Neuropsychological Sequelae in a Series of Patients with End-Stage Cystic Fibrosis

Archives of Clinical Neuropsychology, Vol. 15, No. 1, pp. 59–70, 2000 Copyright © 1999 National Academy of Neuropsychology Printed in the USA. All rights reserved 0887-6177/00 $–see front matter

PII S0887-6177(98)00158-9

Neuropsychological Sequelae in a Series of Patients with End-Stage Cystic Fibrosis: Lung Transplant Evaluation W. David Crews, Jr. University of Virginia Health Sciences Center

Angela L. Jefferson Loyola College

Donna K. Broshek, Jeffrey T. Barth, and Mark K. Robbins University of Virginia Health Sciences Center

There has been a relative absence of studies that examine the neuropsychological profiles of patients suffering from cystic fibrosis. Data are presented here for 18 individuals with end-stage cystic fibrosis who were also potential candidates for lung transplantation. Neuropsychological test results indicated a diversity of memory and executive control deficits, the most frequent of which were immediate and delayed free recall and retrieval impairments on a memory measure involving noncontextual verbal material. The majority of this sample of patients suffering from cystic fibrosis also exhibited clinically significant elevations on the Minnesota Multiphasic Personality Inventory-2 and Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-2/ MMPI-A), which are suggestive of heightened levels of psychological distress (e.g., depressive symptomatology) and multiple somatic complaints. These findings are discussed in light of factors associated with end-stage cystic fibrosis. Implications for clinical practice and future research are also provided. © 1999 National Academy of Neuropsychology. Published by Elsevier Science Ltd Keywords: cystic fibrosis, pulmonary disease, medical disease, neuropsychology, young adults

Cystic fibrosis (CF) is the most common inherited fatal disease in the United States, occurring in approximately 1 of every 3,300 live births (Cystic Fibrosis Foundation, 1997). The primary defect in CF is the altered transport of sodium and chloride ions in the epithelial cells of the lungs, digestive and reproductive tracts, and sweat glands. In the lungs, thick, viscous mucus blocks peripheral airways, which results in chronic pulmonary bronchial infections that lead to progressive lung damage and death. In the pancreas, thick secretions interfere with pancreatic secretion of enzymes, leading to malAddress correspondence to: Jeffrey T. Barth, Division of Neuropsychology, Box 203, University of Virginia Health Sciences Center, Charlottesville, VA 22908.

59

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W. D. Crews et al.

absorption of nutrients and malnutrition (Marelich & Cross, 1996). In addition, adult patients with CF are at high risk for developing diabetes and diabetes-related complications as they age (Fiel, 1995). Once considered a fatal childhood disease, the median age of survival has increased to 30.1 years (Cystic Fibrosis Foundation, 1997). Contributing factors to this increased life span include multidisciplinary care of CF centers, improvements in pulmonary therapy, antibiotics, and improved nutritional therapy (Barbero, 1996). The few studies that have been conducted on the neuropsychological status of patients with CF have typically utilized children with a relatively good health status. In a study of patients with CF ranging from 7 to 17 years of age, scores on intelligence and academic achievement tests were found to be normally distributed (Thompson, Gustafson, Meghdadpour, et al., 1992). Notably, there were significant differences between the Verbal, Performance, and Full Scale IQ scores on the Wechsler Intelligence Scale for Children-Revised (WISC-R)/Wechsler Adult Intelligence Scale-Revised (WAIS-R) between the children (ages 7–12) and the adolescents (ages 13–17), with adolescents performing more poorly. Although the adolescents’ mean intelligence scores still fell within the average range, these results suggest that older patients may demonstrate greater cognitive impairment. A previous study found that adolescents and young adults (mean age 5 15.4) suffering from CF who were assessed with the Army General Classification Test scored higher than their same age and grade level peers, indicating above-average intelligence for the CF group (Goldberg, Isralsky, & Shwachman, 1985). Earlier research also found that patients with CF tend to have above average intelligence (Boyle, di Sant’ Agnese, Sack, Millican, & Kulczycki, 1976; Kulczycki, Regal, & Tantisunthorn, 1973). Studies have also utilized patients with CF as comparison groups for young patient populations with other forms of chronic disease. These studies have found that the intelligence of young patients with CF, ranging from 4 to 20 years of age, fell within the average range (Kent, Murphy, & Milla, 1990; Stewart, Campbell, McCallon, Waller, & Andrews, 1992). An investigation of the neuropsychological functioning of children who underwent liver transplantation utilized 4- to 9-year-old patients with CF as controls and found that the mean performance of these children with CF was within normal limits on all tests comprising the Reitan-Indiana Neuropsychological Test Battery for Children (Stewart, Silver, et al., 1991). A similar study (Stewart, Hiltebeitel, et al., 1991) found that 4- to 14-year-old patients with CF performed within normal limits on the HalsteadReitan Neuropsychological Test Battery for Children with two exceptions. On the Matching Pictures Test, their performance was two standard deviations below the mean and one standard deviation below the mean with both hands on the Marching Test. Although still within normal limits, their performance on the Trail Making Test Part B, was judged to be low average. Both of these studies found that the intellectual abilities of the patients with CF fell within the average range. Adolescents and adult patients with CF must cope with many difficult psychological and psychosocial issues. In addition to facing the likelihood of premature mortality and that of their friends with CF, they also experience delayed pubertal development, high rates of infertility (males are almost always infertile), parental conflict regarding issues of independence and dependence, and underemployment (Barbero, 1996; Keller, Guzman, & Culen, 1985; Marelich & Cross, 1996). In addition, patients must follow a demanding medical regimen and may experience embarrassment as a result of frequent bowel movements, need for bronchial drainage, and oxygen usage (Keller et al., 1985). Children with CF have been found to be at greater risk for psychological distress then healthy children and they have demonstrated an increased rate of anxiety and parent–child discord (Breslau & Marshall, 1985). Research has indicated that 62% of 7- to 12-year-old patients with CF met diagnostic criteria from the Diagnostic and Statistical Manual of

