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Validation of a brief telephone battery for neurocognitive assessment of patients with pulmonary arterial hypertension

Validation of a brief telephone battery for neurocognitive assessment of patients with pulmonary... Background: The effects of pulmonary arterial hypertension on brain function are not understood, despite patients' frequent complaints of cognitive difficulties. Using clinical instruments normally administered during standard in-person assessment of neurocognitive function in adults, we assembled a battery of tests designed for administration over the telephone. The purpose was to improve patient participation, facilitate repeated test administration, and reduce the cost of research on the neuropsychological consequences of acute and chronic cardiorespiratory diseases. We undertook this study to validate telephone administration of the tests. Methods: 23 adults with pulmonary arterial hypertension underwent neurocognitive assessment using both standard in-person and telephone test administration, and the results of the two methods compared using interclass correlations. Results: For most of the tests in the battery, scores from the telephone assessment correlated strongly with those obtained by in-person administration of the same tests. Interclass correlations between 0.5 and 0.8 were observed for tests that assessed attention, memory, concentration/ working memory, reasoning, and language/crystallized intelligence (p ≤ 0.05 for each). Interclass correlations for the Hayling Sentence Completion test of executive function approached significance (p = 0.09). All telephone tests were completed within one hour. Conclusion: Administration of this neurocognitive test battery by telephone should facilitate assessment of neuropsychological deficits among patients with pulmonary arterial hypertension living across broad geographical areas, and may be useful for monitoring changes in neurocognitive function in response to PAH-specific therapy or disease progression. Page 1 of 7 (page number not for citation purposes) Respiratory Research 2005, 6:39 http://respiratory-research.com/content/6/1/39 tion, and major depression requiring hospitalization), Introduction Pulmonary arterial hypertension (PAH) is a devastating known learning disability, prior traumatic brain injury, disease characterized by progressive shortness of breath diagnosis of dementia, cerebral vascular accident, neuro- and the eventual development of life-threatening heart logic disorder (e.g. multiple sclerosis, Huntington's Dis- failure [1-4]. While its effects on cardiovascular function ease, etc.), prior cardiac surgery, or current alcohol or drug have been well documented, little is known about effects abuse. of this disease on other organ systems, notably the brain. Patients frequently complain of changes in memory, con- Patients were recruited for neurocognitive assessment centration and judgment in association with the develop- from a group who had consented to in-person testing. ment of cardiopulmonary symptoms[5]. Objective Sixty-seven patients were screened. Seventeen patients assessments of cognitive function, however, have not declined, two were excluded due to non-fluency in Eng- been performed. lish, and two were medically unstable at the time of eval- uation and died during the recruitment period. Of the 46 The "gold standard" for comprehensive assessment of patients who consented to in-person neurocognitive test- neurocognitive function is a comprehensive battery of ing, 25 consented to additional testing by telephone. individually validated tests that are administered in-per- son by an experienced interviewer. Comprehensive, Patient demographic, medical and laboratory data were standard testing often takes four hours or longer and may collected for all enrolled patients. This study was require two or more separately scheduled sessions. The approved by the University of Pennsylvania and LDS Hos- experience can be stressful and fatiguing, particularly for pital Institutional Review Boards and conformed to insti- chronically ill or physically disabled patients. The stress of tutional and federal guidelines for the protection of additional travel to a testing site adds to the burden. Con- human subjects. sequently, many patients decline to participate in clinical research that uses formal in-person neurocognitive test- Neurocognitive Assessment ing, especially if the protocol includes repeated testing An interdisciplinary team of neuropsychology, traumatic over time [6,7]. brain injury, rehabilitation medicine, and pulmonary dis- ease specialists selected a battery of standardized neuro- To address these concerns, we developed a focused battery cognitive tests amenable to both in-person and telephone of neurocognitive tests for administration over the tele- administration. Tests were also chosen on the basis of phone. The battery is comprised of individually validated established sensitivity in detecting impairment in patients neurocognitive test instruments appropriate for adminis- with cardiopulmonary disorders and concomitant hypox- tration to adults with cardiopulmonary disease who are emia [10-13]. The cognitive domains assessed and the fluent in English and capable of communicating verbally. tests included in the battery are listed in Table 1. All neu- Telephone administration of the test battery has been rocognitive tests included in the battery have been empir- evaluated for feasibility and validity in survivors of the ically validated and standardized [14-17] with established acute respiratory distress syndrome [8]. The