is why the knowledge thatcognitive deficits often precede the diagnosis of ALS is so important. Perhapsit may be prudent for doctors to include the presence of executive functiondeficits in the diagnostic repertoire. It may also be useful for doctors toadminister tests such as the word fluency test in which ALS patients typicallyshow the weakest performance. 

            Theknowledge that dementia and executive function deficits may occur in ALS canalso help with formulating more effective and compassionate treatment plans forpatients. There are and should be differences in the way in which caregiverstreat patients with cognitive disorders and those that do not have thesedeficiencies. First, understanding that there may be changes in the patient’spersonality and cognitive abilities can help the caregiver and the doctor bebetter prepared to deal with the patient. By being prepared and anticipatingthese changes, the caregiver and doctor will be more understanding and bebetter able to understand and handle these changes, which will provide comfortto the patient. Second, when a patient demonstrates cognitive changes or FTD,there are some special considerations that need to be taken into account. Forexample, personality changes associated with FTD can put ALS patients at riskfor harming themselves, as they are more likely to engage in risky activities.Gorging is also a prominent symptom of FTD, so suffers may be at an increasedrisk for chocking and breathing problems, so more structured eating may need tobe established.

            Apartfrom treatment and diagnosis considerations, there are also some controversialissues raised by the discovery and confirmation of cognitive deficiencies inALS patients. Because ALS is normally thought of as a purely motor disorder,there have been few concerns raised about the ability of patients to makedecisions about the course of their treatment and ultimately their wishesconcerning end of life care. This differs from patients with other neuraldisorders such as Alzheimer’s who will typically surrender their power ofattorney to a trusted family member or friend. If an ALS patient has severedementia, or has drastic changes in personality or decreased ability to makejudgments, should this individual have the ability to decide when to end theirown life?

            Inthe study mentioned before that investigated the views of ALS patientsconcerning assisted suicide and the right to die, patients were more likely tosay that they would consider assisted suicide if they had a mental disorder orwere under extreme emotional and psychological distress (4). The results of this study alone explain why it isextremely dangerous to ignore signs of cognitive impairment inALS patients. The ultimate goal in any ALS treatment program is to make thepatient as comfortable as possible, and if a patient is troubled by the loss ofcognitive control, I think that it is worth looking into better treatments andmore educational programs. 

            Ibelieve that ALS researchers need to take a full nervous system and full bodyapproach to their research. Currently I hope that researchers continue todevelop treatments for the motor aspect of ALS, but I would also like to seecontinued research into the nonmotor aspects of ALS. ALS support groups or researchorganizations also need to more efficiently educate the public about cognitiveinvolvement in ALS. On the ALS Association’s website, there was no mention ofcognitive involvement on any of the introductory pages (1). Of immediate concern would be the development ofeffective treatments for FTD that are compatible with the various medicationsnormally taken by ALS patients and also the development of diagnostic toolsthat take cognitive function into account.

            Amyotrophiclateral sclerosis is a horrible disease that desperately needs a cure andbetter treatment options. After looking through many research websites,journals, and books, I know that there are thousands of people workingtirelessly to find these treatments and I feel confident that one day therewill be hope for the thousands of suffers worldwide.

WorksCited

1. The Amyotrophic lateral sclerosis Associationwebsite-good website that has lot’s of links to current research

www.alsa.org

2. Motor Neurone Disease. PJ Shaw In: Handbook ofNeurological Rehabilitation. Eds RJ Greenwood, T M McMillan, MP Barnes, CDWard. Psychology Press Ltd, Chapter 46, pp 639-660;2002

3. Young, J.M., McNicoll, P. Against all odds: Positive lifeexperiences of people with advanced amyothrophic lateral sclerosis.  Health and Social Work 1998; 23: 35-43

4. Gazini, L., Johnston, W.S., McFarland, B.H., Tolle, S.W.,Lee, M.A. Attitudes of patients with amyotrophic lateral sclerosis and theircare givers towards assisted suicide. The New England Journal of Medicine 1998; 339: 967-973.

5. University of California, San Francisco Memory and AgingCenter: Page on Frontotemporal Dementia.

http://memory.ucsf.edu/ftd/

6. Abrahams S, Leigh PN, Goldstein LH. Cognitive change inALS: a prospective study. Neurology2005; 64: 1222–6.

7. Lomen-Hoerth C, Murphy J, Langmore S, et al. Are amyotrophic lateral sclerosis patientscognitively normal? Neurology2003; 60: 1094–7

8. Maekawa S, Al-Sarraj S, Kibble M, et al. Corticalselective vulnerability in motor neuron disease: a morphometric study. Brain2004;127:1237–1251.

9. Kew JJ, Goldstein LH, Leigh PN, et al. The relationship between abnormalities of cognitivefunction and cerebral activation in amyotrophic lateral sclerosis. Aneuropsychological and positron emission tomography study. Brain 1993; 116(Pt 6): 1399–423

10. Talbot PR, Goulding PJ, Lloyd JJ, Snowden JS, Neary D,Testa HJ. Inter-relation between ‘classic’ motor neuron disease and frontotemporaldementia: neuropsychological and single photon emission computed tomographystudy. J Neurol Neurosurg Psychiatry 1995; 58:541–547

11. Neary D, Snowden JS, Mann DM. Cognitive change in motorneurone disease/amyotrophic lateral sclerosis (MND/ALS). J Neurol Sci 2000; 180: 15–20