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Mental Disorders, third edition (DSM-III; American Psychiatric Association, 1980) for a psychiatric disorder, with the most frequent diagnosis consisting of anxiety and oppositional disorders (Thompson, Gustafson, Hamlett, & Spock, 1992). A study of young patients 7 to 14 years of age with CF also found that they most frequently endorsed anxiety, oppositional disorder, enuresis, and conduct disorder (Thompson, Hodges, & Hamlett, 1990). Furthermore, while male adolescent patients with CF have been shown to exhibit better adjustment in emotional tone and sexuality, as compared to a normal healthy sample, female patients demonstrated significantly poorer adjustment compared to controls on 10 of 11 subscales on the Offer Self-Image Questionnaire (Sawyer, Rosier, Phelan, & Bowes, 1995). Adult patients with CF have also been found to have higher levels of state anxiety than 36% of general medical and surgical patients on the State-Trait Anxiety Scale (Spielberger, 1983), and higher levels of trait anxiety than approximately 46% and 43% of general medical and surgical patients, respectively (Keller et al., 1985). This same group also acknowledged significantly higher levels of psychological distress on the Symptom Checklist-90 (Derogatis, 1983) with elevations on anxiety, phobic anxiety, paranoid ideation, and psychoticism dimensions. Low self-esteem has also been observed and appears to become more problematic as the disease progresses (Goldberg et al., 1985). Lung transplantation has increasingly become a life-prolonging option in treating patients with CF (Fiel 1995; Marelich & Cross, 1996). Patients are typically considered for transplantation when they have end-stage cystic fibrosis and experience a progressive deterioration in their health status, pulmonary and nutritive states, and quality of life, despite medical therapies (Marelich & Cross, 1996). As a result of greatly reduced oxygenation and increased risk of diabetes, patients with end-stage cystic fibrosis are also likely to be at greater risk for neurocognitive impairment. The purpose of this study was to examine the neuropsychological profiles of a series of patients with end-stage cystic fibrosis who were being evaluated as potential lung transplant candidates.

