DEPRESSION AND COGNITIVE IMPAIRMENT FOLLOWING RECOVERY FROM THROMBOTIC THROMBOCYTOPENIC PURPURA

Abstract

Purpose

Following recovery from an acute episode of acquired thrombotic thrombocytopenic purpura (TTP), patients often describe problems with memory, concentration, and endurance. We have previously reported the occurrence of depression and cognitive impairment in these patients. In this study we describe the frequency, severity and clinical course of depression and cognitive impairment.

Findings

Fifty-two (85%) of 61 eligible Oklahoma Registry patients who had recovered from TTP, documented by ADAMTS13 activity <10%, have had at least one (median, four) evaluation for depression over 11 years using the Beck Depression Inventory-II; 31 (59%) patients screened positive for depression at least once; in 15 (29%), the results suggested severe depression at least once. Nine of these 15 patients had a psychiatric interview, the definitive diagnostic evaluation; the diagnosis of major depressive disorder was established in eight (89%) patients. In 2014, cognitive ability was evaluated in 33 patients by the Montreal Cognitive Assessment (MoCA) and the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Both tests detected significant cognitive impairment in the patients as a group. Fifteen of the 33 patients had been evaluated by extensive cognitive tests in 2006. The 2014 RBANS results were significantly worse than the 2006 results for the overall score and two of five RBANS domains (immediate and delayed memory). Neither depression nor cognitive impairment was significantly associated with the occurrence of relapses or ADAMTS13 activity <10% during remission.

Conclusion

These observations emphasize the importance of screening evaluations for depression and cognitive impairment following recovery from acquired TTP.

Introduction

Because acquired autoimmune thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder,(1) we began regular meetings for survivors and their families in 1996 to help them understand their illness.(2;3) An unexpected outcome was that our patients helped us understand their long-term outcomes. Although our patients had returned to their normal activities and occupations, they and their families reported an incomplete return to their normal mental and physical functioning. They described persistent problems with memory, concentration, and endurance. To address these problems, we evaluated health-related quality-of-life, which documented significant deficits involving both physical and mental health domains.(4) We then evaluated neurocognitive function, which documented significant abnormalities in domains measuring complex attention and concentration skills, information processing speed, rapid language generation, and rote memorization, characteristic features of diffuse subcortical microvascular disorders.(5) We also documented significantly increased frequency of severe depression.(6)

In this report we describe our continuing evaluations to document the frequency, severity, and clinical course of depression and cognitive impairment following recovery from TTP.

Methods

Oklahoma TTP-HUS Registry patients

The Oklahoma TTP-HUS (hemolytic-uremic syndrome) Registry has enrolled all consecutive patients for whom the Oklahoma Blood Institute (OBI) was requested to provide plasma exchange treatment for a diagnosis of TTP, HUS, or another thrombotic microangiopathy (TMA) since January 1, 1989.(7;8) The OBI is the sole provider of plasma exchange services for all hospitals in 58 of the 77 Oklahoma counties. Therefore the Registry includes all consecutive patients within a defined geographic region in whom the diagnosis of TTP, HUS, or TMA was suspected and a decision to initiate plasma exchange treatment was made. There are no exclusion criteria; there is no referral or selection bias. All identified patients have been enrolled in the Registry. The Oklahoma TTP-HUS Registry is approved for long-term follow-up of all patients by the institutional review boards of the University of Oklahoma Health Sciences Center and each participating hospital.

Patient evaluations

ADAMTS13 measurements

Since November 1995, serum samples have been routinely collected immediately before the first plasma exchange. ADAMTS13 activity was measured in all samples by both quantitative immunoblotting and a fluorogenic assay using FRETSVWF73 substrate by Dr. Johanna Kremer Hovinga (University of Bern, Switzerland). Severe deficiency was defined as ADAMTS13 activity <10% by either method.(8) Acquired autoimmune TTP was defined by the presence of severe ADAMTS13 deficiency with an ADAMTS13 activity inhibitor or by the recovery of ADAMTS13 activity during remission.

Annual patient evaluations

Beginning in 2004, all patients who had recovered from acquired TTP have been asked to participate in annual evaluations. ADAMTS13 activity was measured at each evaluation. Assessments for depression and cognitive impairment were performed at some of these evaluations, as described below. The highest level of educational attainment was determined at the 2014 evaluation. All patients were in clinical remission at the time of their assessments for depression and cognitive impairment.

