Abstract
Objective:
Childhood trauma is common and associated with both worse cognitive performance and disruption to the hypothalamic-pituitary-adrenal axis in younger adults. The extent to which these associations persist into older adulthood remains unknown. The aim of this current study was to investigate self-reported childhood trauma in relation to cognitive performance, and the extent to which cortisol explained this association, in two independent samples of older adults.
Method:
In this cross-sectional study, participants in the discovery sample (N=76) consisted of older adults with a DSM-IV diagnosis of Generalized Anxiety Disorder (N=57) and age-equated psychiatrically healthy comparison subjects (N=19) who were referred largely through primary care clinics between 2004-2006. The replication sample (N=48) consisted of older adults with a DSM-IV anxiety or depressive disorder in 2011. Participants were administered the Early Trauma Inventory Self Report-Short Form and a neuropsychological assessment (primary outcome).
Results:
Across both samples, childhood trauma was significantly associated with worse performance on measures of processing speed, attention, and executive functioning. The effect of trauma exposure was stronger when specifically examining general, physical, and sexual traumatic events (all p < 0.05). Childhood trauma was not associated with cortisol levels, and cortisol did not explain the association between trauma and cognitive functioning.
Conclusions:
Self-reported traumatic events experienced in childhood are associated with poorer cognitive performance in anxious and depressed older adults. Findings demonstrate a deleterious impact of childhood trauma on brain health in old age.
Keywords: Older adults, childhood trauma, cognition, anxiety, depression, cortisol
Introduction
Experiencing a traumatic event (e.g. death of a parent, friend, or family member, physical, emotional, or sexual abuse) during childhood is common1 and a significant public health problem2. Additionally, the population of the United States is growing older, with the number of adults age 65 or older estimated to more than double to just under 100 million by the year 20603. As many as 47% of older adults report experiencing a childhood trauma, with some evidence to suggest this prevalence is higher in recent cohorts4. Despite this, the long-term effects of childhood trauma on health outcomes in older adulthood remains understudied. With older adults comprising the fastest growing segment of the population, understanding the associations between childhood trauma and later-life health outcomes will only grow in importance as adult survivors of childhood trauma continue to age.
Childhood trauma has been associated with poor brain health. Younger adults who have experienced childhood trauma are at increased risk of poor physical health and psychiatric distress, such as Generalized Anxiety Disorder (GAD), Posttraumatic Stress Disorder (PTSD), and mood disorders1, 5, 6. Early life traumatic events may also negatively affect cognitive functioning7, 8, particularly slower information processing speed and worse attention, memory, and executive functioning in children and younger adults9-11. Many of these studies find that general (e.g., unexpected death of a family member, witnessing physical violence), physical, and sexual traumas are particularly harmful to cognitive functioning12-14. Additionally, experiencing one childhood traumatic event is a risk factor for experiencing subsequent traumas, and multiple traumatic events in childhood are associated with worse outcomes than a single traumatic event15.
Despite the strong implications of increased incidence of cognitive decline and disorders in later life, the extent to which childhood trauma is associated with cognitive performance in older adults is largely understudied. Childhood adversity comorbid with depression was associated with greater declines in processing speed in 1,312 older adults in the Longitudinal Aging Study Amsterdam16. Longitudinal research with 846 community-dwelling older adults found that repeated early life sexual assault was associated with greater declines in verbal fluency and Trails-B performance in older adulthood 17. Studies have been mixed, however, with some studies reporting no association between childhood trauma and worse cognitive performance in later life18 and other studies reporting childhood adversity was protective against decline on a cognitive performance composite score over time19. No research has examined the association between cognitive performance and childhood trauma in clinical samples of older adults with anxiety disorders, despite the fact that anxious older adults typically report higher rates of childhood trauma compared to psychiatrically healthy older adults20.
Neurobiological mechanisms involving chronic inflammation21, decreased neuroplasticity22, and epigenetic modification of stress-related pathways23 may explain the possible association between early life trauma and poorer cognitive performance in later life. The hypothalamus-pituitary-adrenal (HPA) axis is thought to play a particularly important role in this association. The HPA axis activates under stress, resulting in elevated levels of the cortisol hormone and certain severe and/or chronic stressors, particularly if experienced early in life, may permanently alter HPA axis function24. Studying this association is important, as chronically elevated cortisol levels have been associated with worse neuropsychological performance in later life25, 26.
The purpose of this study was to investigate the association between childhood trauma, cortisol, and cognitive performance in two samples of older adults. The discovery cohort consisted of a case-comparison sample of older adults with GAD and age-equated psychiatrically healthy comparison subjects, and the replication sample consisted of older adults with a major depressive disorder or an anxiety disorder. We hypothesized that childhood trauma would be associated with worse processing speed, attention, memory, and executive functioning. We also hypothesized that childhood trauma would be associated with higher cortisol levels and cortisol would mediate the relationship between childhood trauma and cognitive performance.