METHOD Participants This study examined 18 individuals with end-stage cystic fibrosis who had been referred for neuropsychological evaluation as part of the lung transplant screening protocol at a large tertiary care medical center. The sample consisted of 11 males and 7 females who ranged in age from 15 to 48 years (M 5 26.33 years, SD 5 8.97). The educational level of the sample ranged from 8 to 16 1 years (M 5 12.33 years, SD 5 2.14). Demographic data for each patient is provided in Table 1. Procedures To evaluate patients’ cognitive and behavioral functioning, a series of neuropsychological tests were administered. All testing sessions were conducted by experienced neuropsychological test technicians under the supervision of licensed clinical neuropsychologists. The standardized administration and scoring procedures were followed. After brief rapport-building sessions and clinical interviews, tests were selected and administered from the following battery: portions of the Wechsler Intelligence Scale for Children-III (WISC-III; Wechsler, 1991) or the Wechsler Adult Intelligence Scale-Revised (WAIS-R; Wechsler, 1981), Trail Making Test (TMT; Parts A and B; Reitan, 1979; Reitan & Wolfson, 1993), Wisconsin Card Sorting Test (WCST; Heaton, 1981), portions of the Wechsler Memory Scale (WMS; Wechsler, 1974; administered prior to publication

Gender (M/F) Age Education WAIS-R/WISC-III (Age-corrected) Vocabulary Block Design Similarities Trail Making Test Part A (time in seconds, errors) Part B (time in seconds, errors) Wisconsin Card Sorting Test Correct Errors Perseveration Responses Nonperseverative Errors Perseverative Errors Categories WMS/WMS-R Logical Memory I Logical Memory II Logical Memory (%) Visual Reproduction I Visual Reproduction II Visual Reproduction (%)

M 46 161

12 11 15

35, 0 68, 0

05 11 00 04 07 06

31 25 81 18a 17a 92

12 12 10

25, 0 93,a 1

05 06 00 03 03 06

15a 17 100 37 30 81

2

M 48 14

1

28 26 93 33 33 100

01 04 01 02 01 06

32,a 0 76, 0

10 09 12

M 32 13

3

07 12 08

05a 08 06a

23 16 70 40 40 100

10 07 00 04 03 06 6.5a,b 6.5a,b 100b 10b 05a,b 50b

37 46a 10 25a 21a 04a 24 15 63 39 36 92

13 13 00 08 05 06

28, 0 66, 1

M 24 08

6

M 26 12

5

29, 0 33,a 0 82, 0 102,a 2

10 12 09

M 27 12

4

24 15 62 37 38 100

27 27 06 17 10 01a

58,a 0 60, 1

10 11 07

M 22 13

7

23 15 65 – – –

– – – – – –

– –

14 09 07

M 21 14

8

33 31 94 41 41 100

03 03 00 03 00 06

27, 0 44, 0

10 07 09

M 20 14

9

33 31 94 – – –

– – – – – –

23, 0 55, 0

12 13 12

M 18 13

10

Patient Number

31 26 84 36 36 100

18 32 00 15 17 06

17, 0 34, 0

16 11 14

M 15 09

11

TABLE 1 Demographic Characteristics and Neuropsychological Test Data

25 22 88 36 38 106

68 31 09 22a 09 06

25, 0 75, 1

11 07 10

F 33 12

12

15a,b 14b 93b – – –

07 06 00 02 04 06

13, 0 42, 0

15 13 15

F 28 16

13

30 24 80 38 31 82

12 19 00 03 16 06

18, 0 45, 0

07 09 12

F 27 12

14

19a 13a 68 32 33 103

05 08 00 04 04 06

31, 0 85, 0

07 06a 07

F 26 10

15

26 20 77 39 40 103

24 16 03 06 07 06

23, 0 72, 1

10 08 08

F 24 12

16

07 05a 09

F 16 10

18

27 25 93 39 39 100

38 64a 00 08 56a 03a

(continued)

28 28 100 39 40 103

91 37 21a 19 18 05

14, 0 36,a 0 35, 0 70,a 0

11 10 10

F 21 12

17

62 W. D. Crews et al.

123 116 07 122 06 09 08a 10 10/11 09/12a 12/12

1

3

4

107a 122 115a 100a 115 99a 07 07 16 124 120 98a a 43 98 95a 56a 16 03 11a 00 01 12 10 12 10/11 10/11 10/11 a 09/12 12/12 11/12 12/12 12/12 11/12

2

85a 56a 29 67a 39a 16 08a 12 06/11a 04/12a 08/12a

5

99a 77a 22 81a 64a 12 00 12 10/11 09/12a 12/12

6

96a 50a 54a 54a 27a 09 14a 12 06/11a 03/12a 12/12

7

9

119 141 108a 142 11 00 114 140 a 91 146 16 00 00 03 12 05 11/11 11/11 11/12 12/12 12/12 12/12

