Abstract
Purpose.
Hematopoietic stem cell transplant (HSCT) recipients are at risk for cognitive decline. Cross-sectional studies show patients’ complaints of cognitive decline do not correlate well with concurrently measured objective neuropsychological performance, but rather with emotional variables and health-related quality of life. This longitudinal study investigated whether patient self-report of cognitive status would be concordant with objectively measured neuropsychological performance after accounting for change from their own pre-transplant objective baseline.
Methods.
Pre-HSCT and at 30- and 100-days post-HSCT, 46 patients underwent computerized neuropsychological testing (CogState) and completed surveys assessing patient-reported cognitive complaints, emotional symptoms (depression, anxiety), sleep quality, daytime sleepiness, physical and functional well-being. Correlations were calculated between cognitive complaints and neuropsychological performance (at each time-point and across time-points), as well as all other patient-reported variables.
Results.
Patient-reported cognitive complaints were largely independent of concurrently assessed objective neuropsychological performance. Uniquely, our longitudinal data demonstrated significant medium to large effect size associations between subjective cognitive complaints post-HSCT with objectively measured change from pre-HSCT in attention, visual learning and working memory (p <.05 - .01). Subjective cognitive complaints post-HSCT were also associated with depression, anxiety, daytime sleepiness and physical well-being (p < .05 - .001).
Conclusions.
Patients appear better able to assess their cognitive functioning relative to their own baseline and changes across time rather than relative to community norms. Thus, patient complaints of cognitive compromise justify further in-depth neuropsychological, emotional, and functional assessment. Future research into relationships between cognitive complaints and neuropsychological performance should account for changes in performance over time.
BACKGROUND
Following hematopoietic cell transplantation (HSCT), up to 60% of patients experience neuropsychological decline and 40% continue to show deficits at one- and five-years post-HSCT [1,2]. Domains most affected are attention/concentration, learning, memory, psychomotor speed executive functioning [3]. Worse executive functioning and working memory predict poorer adherence and worse medication self-management [4]. In the acute phase after HSCT, when patients are typically on multiple medications (immunosuppressive, antimicrobial, supportive) with a variety of different administration regimens, even mild neuropsychological impairment has potential to compromise adherence. In turn, compromised adherence could affect morbidity such as increase the risk of infection or graft versus host disease. Longer term neuropsychological impairment also negatively affects return to work or school [3] and health-related quality of life [1]. Further, neuropsychological dysfunction in HSCT survivors is related to more depressed mood, greater fatigue, poorer sleep and decreased physical quality of life [5,6].
Current HSCT guidelines recommend annual long-term monitoring via patient-reports of cognitive functioning [7] and neuropsychological evaluation “if symptoms of cognitive deficits disrupt daily activities or safety” [8]. However, the few HSCT studies that examined the degree of concordance between patient-perceived cognitive dysfunction and objective neuropsychological assessments have not reached consensus [1]. Cognitive complaints by HSCT recipients have been found to correlate strongly with depression, anxiety, sleep problems, physical and functional well-being [9,10], but generally not with objective neuropsychological performance [5,6,9].
These findings mirror the general cancer literature wherein the majority of studies of cancer patients reviewed (66–69%) [11,12] reported subjective cognitive complaints and objective assessment were independent of one another. This discrepancy presents practical dilemmas. Neuropsychological testing, generally regarded as the “gold standard” for accurate and thorough measurement of cognitive function [13], tends to be more burdensome in time, cost and specialized personnel. Patient self-report, the more pragmatic alternative, may be inadequate to assess research outcomes or need for clinical intervention to address cognitive functioning.
Why this lack of concordance exists has not been resolved but could be theoretically due to several reasons [14], one of which is that self-report involves comparison with perceived subjective baseline [12,15] but to our knowledge this has not been empirically tested in an HSCT sample to date. Therefore, the purpose of this prospective longitudinal study was to extend the cross-sectional HSCT literature on validity of patient-reported cognitive complaints relative to (a) concurrent objectively-measured neuropsychological performance and (b) changes from pre- to post-HSCT objectively-measured neuropsychological performance. We hypothesized patient-reported cognitive complaints would not correlate with concurrently assessed neuropsychological performance but would correlate with objective neuropsychological change scores and with worse depression and anxiety, poorer sleep quality, more daytime sleepiness, and decreased physical and functional well-being.