Methods
Samples
Discovery Sample
Participants in the discovery sample consisted of 57 older adults with GAD and 19 psychiatrically healthy age-equated comparison participants. A detailed description of the discovery sample can be found elsewhere27, 28. The discovery sample was recruited at the University of Pittsburgh. Participants in the discovery sample were community-dwelling adults who were at least 60 years old, did not have a diagnosis of dementia, and had a score of 24 or higher on the Mini-Mental Status Examination (MMSE)29. The participants with GAD were diagnosed via the Structured Clinical Interview for DSM-IV Axis I disorders30 and were taking part in a clinical trial investigating the efficacy of escitalopram for late-life GAD27. Data presented in the current report were drawn from the pre-treatment baseline assessment of this trial. The 19 comparison participants had no history of DSM-IV diagnosis and were equated to the clinical sample on demographic characteristics.
Replication sample
We also examined the associations between childhood trauma and cognitive performance in a replication sample of 48 older adults experiencing a DSM-IV depressive or anxiety disorder and cognitive complaints who were recruited for a clinical trial examining Mindfulness-Based Stress Reduction (MBSR) at the University of California, San Diego. Participants in the replication sample were aged 65 or older, had a score of 22 or higher on the abbreviated-Penn State Worry Questionnaire31, and reported that they were experiencing problems with their memory or concentration as ascertained by an affirmative response to the question “Have you noticed any changes in your memory or thinking (as you have gotten older)?”. Individuals with dementia, as assessed by committing ten or more errors on the Short Blessed Test32, a medical chart diagnosis of dementia, or prescription of cognitive enhancing medication, were excluded from the study. Other exclusion criteria across both studies included a lifetime diagnosis of a psychotic disorder, active alcohol or substance abuse, or an unstable medical condition.
The Institutional Review Boards at both sites approved all study procedures and all participants provided written informed consent.
Measures
Childhood trauma
Childhood trauma was self-reported using the Early Trauma Inventory-Self Report Short Form (ETISR-SF)33, a reliable and well-validated measure of childhood trauma. The ETISR-SF consists of 28 items capturing four types of early childhood traumatic events, including general trauma (12 items), physical abuse (5 items), emotional abuse (5 items), and sexual abuse (6 items). Scores represent the total number of events experienced before the age 18, with scores in this sample ranging from 0-17. Because research documents links between general, physical, and sexual abuse and poorer cognitive functioning34, 35, we exclusively examined the ETISR-SF composite of these subscales. The ETISR-SF was administered in both the discovery and replication samples.
Cognitive functioning
For both samples, a neuropsychological battery was administered that assessed multiple domains of functioning. In the discovery sample, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) 36 was administered. The RBANS consists of subscales measuring attention, immediate memory, visuospatial construction, language, and delayed memory abilities. To examine psychomotor speed and attention, the RBANS Coding and Digit Span subtests were also examined separately. Raw scores were transformed into age-adjusted standard scores using normative data from the RBANS manual. Working memory was assessed using the Letter-Number Sequencing age-adjusted standard score from the Wechsler Adult Intelligence Scale-III37. Executive function inhibition ability was measured using the Stroop Neuropsychological Screening Test38. Number of correct responses was transformed to standard scores using normative data provided in the manual. Executive function problem-solving ability was also measured using the total number of correct sorts transformed to an age-adjusted standard score from the Delis-Kaplan Executive Function System (D-KEFS)39 Sorting Test. All normed scores were transformed to standard scores with a mean of 100 and SD of 15 in order to be consistent across all outcomes.
The neuropsychological battery administered in the replication study assessed the same general domains of cognitive functioning. Attentional abilities were measured using the Digit Vigilance Test (DVT)40 and the Digit Span subtest from the RBANS. Demographically corrected T-scores41 were obtained for DVT total time and total errors. Age-adjusted z-scores were derived for Digit Span performance. Immediate and delayed memory was assessed by a list learning task and contextual memory. A 16-word list learning task42, similar to the Rey Auditory Verbal Learning test, was administered to assess immediate and delayed list recall. Contextual recall was also assessed by reading participants two paragraphs containing 44 pieces of information and having them immediately recall the information in the paragraphs43. Delayed contextual memory was assessed by asking participants to repeat the contextual information after a 30-minute delay. Because age-corrected normative data were not available for both the list learning and contextual memory tasks, we analyzed the raw test scores. The Color-Word Interference and Verbal Fluency subtests from the D-KEFS39 were administered to assess executive functioning. The age-corrected scaled score was computed for the time based color naming with interference condition (condition 3) of the Color-Word Interference test, and the age-corrected scaled score of the Verbal Fluency subtest was utilized. Similar to the discovery sample, all normed scores were transformed to standard scores in order to put all neuropsychological outcomes on the same scale.