8

– – – – – – – – – – –

10

129 127 02 130 124 03 12a 06 11/11 12/12 12/12

11

115 99 17 104 91 08 02 12 08/11a 09/12 12/12

12

14

15

16

17

18

136 129 92a 119a 132 138 135 125 72a 114 124 138 01 04 20 15 08 00 135 126 91a 125 124 138‘ a a 135 123 40 90 124 138 00 02 28 24 00 00 00 00 00 00 00 00 05 06 12 12 07 04 10/11 11/11 06/11a 11/11 11/11 11/11 11/12 12/12 06/12a 10/12a 11/12 12/12 12/12 12/12 12/12 12/12 12/12 12/12

13

WAIS-R 5 Wechsler Adult Intelligence Scale-Revised; WISC-III 5 Wechsler Intelligence Scale for Children, 3rd ed.; WMS 5 Wechsler Memory Scale; WMS-R 5 Wechsler Memory Scale-Revised. aimpaired. bWMS.

Selective Reminding Test Recall Long-Term Retrieval (LTR) Short-Term Recall Long-Term Storage Consistent LTR Random LTR Total Intrusions Total Trials Cued Recall Delayed Recall Delayed Recognition

Patient Number

TABLE 1 (Continued)

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W. D. Crews et al.

of the revised version) or the Wechsler Memory Scale-Revised (WMS-R; Wechsler, 1987), the Selective Reminding Test (SRT; Buschke & Fuld, 1974), the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Hathaway & McKinley, 1989) or the Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A; Butcher, Graham, Williams, & Kaemmer, 1992). To interpret each individual’s neuropsychological test performances, scores were compared to published normative data for each test, while taking into consideration such demographic variables as gender, age, and educational level. For example, when using the normative data compiled by Heaton, Grant, and Matthews (1991), each individual’s scores were compared to norms representing a sample of participants of similar gender, age, and educational level. Norms and/or interpretations were obtained from the following sources: Archer, Krishnamurthy, and Jacobson (1994); Graham (1993); Heaton, Chelune, Talley, Kay, and Curtiss (1993); Heaton et al., (1991); Sattler (1990); Spreen and Strauss (1991); and Wechsler (1974, 1987).

RESULTS The neurocognitive test results for each patient are provided in Table 1. Overall, 3 of the 18 patients demonstrated no notable cognitive impairments across any of the neurocognitive measures, although test data for 1 of these individuals were incomplete. Eight additional patients exhibited neuropsychological impairment on only one of the test measures. For the intelligence testing data, 17 of 18 (94.45%) patients exhibited scaled scores on the Wechsler Scales Vocabulary and Similarities subtests, which fell within the low average to very superior ranges. In contrast, one individual displayed scaled scores on both subtests, which fell within the borderline range. For the Block Design subtest, 16 of 18 (88.89%) patients demonstrated scaled scores within the low to high average ranges, while two (11.11%) patients displayed borderline performances. On the TMT Part A, 4 of 17 (23.50%) patients exhibited performances that fell between the mildly to severely impaired range, while 3 (17.60%) of these individuals also displayed mild to severe impairment on Part B of this test. For the WCST, 2 of 16 (12.50%) individuals displayed an elevated number of errors while 1 of 16 persons produced an abnormally high number of perseverative responses. Furthermore, elevated numbers of nonperseverative and perseverative errors were noted in 2 of 16 (12.50%) and 2 of 16 (12.50%) patients, respectively. Three out of 16 (18.75%) individuals also failed to achieve the expected number of categories on this test. All other patient performances on these purported executive control measures (TMT, WCST) were within normal limits to above average. On the WMS/WMS-R Logical Memory I subtest, 4 of 18 (22.22%) patients exhibited impairments ranging from mild to severe, while 2 of 18 (11.11%) of these persons displayed mild to moderate deficits on the Logical Memory II subtest. On the WMS/WMS-R Visual Reproduction I subtest, 1 of 15 individuals obtained a severely deficient score, while 2 of 15 (13.33%) patients displayed moderate to severe impairment on the Visual Reproduction II subtest. On the Selective Reminding Test, 7 of 17 (41.18%) patients exhibited impaired immediate and delayed (30 minutes) recall as well as deficient long-term retrieval strategies, which ranged from mild to severe. Eight of 17 (47.06%) individuals demonstrated impaired consistent long-term retrieval strategies, while 5 of 17 (29.41%) patients exhibited impaired long-term storage strategies. Five of 17 (29.41%) patients also exhibited an ex-