METHODS
Study design
This study comprises secondary analysis of data collected in a previously reported IRB approved (HUM00096406) ancillary study (ClinicalTrials.gov NCT02409134) [16] to a primary clinical trial (ClinicalTrials.gov NCT01790568). As previously reported [16], of the 18 allogeneic patients with matched unrelated donors eligible to receive the experimental drug in that clinical trial, 5 declined to participate and the 9 who completed all time points were included in this study. Thirty-five patients in a concurrent neuropsychological study were selected as matched controls based on key demographic variables. All 35 matched controls had completed assessments at all time points. Recruitment was conducted by clinical research coordinators. Patients were assessed pre-HSCT and at 30- and 100-days post-HSCT during their routine outpatient clinical appointments.
Participants
As in the previously reported study [16], eligible participants were at least 18 years old, were diagnosed with a hematologic malignancy, were scheduled to receive myeloablative conditioning HSCT, had a Karnofsky performance score of ≥70% and had a life expectancy of >6 months. The graft source was either bone marrow or peripheral blood stem cells. Inclusion criteria also included willingness and ability to provide written informed consent, as well as competence in reading, speaking and understanding English. Exclusion criteria were documented evidence of cognitive impairment prior to enrollment, including diagnoses of dementia, mild cognitive impairment, severe mental illness (diagnosis of schizophrenia or bipolar disorder) or other neurological illnesses that impact cognition. Patients undergoing a Total Body Irradiation-based conditioning regimen (e.g., 1200 cGy) were excluded from the study.
Measures
Objective Neuropsychological Performance.
CogState [17], a validated computerized neuropsychological screening battery [18], was used to assess psychomotor speed, attention, visual learning, working memory, problem-solving (indicative of executive function), and delayed memory. Scores are normed based on age. Visual learning and working memory are accuracy-based scores, such that higher scores indicate better functioning. The remaining four neuropsychological subtests are speed-based, such that higher scores indicate longer time to respond, thus worse functioning. Therefore, for ease of interpretation and discussion of findings, we reverse scored the speed-based subtests so higher scores indicate better functioning across all domains.
Patient-Reported Outcomes.
Well-validated measures were used, assessing patient-reported cognitive complaints, depression, anxiety, sleep quality, daytime sleepiness, and quality of life. These measures are described briefly below, and more detailed information is provided in Table 1.
Table 1.
Patient-reported outcomes assessed at pre-transplant, day 30, and day 100
| MEASURE | DESCRIPTION | SCORING AND PSYCHOMETRICS | |
|---|---|---|---|
| Patient-Reported Cognitive Function | Perceived Cognitive Impairment [Cognitive Complaints (Patients)] [13] | 20-item subscale of Functional Assessment of Cancer Therapy – Cognitive Scale Version 3 (FACT-cog) assessing cancer patients’ perception of their cognitive functioning. | 5-point Likert scale, 0 – 4. Total 0 – 80. Internal reliability: Pre-HCT = .96; Day 30 = .96; Day 100 = .95. Higher scores = higher functioning. |
| Comments from Others [Cognitive Complaints (Others)] [13] | 4-item subscale of FACT-cog assessing patients’ perception of other peoples’ assessment of the patients’ cognitive functioning. | 5-point Likert scale, 0 – 4. Total 0 – 20. Internal reliability: Pre-HCT = .92; Day 30 = .92; Day 100 = .74. Higher scores = higher functioning. |
|
| Depression | Patient Health Questionnaire-9 (PHQ-9) [19] | 9-item screener for criteria-based diagnoses of depressive disorders. | 4-point Likert scale, 0 – 3. Total 0 – 27. Score ≥ 10 = significant depression. Internal reliability: Pre-HCT = .89; Day 30 = .84; Day 100 = .81. Higher scores = more depression. |
