Sandra A. Mitchell, CRNP, MScN, AOCN National Cancer Institute, Bethesda, MD

1. Cognitive Dysfunction In Patients with a Primary Brain Tumor: Exploring and Navigating Uncharted Waters • Sandra A. Mitchell, CRNP, MScN, AOCN National Cancer Institute, Bethesda, MD • Sherry W. Fox, PhD, RN, CNRN University of Virginia School of Nursing, Charlottesville, VA • Margaret Booth-Jones, PhD Moffitt Cancer Center and Research Institute, Tampa, FL

2. Objectives • Analyze the domains of cognitive function. • Identify and select tools/approaches for evaluating cognitive function in the clinic. • Explain the indications for neuropsychological evaluation. • Plan a program of support, accommodation, and rehabilitation for patients with a primary brain tumor who are experiencing cognitive dysfunction.

3. Case #1: Janet • 37 y/o right-handed, Caucasian married female • Mother of 3 (ages 5, 9, and 10) • 1 month s/p 80% resection of left frontotemporal oligodendroglioma (WHO grade 2, with elevated MIB-1 index) • Considering XRT and/or chemotherapy vs. surveillance • Partial motor seizures, controlled on Dilantin • College educated, and working part-time at a public school • No prior medical or psychiatric history • Patient reporting depressed mood, increased tearfulness, reduced energy, and word-finding difficulties • Husband is concerned about her mood and ability to accomplish daily tasks, including caring for their 3 children

4. Case #2: Bernie • 58 y/o ambidextrous Israeli male. Married to his second wife • 2 adult children from first marriage • 2 weeks s/p gross total resection of a right frontal Glioblastoma Multiforme (GBM) (WHO grade 4) • Scheduled to begin treatment with XRT and concurrent temozolomide • Currently prescribed Dilantin, Decadron and Anzemet • No previous psychiatric history; history of HTN • Has an MBA and is working as an executive in a major corporation – currently on sick leave • Patient denies emotional distress or cognitive problems • Wife and adult children are very concerned about his change in personality and decision making abilities

5. Factors Contributing to Neurobehavioral Changes Associated with Brain Tumors • Location of the tumor • Pathologic type • Patient characteristics

6. PARIETAL • Somatosensory changes • Impaired spatial relations • Hemispatial neglect • Homonymous visual deficits • Agnosia (non-perceptual disorders of recognition) • Language comprehension impairments • Alexia (disorders of reading) • Agraphia (disorders of writing) • Apraxia (disorders of skilled movement) • FRONTAL • Personality changes (impulsivity, lack of inhibition, lack of concern) • Delayed initiation/apathy • Executive dysfunction • Diminished self-awareness of impaired neurologic or neuropsychological functioning (anosognosia) • Language deficits • OCCIPITAL • Alexia (disorders of reading) • Homonymous hemianopsia • Impaired extraocular muscle movements • Color anomia • Achromatopsia (impairment in color perception) • TEMPORAL • Auditory and perceptual changes • Memory and learning impairments • Aphasia and other language disorders • CEREBELLUM • Ataxia • CORPUS CALLOSUM • Transmission of visual information • Integration of sensory input • Transmission of somatosensory information • BRAINSTEM • Diplopia • Altered consciousness and attention • Cranial neuropathies (visual field loss, dysarthria, impaired extraocular muscle movements)

7. Factors Contributing to the Neurobehavioral Changes Associated with Brain Tumors • Pathologic type • Low grade histology • High grade histology • Patient characteristics • Age • Physical co-morbidities • Psychological co-morbidities • Symptom experience • Fatigue • Pain

8. Factors Contributing to the Neurobehavioral Changes Associated with Brain Tumors • Adverse effects of treatment • surgery • radiation therapy • chemotherapy • Side effects of adjunctive medications • corticosteroids, • anticonvulsants • psychoactive medications • Medical complications • endocrine dysfunction • seizures • infection • anemia • sleep disorders

9. Effects of Cognitive Dysfunction on Patient, Family and Health Care Team • Physical, psychological, social and vocational functioning • Level of distress • Quality of individual and family life • Insight and self-appraisal • Self care abilities, decision-making and treatment adherence

10. Cognitive Function • Cognitive function encompasses the processes by which sensory input is elaborated, transformed, reduced, stored, recovered and used.

11. Domains of Cognitive Function • Attention and concentration • Visuo-spatial and constructional skills • Sensory perceptual function • Language • Memory • Executive function • Intellectual function • Mood, thought content, personality and behavior Source: Halligan, Kischka & Marshall, 2003

12. Attention-Capacity to Detect and Orient to Stimuli • Prioritize signals from one spatial location • spatial attention • Prioritize some forms of information and to suppress others on the basis of a functional goal • selective or focused attention • Self maintain an alert and ready-to-respond state • arousal/sustained attention

13. Concentration-Directing Thoughts and Actions Toward a Stimulus • Capacity- refers to the amount of information processing a person can do in a given time • Control refers to an individual’s ability to direct concentration capacities. • Concentration exists in three forms: • sustained concentration • focused concentration(selective) • divided (alternating) • Distractions • environmental – external • self – internal

14. Visuospatial and Contructional Skills -Apraxia • Difficulty performing a planned motor activity in the absence of paralysis of the muscles normally used in the performance of that act. • Can also be considered a disorder of language as many procedural tasks are verbally mediated.