present study reliability, internal and external validity[12,14,16,18,19]. establishes the validity of telephone administration of the The neurocognitive tests were administered in a random test battery by comparing the results of telephone testing sequence to minimize order effects. However, as a delay is against "gold standard" in-person administration in adult required between the Wechsler Memory Scale-III Logical ambulatory patients with moderately to severely sympto- Memory I and II tests, Logical memory I (immediate matic PAH. recall) was the first and Logical Memory II (delay recall) the last test administered in each session. Methods Study Population The in-person assessment was carried out in a private Consecutive patients diagnosed with pulmonary arterial office at LDS Hospital. The identical tests were adminis- hypertension according to standard criteria [2,9] were tered subsequently by telephone at a prearranged time prospectively recruited for neurocognitive testing from the when patients were at home and free from distraction. To Pulmonary Hypertension Clinic at LDS Hospital. Written minimize potential learning effects, telephone testing was informed consent was obtained from the patients for both performed at least 2.5 months following in-person assess- the in-person and telephone neuropsychological testing. ment, except with one patient who was tested 57 days Inclusion criteria were age 18 years or older and the ability after in-person evaluation. A Ph.D. neuropsychologist to give informed consent. Exclusion criteria included non- (ROH) administered the in-person tests and a neuropsy- fluency in English, a history of major psychiatric illness chology doctoral student administered the telephone tests (e.g. schizophrenia, schizoaffective disorder, bipolar dis- with no knowledge of the results of the previous in-person order, psychoses requiring medication and/or hospitaliza- testing. During both the in-person and telephone tests, Page 2 of 7 (page number not for citation purposes) Respiratory Research 2005, 6:39 http://respiratory-research.com/content/6/1/39 Table 1: Neurocognitive Battery for Telephone Administration COGNITIVE DOMAIN TEST INSTRUMENT Attention WMS-III: Digits Forward Concentration/Working Memory WMS-III: Digits Backward WMS-III: Letter-Number Sequencing Executive Function Hayling Sentence Completion Test Reasoning WAIS-III: Similarities Language / Crystallized Intelligence WAIS-III Vocabulary Memory WMS-III: Logical Memory I & II Table 2: Demographic and Medical Data Mean ± SD Range Gender (% female) (n = 25) 83% Education (years) 13.6 ± 3.0 6 to 20 Age (years) 49.7 ± 13.9 20 to 69 Time Since Diagnosis (years) 1.8 ± 1.5 0.8 to 5.3 PaO mmHg 62.6 ± 13.5 38 to 97 Most recent 6 minute walk (meters) 455 ± 132 227 to 877 New York Heart Functional Class (N) Class 1 0 Class 2 3 Class 3 20 Class 4 0 Supplemental Oxygen (N) 2 Liters per minute 7 3 Liters per minute 8 4 Liters per minute 4 patients were instructed not to write down information 0.41 to 0.60; substantial correlation 0.61 to 0.80; and and to answer questions without assistance. The in-person almost perfect correlation 0.81 to 1.00 [20]. and telephone assessments were both conducted in single sessions, and each took 35 to 45 minutes to complete. To assess potential learning effects, systematic differences between first and second administrations for each of the All neuropsychological tests were scored according to the tests were assessed using paired sample t-tests. The differ- published guidelines. Each test yields a raw score that was ences between the in-person and telephone test results are converted into a scaled score (mean = 10; SD = 3), which expressed as standardized effects sizes (T2-T1 differences was used for statistical analyses, except for Logical Mem- divided by T1 standard deviation) [21]. ory where the raw scores are used. Results Statistical Analysis Twenty-five patients with pulmonary arterial hyperten- Descriptive statistics were carried out for demographic sion were enrolled for neurocognitive evaluation using and medical data. The neuropsychological test scores both in-person and telephone testing. All 25 patients from the in-person administration were compared to tel- completed in-person testing. Telephone testing could not ephone test scores using interclass correlations. To facili- be completed on one subject due to a non-functioning tel- tate interpretation of significant correlations (p ≤ 0.05) ephone line, and one subject died of progressive right and because traditional significance levels for correlations heart failure. All of the remaining 23 subjects completed coefficients are influenced by factors such as group size, both the in-person and telephone assessments and were range of scores, and multiple comparisons, we used the included in the validation group. Eighty-three percent (n following conservative classification: fair correlation with = 19) of these subjects were women. The mean ± SD age coefficients between 0.21 and 0.40; moderate correlation was 49.7 ± 13.9 years (range 20 to 60 years) and the mean Page 3 of 7 (page number not for citation purposes) Respiratory Research 2005, 6:39 http://respiratory-research.com/content/6/1/39 Table 3: In-person and telephone neuropsychological test scores. Test Mean Median SD Range Number-letter Sequencing In-person 9.3 10 2.6 5 to 14 Telephone 9.3 9 2.5 5 to 15 Logical Memory Immediate Recall† In-person 24.4 23 5.9 14 to 33 Telephone 27.0 26 8.2 17 to 44 Delay Recall† In-person 18.8 18 5.4 10 to 30 Telephone 22.0 23 7.5 6 to 34 Digit Span In-person 11.6 11 3.2 6 to 18 Telephone 9.3 9 2.4 5 to 15 Hayling Sentence