Screening evaluation for depression

Depressive symptoms were assessed by the Beck Depression Inventory (BDI)-II(9) during six of the annual evaluations: 2004, 2006, 2009-2011, 2014. The BDI-II is a 5-10 minute self-reported screening questionnaire with 21 statements related to the patient's symptoms during the previous two weeks. The response for each statement ranges from zero, indicating no or minimal problems, to 3, indicating severe problems. Scores of 0-13 are interpreted as no or minimal depression, 14-19 as mild depression, 20-28 as moderate depression, and 29-63 as severe depression. Comparison U.S. population values were obtained from a survey of 333 primary care medical outpatients who were demographically similar to our patients.(10) The BDI-II test materials were ordered from Pearson Education, Inc., San Antonio, TX.

Psychiatric interview and Revised Hamilton Rating Scale for Depression (RHRSD)

The standard of care in mental health for validation of a suspected diagnosis of major depressive disorder is a psychiatric interview.(11) Therefore patients with BDI-II scores suggesting moderate or severe depression on at least one occasion were asked to take part in a psychiatric interview performed by a senior resident in psychiatry (L.H.S.) during their annual evaluation in 2011. The diagnoses established by the psychiatric interview were: major depressive disorder, no major depressive disorder but the presence of depressive symptoms, and no major depressive disorder and no depressive symptoms.(12) Based on the data from the interview, L.H.S. completed the RHRSD, an observer-rated measure with 25 items related to the previous two weeks, which provides a numerical record of standardized scores for comparability. Scores of 0-9 are interpreted as no depression, 10-16 as minor depression, 17-25 as major depression, and 26 and higher as severe depression. The RHRSD test materials and manual were ordered from WPS (Western Psychological Services), Inc., Torrance, CA.

Screening for cognitive impairment

During the 2006 annual evaluations, extensive cognitive evaluations were performed that included 23 individual tests assessing 11 domains of cognitive function and required approximately 2.5 hours to complete. The results have been previously published.(5) During the 2014 annual evaluations, patients were screened for cognitive impairment with two tests, the Montreal Cognitive Assessment (MoCA) and the Repeatable Battery for Assessment of Neuropsychological Status (RBANS).

The MoCA is a 5-10 minute test of immediate memory, delayed memory, attention, language, visuospatial ability, and executive function. The MoCA was chosen because of its ease of administration and its convenience for screening TTP patients during routine primary care follow-up evaluations. It is available from the website (http://www.mocatest.org/) at no cost. The MoCA website has normal population values adjusted for education; one point is added for individuals who have less than or equal to 12 years of formal education. The maximum score for the MoCA is 30; scores of 26 or higher are defined as normal; the mean normal score is 27.4. In our evaluation the MoCA was administered first; patients scoring less than 20 did not have further evaluation with the RBANS. This represents our clinical practice; patients who score less than 20 with the MoCA likely have significant dementia and are unlikely to be able to comply with the cognitive demands of the RBANS.

The RBANS, a 30 minute test, was chosen because it is a comprehensive screening test with five individual domains (immediate memory, delayed memory, attention, language, visuospatial ability) comparable to our previously performed extensive cognitive evaluations.(5) Results of the RBANS are reported as a total scale (overall score) and scores for each individual domain, based on normal population values adjusted for age, provided by the RBANS manual. The overall score is a summarizing of performance across all five individual domain scores. Scores are standardized to a mean score of 100 with a standard deviation of 15. The RBANS test materials and scoring manual were ordered from Pearson Education, Inc., San Antonio, TX.

Statistical analysis

The 2014 BDI-II, RBANS and MoCA results were analyzed as continuous variables of their scores. All variables utilized for analysis were tested for normality using the Shapiro-Wilk test. If data were normally distributed, one-sample t-tests and paired t-tests were utilized. If a non-normal distribution was found then non-parametric methods were utilized, such as the Wilcoxon-Mann-Whitney test, Spearman correlation coefficient, and a bootstrapped 95% empirical confidence interval. The comparisons that were analyzed, the statistical tests that were used, and the P values for all comparisons are presented in Supplement Table SI. Not all P values are included in the text.