15. Visuospatial and Contructional Skills -Apraxia • Ideational apraxia • Basic sequence of events and logical plan underlying a chain of simple actions is disrupted • Ideomotor apraxia • Dissociation between the areas of the brain that contain the ideas for movements and the motor areas that actually execute the movements. • Constructional apraxia • Inability to produce properly organized constructions such as drawings or simple building tasks • Motor apraxia • Not generally reported by patient, but family will often describe difficulty with using common objects (toothbrush, eating utensils).

16. Visuospatial and Constructional Skills • Loss of topographical memory • Inability to find the way and tendency to become lost in familiar and unfamiliar environments

17. Visuospatial and Constructional Skills • Apraxic agraphia- • poor letter formation • spatial distortions • patient/family report illegible handwriting

18. Visuospatial and Constructional Skills • Alexia (difficulty reading) • may occur as a result of an inability to perform the continuous and systematic scanning eye movements necessary for reading • may also be considered a language deficit

19. Visuospatial and Constructional Skills • Acalculia (difficulty with calculation) • may result from misplacement of digits, misalignment of columns, or aphasia for number symbols

20. Sensory-Perceptual Function • Distinction between sensation and perception: • The senses capture information from the environment • Subsequent elaborations and interpretations in different parts of the brain enable one to perceive or become aware of external stimulation • The most common perceptual deficits are: • auditory • tactile • visual

21. Factors Influencing Evaluation of Sensory-Perceptual Function • Underlying primary sensory deficit (eg. color blind at baseline, hypoacusis at baseline secondary to age-related hearing loss) • Advancing age may diminish senses and dull perception • The state of the perceiver(e.g. anxiety, physical discomfort) may influence the perception of a stimulus • Severe language problems can impair a patient’s ability to respond appropriately to tests of sensory function

22. Common Sensory-Perceptual Deficits in Patients with a Primary Brain Tumor • Agnosia- literally, without knowledge, inability to know or interpret sensory experiences • Tactile agnosia (inability to name common objects placed in one hand). Place a common object such as coin (dime, nickel, quarter), paper clip, pen, randomly in either hand. • If patient is aphasic, they will have difficulty naming objects placed in either hand. When they have a specific difficulty in naming objects palpated with only one hand, tactile agnosia or astereoagnosis is present.

23. Anosognosia • Lack of awareness of impaired neurologic or neuropsychological function which is obvious to the clinician and other reasonably attentive individuals.

24. Common Sensory-Perceptual Deficits in Patients with a Primary Brain Tumor • Diplopia (double vision) • Visual field deficits (hemianopia, quadrantanopia)

25. Common Sensory-Perceptual Deficits in Patients with a Primary Brain Tumor • Achromatopsia - impairments in color perception • Color anomia - inability to name colors or to select a color from an array of colors when requested

26. Common Sensory-Perceptual Deficits in Patients with a Primary Brain Tumor • Visual hallucinations (photopsia) • stars, dots, lines, fog, wavy lines • Illusions (metamorphopsia) • distorted objects, faces, scenes

27. Common Sensory-Perceptual Deficits in Patients with a Primary Brain Tumor • Alexia (reading difficulties) • words or syllables missing • change of lines, or reduced reading span (hemianopic alexia)

28. Common Sensory-Perceptual Deficits in Patients with a Primary Brain Tumor • Problems with figure-ground discrimination • Problems in estimating depth on a staircase or reaching for a cup/door handle • Bumping into obstacles or failure to notice persons on one side (hemispatial-neglect, hemianopia) • Difficulty detecting the movements of targets in space - visual scenes may appear as a series of static snapshots

29. Language • Aphasia/dysphasia • language production (expressive aphasia/dysphasia) • language comprehension (receptive aphasia/dysphasia) • May be accompanied by • alexia (loss or impairment of the ability to read) and/or • agraphia (loss or impairment of the ability to produce written language)

30. Language • Dysarthria • sensorimotor disorder affecting the respiratory and articulatory functions involved in speech sound production • speech may be garbled, slurred or muffled, while grammar, comprehension, and word choice are intact • Dysprosody • interruption of speech inflections and rhythm (i.e. speech melody) • resultant monotone or halting speech

31. Evaluation of Spontaneous Speech • Can communication be established? • Does the patient produce speech at all? • Is the patient's speech comprehensible (if not, is it because of semantic errors or because of dysarthria)? • Is the patient's speech fluent or nonfluent? • Are there semantic errors?