Completion Test In-person 5.7 6 1.1 4 to 8 Telephone 6.6 6 0.89 6 to 10 Similarities In-person 11.0 12 2.9 4 to 16 Telephone 10.9 10 3.1 5 to 16 Vocabulary In-person 10.6 11 2.6 6 to 16 Telephone 11.5 11 2.6 7 to 17 All values are scaled scores (mean = 10, standard deviation = 3) except † = raw scores. Logical memory and Number-letter sequencing are from the WMS-III; digit span, similarities and vocabulary are from the WAIS-R. education level was 13.6 ± 3.0 years (range 6 to 20 years). of attention, memory, concentration / working memory, The mean number of days between in-person and tele- reasoning, and language / crystallized intelligence. An phone testing was 121.6 (range 57 to 200 days). The eti- almost perfect correlation was observed in the assessment ology of PAH was: idiopathic ("primary") PAH in ten of reasoning (Similarities). Substantial correlations were patients (43%), associated with anorexigen use in six found for the Digit Span, Similarities, and Vocabulary (26%), collagen vascular disease in four (17%), congeni- tests (.61 to .80) and moderate correlations (.41 to .60) tal heart disease in two (9%) and one with portopulmo- were found for each Logical Memory immediate and delay nary hypertension (4%). The mean (± SD) right atrial recall. A moderate correlation (0.56) was seen with the in- pressure was 5.1 ± 1.8 mmHg, mean pulmonary artery person and telephone administration of the Digit-Span- pressure 52.1 ± 16.9 and pulmonary capillary wedge pres- backward (concentration / working memory). Only a fair sure 12.1 ± 6.2. The mean cardiac output was 5.1 ± 1.8 L/ correlation (0.28; p= 0.09) was found between the in-per- min. Demographic and medical data are shown in Table son and telephone administration of the Hayling Sen- 2. tence Completion test of executive function. For Letter- Number Sequence test (concentration/working memory) The results of the telephone and in-person neurocognitive scores were not correlated for the in-person and telephone assessments are shown in Table 3. The correlation coeffi- tests. cients for the comparison between in-person and tele- phone testing are presented in Table 4. Interclass Stability over time was greatest for the Similarities and correlation coefficients of at least 0.54 (p < 0.05 to < Vocabulary tests. The effects of learning showed that test 0.0001) were found for the agreement of telephone and scores tended to increase between the in-person and tele- in-person scores on tests assessing the cognitive domains Page 4 of 7 (page number not for citation purposes) Respiratory Research 2005, 6:39 http://respiratory-research.com/content/6/1/39 Table 4: Reliability of the in-person and telephone neuropsychological test scores. Neuropsychological Learning Effect (Improvement Intraclass Correlation 95% C.I. p Test T1 to T2 expressed in SDs) Number-letter Sequencing .78 (0 to 3.1) .15 -.28 to .52 0.25 Logical Memory Immediate Recall† 1.3 (0 to 5.0) .55 -.20 to .72 0.05 Delay Recall† 1.2 (.18 to 3.4) .54 -.24 to .82 0.05 Digit Span Forward† .74 .41 to .90 0.0002 Backward† .56 -.24 to .84 0.05 Both .83 (0 to 1.9) .63 .29 to .83 0.0006 Hayling Sentence .98 (0 to 3.8) .28 -.14 to .61 0.09 Completion Test Similarities .65 (0 to 2.0) .82 .62 to .92 <0.0001 Vocabulary .53 (0 to 1.5) .68 .38 to .85 0.001 All scores shown are scaled scores (mean = 10, standard deviation = 3), except † = raw scores. Logical memory and Number-letter sequencing are from the WMS-III; digit span, similarities and vocabulary are from the WAIS-R. phone tests, with the most improvement for verbal mem- approached significance (p = 0.09). The in-person and tel- ory (e.g. logical memory immediate and delayed recall). ephone administrations of the Letter-Number-Sequenc- ing component of the WMS III (a test of concentration/ working memory) did not correlate well. Some subjects Discussion We found the battery of well-established neurocognitive appeared to have difficulty discriminating phonetically tests to be amenable to administration by telephone and similar sounds (e.g. the letters 'm' and 'n') when presented valid for the identification of neurocognitive deficits in during telephone sessions; visual cues may have alleviated patients with PAH. Testing was readily completed in a sin- such issues at in-person sessions. In contrast, another gle, 30–60 minute session, and required neither special- component of the WMS III (Digits Backward) evaluating ized testing facilities nor travel by physically debilitated the same cognitive domain (concentration/working patients spread across a broad geographic area. memory) had substantial correlations. Our study was designed to validate the administration by Although the correlations we found between in-person telephone of a battery of neurocognitive tests against the testing and subsequent telephone administration of the in-person ("gold standard") performance of these same same test battery were moderate or higher, they were not assessments. Each of the tests in the battery has been pre- perfect. The effects of learning or practice suggest that test viously validated for the identification of neurocognitive scores increase between the in-person and telephone tests, deficits in various populations, including those with car- with the most improvement in verbal memory. Thus, the diopulmonary disease-. As such, our subjects' scores improvement in test scores on the telephone administra- during in-person testing served as matched controls for tion of the test likely reflects practice effects. An alternative comparison with the results obtained upon application of explanation for the tendency of subjects to perform better these