The 2014 RBANS scores were compared to the results of our 2006 cognitive evaluations(5) in the 15 patients who had completed both evaluations. The five individual domains of the RBANS were compared to the related 2006 cognitive tests (Supplement Table SII). The overall score was compared to the average of the five groups of 2006 scores that were compared to the individual RBANS domains. The results of the RBANS evaluations and the previous 2006 cognitive tests were converted to standardized scores based on normative data generated from neurologically normal population values according to the subject’s age. Therefore these standardized scores provided a valid common metric for the comparisons of individual patients across the 8 years from 2006 to 2014. The standardized scores were expressed as Z-scores with a mean value of 0 and a standard deviation of 1. To obtain a quantitative measure of the magnitude of the differences, the effect size was calculated for the overall score and each domain by dividing the mean change by the standard deviation.(13)

Results

Depression

From 1995 through 2013, 77 consecutive patients with acquired TTP have been enrolled at the time of their initial episode. Thirteen (17%) of the 77 patients died with their initial episode; three additional patients died before our annual evaluations began in 2004. Fifty-two (85%) of the 61 surviving patients have been screened for depression by the BDI-II one-six times (median, four times) (Figure 1); they have attended 85% of their possible annual evaluations. Individual patient data for all 61 patients for each of the six years of BDI-II evaluations are presented in Supplement Table SIII.

Figure 1.

Patients evaluated by the BDI-II and their results, 2004-2014

In 2014, 36 (68%) of the 53 surviving patients were seen for the annual evaluation (Supplement Table SIV). One patient did not complete the BDI-II. Sixteen (46%) of the 35 patients who completed the BDI-II had scores suggesting mild, moderate, or severe depression; 19 (54%) had scores suggesting no or minimal depression. The 35 patients’ BDI-II scores (mean, 14.1; 95% CI 10.5, 19.1) were significantly worse than the BDI-II scores of primary care medical outpatients who were demographically similar to our patients (mean, 8.7).(10) Across all six evaluations, 2004-2014, thirty-one (59%) of the 52 patients had scores suggesting mild, moderate, or severe depression on at least one evaluation; 15 patients (29%) had scores suggesting severe depression at least once (Figure 1). The distributions of the 2014 BDI-II scores were not significantly different related to race (black vs. non-black), level of education (high school/general educational development (GED) vs. higher education) gender, number of TTP episodes (one [25 patients] vs. more than one [10 patients]) or ADAMTS13 activity during remission (<10% ever [10 patients] vs. never <10% [25 patients]) (P = 0.0956-0.9368, Supplement Table SI). The 2014 BDI-II scores were also not significantly associated with age (P = 0.2919). The BDI-II scores of the 14 patients who were evaluated in both 2006 and 2014 were not different (P = 0.8315). The mean BDI-II score for these patients was 13.8 in 2006 and 14.2 in 2014; the mean difference between the 2006 and 2014 scores was 0.43 (95% CI: −3.84, 4.69).

In 2011, 11 of the 15 patients who had previously had a BDI-II score suggesting severe depression were available for a psychiatric interview. Three of the 15 patients had died prior to 2011; one patient was not enrolled in the Registry until 2013. Psychiatric interviews and the RHRSD were conducted with nine of the 11 patients. At the time of their interview, six patients had BDI-II scores in the severe range and three had scores suggesting moderate depressive symptoms. The psychiatric interview confirmed a diagnosis of major depressive disorder in eight (89%) of the nine patients; one patient did not meet criteria for major depressive disorder. The RHRSD supported the diagnosis of depression in all nine patients. In 2011, all eight patients who had previously had BDI-II scores suggesting moderate depression, but never severe depression, were alive. Among these eight patients, four (50%) were evaluated by a psychiatric interview and the RHRSD. One of these patients was diagnosed with a major depressive disorder by the psychiatric interview and major depression by the RHRSD (Table I).

Table I.

Testing for depression with three methods: BDI-II screening, psychiatric interview, and Revised Hamilton Rating Scale for Depression (RHRSD)

Patient No.*	BDI-II Score**	Psychiatric Interview Diagnosis	RHRSD Score†
Patients with a BDI-II score suggesting severe depression during one of our previous annual evaluations
30††	42	Major Depressive Disorder	26
37	44	Major Depressive Disorder	25
6††	42	Major Depressive Disorder	23
11	39	Major Depressive Disorder	17
24	22	Major Depressive Disorder	21
35††	37	Major Depressive Disorder	14
44	31	Major Depressive Disorder	13
36	26	Major Depressive Disorder	16
32	21	No Major Depressive Disorder, Depressive Symptoms	11
Patients with a BDI-II score suggesting moderate depression but never severe depression during one of our previous annual evaluations
40	25	Major Depressive Disorder	22
43	20	No Major Depressive Disorder, Depressive Symptoms	10
45	27	No Major Depressive Disorder, No Depressive Symptoms	1
3	15	No Major Depressive Disorder, No Depressive Symptoms	2

^*Patient numbers are from Supplement Table SIII.