32. Language Production Difficulties • Pauses, hesitancy • Restricted range of vocabulary • Use of circumlocutions • Discontinuation of a phrase • Substitution of a presumably-intended word by another word (verbal paraphasia) • Substitution of a presumably-intended word by a meaning related word (semantic paraphasia) • Difficulty with grammatical construction • Telegraphic speech style

33. Language Production Difficulties • Repetitive speech • Automatisms • Perseveration • Stereotypy

34. Language Comprehension Difficulties • Difficulty following multistep commands • Problems comprehending television or movies, difficulties reading, working on the computer or participating in conversation • May be difficult to differentiate from problems with attention, and can overlap with stress and fatigue • May lead to conflict and frustration in families

35. Memory • Remote memory (memories from childhood and early adulthood) • usually preserved • Recent memory • Recall is uncued information retrieval • Recognition is cued information retrieval in which the individual “remembers” by selecting from a number of pieces of information, including the target information

36. Memory Loss Symptoms • Examples of memory loss symptoms: • Forgetting a message • Losing track of a conversation • Forgetting to do things • Forgetting what has been read or events in movies/TV programs • Inability to navigate in familiar places

37. Memory Loss Symptoms • Assess: • Severity? • Onset gradual or sudden? • Memory impaired consistently or only on occasions? • Fluctuation in severity? • Is it an isolated symptom or are there other cognitive impairments? • How is it affecting work or pastimes?

38. Executive Function • Adaptive abilities that enable us to: • analyze what we want • develop and carry out a plan

39. Executive Function • Establish new behavior patterns and ways of thinking about and reflecting upon our behavior • Understanding of complex social behavior such as understanding how others see us, being tactful or deceitful. Burgess et al (2000)

40. Executive Dysfunction • Difficulties with abstract thinking, planning, decision-making • Difficulty with goal formulation • Difficulty with complex, multistage tasks • Poor temporal sequencing • Problems with reasoning and problem-solving • Difficulty with carrying out everyday routine activities (eg. making a cup of tea, brushing teeth, dressing)

41. Executive Dysfunction • Lack of insight • Distractibility • Marked reduction in spontaneous purposeful activity • Confabulation • Perseveration • Lack of concern • Shallow affect, impulsiveness, disinhibition, aggression, unconcern for social rules

42. Mood,Thought, Personality, Behavior • Mood • Thought content and processes • Baseline personality and coping style • Behavior

43. Case #1: Janet • 37 y/o right-handed female, status post 80% resection of left frontotemporal oligodendroglioma (WHO grade 2, with elevated MIB-1 index). Considering XRT and/or chemotherapy vs. surveillance. Partial motor seizures, controlled on Dilantin • Patient reporting depressed mood, increased tearfulness, reduced energy, and word-finding difficulties. • Husband is concerned about her mood and ability to accomplish daily tasks, including caring for their 3 children

44. Case #1: Janet- Clinical Issues • Cognitive function • Short-term memory problems • Frustrated by problems with expressive dysphasia • Diminished initiative, feels somewhat apathetic • Executive dysfunction: Problems with planning Overwhelmed by complexities of busy household • Diminished mental concentration • Overlay of: • Fatigue • Depression • Side effects of anticonvulsants

45. Case #2: Bernie • 58 y/o ambidextrous male, status post gross total resection of a right frontal Glioblastoma (WHO grade 4). Scheduled to begin treatment with XRT and concurrent temozolomide • Currently prescribed Dilantin, Decadron and Anzemet • Family concerned about personality changes and decision-making capacities. Patient denies any current concerns.

46. Case #2: Bernie- Clinical Issues • Clinical Issues: • Cognitive dysfunction: Mild short term memory problems Markedly diminished mental concentration • Personality changes (impulsive, lacking tact, easily frustrated) • Anosognosia (diminished awareness of impaired functioning) • Overlay of: • Cultural factors • Side effects of steroids (patient is not sleeping) • Situational anxiety

47. Cognitive Screening: Clinical Context • Evaluation of brain function • Occurs with each verbal and non-verbal interaction with a patient • Screening may be formal or informal • Screening may also be conscious or unconscious • Screening may be part of a professional or a social interaction

48. Cognitive Screening: Clinical Context • Cognitive impairment is common in persons with primary brain tumors (Fox, et al., 2004; Tucha et al., 2000) • Cognitive impairment may have different patterns according to tumor types and treatment • Caregivers or informant descriptions of cognitive decline, should be taken seriously and cognitive assessment and follow-up initiated (Guideline, 2001; Patterson & Glass, 2001)

49. Nursing Implications for Cognitive Screening in the Clinic • To identify issues in decision-making • To identify ways to improve quality of life • To identify best methods to assist caregivers • To identify a changing illness trajectory • To promote safety for the patient • To improve the patient/nurse relationship • To facilitate effective advocacy

50. Evidence Supporting Cognitive Screening • Patients with mild cognitive impairment should be recognized and monitored for decline due to their increased risk for subsequent dementia (guideline). • General cognitive screening instruments should be considered for the detection of dementia (guideline). • Interview based techniques may be considered in identifying patients with dementia, particularly in an at-risk population (option). American Academy of Neurology Guidelines on Early Detection of Dementia and Mild Cognitive Impairment, (2001) Patterson & Glass (2001) Screening for Cognitive Impairment and Dementia in the Elderly