same tests over the telephone. on the telephone test battery may be environmental fac- tors. For example subjects scored higher on certain tasks The scores from telephone and in-person assessments cor- when assessed at home as compared to similar tasks per- related strongly for the majority of tests. Overall, the formed in a clinic setting [26]. Improved orientation to strengths of the correlations with in-person testing found time and place have been found when patients were tested here are comparable to those that we reported previously in their own residence [22]. Further, patients report less for the same test battery applied to ARDS survivors [8] and anxiety and prefer telephone testing compared to in-per- the correlations reported for other telephone neurocogni- son evaluation [27]. In addition to the pragmatic advan- tive test batteries [21-25]. Two items in the test battery did tages, telephone testing may provide a better assessment not correlate as well as the others. The interclass correla- of patients' cognitive function in their normal environ- tions for the Hayling Sentence Completion test only ment. Finally, it is possible that neurocognitive function Page 5 of 7 (page number not for citation purposes) Respiratory Research 2005, 6:39 http://respiratory-research.com/content/6/1/39 improved during the interval between the two test ses- Conclusion sions (mean 122 days). The reason for a potential This study has demonstrated that scores on a battery of improvement in neurocognitive performance will be neurocognitive tests obtained by telephone administra- important in future studies that use repeated test adminis- tion correlated well with in-person testing in patients with tration to determine the effect of drugs for PAH or other pulmonary arterial hypertension. The strong correlations interventions on neurocognitive function. observed are comparable to previous studies that assessed in-person and telephone versions of neurocognitive tests. An important limitation of our study was our inability to With minor modification, the telephone neuropsycholog- reverse the order of administration (in-person and tele- ical test battery described here provides an economical phone) [28]. Our subjects were enrolled in another ongo- and reliable method for assessing cognitive function in ing study, which required in-person assessments prior to patients with pulmonary arterial hypertension. enrollment in this study of telephone testing [29]. An alternative would be to repeat in-person and telephone List of Abbreviations Used assessments in random order following the initial inter- PAH: Pulmonary Arterial Hypertension view. Such additional testing, however, might have increased the potential for learning or practice affects, and SD: Standard Deviation the further time and travel commitments for patients likely impacting study participation. Future studies ARDS: Acute Respiratory Distress Syndrome should counterbalance the order of in-person and tele- phone administration. Due to pragmatic limitations the WMD: Wechsler Memory Scale time interval between in-person and telephone testing was somewhat longer than the minimum time necessary WAIS: Wechsler Adult Intelligence Scale to minimize recall and learning effects. Competing Interests Telephone testing has been used successfully in the assess- The author(s) declare that they have no competing ment of neruocognitive impairment in other patient pop- interests. ulations. Further, the ease in application and relative low cost of telephone testing have enabled assessments in sev- Authors' Contributions eral large clinical studies of cognitive function: screening DBT, JHF, HIP and ROH designed and SK coordinated of 4,932 elderly patients for Alzheimer's Disease using the this study. RP and JC designed the neurocognitive testing modified Mini-Mental State Examination for telephone battery. JM, JW and ROH performed and interpreted the administration [30]; cognitive function in 4,023 patients neuropsychological assessments and ROH the statistical with cardiovascular risk factors [31]; 466 patients with analysis. CGE recruited patients and assessed results. The coronary artery bypass graft surgery [32], and in a self- manuscript was written by DBT, JHF and ROH and has referred ARDS patient group [8]. In addition to neurocog- been read and approved by all authors. nitive testing, telephone-based assessments have provided accurate determinations of quality of life, medication Acknowledgements These studies were supported by a Development Partner's Junior Faculty usage, 24-hour physical activity and dietary recall [33-35]. Award from GSK Pharmaceuticals (DBT). ROH is a recipient of grant sup- port from the National Institute of Mental Health (R01 MH065406-01A1). 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Breitner JC, et al.: APOE-epsilon4 count predicts age when peer reviewed and published immediately upon acceptance prevalence of AD increases, then declines: the Cache County cited in PubMed and archived on PubMed Central Study. Neurology 1999, 53(2):321-31. 31. Garrett KD, et al.: The relationship between cardiovascular yours — you keep the copyright risk factors and cognitive decline. J Int Neuropsychol Soc 2003, BioMedcentral 9:243. Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 7 of 7 (page number not for citation purposes) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Respiratory Research Springer Journals

Validation of a brief telephone battery for neurocognitive assessment of patients with pulmonary arterial hypertension

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Copyright © 2005 by Taichman et al.