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cessive number of intrusions, while 1 of 17 (5.88%) individuals demonstrated severely impaired delayed recognition. All other patient performances on the memory measures (WMS/WMS-R, Selective Reminding Test) were within normal limits to above average. Results for the MMPI-2/MMPI-A for each patient are provided in Table 2. Nine of 15 (60.00%) patients who completed the MMPI-2/MMPI-A exhibited valid profiles with no significantly elevated (T $ 65) validity scales. Alternatively, 4 of the 15 (26.67%) patients obtained significant T-scores (T $ 65) elevations on the Lie (L) scale, while 2 of 15 (13.33%) of these individuals exhibited elevated T-scores on the Infrequency (F) and Correction (K) scales. One out of 15 of these patients (i.e., patient 15) was judged to exhibit an invalid profile and was subsequently eliminated from the analysis of the clinical scales. Regarding the MMPI-2/MMPI-A basic clinical scales, only 2 of 14 (14.29%) patients displayed no significant T-score elevations on any of these scales, although one of these individuals exhibited an elevated validity scale score (i.e., Correction [K] scale). Eleven of 14 (78.57%) patients demonstrated significant elevations on Scale 1 (Hypochondriasis), followed by 10 of 14 (71.43%) individuals on Scale 3 (Conversion Hysteria), and 9 of 14 (64.29%) patients on Scale 2 (Depression). Scores on Scale 0 (Social Introversion) reached clinical significance in 7 of 14 (50.00%) patients, while Scale 7 (Psychasthenia) was elevated in 6 (42.86%) individuals. Two of 14 (14.29%) patients obtained clinically significant elevations on Scales 5 (Masculinity-Femininity) and 8 (Schizophrenia), followed by 1 of 14 individuals on Scale 6 (Paranoia). Interestingly, none of the current sample obtained clinically significant T-scores on Scales 4 (Psychopathic-Deviate) or 9 (Hypomania). The mean MMPI-2/MMPI-A profile for this sample of patients with cystic fibrosis appears in Figure 1. All of the validity scales were within normal limits, which suggested a valid mean profile. For the clinical scales the samples’ mean code type was found to be a 1-3-2 (i.e., mean T-scores of 72.79, 69.71, and 68.21, respectively).

DISCUSSION The present study examined the neuropsychological profiles of 18 patients with endstage cystic fibrosis who were evaluated as potential lung transplant candidates. The TABLE 2 Minnesota Multiphasic Personality Inventory-2/Minnesota Multiphasic Personality Inventory-Adolescent Data Patient Number 1

L (Lie) F (Infrequencey) K (Correction) 1 (Hypochondriasis) 2 (Depression) 3 (Conversion Hysteria) 4 (Psychopathic Deviate) 5 (Masculinity-Femininity) 6 (Paranoia) 7 (Psychasthenia) 8 (Schizophrenia) 9 (Hypomania) 0 (Social Introversion) aclinically

elevated.

65a 55 47 71a 58 74a 48 56 64 41 56 47 56

2

56 48 53 75a 74a 81a 55 40 39 55 45 43 56

3

61 48 58 64 64 74a 35 48 47 34 30 35 58

4

61 45 60 68a 70a 64 48 46 49 57 47 43 72a

5

6

– – – – – – – – – – – – –

65a 58 68a 73a 76a 55 64 32 42 66a 62 38 71a

7

– – – – – – – – – – – – –

8

43 58 39 79a 65a 69a 40 38 46 69a 66a 48 66a

9

43 48 56 57 45 54 44 38 49 44 51 47 43

10

11

– – – – – – – – – – – – –

67a 51 62 69a 74a 77a 60 67a 56 55 52 45 69a

12

56 73a 37 97a 87a 89a 62 76a 68a 85a 74a 56 59

13

57 44 63 74a 51 75a 53 55 52 51 46 59 33

14

15

16

17

18

71a

57 51 50 67a 81a 73a 63 38 56 73a 57 37 65a

38 48 48 92a 90a 75a 49 52 59 77a 60 43 73a

49 43 65a 53 41 36 44 64 39 36 40 41 43

52 44 113a 48 32 80a 90a 79a 77a 80a 68a 53 66a 33 47 63 70a 77a 64 53 84a 41 62 67a 63

