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Cognitive Dysfunction In MS: Addressing the Emotional, Social, and Vocational Impact Cognitive Dysfunction In MS: Addressing the Emotional, Social, and Vocational Impact

Outline • • Historical perspective Frequency and severity of cognitive changes in MS Relationship Outline • • Historical perspective Frequency and severity of cognitive changes in MS Relationship to other disease characteristics Functions that are affected; functions that are preserved Impact of cognitive dysfunction § Emotional § Social § Vocational § Medical How, when, and why of assessment Treatment options Strategies for clinicians

Jean-Martin Charcot 1825 -1893 Charcot with Marie Whittman and Joseph Babinski André Brouillet - Jean-Martin Charcot 1825 -1893 Charcot with Marie Whittman and Joseph Babinski André Brouillet - 1887

Jean-Martin Charcot Second Lecture on Multiple Sclerosis, 1868 There is marked enfeeblement of the Jean-Martin Charcot Second Lecture on Multiple Sclerosis, 1868 There is marked enfeeblement of the memory; conceptions are formed slowly; the intellectual and emotional faculties are blunted in their totality. The dominant feeling in the patients appears to be a sort of almost stupid indifference in reference to all things. It is not rare to see them give way to foolish laughter for no cause, and sometimes, on the contrary, to melt into tears for no reason. Nor is it rare, amid this state of mental depression, to find psychic disorders arise which assume one or other of the classic forms of mental alienation.

Long-Standing Misconceptions about MS and Cognition • • • Cognitive impairment (CI) is rare Long-Standing Misconceptions about MS and Cognition • • • Cognitive impairment (CI) is rare in MS. CI only occurs in late stage MS or severe MS. MS is a white-matter disease and does not affect: 1) brain volume, 2) gray matter, 3) the cerebral cortex. If an MS patient can pass the mental status exam, everything is OK. Memory problems reported by MS patients are caused by stress, anxiety, and/or depression. Discussing CI will upset MS patients/families and ruin the “image” of MS.

Cognition and Other Disease Characteristics • • • Cognitive function correlates with number of Cognition and Other Disease Characteristics • • • Cognitive function correlates with number of lesions and lesion area on MRI, as well as brain atrophy. Cognitive dysfunction can occur at any time but is more common later in the disease. Cognitive dysfunction can occur with any disease course, but is slightly more likely in progressive MS. Being in an exacerbation is a risk factor for cognitive dysfunction. Depression can worsen cognition, particularly executive functions (Arnett et al. , 1999).

Prevalence of cognitive impairment in MS Prevalence of cognitive impairment in MS

Cognitive Impairment over a 10 -Year Period Adapted from Amato, MP et al, Archives Cognitive Impairment over a 10 -Year Period Adapted from Amato, MP et al, Archives of Neurology 2001; 58: 1602 -1606.

Longitudinal Study of Cognitive Impairment in MS • • • Percent Impaired at Baseline: Longitudinal Study of Cognitive Impairment in MS • • • Percent Impaired at Baseline: 26% Percent Impaired after 10 Years: 56% Predictors of Cognitive Dysfunction after 10 Years: § Higher EDSS § Progressive course § Older age Amato, MP et al, Archives of Neurology 2001; 58: 1602 -1606.

Cognitive Changes in Multiple Sclerosis Cognitive Changes in Multiple Sclerosis

The Impact of Cognitive Dysfunction In Daily Functioning Work status P<0. 01 Social activity The Impact of Cognitive Dysfunction In Daily Functioning Work status P<0. 01 Social activity P<0. 05 Personal assistance P<0. 01 Community services Financial status Cognitively intact (n=52) Transportation Cognitively impaired (n=48) Personal residence 0 1 2 Mean scale score Rao et al. Neurology. 1991; 41: 692. Worsening 3

Impact of Cognitive Impairment on Employment Rao et al. Neurology. 1991; 41: 692. Impact of Cognitive Impairment on Employment Rao et al. Neurology. 1991; 41: 692.

Cognitive Functions Affected in MS • • • Memory - acquisition and retrieval Attention Cognitive Functions Affected in MS • • • Memory - acquisition and retrieval Attention & concentration - working memory Speed of information processing Executive Functioning Visual/spatial organization Verbal fluency - word finding De. Luca, J. What we know about cognitive changes in multiple sclerosis. In La. Rocca, N & Kalb, R (eds. ) Multiple sclerosis: understanding the cognitive challenges. New York: Demos Medical Publishing, 2006.