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Medicine & Public Health; Pneumology/Respiratory System
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Abstract

Background: The effects of pulmonary arterial hypertension on brain function are not understood, despite patients' frequent complaints of cognitive difficulties. Using clinical instruments normally administered during standard in-person assessment of neurocognitive function in adults, we assembled a battery of tests designed for administration over the telephone. The purpose was to improve patient participation, facilitate repeated test administration, and reduce the cost of research on the neuropsychological consequences of acute and chronic cardiorespiratory diseases. We undertook this study to validate telephone administration of the tests. Methods: 23 adults with pulmonary arterial hypertension underwent neurocognitive assessment using both standard in-person and telephone test administration, and the results of the two methods compared using interclass correlations. Results: For most of the tests in the battery, scores from the telephone assessment correlated strongly with those obtained by in-person administration of the same tests. Interclass correlations between 0.5 and 0.8 were observed for tests that assessed attention, memory, concentration/ working memory, reasoning, and language/crystallized intelligence (p ≤ 0.05 for each). Interclass correlations for the Hayling Sentence Completion test of executive function approached significance (p = 0.09). All telephone tests were completed within one hour. Conclusion: Administration of this neurocognitive test battery by telephone should facilitate assessment of neuropsychological deficits among patients with pulmonary arterial hypertension living across broad geographical areas, and may be useful for monitoring changes in neurocognitive function in response to PAH-specific therapy or disease progression. Page 1 of 7 (page number not for citation purposes) Respiratory Research 2005, 6:39 http://respiratory-research.com/content/6/1/39 tion, and major depression requiring hospitalization), Introduction Pulmonary arterial hypertension (PAH) is a devastating known learning disability, prior traumatic brain injury, disease characterized by progressive shortness of breath diagnosis of dementia, cerebral vascular accident, neuro- and the eventual development of life-threatening heart logic disorder (e.g. multiple sclerosis, Huntington's Dis- failure [1-4]. While its effects on cardiovascular function ease, etc.), prior cardiac surgery, or current alcohol or drug have been well documented, little is known about effects abuse. of this disease on other organ systems, notably the brain. Patients frequently complain of changes in memory, con- Patients were recruited for neurocognitive assessment centration and judgment in association with the develop- from a group who had consented to in-person testing. ment of cardiopulmonary symptoms[5]. Objective Sixty-seven patients were screened. Seventeen patients assessments of cognitive function, however, have not declined, two were excluded due to non-fluency in Eng- been performed. lish, and two were medically unstable at the time of eval- uation and died during the recruitment period. Of the 46 The "gold standard" for comprehensive assessment of patients who consented to in-person neurocognitive test- neurocognitive function is a comprehensive battery of ing, 25 consented to additional testing by telephone. individually validated tests that are administered in-per- son by an experienced interviewer. Comprehensive, Patient demographic, medical and laboratory data were standard testing often takes four hours or longer and may collected for all enrolled patients. This study was require two or more separately scheduled sessions. The approved by the University of Pennsylvania and LDS Hos- experience can be stressful and fatiguing, particularly for pital Institutional Review Boards and conformed to insti- chronically ill or physically disabled patients. The stress of tutional and federal guidelines for the protection of additional travel to a testing site adds to the burden. Con- human subjects. sequently, many patients decline to participate in clinical research that uses formal in-person neurocognitive test- Neurocognitive Assessment ing, especially if the protocol includes repeated testing An interdisciplinary team of neuropsychology, traumatic over time [6,7]. brain injury, rehabilitation medicine, and pulmonary dis- ease specialists selected a battery of standardized neuro- To address these concerns, we developed a focused battery cognitive tests amenable to both in-person and telephone of neurocognitive tests for administration over the tele- administration. Tests were also chosen on the basis of phone. The battery is comprised of individually validated established sensitivity in detecting impairment in patients neurocognitive test instruments appropriate for adminis- with cardiopulmonary disorders and concomitant hypox- tration to adults with cardiopulmonary disease who are emia [10-13]. The cognitive domains assessed and the fluent in English and capable of communicating verbally. tests included in the battery are listed in Table 1. All neu- Telephone administration of the test battery has been rocognitive tests included in the battery have been empir- evaluated for feasibility and