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Outcome After Traumatic Brain Injury Sustained in Older Adulthood: A One-Year Longitudinal Study
Outcome After Traumatic Brain Injury Sustained in Older Adulthood: A One-Year Longitudinal Study Mark J. Rapoport, M.D., F.R.C.P.C., Nathan Herrmann, M.D., F.R.C.P.C., Prathiba Shammi, Ph.D., Alex Kiss, Ph.D., Andrea Phillips, B.A., Anthony Feinstein, M.Phil., Ph.D., M.R.C.Psych., F.R.C.P.C.
Objective: The objective of this study was to explore the effects of traumatic brain injury (TBI) on cognition and functioning in older adults in a one-year longitudinal study. Methods: Participants with mild-to-moderate TBI were compared with an age-, gender-, and education-matched healthy comparison group on aspects of cognition. Neuropsychologic tests were administered at one year. Self-reported measures of functioning were completed at baseline, six months, and one year. Informants rated instrumental functioning at one year. Results: Sixty-nine subjects aged 50 years and over (mean: 67 years; standard deviation: 7.9) and a comparison group of 79 participants were assessed. Patients with TBI had poorer processing speed, verbal memory, language, and executive function; they self-reported more psychologic distress, psychosocial dysfunction, and postconcussive symptoms; and they were rated as more impaired in functioning than the comparison group. TBI of moderate severity accounted for most of the between-group differences. Conclusion: TBI, particularly of moderate severity, led to poorer cognitive and psychosocial functioning one year postinjury among older adults. The clinical significance of this may become more evident with time in this vulnerable population. (Am J Geriatr Psychiatry 2006; 14: 456–465) Key Words: Traumatic Brain Injury, cognition, major depression
T
raumatic brain injury (TBI) occurs in roughly 1.5 million Americans1 annually. Although TBI is the most common neurologic cause of death in young adults, there is a second peak in TBI incidence in older adulthood,2 and TBI is often unrecognized
by clinicians. Older adults are more likely to have substantial disability and fatalities in the acute period compared with younger adults, even after milder injuries,3 although the age differences in outcome narrow by six months postinjury among those
Received February 8, 2005; revised October 27, 2005; accepted November 21, 2005. From Sunnybrook and Women’s College Health Sciences Centre, University of Toronto. Send correspondence and reprint requests to Mark Rapoport, MD, FRCPC, FG37-2075 Bayview Ave., Toronto, Ontario M4N 3M5, Canada. © 2006 American Association for Geriatric Psychiatry
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Rapoport et al. who survive.4 There are few prospective studies to date examining the consequences of TBI sustained in older adulthood. Cognitive deficits in the realms of attention, memory, and executive functioning have been well-documented in younger adults after TBI,5 and TBI has been linked in various epidemiologic studies to the later development of dementia.6 Prospective studies of cognitive sequelae of TBI in old age, however, have been limited by small sample sizes,7,8 shortterm follow up,9 sole reliance on informant report,7 variable length of follow up,7,10 absence of a control group,10 or failure to exclude those with premorbid cognitive decline.10 Prospective research into psychosocial outcome after TBI in older adults is similarly lacking. Nonetheless, there is some preliminary evidence in smaller samples that older adults have more mood disturbance and psychosocial dysfunction than agematched control subjects shortly after TBI.7,11 The purpose of the present study was to investigate the impact of mild and moderate TBI sustained in older adulthood on cognition, major depression, psychosocial dysfunction, psychologic distress, and postconcussive symptoms in the first year after TBI.