Cognitive Functions Unaffected in MS • • • General intellect Long-term (remote) memory Recognition Cognitive Functions Unaffected in MS • • • General intellect Long-term (remote) memory Recognition memory Conversational skill Reading comprehension De. Luca, J. What we know about cognitive changes in multiple sclerosis. In La. Rocca, N & Kalb, R (eds. ) Multiple sclerosis: understanding the cognitive challenges. New York: Demos Medical Publishing, 2006.

Recognizing Memory Problems • • Difficulty learning new material or needing to spend longer Recognizing Memory Problems • • Difficulty learning new material or needing to spend longer to make it stick Forgetting recent conversations, TV shows, movies Forgetting appointments Losing track of medication schedules Neglecting to do planned tasks Losing or misplacing things Forgetting names, phone numbers, etc.

Recognizing Impaired Attention and Concentration • • • Difficulty with focus Cannot stick to Recognizing Impaired Attention and Concentration • • • Difficulty with focus Cannot stick to one task without getting distracted Problems screening out distractions Difficulty with divided attention tasks, e. g. , listening to a family member talk while cooking Running out of steam when trying to concentrate on reading material or other intellectual tasks Poor recall due to lack of attention when information is being learned

Recognizing Slowed Information Processing • • Quality of work is the same but output Recognizing Slowed Information Processing • • Quality of work is the same but output is much less Cannot respond quickly when a lot of information is being presented Trouble dealing with tasks having a time element, e. g. , card games, word games, deadlines Difficulty processing information coming from several different sources simultaneously

Recognizing Problems in Executive Functioning • • • Inability to perform jobs requiring analytic Recognizing Problems in Executive Functioning • • • Inability to perform jobs requiring analytic skills Difficulty following complex arguments or explanations; missing the point in conversations Trouble following through with complicated tasks Being too literal or concrete Need for increased direction on the job because of difficulty in setting priorities, organizing time, and meeting deadlines Trouble with “multi-tasking”

Recognizing Impaired Visual/Spatial Organization • • • Gets lost when driving; confused about right/left, Recognizing Impaired Visual/Spatial Organization • • • Gets lost when driving; confused about right/left, north/south Can’t do puzzles or assemble “some assembly required” items Trouble operating machines Difficulty understanding diagrams Problems visualizing objects without a picture— e. g. , from a description, incomplete picture, or disassembled picture

A Word about Cognition and Fatigue • • • Physical fatigue has less impact A Word about Cognition and Fatigue • • • Physical fatigue has less impact on cognitive performance than people think. Cognitive fatigue refers to a decline in cognitive performance following cognitively challenging tasks. Cognitive fatigue can occur even in the absence of physical fatigue. De. Luca, J. What we know about cognitive changes in multiple sclerosis. In La. Rocca, N & Kalb, R (eds. ) Multiple sclerosis: understanding the cognitive challenges. New York: Demos Medical Publishing, 2006.

The Psychosocial Impact of Cognitive Changes (La. Rocca & Kalb, 2006) • • • The Psychosocial Impact of Cognitive Changes (La. Rocca & Kalb, 2006) • • • The ability to think, remember, and reason is central to a person’s identity. Changes in cognitive abilities: § Threaten the sense of self § Damage self-esteem and self-confidence Cognitive abilities form the basis of our interactions with others. Cognitive impairments: § Alter communication patterns § Impact other people’s perceptions § Interfere with role performance § Affect the balance in a partnership

I TOLD YOU THAT THIS MORNING!? ! I DON’T THINK YOU’RE PAYING ATTENTION—OR MAYBE I TOLD YOU THAT THIS MORNING!? ! I DON’T THINK YOU’RE PAYING ATTENTION—OR MAYBE YOU JUST DON’T CARE ABOUT WHAT I HAVE TO SAY ANYMORE….

I TOLD YOU THAT THIS MORNING… • • • Possible cognitive deficit(s)? Possible feelings? I TOLD YOU THAT THIS MORNING… • • • Possible cognitive deficit(s)? Possible feelings? § Wife with MS § Husband Recommended strategies?

I TOLD YOU THAT THIS MORNING… • • • Possible cognitive deficit(s): memory, attention, I TOLD YOU THAT THIS MORNING… • • • Possible cognitive deficit(s): memory, attention, info processing Possible feelings: §Wife with MS: denial, anger, anxiety, guilt, inadequacy §Husband: frustration, anxiety, abandonment Recommended strategies: written note, family calendar, non-distracting environment for conversations

HOW COULD YOU GET LOST? !? YOU’VE DRIVEN THAT ROUTE 100 TIMES!! HOW COULD YOU GET LOST? !? YOU’VE DRIVEN THAT ROUTE 100 TIMES!!

HOW COULD YOU GET LOST… • Possible cognitive deficit(s)? • Possible feelings? § Wife HOW COULD YOU GET LOST… • Possible cognitive deficit(s)? • Possible feelings? § Wife § Husband with MS • Recommended strategies?