validity in survivors of the ically validated and standardized [14-17] with established acute respiratory distress syndrome [8]. The present study reliability, internal and external validity[12,14,16,18,19]. establishes the validity of telephone administration of the The neurocognitive tests were administered in a random test battery by comparing the results of telephone testing sequence to minimize order effects. However, as a delay is against "gold standard" in-person administration in adult required between the Wechsler Memory Scale-III Logical ambulatory patients with moderately to severely sympto- Memory I and II tests, Logical memory I (immediate matic PAH. recall) was the first and Logical Memory II (delay recall) the last test administered in each session. Methods Study Population The in-person assessment was carried out in a private Consecutive patients diagnosed with pulmonary arterial office at LDS Hospital. The identical tests were adminis- hypertension according to standard criteria [2,9] were tered subsequently by telephone at a prearranged time prospectively recruited for neurocognitive testing from the when patients were at home and free from distraction. To Pulmonary Hypertension Clinic at LDS Hospital. Written minimize potential learning effects, telephone testing was informed consent was obtained from the patients for both performed at least 2.5 months following in-person assess- the in-person and telephone neuropsychological testing. ment, except with one patient who was tested 57 days Inclusion criteria were age 18 years or older and the ability after in-person evaluation. A Ph.D. neuropsychologist to give informed consent. Exclusion criteria included non- (ROH) administered the in-person tests and a neuropsy- fluency in English, a history of major psychiatric illness chology doctoral student administered the telephone tests (e.g. schizophrenia, schizoaffective disorder, bipolar dis- with no knowledge of the results of the previous in-person order, psychoses requiring medication and/or hospitaliza- testing. During both the in-person and telephone tests, Page 2 of 7 (page number not for citation purposes) Respiratory Research 2005, 6:39 http://respiratory-research.com/content/6/1/39 Table 1: Neurocognitive Battery for Telephone Administration COGNITIVE DOMAIN TEST INSTRUMENT Attention WMS-III: Digits Forward Concentration/Working Memory WMS-III: Digits Backward WMS-III: Letter-Number Sequencing Executive Function Hayling Sentence Completion Test Reasoning WAIS-III: Similarities Language / Crystallized Intelligence WAIS-III Vocabulary Memory WMS-III: Logical Memory I & II Table 2: Demographic and Medical Data Mean ± SD Range Gender (% female) (n = 25) 83% Education (years) 13.6 ± 3.0 6 to 20 Age (years) 49.7 ± 13.9 20 to 69 Time Since Diagnosis (years) 1.8 ± 1.5 0.8 to 5.3 PaO mmHg 62.6 ± 13.5 38 to 97 Most recent 6 minute walk (meters) 455 ± 132 227 to 877 New York Heart Functional Class (N) Class 1 0 Class 2 3 Class 3 20 Class 4 0 Supplemental Oxygen (N) 2 Liters per minute 7 3 Liters per minute 8 4 Liters per minute 4 patients were instructed not to write down information 0.41 to 0.60; substantial correlation 0.61 to 0.80; and and to answer questions without assistance. The in-person almost perfect correlation 0.81 to 1.00 [20]. and telephone assessments were both conducted in single sessions, and each took 35 to 45 minutes to complete. To assess potential learning effects, systematic differences between first and second administrations for each of the All neuropsychological tests were scored according to the tests were assessed using paired sample t-tests. The differ- published guidelines. Each test yields a raw score that was ences between the in-person and telephone test results are converted into a scaled score (mean = 10; SD = 3), which expressed as standardized effects sizes (T2-T1 differences was used for statistical analyses, except for Logical Mem- divided by T1 standard deviation) [21]. ory where the raw scores are used. Results Statistical Analysis Twenty-five patients with pulmonary arterial hyperten- Descriptive statistics were carried out for demographic sion were enrolled for neurocognitive evaluation using and medical data. The neuropsychological test scores both in-person and telephone testing. All 25 patients from the in-person administration were compared to tel- completed in-person testing. Telephone testing could not ephone test scores using interclass correlations. To facili- be completed on one subject due to a non-functioning tel- tate interpretation of significant correlations (p ≤ 0.05) ephone line, and one subject died of progressive right and because traditional significance levels for correlations heart failure. All of the remaining 23 subjects completed coefficients are influenced by factors such as group size, both the in-person and telephone assessments and were range of scores, and multiple comparisons, we used the included in the validation group. Eighty-three percent (n following conservative classification: fair correlation with = 19) of these subjects were women. The mean ± SD age coefficients between 0.21 and 0.40; moderate correlation was 49.7 ± 13.9 years (range 20 to 60 years) and the mean Page 3 of 7 (page number not for citation purposes) Respiratory Research 2005, 6:39 http://respiratory-research.com/content/6/1/39 Table 3: In-person and telephone neuropsychological test