Salivary cortisol
For two consecutive days before the baseline assessment, participants collected cortisol. In the discovery sample, cortisol was taken six times over the course of the day, whereas for the replication sample, cortisol was collected three times over the course of the day (upon waking, 30 minutes after waking, and at bedtime). Data were averaged across the two days. Cortisol was log-transformed and normalized. Two cortisol outcomes were examined: peak daily cortisol and the area under the curve (AUC). A total of 19 participants in the discovery sample were missing cortisol data; therefore, all analyses with the discovery sample cortisol included 57 people. A more detailed description of cortisol data collection is presented elsewhere28.
Covariates
Physical health was quantified using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G)44. Worry was measured using the Penn State Worry Questionnaire-Abbreviated (PSWQ-A31). Depressive symptoms were measured in the discovery sample using the 17 item Hamilton Rating Scale for Depression (HRSD)45. Depressive symptoms were measured in the replication sample using the National Institute of Health PROMIS Depression items46. The apolipoprotein ε4 (APOE ε4) allele is a genetic risk factor for cognitive decline and Alzheimer’s disease. APOE genotyping was available for a subsample of the discovery sample (N = 39) and for all participants in the replication sample (N = 48). DNA was extracted from the blood using standard procedures for both samples.
Data Analysis
The three groups within the two samples were compared on descriptive variables that were common to both samples using one-way ANOVA and chi-square tests for categorical variables. The two clinical groups (GAD in the discovery sample and the replication sample) were also compared. Hierarchical multiple regression analyses were used to examine the associations between number of childhood traumas and each cognitive outcome. Each model was run with the ETISR-SF total composite score, as well as a composite of the general, physical, and sexual trauma subscale score. The structure of the models was as follows: Step 1- controlling for age, sex, years of education, GAD status, and CIRS-G; Step 2- depressive and worry symptoms and diagnosis of Posttraumatic Stress Disorder were added to the model; and Step 3- peak cortisol was added to the model to examine the extent to which cortisol mediated the association between trauma and cognitive performance. These analyses were duplicated in the replication sample. In the replication sample APOE genotype (no ε4 allele = 0; presence of ε4 allele = 1) was included as a covariate to the Step 2 models.
Results
Sample characteristics and frequency of childhood trauma
Table 1 provides descriptive statistics of the discovery and replication samples. Compared to the discovery sample, participants in the replication sample completed significantly more years of education. When compared to the two clinical groups, the healthy comparison participants endorsed significantly less worry and less childhood trauma. Table 2 presents the frequencies of each self-reported childhood trauma.
Table 1.
Descriptive statistics and comparisons between the health comparisons (N=19) and GAD (N=57) participants in the discovery sample and replication sample (N=48)
| Discovery Sample M (SD) OR % (N) |
Replication sample M (SD) or % (N) (N=48) |
Omnibus F Or chi- square |
Compare F GAD and Replication |
||
|---|---|---|---|---|---|
| Comparison (N=19) |
GAD (N=57) |
||||
| Age | 75.32 (6.96) | 71.75 (8.32) | 72.33 (5.31) | 1.27 | 0.17 |
| Percent Women | 78.90 (15) | 68.40 (39) | 64.60 (31) | 1.30 | 0.17 |
| Education (Years) | 14.95 (2.55) | 14.12 (2.64) | 16.08 (2.70) | 6.25* | 14.10** |
| Childhood trauma full | 2.68 (3.00) | 4.61 (3.92) | 5.51 (3.79) | 7.33** | 1.44 |