HOW COULD YOU GET LOST… • • • Possible cognitive deficit(s): memory, attention, visual HOW COULD YOU GET LOST… • • • Possible cognitive deficit(s): memory, attention, visual -spatial, sequencing Possible feelings: § Wife: anxiety, loss of respect/confidence, anger § Husband with MS: anxiety, anger, embarrassment, loss of confidence Recommended strategies: pre-planning of route: maps in memory book; minimal distractions in car

YOU REALLY MESSED UP THE CHECKBOOK THIS TIME!! YOU REALLY MESSED UP THE CHECKBOOK THIS TIME!!

YOU REALLY MESSED UP THE CHECKBOOK… • • • Possible cognitive deficit(s): attention/concentration, organization, YOU REALLY MESSED UP THE CHECKBOOK… • • • Possible cognitive deficit(s): attention/concentration, organization, planning/sequencing, problem-solving Possible feelings: • Wife with MS: embarrassment, guilt, anxiety • Husband: anger, anxiety, loss of partnership Recommended strategies: template, distraction-free environment

“WHERE ARE YOU? !? OUR MEETING WITH THE CLIENT STARTED AN HOUR AGO? ” “WHERE ARE YOU? !? OUR MEETING WITH THE CLIENT STARTED AN HOUR AGO? ”

WHERE ARE YOU? !? . . • • • Possible cognitive deficit(s): memory, planning WHERE ARE YOU? !? . . • • • Possible cognitive deficit(s): memory, planning organization, attention, visual/spatial skills Possible feelings: § Boss: anger, frustration, confusion, anxiety § Employee with MS: embarrassment, frustration, fear Recommended strategies: calendar, tickler system, pre-route planning

MOM—I TOLD YOU YESTERDAY THAT I WAS GOING TO SARA’S HOUSE AFTER SCHOOL! MOM—I TOLD YOU YESTERDAY THAT I WAS GOING TO SARA’S HOUSE AFTER SCHOOL!

MOM—I TOLD YOU YESTERDAY… • Possible cognitive deficit(s): attention/concentration, organization • Possible feelings: § MOM—I TOLD YOU YESTERDAY… • Possible cognitive deficit(s): attention/concentration, organization • Possible feelings: § Mom with MS: embarrassment, guilt, anxiety anger, suspiciousness (if not true) § Child: anxiety, loss of confidence, guilt (if not being truthful) • Recommended strategies: family calendar, distraction-free environment

When Cognitive Evaluation is Appropriate • • • To establish a baseline There are When Cognitive Evaluation is Appropriate • • • To establish a baseline There are reported changes in ability There is a potentially treatable condition Person is being started on a new treatment When considering an application for SSDI or vocational rehabilitation When there is a need to know Note: The standard mental status examination will miss 50% of cognitively impaired patients (Peyser, 1980)

Cognitive Evaluation • • • Battery of tests designed to assess areas of reported Cognitive Evaluation • • • Battery of tests designed to assess areas of reported difficulties, as well as pre-existing and current strengths Clinical neuropsychologist, occupational therapist, speech-language pathologist Full test battery = 6 -8 hours over two days Expensive/often without insurance coverage Various screening batteries available, including a 5 minute self-report instrument (MS Neuropsychological Screening Questionnaire [Benedict et al. , 2003; 2004])

Treatment of Cognitive Dysfunction • • • Symptomatic treatments Disease modifying agents Cognitive rehabilitation Treatment of Cognitive Dysfunction • • • Symptomatic treatments Disease modifying agents Cognitive rehabilitation

Symptomatic Treatments – as of 2012, none shown to be effective in controlled clinical Symptomatic Treatments – as of 2012, none shown to be effective in controlled clinical trials • Acetylcholinesterase inhibitors donepezil • Anti-fatigue agents amantadine modafinil • Stimulants • Potassium channel methylphenidate [attention] blockers 4 -aminopyridine 3, 4 -diaminopyridine

Disease Modifying Agents • • • fingolimod interferon beta 1 a (Cohen et al. Disease Modifying Agents • • • fingolimod interferon beta 1 a (Cohen et al. , 2002) interferon beta 1 b (Flechter et al. , 2007) glatiramer acetate (Schwid et al. , 2007) natalizumab (Iaffaldano et al. , 2012; Portaccio et al. , 2012; • • mitoxantrone (Zéphir et al. , 2008) teriflunomide Mattioli et al. , 2011)