scores. Test Mean Median SD Range Number-letter Sequencing In-person 9.3 10 2.6 5 to 14 Telephone 9.3 9 2.5 5 to 15 Logical Memory Immediate Recall† In-person 24.4 23 5.9 14 to 33 Telephone 27.0 26 8.2 17 to 44 Delay Recall† In-person 18.8 18 5.4 10 to 30 Telephone 22.0 23 7.5 6 to 34 Digit Span In-person 11.6 11 3.2 6 to 18 Telephone 9.3 9 2.4 5 to 15 Hayling Sentence Completion Test In-person 5.7 6 1.1 4 to 8 Telephone 6.6 6 0.89 6 to 10 Similarities In-person 11.0 12 2.9 4 to 16 Telephone 10.9 10 3.1 5 to 16 Vocabulary In-person 10.6 11 2.6 6 to 16 Telephone 11.5 11 2.6 7 to 17 All values are scaled scores (mean = 10, standard deviation = 3) except † = raw scores. Logical memory and Number-letter sequencing are from the WMS-III; digit span, similarities and vocabulary are from the WAIS-R. education level was 13.6 ± 3.0 years (range 6 to 20 years). of attention, memory, concentration / working memory, The mean number of days between in-person and tele- reasoning, and language / crystallized intelligence. An phone testing was 121.6 (range 57 to 200 days). The eti- almost perfect correlation was observed in the assessment ology of PAH was: idiopathic ("primary") PAH in ten of reasoning (Similarities). Substantial correlations were patients (43%), associated with anorexigen use in six found for the Digit Span, Similarities, and Vocabulary (26%), collagen vascular disease in four (17%), congeni- tests (.61 to .80) and moderate correlations (.41 to .60) tal heart disease in two (9%) and one with portopulmo- were found for each Logical Memory immediate and delay nary hypertension (4%). The mean (± SD) right atrial recall. A moderate correlation (0.56) was seen with the in- pressure was 5.1 ± 1.8 mmHg, mean pulmonary artery person and telephone administration of the Digit-Span- pressure 52.1 ± 16.9 and pulmonary capillary wedge pres- backward (concentration / working memory). Only a fair sure 12.1 ± 6.2. The mean cardiac output was 5.1 ± 1.8 L/ correlation (0.28; p= 0.09) was found between the in-per- min. Demographic and medical data are shown in Table son and telephone administration of the Hayling Sen- 2. tence Completion test of executive function. For Letter- Number Sequence test (concentration/working memory) The results of the telephone and in-person neurocognitive scores were not correlated for the in-person and telephone assessments are shown in Table 3. The correlation coeffi- tests. cients for the comparison between in-person and tele- phone testing are presented in Table 4. Interclass Stability over time was greatest for the Similarities and correlation coefficients of at least 0.54 (p < 0.05 to < Vocabulary tests. The effects of learning showed that test 0.0001) were found for the agreement of telephone and scores tended to increase between the in-person and tele- in-person scores on tests assessing the cognitive domains Page 4 of 7 (page number not for citation purposes) Respiratory Research 2005, 6:39 http://respiratory-research.com/content/6/1/39 Table 4: Reliability of the in-person and telephone neuropsychological test scores. Neuropsychological Learning Effect (Improvement Intraclass Correlation 95% C.I. p Test T1 to T2 expressed in SDs) Number-letter Sequencing .78 (0 to 3.1) .15 -.28 to .52 0.25 Logical Memory Immediate Recall† 1.3 (0 to 5.0) .55 -.20 to .72 0.05 Delay Recall† 1.2 (.18 to 3.4) .54 -.24 to .82 0.05 Digit Span Forward† .74 .41 to .90 0.0002 Backward† .56 -.24 to .84 0.05 Both .83 (0 to 1.9) .63 .29 to .83 0.0006 Hayling Sentence .98 (0 to 3.8) .28 -.14 to .61 0.09 Completion Test Similarities .65 (0 to 2.0) .82 .62 to .92 <0.0001 Vocabulary .53 (0 to 1.5) .68 .38 to .85 0.001 All scores shown are scaled scores (mean = 10, standard deviation = 3), except † = raw scores. Logical memory and Number-letter sequencing are from the WMS-III; digit span, similarities and vocabulary are from the WAIS-R. phone tests, with the most improvement for verbal mem- approached significance (p = 0.09). The in-person and tel- ory (e.g. logical memory immediate and delayed recall). ephone administrations of the Letter-Number-Sequenc- ing component of the WMS III (a test of concentration/ working memory) did not correlate well. Some subjects Discussion We found the battery of well-established neurocognitive appeared to have difficulty discriminating phonetically tests to be amenable to administration by telephone and similar sounds (e.g. the letters 'm' and 'n') when presented valid for the identification of neurocognitive deficits in during telephone sessions; visual cues may have alleviated patients with PAH. Testing was readily completed in a sin- such issues at in-person sessions. In contrast, another gle, 30–60 minute session, and required neither special- component of the WMS III (Digits Backward) evaluating ized testing facilities nor travel by physically debilitated the same cognitive domain (concentration/working patients spread across a broad geographic area. memory) had substantial correlations. Our study was designed to validate the administration by Although the correlations we found between in-person telephone of a battery of neurocognitive tests against the testing and subsequent telephone administration of the in-person ("gold standard") performance of these same same test battery were moderate or higher, they were not assessments. Each of the tests in the battery has been pre- perfect. The effects of learning or practice