| Childhood trauma general, physical, and sexual abuse | 1.89 (1.91) | 3.24 (2.60) | 3.55 (2.59) | 4.91* | 0.39 |
| Psychiatric and medical comorbidity | |||||
| PSWQ-A | 12.63 (4.52) | 26.18 (7.59) | 25.52 (7.55) | 23.26** | 0.16 |
| Hamilton Depression | 1.37 (1.67) | 11.12 (3.41) | … | 143.20** | … |
| PROMIS Depression | … | … | 18.08 (7.66) | … | … |
| CIRS-G | 8.42 (2.80) | 8.91 (3.95) | 7.77 (3.17) | 1.25 | 2.60 |
| PTSD Diagnosis | 0.0 (0) | 3.50 (2) | 4.30 (2) | 0.80 | 0.04 |
| Cognitive performance | |||||
| RBANS | |||||
| Total SS | 97.37 (10.13) | 94.25 (14.70) | … | 0.74 | … |
| Immediate Memory SS | 103.11 (15.37) | 97.60 (15.22) | … | 1.86 | … |
| Visuospatial Ability SS | 91.21 (18.12) | 83.16 (16.86) | … | 3.13 | … |
| Delayed Memory SS | 97.95 (11.28) | 94.72 (14.31) | … | 2.13 | … |
| Attention SS | 102.42 (10.52) | 101.33 (17.58) | … | 0.07 | … |
| Language SS | 97.26 (8.98) | 102.18 (13.68) | … | 0.80 | … |
| Coding SS | 103.04 (14.56) | 96.74 (19.09) | … | 1.73 | … |
| WAIS-III LN Sequencing SS | 104.47 (11.77) | 105.18 (11.30) | … | 0.05 | … |
| D-KEFS Sorting SS | 114.21 (14.84) | 111.05 (15.29) | … | 0.62 | … |
| Digit Span SS | 101.11 (16.78) | 101.73 (17.75) | 92.88 (15.41) | 5.67* | 7.29** |
| Trenerry Stroop Interference SS | 95.50 (14.90) | 94.57 (14.95) | … | 0.05 | … |
| Digit Vigilance Time SS | … | … | 95.31(13.26) | … | … |
| Digit Vigilance Errors SS | … | … | 92.84 (18.90) | … | … |
| List Learning Immediate Recall (# words) | … | … | 26.29 (7.77) | … | … |
| List Learning Delayed Recall (# words) | … | … | 5.12 (2.94) | … | … |
| Paragraph 1 Immediate Recall (# words) | … | … | 17.46 (6.15) | … | … |
| Paragraph 2 Immediate Recall (# words) | … | … | 16.23 (5.66) | … | … |
| Paragraph 1 Delayed Recall (# words) | … | … | 13.54 (6.63) | … | … |
| Paragraph 2 Delayed Recall (# words) | … | … | 12.41 (5.56) | … | … |
| D-KEFS Stroop Color-Word SS | … | … | 101.35 (18.27) | … | … |
| D-KEFS Verbal Fluency SS | … | … | 101.25 (16.71) | … | … |
| Max Cortisol | 3.16 (1.23) | 5.23 (1.78) | 4.99 (2.45) | 6.21* | 0.27 |
Childhood trauma full = composite score of all subscales from the Early Trauma Inventory Self Report-Short Form (ETISR-SF)
Childhood trauma general, physical, and sexual abuse = composite score of these subscales
The symbol … represents not applicable
indicated p < 0.05
indicates p < 0.01
Abbreviations: CIRS = Cumulative Illness Rating Scale-Geriatrics; D-KEFS = Delis-Kaplan Executive Function System; PSWQ-A = Penn State Worry Questionnaire- Abbreviated; SS = standard score; WAIS-III = Wechsler Adult Intelligence Scale version III
Table 2.
Items and frequency of endorsing each item from the Early Trauma Inventory Self Report- Short Form (ETISR-SF) between the healthy comparison (N=19) and GAD (N=57) participants in the discovery sample and replication sample (N=48)
| Traumatic Event | Discovery | Replication | |
|---|---|---|---|
| Comparison % (n) |
GAD % (n) |
% (n) | |
| General Trauma | |||
| 1. Exposed to life-threatening natural disaster? | 5.3 (1) | 1.8 (1) | 20.8 (10) |
| 2. Were you ever exposed to a life-threatening event due to war, terrorist attack, or political conflict? | 0.0 (0) | 1.8 (1) | 10.4 (5) |
| 3. Were you involved in a serious accident? | 0.0 (0) | 14.0 (8) | 25.0 (12) |
| 4. Did you ever suffer a serious personal injury or illness? | 31.6 (6) | 26.8 (15) | 29.2 (14) |
| 5. Did you ever experience the death or serious illness of a parent or a primary caretaker? | 26.3 (5) | 43.9 (25) | 40.0 (19) |
| 6. Did you experience the divorce or separation of your parents? | 5.3 (1) | 10.5 (6) | 16.7 (8) |
| 7. Did you experience the death or serious injury of a sibling? | 10.5 (2) | 12.3 (7) | 16.7 (8) |
| 8. Did you experience the death or serious injury of a friend? | 15.8 (3) | 38.6 (22) | 31.3 (15) |