| Anxiety | General Anxiety Disorder-7 (GAD-7) [21, 22] | 7-item screener for criteria-based diagnoses of anxiety disorders. | 4-point Likert scale, 0 – 3 Total 0 – 21. Score ≥ 10 = significant anxiety. Internal reliability: Pre-HCT = .91; Day 30 = .91; Day 100 = .80. Higher scores = more anxiety. |
| Sleep | Subjective rating of Overall Sleep Quality from Pittsburgh Sleep Quality Index (PSQI) [23, 24] | 1-item measure of subjective sleep quality over the prior month. | 4-point Likert scale, 0 – 3. Range statistic: Pre-HCT = 3; Day 30 = 2; Day 100 = 3. Skewness: Pre-HCT = .12; Day 30 = −.08; Day 100 = .34. Higher scores = worse sleep quality. |
| Excessive Daytime Sleepiness from Pittsburgh Sleep Quality Index (PSQI) [23] | 1-item measure of subjective excessive daytime sleepiness. | 4-point Likert scale, 0 – 3. Range statistic Pre-HCT = 3; Day 30 = 3; Day 100 = 2. Skewness Pre-HCT = 2.29; Day 30 = 2.15; Day 100 = 2.82. Higher scores = more daytime sleepiness. |
|
| Quality of life | Functional Assessment of Cancer Therapy – General (FACT-G) [26] | 14 items constituting the physical and functional well-being subscales of this cancer-related quality-of-life measure were used in the current analyses. | 5-point Likert scale, 0 – 4. Physical functioning well-being internal reliability: Pre-HCT = .82; Day 30 = .85; Day 100 = .88. Functional well-being internal reliability: Pre-HCT = .80; Day 30 = .80; Day 100 = .81. Higher scores = better quality of life. |
Notes. Internal reliability was calculated using Cronbach’s alpha. Beacause internal reliability could not be calculated for individual sleep items, range statistic and skewness were reported to indicate the distribution of score for the items. Range statistics indicates the range of values that were endorsed among this sample and the broader the range the better. Skeweness described the symmetry in the distribution of scores.
1. Subjective cognitive complaints.
Two subscales of the Functional Assessment of Cancer Therapy—Cognitive Scale version 3 (FACT-Cog) [13], designed specifically for cancer patients were used. The first subscale, “Perceived Cognitive Impairment,” assesses patients’ own perception of their cognition. The second subscale, “Comments from Others,” assesses patients’ perception of other people’s assessment of the patients’ cognition. For the purposes of this paper, we refer to these subscales as “Cognitive Complaints (Patients)” and “Cognitive Complaints (Others)” respectively. Higher scores indicate higher functioning.
2. Depression.
The Patient Health Questionnaire-9 (PHQ-9) [19] is a diagnostic screener for criteria-based diagnoses of depressive disorders [20]. Higher scores indicate worse depression.
3. Anxiety.
General Anxiety Disorder-7 (GAD-7) [21] is a diagnostic screener for criteria-based diagnoses of anxiety disorders [22]. Higher scores indicate worse anxiety.
4. Sleep quality.
Two items from Pittsburgh Sleep Quality Index (PSQI) [23] were assessed. The first item, Subjective Rating of Overall Sleep Quality, has the highest item-total correlation with the total PSQI among HSCT patients [24]. The second item, Excessive Daytime Sleepiness during activities (i.e., “During the past month, how often have you had trouble staying awake while driving, eating meals, or engaging in social activity?”) is significantly associated with a measure of excessive daytime sleepiness, the Epworth Sleepiness Scale [25]. Higher scores indicate more problematic sleep quality.
4. Quality of life.
Two subscales of the Functional Assessment of Cancer Therapy – General (FACT-G) [26], designed specifically for patients undergoing cancer treatments were used in analyses: the Physical Well-Being and Functional Well-Being subscales. Higher scores indicate higher quality of life.