suggest that test viously validated for the identification of neurocognitive scores increase between the in-person and telephone tests, deficits in various populations, including those with car- with the most improvement in verbal memory. Thus, the diopulmonary disease-. As such, our subjects' scores improvement in test scores on the telephone administra- during in-person testing served as matched controls for tion of the test likely reflects practice effects. An alternative comparison with the results obtained upon application of explanation for the tendency of subjects to perform better these same tests over the telephone. on the telephone test battery may be environmental fac- tors. For example subjects scored higher on certain tasks The scores from telephone and in-person assessments cor- when assessed at home as compared to similar tasks per- related strongly for the majority of tests. Overall, the formed in a clinic setting [26]. Improved orientation to strengths of the correlations with in-person testing found time and place have been found when patients were tested here are comparable to those that we reported previously in their own residence [22]. Further, patients report less for the same test battery applied to ARDS survivors [8] and anxiety and prefer telephone testing compared to in-per- the correlations reported for other telephone neurocogni- son evaluation [27]. In addition to the pragmatic advan- tive test batteries [21-25]. Two items in the test battery did tages, telephone testing may provide a better assessment not correlate as well as the others. The interclass correla- of patients' cognitive function in their normal environ- tions for the Hayling Sentence Completion test only ment. Finally, it is possible that neurocognitive function Page 5 of 7 (page number not for citation purposes) Respiratory Research 2005, 6:39 http://respiratory-research.com/content/6/1/39 improved during the interval between the two test ses- Conclusion sions (mean 122 days). The reason for a potential This study has demonstrated that scores on a battery of improvement in neurocognitive performance will be neurocognitive tests obtained by telephone administra- important in future studies that use repeated test adminis- tion correlated well with in-person testing in patients with tration to determine the effect of drugs for PAH or other pulmonary arterial hypertension. The strong correlations interventions on neurocognitive function. observed are comparable to previous studies that assessed in-person and telephone versions of neurocognitive tests. An important limitation of our study was our inability to With minor modification, the telephone neuropsycholog- reverse the order of administration (in-person and tele- ical test battery described here provides an economical phone) [28]. Our subjects were enrolled in another ongo- and reliable method for assessing cognitive function in ing study, which required in-person assessments prior to patients with pulmonary arterial hypertension. enrollment in this study of telephone testing [29]. An alternative would be to repeat in-person and telephone List of Abbreviations Used assessments in random order following the initial inter- PAH: Pulmonary Arterial Hypertension view. Such additional testing, however, might have increased the potential for learning or practice affects, and SD: Standard Deviation the further time and travel commitments for patients likely impacting study participation. Future studies ARDS: Acute Respiratory Distress Syndrome should counterbalance the order of in-person and tele- phone administration. Due to pragmatic limitations the WMD: Wechsler Memory Scale time interval between in-person and telephone testing was somewhat longer than the minimum time necessary WAIS: Wechsler Adult Intelligence Scale to minimize recall and learning effects. Competing Interests Telephone testing has been used successfully in the assess- The author(s) declare that they have no competing ment of neruocognitive impairment in other patient pop- interests. ulations. Further, the ease in application and relative low cost of telephone testing have enabled assessments in sev- Authors' Contributions eral large clinical studies of cognitive function: screening DBT, JHF, HIP and ROH designed and SK coordinated of 4,932 elderly patients for Alzheimer's Disease using the this study. RP and JC designed the neurocognitive testing modified Mini-Mental State Examination for telephone battery. JM, JW and ROH performed and interpreted the administration [30]; cognitive function in 4,023 patients neuropsychological assessments and ROH the statistical with cardiovascular risk factors [31]; 466 patients with analysis. CGE recruited patients and assessed results. The coronary artery bypass graft surgery [32], and in a self- manuscript was written by DBT, JHF and ROH and has referred ARDS patient group [8]. In addition to neurocog- been read and approved by all authors. nitive testing, telephone-based assessments have provided accurate determinations of quality of life, medication Acknowledgements These studies were supported by a Development Partner's Junior Faculty usage, 24-hour physical activity and dietary recall [33-35]. Award from GSK Pharmaceuticals (DBT). ROH is a recipient of grant sup- port from the National Institute of Mental Health (R01 MH065406-01A1). 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