Cognitive Rehabilitation • • Direct retraining of impaired functions § Memory exercises § Attention Cognitive Rehabilitation • • Direct retraining of impaired functions § Memory exercises § Attention training Compensatory strategies § Notebooks, lists, organizers § Time and energy management § Substitution strategies

Guidelines for Treatment (for now) • • Symptomatic Treatments – slow progress § Not Guidelines for Treatment (for now) • • Symptomatic Treatments – slow progress § Not much of real value has emerged; all clinical trials have had negative results § Disease Modifying Agents – may be most important § Modest results so far, but if they can slow or halt accumulation of cerebral lesions. . . Cognitive Rehabilitation – common-sense help § Disappointing thus far but common-sense points to compensatory measures as best strategy § Address affective and social issues related to MS

Implications for patient care Even mild cognitive dysfunction can impact treatment: • • Your Implications for patient care Even mild cognitive dysfunction can impact treatment: • • Your patients may not: § Show up on time for appointments § Follow complex explanations § Remember what they’ve been told § Follow through on treatment plans You may want to: § Provide informational brochures § Provide appointment reminders § Write down specific instructions § Remind patients to write down their questions § Invite patients to bring a family member or friend to appointments

Recommended Strategies for Your Patients • • • Get someone to work with you. Recommended Strategies for Your Patients • • • Get someone to work with you. Make up your mind that it’s OK to do things a little differently than in the past. Although abilities may not improve, function can be enhanced. Compensation is key—e. g. , many memory problems can be solved with better organization. Consistency is essential. Stick with your program and follow through with your new strategies. Keep the mind active and stimulated.

Summary • • More that 60% of people with MS experience cognitive changes. Cognitive Summary • • More that 60% of people with MS experience cognitive changes. Cognitive dysfunction is more related to MRI changes than to other disease characteristics. While many functions can be affected, some are more likely to be affected than others. The impact on individuals and families is significant. Disease-modifying therapies are the best protection; symptomatic medications have been shown to be of no benefit in large-scale clinical trials. Compensatory strategies are essential. Adequately treating depression may improve cognitive functioning.

National MS Society Resources for Your Patients • • • Booklets Available from the National MS Society Resources for Your Patients • • • Booklets Available from the National Multiple Sclerosis Society (by calling 1 -800 -344 -4867; or online at www. nationalmssociety. org/Brochures) § MS and the Mind § Solving Cognitive Problems § Fatigue: What You Should Know § Hold that Thought Webcast: Hold that Thought: Cognition and MS (http: //www. nationalmssociety. org/multimedia-library/webcasts-podcasts/ms-hold-that-thought/index. aspx) Website (http: //www. nationalmssociety. org/about-multiplesclerosis/symptoms/cognitive-function/index. aspx)

National MS Society Resources for Clinicians • MS Clinical Care Network § § § National MS Society Resources for Clinicians • MS Clinical Care Network § § § Website: www. national. MSsociety. org/MSClinical. Care; E-mail: [email protected] org Clinical consultations with MS specialists Literature search services Professional publications (Clinical Bulletins; Expert Opinion Papers; Talking with Your MS Patients about Difficult Topics; Pamela Cavallo Education Series for nurses, rehab professionals, mental health professionals, and pharmacists Professional Education Programs (Nursing, Rehab, Mental Health) Consultation on insurance and long-term care issues Quarterly professional e-newsletter

Recommended Readings Books • • Feinstein A. The Clinical Neuropsychiatry of Multiple Sclerosis (2 Recommended Readings Books • • Feinstein A. The Clinical Neuropsychiatry of Multiple Sclerosis (2 nd ed. ). Cambridge: Cambridge University Press, 2007. Gingold J. Facing the Cognitive Challenges of Multiple Sclerosis. New York: Demos Medical Publishing, 2006. Kalb R, Holland N, Giesser B. Multiple Sclerosis for Dummies. Hoboken NJ: Wiley Publishing, 2007. La. Rocca N. Cognitive Challenges: Assessment and Management. In R. Kalb (ed. ) Multiple Sclerosis: The Questions You Have; The Answers You Need (4 th ed. ) New York: Demos Medical Publishing, 2007.

Recommended Readings, cont’d • La. Rocca N & Kalb R. Multiple Sclerosis: Understanding the Recommended Readings, cont’d • La. Rocca N & Kalb R. Multiple Sclerosis: Understanding the Cognitive Challenges. New York: Demos Medical Publishing, 2006. Society Publications • • Expert Opinion Paper: Assessment and Management of Cognitive Impairment in Multiple Sclerosis, 2008 (www. national. MSsociety. org/Expert. Opinion. Papers). La. Rocca N. Talking with Your MS Patient about Cognitive Dysfunction, 2009 (www. national. MSsociety. org/PRCPublications).