METHODS Subject Selection Cases. A consecutive sample of patients age 50 years and over attendinga TBI clinic was assessed within two months of their injury and followed prospectively for one year. Although this age range represents a “younger” spectrum of older patients, it is consistent with other studies of TBI in older adults.9,10 Patients who were seen through the emergency room and trauma ward for possible TBI were screened for assessment in the TBI Clinic and then for participation in the study. Mild TBI is defined as loss or alteration of consciousness at the time of injury for 20 minutes or less, an initial Glasgow Coma Score (GCS) of 13–15, and posttraumatic amnesia of less than 24 hours (PTA).12 Subjects with moderate TBI had a GCS of 9 –12 and a PTA of less than one week13 or met criteria for mild TBI but had an intracranial complication of TBI (e.g., contusion). Exclusion criteria were a preinjury history of neuro-
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logic disease, serious acute medical illness, schizophrenia, or bipolar disorder. Subjects with preexisting cognitive decline were excluded based on history and a score of ⬎3.38 on the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE).14 The IQCODE assesses cognitive decline over time according to an informant who has known the subject for at least 10 years. For the present study, the IQCODE was modified to indicate cognitive changes over 10 years before the injury, and it was administered at the first visit, i.e., within two months of injury, to avoid further retrospective informant recall bias. Most cases brought an informant with them;those who did not provided a contact and the IQCODE was given over the telephone. Fifty-two percent of informants were a spouse, 33.3% an adult child, and 14.7% were others. Patients unable to provide an informant were not included in the study. Comparison Group. Cases were compared with a community comparison group who were recruited from newspaper advertisements. An orthopedic comparison group was not chosen because previous research suggests that such subjects may have preexisting cognitive impairment.8 Furthermore, TBI is difficult to exclude definitively in patients with orthopedic injuries, and 55% of our TBI sample had orthopedic trauma. The comparison group was matched to the TBI group by age decade (i.e., 50 –59, 60 – 69, 70 –79), education group (i.e., less than 13 years of education or greater than or equal to 13 years of education), and gender. Each case was matched, using the three previously mentioned variables, with one member of the comparison group or more when available. Exclusion criteria were the same as that for cases. Because the comparison group was not asked to bring an informant, they provided the name of one and the IQCODE was conducted over the telephone. Thirty-nine percent of the comparison group informants were a spouse, 30.4% an adult child, and 30.6% were others. Ethics. The institutional ethics board approved the study, and participants provided written informed consent. Data Collection Demographic, Medical/Psychiatric, and Injury Variables. These were collected from a clinician’s review of the chart and discussion with the patient and
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Outcomes After TBI Sustained in Older Adulthood informant. Demographic information included age, gender, marital status, living situation, employment, educational history, substance history, and the presence or absence of a prior diagnosis of psychiatric disorder or family psychiatric disorder in a first- or second-degree relative. Medical history was coded using the Cumulative Illness Rating Scale (CIRS)15– severity subscale. Injury data for the cases, namely the mechanism of accident, loss of consciousness (LOC), GCS score at the time seen by physicians in the emergency room, duration of PTA (based on the patient’s recollection of events after the injury), other musculoskeletal injuries, and results of the brain computed tomography (CT) scans reported on by a radiologist (coded as yes/no regarding focal abnormalities, i.e., contusions, subarachnoid hematomas, subdural hematomas, and so on), were recorded. Self-Reported Outcome Measures. Self-report measures included the Rivermead Head Injury Follow-up Questionnaire (RHFQ),16 a validated instrument that gives a detailed description of psychosocial functioning post-TBI encompassing relationships, work, and domestic activities. Psychologic distress was measured using the General Health Questionnaire (GHQ)17 with questions pertaining to somatic distress, social dysfunction, anxiety, and depression. The Rivermead Post Concussion Disorder Questionnaire (RPDQ)18 has been validated in mild TBI19 and was used to measure physical and emotional symptoms commonly seen after TBI. A “somatic” subscale was created to exclude those symptoms that overlap with major depression (e.g., insomnia, irritability) and only include those related to physical symptoms (e.g., headaches, dizziness). Additionally, at one year postinjury (or enrollment for control subjects), subjects were asked whether they were having memory problems that were worse than before the injury and worse than their age peers. Depression. Participants were assessed for the presence of a major depressive episode using the depression module of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) axis I disorders (SCID).20 DSM criteria are considered reliable and valid in TBI samples.21 Subsyndromal depression was also assessed using the criteria of a minimum of three DSM–IV symptoms of a major depressive episode, at least one of which is persistent depressed