Statistical Analyses
SPSS 24 [27] was used to perform the statistical analyses. Demographic and clinical characteristics were derived using means, standard deviations, ranges, frequencies, and percentages, as appropriate. Change in neuropsychological performance was calculated by subtracting pre-HSCT from post-HSCT standardized scores. Pearson’s pairwise correlation was calculated to determine the degree of association of patient-reported cognitive complaints with neuropsychological performance (at each time-point and change scores between time points), and with depression, anxiety, sleep, and physical and functional well-being at each time-point. Test assumptions were assessed for all variables and outliers were removed from pairwise comparisons .
RESULTS
Patient characteristics and demographics.
Mean age of the sample (n = 46) was 56 years (SD = 10; range 27–72) and 52% were male. A Bachelor’s Degree was the modal level of education received (n = 15). Acute myeloid leukemia and multiple myeloma were the most common indications for transplant (autologous, n = 19; allogeneic, n = 27). Mean length of transplant hospital stay was 22 days (SD = 6; range 13–47). See Table 2 for descriptive statistics of the sample. Compared to baseline, mean depression peaked at day 30 whereas anxiety declined steadily over time. Excessive daytime sleepiness declined as overall sleep quality improved over time. See Tables 3a and 3b for descriptive statistics of psychological functioning and neuropsychological performance respectively.
Table 2.
Sample Demographics (N = 46)
| n | % | |
|---|---|---|
| Transplant Type | ||
| Autologous | 19 | 41.30 |
| Allogeneic | 27 | 58.70 |
| Diagnosis | ||
| Acute Myeloid Leukemia | 18 | 39.10 |
| Multiple Myeloma | 11 | 23.90 |
| Non-Hodgkin Lymphoma | 7 | 15.20 |
| Myelodysplastic Syndrome | 6 | 13.10 |
| Chronic Myeloid Leukemia | 2 | 4.30 |
| Hodgkin Lymphoma | 1 | 2.20 |
| Refractory Anemia with Excess | 1 | 2.20 |
| Blasts | ||
| Gender | ||
| Male | 24 | 52.20 |
| Female | 22 | 47.80 |
| M | SD | |
| Age (years) | 55.78 | 10.28 |
| Level of education (years) | 14.26 | 2.42 |
| Length of hospital stay (days) | 21.59 | 5.81 |
Note. M = Mean; SD = standard deviation
Table 3a-b.
Descriptive Statistics
| a. Desriptive Statistics of Patient-Reported Outcomes | ||||||
|---|---|---|---|---|---|---|
| Pre-HSCT | Day 30 Post-HSCT | Day 100 Post-HSCT | ||||
| M (SD) | Range | M (SD) | Range | M (SD) | Range | |
| 57.96 (12.83) | 21 – 72 | 60.21 (13.11) | 15 – 72 | 62.68 (10.76) | 17 – 72 | |
| Cognitive Complaints (Others)a | 14.89 (1.80) | 8 – 16d | 14.80 (2.35) | 6 – 16 | 15.29 (1.55) | 9 – 16 |
| Depressionb | 3.98 (3.20) | 0 – 12d | 5.96 (4.93) | 0 – 24 | 4.42 (4.09) | 0 – 19 |
| Anxietyb | 2.53 (2.82) | 0 – 10d | 1.98 (3.10) | 0 – 13 | 1.05 (1.80) | 0 – 8d |
| Daytime Sleepinessb,c | 0.35 (0.68) | 0 – 3 | 0.39 (0.87) | 0 – 3 | 0.17 (0.45) | 0 – 2 |
| Sleep Qualityb,c | 1.22 (0.72) | 0 – 3 | 1.22 (0.59) | 0 – 2 | 1.03 (0.77) | 0 – 3 |
| Physical Well-Beinga | 22.44 (4.90) | 9 – 28 | 20.38 (5.54) | 6 – 28 | 23.03 (4.13) | 10 – 28d |
| Functional Well-Beinga | 17.72 (5.82) | 5 – 28 | 15.07 (5.43) | 5 – 27 | 17.72 (5.82) | 7 – 28 |