| 9. Did you ever witness violence towards others, including family members? | 15.8 (3) | 26.3 (15) | 27.1 (13) |
| 10. Did anyone in your family ever suffer from mental or psychiatric illness or have a “breakdown”? | 5.3 (1) | 29.8 (17) | 25.0 (12) |
| 11. Did your parents or primary caretaker have a problem with alcoholism or drug abuse? | 15.8 (3) | 28.1 (16) | 25.0 (12) |
| 12. Did you ever see someone murdered? | 0.0 (0) | 1.8 (1) | 0.0 (0) |
| Physical Punishment | |||
| 1. Were you ever slapped in the face with an open hand? | 15.8 (3) | 15.8 (9) | 25.0 (12) |
| 2. Were you ever burned with hot water, a cigarette or something else? | 0.0 (0) | 0.0 (0) | 0.0 (0) |
| 3. Were you ever punched or kicked? | 0.0 (0) | 7.0 (4) | 16.7 (8) |
| 4. Were you ever hit with an object that was thrown at you? | 0.0 (0) | 7.0 (4) | 8.3 (4) |
| 5. Were you ever pushed or shoved? | 5.3 (1) | 12.3 (7) | 10.4 (5) |
| Emotional Abuse | |||
| 1. Were you often put down or ridiculed? | 26.3 (5) | 33.3 (19) | 50.0 (24) |
| 2. Were you often ignored or made to feel that you didn’t count? | 10.5 (2) | 26.3 (15) | 43.8 (21) |
| 3. Were you often told you were no good? | 10.5 (2) | 15.8 (9) | 27.1 (13) |
| 4. Most of the time were you treated in a cold, uncaring way or made to feel like you were not loved? | 21.1 (4) | 26.3 (15) | 43.8 (21) |
| 5. Did your parents or caretakers often fail to understand you or your needs? | 10.5 (2) | 35.1 (20) | 43.8 (21) |
| Sexual Events | |||
| 1. Were you ever touched in an intimate or private part of your body (e.g. breasts, thighs, genitals) in a way that surprised you or made you feel uncomfortable? | 15.8 (3) | 19.3 (11) | 22.9 (11) |
| 2. Did you ever experience someone rubbing their genitals against you? | 5.3 (1) | 10.5 (6) | 10.4 (5) |
| 3. Were you ever forced or coerced to touch another person in an intimate or private part of their body? | 5.3 (1) | 5.3 (3) | 2.1 (1) |
| 4. Did anyone ever have genital sex with you against your will? | 5.3 (1) | 1.8 (1) | 4.2 (2) |
| 5. Were you ever forced or coerced to perform oral sex on someone against your will? | 0.0 (0) | 1.8 (1) | 0.0 (0) |
| 6. Were you ever forced or coerced to kiss someone in a sexual rather than an affectionate way? | 5.3 (1) | 0.0 (0) | 4.2 (2) |
Association of childhood trauma with cognitive performance
Table 3 displays results from the linear regression models investigating self-reported trauma exposure in relation to cognitive performance in the discovery sample. After controlling for age, sex, education, physical health, and GAD status, childhood trauma was associated with a worse total index score on the RBANS. This score was driven by worse performance on the Attention Index. Childhood trauma was also associated with worse Coding, Digit Span, Stroop Color-Word Interference performance, and sorting abilities. After adjusting for PTSD diagnosis, depressive and worry symptoms, childhood trauma remained associated with worse attention performance, Stroop Color-Word Interference, and sorting performance. When examining these associations in the subsample for which APOE data was available the magnitude of the results did not significantly change when we adjust for APOE (see supplemental table 1). See figure 1 for graphs of the estimated test performance for individuals with no trauma, those reporting the mean number of traumatic events, and those reporting high number of traumatic events.
Table 3.
Discovery sample results from the hierarchical linear regression examining number of traumatic events reported in relation to cognitive test performance and hierarchical linear regression examining number of general, physical, and sexual traumatic events reported in relation to cognitive test performance.
| Predictor: Childhood trauma full composite score Outcome: |