66

W. D. Crews et al.

FIGURE 1. Mean Minnesota Multiphasic Inventory-2/Minnesota Multiphasic Inventory-Adolescent profiles.

most frequent neurocognitive impairments across these cases were exhibited on a noncontextual verbal (i.e., unrelated word list) memory measure (i.e., SRT). Specifically, over 40% of the patients in the current study displayed both immediate and delayed (30 minutes) free recall impairments as well as long-term and consistent long-term retrieval deficits. Close to 30% of these individuals also demonstrated long-term storage deficits, although only one patient exhibited impaired delayed (30 minutes) recognition of this noncontextual verbal material. Taken together, these findings are suggestive of relative greater impairment of these patients’ retrieval (e.g., free recall) abilities versus their encoding or storage strategies for such unrelated material. As compared to their performances on the Selective Reminding Test, only 11.11% and 22.22% of the present sample exhibited impairments on a memory test (WMS/ WMS-R Logical Memory I and II) assessing delayed and immediate recall of contextual verbal material, respectively. These findings indicate that close to two to four times more individuals exhibited impairments on tasks assessing immediate and delayed free recall/retrieval of noncontextual verbal material respectively, as compared to a memory test involving contextual verbal material. It should also be noted that the large majority of these patients demonstrated intact immediate and delayed (30 minutes) free recall of nonverbal/figural material (i.e., on the WMS/WMS-R Visual Reproduction I and II subtests). The fact that this sample exhibited greater deficits in noncontextual, versus contextual, verbal memory (or figural memory) suggests greater deficits in executive control functioning (i.e., organizing verbal information) in the group of patients with CF. Deficits were also noted on measures purported to be sensitive to executive control functioning. These tests were administered to assess aspects of patients’ cognitive abili-

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ties, such as cognitive flexibility, sequencing, and reasoning, that were thought to promote compliance with their often complicated medical treatment regimens. Specifically, 23.5% and 17.6% of this sample of patients with CF exhibited impairments of their simple (TMT Part A) and complex (TMT Part B) cognitive processing speed, sequencing/ flexibility, and visuo-motor scanning abilities respectively. On the WCST, approximately 19% of these patients did not achieve the expected number of categories on this test. Perseverative and nonperseverative errors were also noted in 12.5% of this sample. These findings indicated the presence of impaired shift of set and/or maintenance of response strategies abilities in at least 25% of the present sample. Taken together, the impairments noted on the TMT (especially Part B) and the WCST suggested that a number of these patients with CF were possibly suffering from some degree of executive control dysfunction. In contrast, for the large majority (n 5 15) of the present sample, estimates of Verbal and Performance (nonverbal) IQs ranged from low average to very superior. These results indicated an overall absence of deficits in intellectual functioning in this sample of patients with end-stage cystic fibrosis disease and supported the findings from previous research (Boyle et al., 1976; Goldberg et al., 1985; Kent et al., 1990; Kulczycki et al., 1973; Stewart, et al., 1992; Thompson, Gustafson, Meghdadpour, et al., 1992). The MMPI-2/MMPI-A results indicated that the majority of the present sample exhibited significant elevations (T-scores $ 65) on Scales 1 (Hypochondriasis), 2 (Depression), and 3 (Conversion Hysteria), which suggested that these patients with CF had similar concerns and reported both somatic and depressive symptomatology (Graham, 1993). The patients’ mean MMPI-2/MMPI-A clinical profile (i.e., 1-3-2) also indicated that they acknowledged somatic/depressive complaints, which were likely to be diverse in nature, including gastrointestinal symptoms, sleep disturbances, weakness, low energy, and fatigue (Archer et al., 1994; Graham, 1993). Such symptomatology are to be expected in patients with end-stage CF, especially in light of their multiple somatic complications. Individuals with this profile may also suffer from depressive disorders and acknowledge feelings of hopelessness and despondency (Archer et al., 1994; Graham, 1993). Dependency conflicts are common and patients with this profile may attempt to maintain an emotional distance from others and experience difficulty asserting themselves (Graham, 1993). They may also utilize repression and denial, and tend to lack insight into their psychological distress (Graham, 1993). Typically, however, patients with this profile demonstrate good, overall adjustments in interpersonal relationships and at school and work (Graham, 1993). The mean MMPI-2/MMPI-A clinical profile for these patients with CF was consistent with literature indicating that dependency issues are prominent in such chronically ill adults (Barbero, 1996). Despondency and depression were common in our sample of patients with CF and suggest that these symptoms may be more prominent in patients with end-stage disease, as they experience decreased health statuses, end-of-life issues, and the possibility of lung transplantation. These patients may have also had difficulty acknowledging their psychological distress or asserting themselves with their parents and health-care professionals (Graham, 1993). Because of their apparent good adjustment, their needs for psychotherapeutic interventions may be overlooked. Patients with endstage CF, however, may benefit from psychotherapy that addresses their depression, despondency, and dependency issues. Assertiveness training may also aid these patients in taking greater responsibility for their medical regimens, expressing their opinions/decisions to health-care professionals, and communicating their independence from their parents. Although the mean MMPI-2/MMPI-A clinical profile did not reveal significant anxi-