^**The BDI-II screening evaluation was completed by the patient immediately preceding the psychiatric interview. The BDI-II score interpretation is: 0-13, no or minimal depression; 14-19, mild depression; 20-28, moderate depression; 29-63, severe depression

^†The RHRSD was completed by the psychiatrist immediately following the psychiatric interview, based on the data learned from the interview. The RHRSD scores are interpreted as: <10, not depressed; 10-16, minor depression; 17-25, major depression; ≥26, severe depression

^††Anti-depressant medication was taken at the time of these evaluations

At the time of their annual evaluations, all patients with BDI-II scores suggesting depression were provided with resources for mental health care in their community. The 23 patients with scores suggesting severe or moderate depression were also contacted by a follow-up telephone call to further encourage mental health care and to offer help with referral. One patient who expressed active suicidal thoughts had an immediate hospital evaluation. Other patients who voiced passive suicidality were managed in collaboration with their primary physicians with standard care for suicidal patients. Twelve (52%) of 23 patients have received medications for their depression.

Cognitive impairment

Of the 36 patients seen in 2014, one chose not to participate in the cognitive evaluations. Two of the 35 patients who participated scored less than 20 on the MoCA test and therefore were not evaluated by the RBANS test. Both of these patients live independently without overt dementia. One patient is age 59; she has had Crohn's disease for many years. The other patient is age 79 and frail. Neither had apparent severe cognitive impairment. The patients as a group performed significantly worse than normative population values on the MoCA, the RBANS overall score, and also for all of the five individual RBANS domains (Table II). Among the 33 patients who were evaluated by both cognitive tests, there was a significant association between scores on the MoCA and the RBANS overall scores (P = 0.0200, r=0.40). The MoCA and RBANS overall scores were not associated with time since the initial TTP episode. (MoCA, P = 0.9479, r = −0.01442; RBANS, P = 0.7775,r = −0.06390). The RBANS overall scores were not significantly different between patients who had one (22 patients) or more than one (11 patients) previous episode of TTP (P = 0.978) and also not significantly different between patients who had ever had ADAMTS13 activity <10% during remission (10 patients) or who had all measurements ≥10% (23 patients) (P = 0.282).

Table II.

Comparison of cognitive ability of patients evaluated in 2014 to normative population values

Cognitive Test	Patient Scores Mean Values (95% Confidence Intervals)	Population Mean Values
MoCA	25.2 (24.1, 26.3)	27.4
RBANS Overall Score*	89.5 (86.4, 92.5)	100
RBANS Individual Domain Scores
Immediate Memory	91.3 (87.5, 95.1)	100
Delayed Memory	90.6 (87.0, 94.3)	100
Attention	92.1 (85.8, 98.3)	100
Language	92.9 (89.7, 96.1)	100
Visuospatial	92.9 (87.3, 98.6)	100

Data are presented for the patients’ scores on the Montreal Cognitive Assessment (MoCA) and the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Thirty-five patients participated in the MoCA evaluation; 33 patients participated in the RBANS evaluation. MoCA scores are based on a maximum of 30. RBANS scores are normalized to a mean of 100 with a standard deviation of 15 for the overall score as well as the score of each individual domain. Normative population values for the MoCA assessments were adjusted for educational level; the population mean was 27.4. Normative population values for the RBANS assessments were adjusted for age; the population mean for the overall RBANS and RBANS domains was 100. Patient scores for all evaluations were significantly less than the population data (P <0.05) because the 95% confidence intervals did not include the population mean values.

^*Bootstrapped 95% Empirical Confidence Intervals, not adjusted for bootstrap bias, due to non-normal distribution.

In 2006 we performed extensive cognitive evaluations in 24 (83%) of the 29 living patients.(5) Fifteen (63%) of these 24 patients were evaluated by the RBANS in 2014; three of the other nine patients had died; three had moved away from Oklahoma; three did not participate. The 2014 RBANS scores of these 15 patients were compared to the related tests of their 2006 evaluations. The results for the RBANS total score and for two of the five RBANS domains (immediate memory and delayed memory) were significantly worse than the related tests performed in 2006 (Table III). The effect sizes for the differences between 2006 and 2014 for these three RBANS scores were 0.65-0.79. One patient had an abnormal score (>1 SD below the age, gender, education-adjusted US normal population) in 2006; she plus two other patients were abnormal in 2014. The scores of 10 of the remaining 12 patients decreased from 2006 to 2014, although they did not reach the abnormal range. Therefore, for the group of 15 patients, the difference between 2006 and 2014 was significant.