Step 1: Adjust for demographics and health (N=76) |
Step 2: Adjust for depression and anxiety (N=76) |
Step 3: Adjust for cortisol (N=57) |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Trauma β |
95% CI | p | Trauma β |
95% CI | p | Trauma β |
95% CI | p | |
| RBANS | |||||||||
| Total IS | −0.99 | −1.84 to −0.14 | 0.03 | −0.81 | −1.67 to 0.06 | 0.07 | −0.60 | −1.65 to 0.44 | 0.25 |
| Attention IS | −1.70 | −2.66 to −0.73 | <0.01 | −1.59 | −2.59 to −0.58 | <0.01 | −1.55 | −2.80 to −0.30 | 0.02 |
| Coding SS | −1.33 | −2.47 to −0.20 | 0.02 | −1.10 | −2.27 to 0.07 | 0.06 | −0.88 | −2.34 to 0.59 | 0.23 |
| Digit SS | −1.53 | −2.60 to −0.47 | <0.01 | −1.48 | −2.60 to −0.36 | 0.01 | −1.68 | −3.13to −0.23 | 0.02 |
| Immediate Memory IS | −0.54 | −1.55 to 0.47 | 0.29 | −0.37 | −1.40 to 0.67 | 0.48 | 0.03 | −1.35to 1.41 | 0.97 |
| Visuospatial Function IS | −0.74 | −1.83 to 0.34 | 0.18 | −0.61 | −1.74 to 0.52 | 0.28 | −0.69 | −2.11 to 0.72 | 0.33 |
| Delayed Memory IS | −0.61 | −1.49 to 0.27 | 0.17 | −0.58 | −1.50 to 0.34 | 0.21 | −0.32 | −1.47 to 0.83 | 0.58 |
| Language IS | −0.12 | −0.90 to 0.66 | 0.76 | 0.06 | −0.72 to 0.85 | 0.87 | 0.37 | −0.64 to 1.38 | 0.46 |
| Letter Number Sequencing SS | −0.62 | −1.36 to 0.12 | 0.10 | −0.47 | −1.22 to 0.29 | 0.22 | −0.22 | −1.20 to 0.76 | 0.66 |
| Confirmed Correct Sorts SS | −1.14 | −2.04 to −0.24 | 0.01 | −1.19 | −2.14 to −0.24 | 0.01 | −1.11 | −2.08 to −0.13 | 0.03 |
| Stroop Color-Word interference SS | −1.00 | −1.92 to −0.08 | 0.03 | −1.00 | −1.95 to −0.04 | 0.04 | −1.61 | −2.83 to −0.39 | 0.01 |
| Predictor: Childhood general, physical, and sexual trauma composite score Outcome: |
Step 1: Adjust for demographics and health (N=76) |
Step 2: Adjust for depression and anxiety (N=76) |
Step 3: Adjust for cortisol (N=57) |
||||||
| Trauma β |
95% CI | p | Trauma β |
95% CI | p | Trauma β |
95% CI | p | |
| RBANS | |||||||||
| Total IS | −1.50 | −2.78 to −0.22 | 0.02 | −1.25 | −2.54 to 0.03 | 0.06 | −0.81 | −2.39 to 0.76 | 0.30 |
| Attention IS | −2.31 | −3.78 to −0.84 | <0.01 | −2.14 | −3.66 to −0.62 | <0.01 | −1.89 | −3.80 to 0.02 | 0.053 |
| Coding SS | −1.82 | −3.54 to −0.11 | 0.04 | −1.55 | −3.30 to 0.18 | 0.08 | −1.11 | −3.32 to 1.09 | 0.32 |
| Digit SS | −2.39 | −3.99 to −0.80 | <0.01 | −2.30 | −3.96 to −0.64 | <0.01 | −2.45 | −4.63 to −0.28 | 0.03 |
| Immediate Memory IS | −0.87 | −2.40 to 0.64 | 0.25 | −0.59 | −2.14 to 0.95 | 0.45 | −0.01 | −2.08 to 2.06 | 0.99 |
| Visuospatial Function IS | −0.96 | 2.60 to 0.67 | 0.24 | −0.80 | −2.49 to 0.88 | 0.35 | −0.63 | −2.77 to 1.50 | 0.53 |
| Delayed Memory IS | −1.15 | −2.46 to 0.16 | 0.08 | −1.06 | −2.42 to 0.30 | 0.12 | −0.61 | −2.33 to 1.10 | 0.48 |
| Language IS | −0.22 | −1.39 to 0.95 | 0.71 | −0.05 | −1.22 to 1.12 | 0.93 | 0.40 | −1.12 to 1.92 | 0.60 |
| Letter Number Sequencing SS | −0.93 | −2.05 to 0.18 | 0.10 | −0.68 | −1.80 to 0.44 | 0.23 | −0.09 | 1.56 to 1.39 | 0.91 |
| Confirmed Correct Sorts SS | −1.99 | −3.33 to −0.66 | <0.01 | −2.00 | −3.39 to −0.60 | <0.01 | −1.79 | −3.24 to −0.34 | 0.02 |
| Stroop Color-Word interference SS | −1.68 | −3.07 to −0.29 | 0.02 | −1.72 | −3.14 to 0.30 | 0.02 | −2.73 | −4.56 to −0.89 | <0.01 |
Step 1 includes age, sex, years of education, cirs-g, PTSD and GAD status
Step 2 adds PSWQ-A and HRSD to the model
Step 3 adds max cortisol to the model
Estimates below p <0.05 are bolded
Abbreviations: CI = Confidence interval; GAD= Generalized Anxiety Disorder; HRSD = Hamilton Rating Scale for Depression; PSWQ-A= Abbreviated Penn State Worry Questionnaire; PTSD = Posttraumatic Stress Disorder; RBANS = Repeatable Battery for the Assessment of Neuropsychological Status; IS=Index Score; SS= Standard Score; Trauma β = estimated effect of Early Trauma Inventory Self Report- Short Form score on cognitive performance.
Figure 1.