| b. Desriptive Statistics of Neuropsychology Performancea,e | ||||||
| Pre-HSCT | Day 30 Post-HSCT | Day 100 Post-HSCT | ||||
| M (SD) | Range | M (SD) | Range | M (SD) | Range | |
| −0.09 (0.94) | −2.27 – 1.55 | −0.30 (1.08) | −3.22 – 1.55 | −0.22 (0.86) | −1.64 – 1.55 | |
| Attention | −0.17 (1.18) | −2.86 – 1.57 | −0.36 (1.10) | −3.37 – 1.71 | −0.05 (0.94) | −2.00 – 2.00 |
| Visual Learning | −0.38 (1.01) | −3.09 – 1.55 | −0.15 (1.25) | −2.00 – 1.55d | −0.22 (1.02) | −2.00 – 1.55 |
| Working Memory | −0.08 (0.87) | −2.33 – 1.33 | −0.14 (1.09) | −2.93 – 1.33 | −0.16 (0.94) | −2.53 – 1.33 |
| Problem-Solving | −0.01 (0.91) | −4.06 – 1.35 d | 0.21 (0.84) | −2.15 – 1.70 | 0.38 (0.73) | −2.86 – 1.61d |
| Delayed Memory | −0.17 (1.12) | −3.30 – 1.64 d | −0.38 (0.91) | −2.17 – 1.83d | 0.65 (0.97) | −2.58 – 2.01 |
Note. M = Mean; SD = standard deviation; range = observed range among participants.
Higher scores indicate higher functioning
Higher scores indicate poorer functioning
Sleep measures were completed by 37 participants
Excluding individual outlier
Neurocognitive performance scores are expressed as Z-scores (M = 0, SD = 1)
Trends in cognitive complaints, and neuropsychological performance.
Patients perceived that their cognitive functioning (i.e., cognitive complaints [patients]) improved significantly from pre-HSCT to day 100 post-HSCT, t (44) = −2.61, p < .05. Additionally, patients’ view of how others perceived their cognitive functioning (i.e., cognitive complaints [others]) also improved during the same time interval but this change was not statistically significant. Overall, neuropsychological performance worsened from pre-HSCT to day 30 post-HSCT and recovered somewhat at day 100 post-HSCT. These changes in neuropsychological performance were not statistically significant with the exception of delayed memory, which improved from pre-HSCT to day 100 post-HSCT, t (37) = 2.83, p <.01.
Cross-sectional analyses within each time-point
Cognitive complaints v. neuropsychological performance.
At day 100, cognitive complaints (patients) and cognitive complaints (others) were related to objectively measured visual learning (r = .38, p < .05; r = .35, p < .05, respectively). Apart from these associations, cognitive complaints (patients) and cognitive complaints (others) were unrelated to all other neuropsychological performance measures at all time-points.
Cognitive complaints v. psychological functioning.
Pre-HSCT, cognitive complaints (patients) were significantly associated with higher anxiety and depression, poorer physical and functional well-being and excessive daytime sleepiness (Table 4a). At day 30, cognitive complaints (patients) were associated with higher depression. Cognitive complaints (patients) and cognitive complaints (others) were associated with increased anxiety, poor physical well-being and excessive daytime sleepiness (Table 4a). At day 100, cognitive complaints (patients) and cognitive complaints (others) were associated with increased depression and poor physical well-being. Cognitive complaints (others) were also associated with increased anxiety (Table 4a).
Table 4a-c.