Table III.

Comparison of cognitive ability across 8 years in 15 patients who were evaluated in both 2006 and 2014

Cognitive Tests, 2014	Mean Difference from Comparable Cognitive Tests, 2006 (95% CI)	P	Effect Size
RBANS Overall Score	−0.4404 (−0.7612, −0.1195)	0.0107	− 0.75
RBANS Individual Domain Scores
Immediate Memory	−0.6239 (−1.0906, −0.1572)	0.0124	− 0.79
Delayed Memory	−0.4751 (−0.8738, −0.0765)	0.0228	− 0.65
Attention	−0.3254 (−0.9562, 0.3055)	0.2873	− 0.28
Language	0.1192 (−0.2865, 0.5249)	0.5387	+ 0.16
Visuospatial	− 0.4789 (−1.0455, 0.0877)	0.0913	− 0.47

Data are presented for the comparison of the 2014 RBANS assessments to the results of the cognitive evaluations performed in 2006. The five individual domains of the RBANS were compared to the related cognitive tests performed in 2006 (Supplement Table S2) for each of the 15 patients. The RBANS overall score for each patient was compared to the average of the five groups of 2006 scores used for the comparison to the individual RBANS domains. Scores for both the 2006 and 2014 tests were adjusted for the patient's age. Effect size was calculated as the mean difference between the 2014 and 2006 results divided by the standard deviation of the difference.

Comparison of BDI-II scores for depression with the RBANS test of cognitive function

In 2014, 32 patients completed both the BDI-II screening test for depression and the RBANS test for cognitive function. The correlation between the RBANS total scores and the BDI-II scores (P = 0.0920, r = 0.31) did not support an association between cognitive impairment and depression for these patients.

Discussion

The frequency of severe depression following recovery from TTP is high, occurring in 29% of our patients across 11 years. We have previously documented that the point prevalence of severe depression in our patients (19%) was significantly greater than the 6% point prevalence of severe depression in the U.S. population adjusted for age, race, gender, and body mass index.(6) The accuracy of our screening for depression with the BDI-II was confirmed by a psychiatric interview. These observations emphasize that regular screening is an essential component of routine patient care following recovery from acquired TTP to ensure that depression is appropriately diagnosed and managed. Symptoms of grief, sadness, and a sense of loss can occur temporarily following any critical illness, s including TTP. However depression is distinct and it is associated with continuing detrimental symptoms that can be dramatically improved with appropriate treatment.

Regular screening for depression is consistent with the recommendation by the U.S. Preventive Services Taskforce that all adults should be screened for depression when staff-assisted depression care supports are in place to assure accurate diagnosis, effective treatment, and follow-up.(14) The screening test that we used, the BDI-II, requires only 5-10 minutes to complete; even shorter screening tests may be effective. For example, asking two simple questions about mood and anhedonia (“Over the past 2 weeks, have you felt down, depressed or hopeless?” and “Over the past 2 weeks have you felt little interest or pleasure in doing things?”) may be as effective as more detailed screening tests.(15) Screening for depression and providing referral for appropriate mental health management is essential since many of our patients had limited insight into their depression and, if they were aware, some were reluctant to ask for help or to take appropriate medication.(16) We screen our patients annually, however the optimal interval for screening for depression is unknown.

Depression is a dangerous disease. It erodes the quality of life and personal productivity(17) and it is associated with a nearly a two-fold increased risk for death.(18) In 2002, depression ranked 4^th in the world as a cause of burden of disease (following perinatal conditions, respiratory infections, and HIV/AIDS), measured by disability-adjusted life years (DALY), which are expressed as the number of years lost due to ill-health, disability or early death.(19) It is projected that in 2030 depression will be the most common cause of disability-adjusted life years in high-income countries.(19)

The reason why the frequency of depression is high among TTP survivors is uncertain. The presence of depression in our patients was not associated with the occurrence of previous relapses or with the occurrence of severe ADAMTS13 deficiency (activity <10%) during remission. Patients with systemic lupus erythematosus (SLE) also have an increased frequency of depression(20) and patients with TTP have an increased risk for developing SLE.(6) SLE and TTP have similar demographic features, with increased occurrence in young black women;(21) these three demographic features are all associated with an increased risk for depression.(22) Morbid obesity (BMI ≥40 kg/m²) is significantly increased among our patients at the time of their initial diagnosis of TTP(6) and obesity also increases the risk for depression.(23)