Graph depicting the estimated performance, with 95% confidence interval, on cognitive tests and cortisol AUC by self-reported childhood trauma controlling for age, sex, education, health, GAD status, PTSD diagnosis, worry, and depressive symptoms.
a Participants were divided into three categories: no traumatic events (ETISR-SF = 0), mean number of traumatic events (ETISR-SF = 4) or high levels of traumatic events (+1 SD, ETISR-SF=8).
When examining composite of general, physical, and sexual traumas in relation to cognitive performance, a similar pattern of results emerged. The number of self-reported events was associated with a lower Total Index Score on the RBANS total and attention indices, Coding subtest, Digit Span subtest, Stroop Color-Word Interference, and Sorting. The effect size of the association between childhood trauma and worse cognitive performance was generally larger when only examining the composite of general, physical, and sexual traumatic events compared to the ETISR-SF total composite score.
In the replication sample, a similar pattern of results of childhood trauma on cognitive performance emerged (see Table 4). The number of traumatic events from the full childhood trauma inventory was associated with worse Digit Span performance. Number of traumatic events was also associated with worse verbal fluency and D-KEFS Color-Word Interference. Similar to the discovery sample, when examining only the total number of general, physical, and sexual traumas reported, the effect size of trauma approximately doubled for most outcomes.
Table 4.
Replication sample results from the hierarchical linear regression examining number of traumatic events reported in relation to cognitive test performance and hierarchical linear regression examining number of general, physical, and sexual traumatic events reported in relation to cognitive test performance in the replication sample (N =48).
| Childhood trauma full composite score | Childhood general, physical, and sexual trauma composite score |
|||||
|---|---|---|---|---|---|---|
| Outcome | Trauma β |
95% CI | p | Trauma β |
95% CI | p |
| Attention | ||||||
| Digit Span (SS) | −1.40 | −2.74 to −0.06 | 0.04 | −2.68 | −4.61 to −0.74 | <0.01 |
| Digit Vigilance Time (SS) | −0.50 | −1.78 to 0.80 | 0.44 | −1.72 | −3.61 to 0.17 | 0.07 |
| Digit Vigilance Errors (SS) | −1.15 | −2.96 to 0.66 | 0.21 | −0.89 | −3.69 to 1.91 | 0.53 |
| Memory | ||||||
| List Immediate. Recall (# words) | −0.46 | −1.13 to 0.20 | 0.17 | −0.92 | −1.91 to 0.07 | 0.06 |
| List Delay Recall (# words) | −0.18 | −0.42 to 0.07 | 0.15 | −0.38 | −0.74 to −0.02 | 0.04 |
| Paragraph 1 Imm. Recall (# pieces) | −0.16 | −0.74 to 0.41 | 0.57 | −0.38 | −1.24 to 0.47 | 0.37 |
| Paragraph 2 Imm. Recall (# pieces) | −0.25 | −0.77 to 0.27 | 0.34 | −0.36 | −1.14 to 0.42 | 0.35 |
| Paragraph 1 Delay Recall (# pieces) | −0.11 | −0.70 to 0.48 | 0.72 | −0.44 | −1.32 to 0.43 | 0.32 |
| Paragraph 2 Delay Recall (# pieces) | −0.29 | −0.80 to 0.22 | 0.26 | −0.47 | −1.24 to 0.30 | 0.22 |
| Executive Functioning | ||||||
| Verbal Fluency Raw | −1.68 | −3.19 to −0.17 | 0.03 | −2.69 | −4.96 to −0.41 | 0.02 |
| Stroop Interference | −1.87 | −3.55 to −0.19 | 0.03 | −3.30 | −5.79 to −0.82 | 0.01 |
Both models include age, sex, years of education, cirs-g, PTSD diagnosis, GAD, PSWQ-A, and PROMIS Depression as covariates.
Abbreviations: CI = Confidence interval; GAD= Generalized Anxiety Disorder; PROMIS = Patient-Reported Outcomes Measurement Information System; PSWQ-A= Abbreviated Penn State Worry Questionnaire; PTSD = Posttraumatic Stress Disorder; RBANS = Repeatable Battery for the Assessment of Neuropsychological Status; SS= Standard Score; Trauma β = estimated effect of Early Trauma Inventory Self Report- Short Form score on cognitive performance.
Cortisol and childhood trauma
To examine whether cortisol levels were explaining the association between childhood trauma and worse cognitive performance, we first examined the association between childhood trauma and cortisol level. The total number of events reported from the full childhood trauma inventory was not associated with higher peak (β = 0.06, 95% CI = −0.09; 0.20, p = 0.44) or area under the curve (β = 0.13, 95% CI = −0.73; 0.10, p = 0.76) cortisol. Trauma was also not associated with either peak or AUC cortisol when examining a composite of general, physical, or sexual traumas (p > 0.31).