68

W. D. Crews et al.

ety for the group overall, 40% of patients did report anxiety. This finding suggests that symptoms of anxiety cannot be merely attributed to pulmonary/somatic symptoms since all patients (including ones not reporting anxiety) were suffering from significant pulmonary/physical complications. Thus, it is likely that those patients who demonstrate elevations on Scale 7 (Psychasthenia) would benefit from behavioral/psychological interventions, such as education into the utilization of progressive muscle relaxation techniques, to reduce and manage their anxiety. Overall, while the majority of patients in this study were cognitively intact on most measures, a diversity of neuropsychological difficulties, including memory impairments, executive control deficits, and a significant degree of psychological distress were found in a number of these patients with end-stage lung disease. However, the most notable deficits were displayed in patients’ immediate and delayed free recall and retrieval abilities on a noncontextual verbal memory measure (i.e., SRT). It is likely that these patients’ neurocognitive functions were negatively impacted by their progressive loss of pulmonary functioning and resulting chronic hypoxia (Cystic Fibrosis Foundation, 1997; Marelich & Cross, 1996; see Lezak, 1995) as well as their impaired nutritional statuses related to the malabsorption of food and possible vitamin deficiencies (Marelich & Cross, 1996; see Lezak 1995). Furthermore, although the prevalence of diabetes in the current sample was unknown, diabetes has been associated with CF as well as with impaired neurocognitive functioning (Fiel, 1995; Lezak, 1995; Marelich & Cross, 1996). The presence of diabetes may have also contributed to the neurocognitive deficits seen in the present sample. Additionally, patients’ neurocognitive (e.g., memory) deficits may have been exacerbated by their reported levels of psychological distress as reflected by their elevated MMPI-2/MMPI-A clinical profiles. The findings from this study appear to have implications for clinical practice. Based on the diversity of neuropsychological dysfunctions found in this sample of patients with CF, in the absence of impaired intellectual functioning, it appears important to complete comprehensive neuropsychological assessments on all patients with end-stage CF who are potential lung transplant candidates. Specifically, since patients with end-stage CF, and those who ultimately undergo lung transplantation, must be able to comply with complicated treatment/medication regimens, comprehensive neuropsychological evaluations can prove beneficial in identifying individuals’ neurocognitive strengths and weaknesses. In turn, appropriate remedial treatments and strategies (e.g., memory enhancement techniques, such as prompts, cues, and lists) can be formulated to assist them compensate for their identified cognitive deficiencies and comply with their medical treatments. Furthermore, as discussed earlier, identification and treatment of those patients with CF who are experiencing psychological problems is important to not only ensure their sense of well-being, but they may also prove beneficial in lessening any neurocognitive dysfunction that may be present (see Lezak, 1995). It should be noted that since only a limited number of patients suffering from endstage CF were seen during any given year, data was collected over 7 years. This fact, along with the retrospective nature of this research, precluded the inclusion of a matched control group. Hence, comprehensive normative data from several sources were utilized to interpret the neuropsychological test performances of this group of patients with CF. Future, large scale, prospective studies are required that compare patients with end-stage CF to matched control groups across a more comprehensive battery of neuropsychological tests and measures. Longitudinal research of patients with CF is also needed to examine potential changes in their neuropsychological functioning over time as their health status deteriorates, or after they undergo successful lung transplantation.

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