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mood or anhedonia, lasting for at least two weeks.22 At baseline, 10 (14.5%) of the cases and three (4%) of the comparison group were taking an antidepressant; and one (1.5%) of the cases and two (2.6%) of the comparison group were taking a benzodiazepine. Formal Cognitive Outcome Measures. A cognitive battery was selected to demonstrate cognitive deficits consistent with TBI and/or dementia. The Mattis Dementia Rating Scale (DRS)23 and the Mini-Mental Status examination (MMSE)24 were used as overall measures of cognitive impairment. Attention and working memory were assessed using the WAIS-III (WAIS-III)24 Digit Span subtest. The WAIS III Digit Symbol subtest was used as an index of processing speed. Verbal memory was assessed using logical memory total delayed recall of both stories from the Wechsler Memory Scale-III (WMS-III)25 and the long-delay free recall score of the California Verbal Learning Test (CVLT).26 Visual memory was assessed using the delayed recall from the Rey-Osterrieth Complex Figure Test (RCFT).27 Language was assessed using the Boston Naming Test (BNT) total score.28 Executive function was assessed using the Controlled Oral Word Association Test (COWAT)28 and the Wisconsin Card Sort Test (WCST) total categories completed and perseverative responses.29 A WAIS-III vocabulary total score of greater than or equal to the 14th percentile was used as an index of fluency in English. Informant Ratings. Informant ratings of instrumental activities of daily living (IADLs) were provided using the Functional Activities Questionnaire (FAQ).30 The FAQ was developed to assess IADLs in early Alzheimer dementia (AD) and has been shown to predict conversion to AD among older adults with mild cognitive impairment.31 Timing of Outcome Assessments. Participants were first seen within two months of injury and had follow-up assessments one year (12 months⫾ 2) postinjury. Six months postinjury (⫾1), self-report questionnaires were mailed to all subjects for completion. The comparison group was enrolled at baseline and followed up at the same time points postenrollment as the cases. Demographic, medical/psychiatric, and injury variables were collected at the baseline visit. At baseline and one year, major depression was assessed and the MMSE administered. Self-reported measures of functioning were completed at baseline, six months, and one year. Neuropsychologic tests
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Rapoport et al. and IADL assessments were administered at one year. Baseline cognitive testing was limited to the MMSE because the goal of the study was to look at long-term implications of TBI. Furthermore, in the period after TBI, cognitive impact is common and patients may still exhibit PTA.
Statistics Baseline Variables. Demographic and past illness variables were compared between patients with and without TBI. For continuous variables, a repeatedmeasures analysis of variance was used to compare the group differences accounting for the matched nature of the cases and control subjects, whereas for categorical variables, a generalized linear model was used to compare the group differences, once again accounting for the matched nature of cases and control subjects. t tests and chi-squared tests were used to compare the background variables between subjects who dropped out of the study before one year with those who remained. Self-Report and Informant-Report Measures. Repeated-measures analyses of covariance (ANCOVAs) were conducted to assess the relationship betweengroup (case versus comparison group) and the selfreport outcome measures as well as the interaction of group with time controlling for age, gender, and baseline MMSE. Paired comparisons were used to compare the informant ratings of cases and the comparison group on the FAQ at one year as well as to compare the presence of cognitive complaints between groups at one year. Because there were five self-/informant-report measures administered, a Bonferroni correction of 0.05/5 tests was applied, yielding a critical value of 0.01 for the self- and informant-report measures. Cognitive Evaluation. Cases and the comparison group were compared on performance on the individual cognitive tests using a repeated-measures analysis of variance accounting for the matched nature of the cases and control subjects. A Bonferroni correction of 0.05/11 tests was applied to the cognitive measures, yielding a critical p value of 0.0045 for the cognitive tests. Repeated-measures ANCOVA was then used to compare the performance of cases and comparison group on the individual cognitive tests controlling for age, sex, education, and severity