Correlations
| a. Correlation between Measures of Patient-Reported Cognitive Complaints and Psychological Functioning | ||||||
|---|---|---|---|---|---|---|
| Pre-HSCT | Day 30 Post-HSCT | Day 100 Post-HSCT | ||||
| Cognitive Complaints (Patients) | Cognitive Complaints (Others) | Cognitive Complaints (Patients) | Cognitive Complaints (Others) | Cognitive Complaints (Patients) | Cognitive Complaints (Others) | |
| −.57*** | −.25 | −.43** | −.26 | −.40** | −.35* | |
| Anxiety | −.52*** | −.05 | −.39** | −.44** | .08 | −.44** |
| Daytime Sleepiness | −.43** | −.32 | −.41* | −.64*** | .08 | .12 |
| Sleep Quality | −.31 | −.28 | −.21 | −.06 | .07 | −.19 |
| Physical Well-Being | .59*** | .13 | .57*** | .42** | .59*** | .55*** |
| Functional Well-Being | .47** | .16 | .15 | .05 | .23 | .16 |
| b. Correlations netween Change in Neuropsychological Performance from Pre-HSCT and Patient-Reported Cognitive Complaints and Psychological Functioning at Day 30 | ||||||
| Psychomotor Speed | Attention | Visual Learning | Working Memory | Problem Solving | Delayed Memory | |
| Cognitive Complaints (Patients) | .08 | .15 | −.02 | .29 | −.05 | −.02 |
| Cognitive Complaints (Others) | −.05 | .40** | .18 | .32* | .27 | −.09 |
| Depression | .20 | −.29 | −.10 | −.14 | −.10 | −.12 |
| Anxiety | .05 | −.19 | −.29 | −.23 | −.29 | −.16 |
| Daytime Sleepiness | −.09 | −.32 | −.10 | −.38* | −.26 | −.14 |
| Sleep Quality | .10 | .03 | .13 | −.05 | .06 | .27 |
| Physical Well-Being | .21 | .40** | .17 | .27 | .14 | .07 |
| Functional Well-Being | .10 | −.02 | .12 | .12 | .05 | −.03 |
| c. Correlation between Change in Neuropsychological Performance from Pre-HSCT to Day 100 Post-HSCT and Patient-Reported Cognitive Complaints and Psychological Functioning at Day 100 | ||||||
| Psychomotor Speed | Attention | Visual Learning | Working Memory | Problem Solving | Delayed Memory | |
| Cognitive Complaints (Patients) | −.23 | .39* | .34* | .24 | −.24 | −.22 |
| Cognitive Complaints (Others) | −.31 | .44** | .51*** | .25 | −.18 | −.22 |
| Depression | .10 | −.36* | −.21 | .03 | .23 | −.46** |
| Anxiety | .10 | .05 | −.32* | −.12 | .06 | .24 |
| Daytime Sleepiness | .16 | .00 | −.18 | .27 | −.09 | .07 |
| Sleep Quality | .28 | .10 | −.03 | .13 | .08 | −.37* |
| Physical Well-Being | −.17 | .37* | .39* | .01 | −.19 | −.15 |
| Functional Well-Being | .06 | −.08 | .12 | .04 | .07 | −.24 |
Note.
p ≤ 0.05,
p ≤ 0.01,
p ≤ 0.001
Objective neuropsychological performance v. psychological functioning.
At day 30, poor attention was associated with increased anxiety (r = −.43; p <.01). Other than this association, neuropsychological performance and psychological, quality of life and sleep variables were unrelated at all time-points.
Analyses across time-points
Change in neuropsychological performance v. cognitive complaints.
At day 30, cognitive complaints (others) were associated with decreased neuropsychological performance compared to pre-HSCT on measures of attention and working memory (Table 4b). At day 100, cognitive complaints (patients) and cognitive complaints (others) were associated with decreased neuropsychological performance compared to pre-HSCT on measures of attention and visual learning (Table 4c).
Change in neuropsychological performance v. psychological functioning.
At day 30 compared to pre-HSCT, worsening attention was associated with poor physical well-being; worsening working memory was associated with daytime sleepiness (Table 4b). At day 100 compared to pre-HSCT, worsening attention was associated with increased depression and poor physical well-being; worsening visual learning was associated with increased anxiety and poor physical well-being; worsening delayed memory was associated with higher depression and poor sleep quality (Table 4c).