We have previously reported cognitive impairment in our patients with deficits characteristic of diffuse, subcortical microvascular lesions.(5) Although our patients had no apparent gross neurologic deficits and they were performing their normal daily activities with a high level of function, their cognitive impairment was clearly noticeable both by themselves and their families.(2;3) The magnitude of cognitive function in our patients was not associated with the duration since their initial episode of TTP, the occurrence of previous relapses or with the occurrence of severe ADAMTS13 deficiency (activity <10%) during remission. Even though we could not document an association between cognitive impairment and depression in our patients, cognitive impairment may contribute to risk for depression.(24)

Our goal for cognitive testing in 2014 was to confirm our initial observations using simpler tests. We used the MoCA because this 5-10 minute screening evaluation is available with no cost and is appropriate for repeated screening assessments. We also used the RBANS, a more extensive screening evaluation that tested five distinct domains. The patients as a group performed significantly worse than standardized values provided by the test developers from neurologically normal individuals on both the MoCA and the RBANS. There was a significant association between scores on the MoCA and the RBANS overall scores, supporting the validity of the MoCA evaluation as a routine follow-up tool. These data were consistent with our previous observations, but they did not provide the detailed evaluation of specific cognitive domains that was possible with our extensive cognitive testing in 2006.(5)

Although the RBANS domains did not correspond precisely to the 23 cognitive tests used for our 2006 evaluations, they allowed a comparison across eight years for the 15 patients who were evaluated in both 2006 and 2014. The decline of cognitive function suggested by this comparison was unexpected. We had assumed that our patients had static lesions related to their previous episodes of TTP that would neither recover nor progress.(25) The domains which demonstrated decreased function were immediate memory and delayed memory. This is consistent with cognitive disorders associated with cerebral small-vessel disease, in which cognitive decline occurs principally in information processing speed and executive function.(26) Both of these components are prerequisite skills for memory. The other domains, which measure attention, language, and visuospatial ability, are more resistant to change. These changes were not only statistically significant, they are clinically important as demonstrated by the magnitude of the effect sizes of 0.65-0.79.(13). The reason for the progressive impairment of cognitive function in TTP survivors is uncertain. It may be consistent with other indications of progressive organ impairment and increased mortality following recovery from TTP.(6;27)

Our experience establishes that major depressive disorder and cognitive impairment are important sequelae for some patients following recovery from acquired TTP. These sequelae of TTP are not unique to TTP; they are similar to sequelae of other acute, episodic, and potentially fatal disorders. The prevalence of major depressive disorder is increased in patients with SLE(20) and multiple sclerosis(28), which also have an autoimmune etiology and share an episodic clinical course. Survival from critical illness of any cause increases risk for both depression and cognitive impairment.(29) The experience of survivors of stroke may be particularly relevant to the experience of TTP survivors. Long-term follow-up of stroke survivors has documented a cumulative incidence of major depressive disorder of 55%, with high rates of recurrence across 15 years.(30) Major depressive disorder can occur years after the primary neurologic deficits of stroke and the initial post-stroke depression have resolved.(31)

Based on our experience, we suggest that annual screening of patients who have recovered from acquired TTP for depression and cognitive function is appropriate. For depression, the BDI-II, a commonly used screening evaluation, has been efficient and easily accepted by our patients. For cognitive function, the MoCA is also a commonly used screening evaluation that is also easy to administer. Each evaluation requires only 5-10 minutes to complete and neither requires a skilled administrator. An abnormality on either screening evaluation requires careful follow-up to ensure that the patient receives appropriate diagnostic evaluation and management.

A limitation of these data is the small number of patients which inevitably impairs the generalizability of our observations. The small number of patients also limited the power to detect differences of the BDI-II and RBANS scores with patient characteristics and an association of the BDI-II and RBANS scores. Another limitation may be that not all patients participated in all evaluations. This could bias our observations if patients with depressive or cognitive symptoms were either more or less likely to attend our evaluations. Our opinion is that these symptoms are unlikely to be related to meeting attendance. Most patients who have not attended our evaluations live a long distance from Oklahoma City; some have moved away from Oklahoma. However a strength of our data is that they are derived from a cohort of consecutive patients who have been followed continually for many years. Data from these patients help to provide understanding of the long-term outcomes following recovery from acute episodes of acquired TTP.

Our experience documents that depression and cognitive impairment affect many patients following recovery from acquired TTP. Both can contribute to impaired quality-of-life throughout the patients’ lifetimes. These observations emphasize the critical importance of continuing surveillance screening for depression and cognitive impairment in these patients.