Discussion
This cross-sectional study investigated the number of self-reported traumatic events experienced in childhood in relation to cognitive functioning in two samples of older adults. Childhood traumatic events were associated with worse attention and poorer executive functioning. These associations were independent of physical health, demographic variables, APOE ε4 genotype, and depressive and worry symptom severity. Furthermore, the effect of trauma on cognitive performance was larger for those reporting general, physical, or sexual trauma, compared to emotional abuse. This association was present in three different groups of older adults: older adults with GAD, psychiatrically healthy older adults, and older adults with anxiety or depressive disorders. These findings supported our initial hypothesis and were present in both the discovery and replication samples. Our second hypothesis was not supported, as the number of traumatic events in childhood was not associated with cortisol levels, and cortisol levels did not explain the association between childhood trauma and cognitive performance.
Early childhood trauma was not associated with current cortisol levels and cortisol did not explain the association between childhood trauma and worse cognitive performance, highlighting the potential importance of other physiological mechanisms. Prior research has also documented associations between childhood trauma and increased inflammation in older adulthood and documented functional and structural changes to the hippocampus and frontal cortex in younger adults47. Childhood trauma may affect neurotrophic factors such as Brain Derived Neurotrophic Factor48. As a result, upon entering older adulthood and experiencing age-related cognitive decline, individuals with childhood trauma may be at risk for greater declines in cognitive performance due to lower brain and/or cognitive reserve stemming from the potential adverse effects of childhood trauma on brain development.
Future studies need to examine the association between childhood trauma and physiological biomarkers further. The extent to which childhood trauma is associated with structural and functional neuroanatomy, inflammation, and neurotrophic factors in older adulthood are important unanswered questions. It is well established that depression is associated with worse cognitive performance in later life49, and a growing body of literature is demonstrating the association between anxiety and worse cognitive performance50, 51. Future research should also examine the extent to which childhood trauma mediates the association between anxiety and cognitive performance in later life. The extent to which childhood trauma is associated with structural and functional neuroanatomy in older adulthood is an important unanswered question that needs to be studied further. Lastly, future research needs to examine the role of resilience factors, such as coping style and cognitive hardiness52, in moderating this association.
This study has several limitations. Childhood trauma was measured with retrospective recall. It is possible that individuals who are particularly distressed, or more cognitively impaired, may exhibit a recall bias and be more likely to endorse traumatic events. Measures of biomarkers other than cortisol, such as inflammatory cytokines, neurotrophic factors, and neuroimaging, were not available, limiting the ability to examine other potential biological mechanisms. Third, although we controlled for diagnosis of PTSD, we did not have a measure of PTSD symptoms. Fourth, the cognitive and clinical measures were not uniform across both studies, although they assessed similar domains with similar tests. Fifth, we were unable to examine the modifying role of ethnicity, and past research has found that the role of early life adversity and cognitive performance in later life may be different for different racial groups12. Lastly, the cross-sectional design does not allow us to make conclusions of causality.
In conclusion, findings demonstrate the public health importance of preventing childhood trauma and developing interventions to help younger and older individuals with history of childhood trauma. Additionally, cortisol levels were not associated with childhood trauma, highlighting the importance of other possible physiological mechanisms.
Supplementary Material
Clinical points.
Childhood trauma is common and associated with poorer brain health, but the association between childhood trauma and cognitive performance in older adulthood is relatively unknown. Findings suggest that older patients with anxiety who have a history of childhood trauma may have worse processing speed, attention, and executive functioning than those without childhood trauma.
Podcast:
In this study, sponsored by the National Institute of Mental Health and the National Center for Complementary and Integrative Health, researchers found that number of retrospectively recalled number of traumatic events experienced in childhood was associated with worse cognitive performance in three groups of older adults: older adults with generalized anxiety disorder, psychiatrically healthy older adults, and older adults with anxiety or depressive disorders. Specifically, the cognitive domains most associated with childhood traumatic events were slower processing speed, worse atttention, and poorer executive functioning. Cortisol, a hormone associated with stress, was not explaining this association signifying the potential importance of other physiological factors. These results highlight the public health significance of childhood trauma and importance of developing interventions to prevent and treat the effects childhood trauma.
Acknowledgments
Sources of direct funding, support, or sponsorship: This work was supported by National Institute of Mental Health (R01 MH070547 to E.J.L; R01 MH072947 to M.A.B. P50 AG005133 (Pittsburgh), NIH R34 AT007064 from the National Center for Complementary and Alternative Medicine (St. Louis), NIH R34 AT007070 (San Diego), National Institutes of Health grant no. R01 AG037985, the Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448 from the National Center for Advancing Translational Sciences (NCATS), and the Taylor Family Institute for Innovative Psychiatric Research.
Footnotes
Role of the sponsor: The supporters had no role in the design, analysis, interpretation, or publication of this study.
Potential conflicts of interest: The authors have declared that there are no conflicts of interest in relation to the subject of the study.
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