DISCUSSION
The purpose of this study was to extend prior research into associations between cognitive complaints and neuropsychological performance among HSCT patients. In doing so, these findings contribute to resolving the question why subjective and objective assessments of cognitive function may not be consistently correlated across studies in cancer populations and, in particular, among HSCT patients.
Our hypothesis that patient-reported cognitive complaints would not correlate with concurrently assessed objective neuropsychological performance was supported at all three time-points with one exception. At day 30, cognitive complaints (patients) were associated with decreased attention. Consistent with prior research [6,9], patients appeared to be poor judges of their own cognitive abilities relative to community norms.
Our hypothesis that patient-reported cognitive complaints would correlate with objective neuropsychological change scores was supported relative to worsening attention and working memory at day 30 as well as worsening attention and visual learning at day 100. All of these associations have medium to large effect sizes [28]. Even after conservatively evaluating the data using the Benjamini-Hochberg method to minimize the false detection rate, the association between cognitive complaints (others) and change in attention at day 30 and day 100 as well as the association between cognitive complaints (others) and change in visual learning at day 100 remained robust. This pattern of findings, novel in the HSCT literature, suggests patients may be more accurate in assessing their cognitive functioning relative to their own baseline and changes across time. Our findings are consistent with those of a longitudinal study of breast cancer patients, indicative of an association between subjective complaints of cognitive difficulties and change in neuropsychological performance [29].
Finally, our hypothesis that patient-reported cognitive complaints would be associated with psychological variables and quality of life was supported. Consistent with prior research, [9,10] fewer cognitive complaints were associated with improved physical well-being, less depression, and less anxiety at all three time points and less daytime sleepiness at pre-HSCT and day 30. Like prior studies [5,6,9], we found few concurrent associations between objective neuropsychological performance and psychological functioning. However, we found decline in objective neuropsychological performance compared to pre-HSCT at day 30 post-HSCT was related to poorer physical well-being and more daytime sleepiness; and at day 100 post-HSCT was related to higher anxiety and depression and poorer physical well-being and sleep quality. Thus, although independent of concurrently measured neuropsychological performance, patient-reported cognitive complaints may be clinically relevant indicators of distress associated with neuropsychological decline.
Study limitations.
Small sample size precluded multivariate regression analyses to account for effects of medical and demographic variables on outcomes. Since this study sample was confined to HSCT, its pattern of findings remains to be replicated among other cancer populations.
Clinical implications.
Clinical implications of our findings are that patients who perform in the average range on standardized assessments yet report cognitive complaints may indeed be experiencing decline from their own prior functioning. Healthcare providers should attend to patients’ cognitive complaints, particularly as they pertain to patients’ ability to adhere to treatment recommendations, and subsequently to their ability to resume their prior job or social roles. As patient complaints of cognitive compromise are associated with psychological distress and functional decline, cognitive complaints could justify further in-depth neuropsychological assessment with a view to mobilizing comprehensive supportive care or rehabilitative services.
Summary.
The major contribution of this study to the field is the evidence afforded by repeated measures that subjective cognitive complaints can be indicative of idiographic deterioration from prior functioning. Therefore, when patients complain of cognitive compromise, medical providers should consider in-depth neuropsychological assessment, in case ability to resume prior work or social roles may be negatively impacted and rehabilitative services may be needed. Further, future research examining validity of cognitive complaints should assess change in neuropsychological performance across time.
ACKNOWLEDGEMENTS
We wish to thank the patients and families who participated in the ancillary clinical trial and acknowledge the support of the University of Michigan Clinical Trials Office. We also wish to thank Marian Ktiri and Alyssa Buthman, the Research Assistants who conducted all the neuropsychological testing.
FUNDING INFORMATION
This work was supported by Gateway for Cancer Research (G-15-200), National Institutes of Health (R21CA198776), Michigan Institute for Clinical and Health Research (UL1TR00043), and Blue Cross Blue Shield of Michigan Foundation Investigator-Initiated Research Program (2193.11).
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Footnotes
CONFLICT-OF-INTEREST STATEMENT
The authors have no conflict-of-interests to disclose.
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