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of comorbid medical illnesses (CIRS severity index). Because the measures of language, memory, and executive dysfunction were strongly based on the English language, we repeated the ANCOVAs on those measures in a subgroup in whom English was their first language. Pearson’s correlation was conducted to investigate the relationship between self-reported and cognitive outcome measures. Role of Injury Severity. Post hoc Scheffe’s tests were used to examine whether the performance on cognitive tests, self-report measures, or ratings on the FAQ differences were between cases and mild TBI and between cases and moderate TBI. RESULTS Subjects. Seven hundred fifteen patients who were seen through the emergency room and trauma ward for possible TBI were screened for assessment in the TBI Clinic and then for participation in the study. After refusals and exclusions (Figure 1), 69 cases with TBI were included in the study at baseline. At baseline, 1.5% of cases were matched to three control subjects, 9% to two control subjects, and 89% to one control subject. There were three cases that were unmatched. Analysis included all cases but treated the matched ones as correlated observations. By one year, 20 of the subjects had been lost to attrition, and 49 (71.0%) remained (Figure 1). Ninetyfour control subjects were recruited through newspaper advertisements, and 78 were matched to the subjects and included in the study. Ten members of the comparison group dropped out by one year, whereas 68 (87.1%) remained (Figure 1). For the subjects with TBI, 37 (53.6%) had mild TBI. The remaining 32 (46.4%) of subjects had moderate TBI, 18 (26.1%) of whom would have met mild criteria but for intracranial abnormalities on CT. Of those subjects with “mild TBI,” 15 (40.5%) did not undergo a CT scan, 15 (40.5%) were found to have a negative CT, three (8%) had general atrophy, three (8%) had atrophy with incidental white matter changes, and one (2.7%) had incidental lacunar infarct. Of those with “complicated mild TBI,” CT scan results demonstrated two (11%) with subarachnoid hematomas, five (27.8%) with subdural hematomas, two (11%) with contusions, seven (38.9%) with injuries at multiple sites, one (5.6%) had general atrophy,
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Outcomes After TBI Sustained in Older Adulthood and one (5.6%) had epidural or sphenoid. Of the moderate TBI subjects, one (7%) had a negative CT scan, two (14.3%) had contusions, eight (57%) had injuries at multiple sites, two (14.3%) had general atrophy, and one (7%) had epidural or sphenoid hematomas. The mechanism of injury was related to falls in 35 (50.7%), motor vehicle accidents in 14 (20.3%), and “other” in 20 (29%). Thirty-eight (55.1%) had other significant injuries, either fractures or intraabdominal injuries. There were no differences in severity or mechanism of injury or of associated other injuries between those who remained in the study at one year (N⫽49) and those who were lost to attrition (N ⫽20).
FIGURE 1.
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Comparison of Background Variables There were no differences between cases and the comparison group in background variables (Table 1). Among those who remained in the study at one year, the comparison group had on average one year higher education than cases (mean: 14.07; standard deviation [SD]: 3.0 versus 12.53; SD: 4.0, respectively, F[1,116] ⫽5.73, p⫽0.019). Compared with those lost to attrition (N⫽ 31), subjects who remained in the study at one year (N ⫽117 cases and comparison group) were more likely to be female (57.3% versus 32.3%, 2[1] ⫽6.14, p ⬍0.05) and to have a psychiatric history (35.9% versus 6.5%, Fisher exact test, p ⬍0.001), but there were no other differences in the
Subject Flow Sheet
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TABLE 1.
Comparison of Baseline Variables
Age in years Male gender Unattached marital status (single, divorced widowed) IQCODE More than 13 years of education Mini-Mental Status Examination CIRS severity index CIRS cardiovascular respiratory illness severity Has had a mild traumatic brain injury in the remote past Has had a psychiatric history Has a family psychiatric history Time seen at one year postinjury
Cases (N ⴝ 69)
Comparison Group (N ⴝ 79)
Statistics, Significance
Mean: 67.00 (SD: 7.9) 33 (47.8%)
Mean: 68.04 (SD: 8.5) 38 (48.1%)
F(1,65) ⫽ 0.23, p ⫽ 0.63 2(1) ⫽ 0.14, p ⫽ 0.71
21 (30.4%) Mean: 2.98 (SD: 0.3) 35 (50.7%) Mean: 27.75 (SD: 2.2) Mean: 1.46 (SD: 0.6)
28 (35.4%) Mean: 3.00 (SD: 0.33) 46 (58.2%) Mean: 29.20 (SD: 1.1) Mean: 1.44 (SD: 0.6)
2(1) ⫽ 0.17, p ⫽ 0.68 F(1,65) ⫽ 0.25, p ⫽ 0.62 2(1) ⫽ 0.28, p ⫽ 0.59 F(1,64) ⫽ 26.23, p ⬍0.0001 F(1,65) ⫽ 0.01, p ⫽ 0.96
17 (24.6%)
13 (16.5%)
F(1,65) ⫽ 2.02, p ⫽ 0.16
8 (11.8%) 18 (26.1%) 18 (26.1%) Mean: 402.53 (SD: 57.3) (N ⫽ 49)
5 (6.3%) 26 (32.9%) 30 (38.0%) Mean: 386.47 (SD: 24.51) (N ⫽ 68)
2(1) ⫽ 2.94, p ⫽ 0.09 2(1) ⫽ 1.07, p ⫽ 0.30 2(1) ⫽ 3.52, p ⫽ 0.06 F(1,65) ⫽ 2.02, p ⫽ 0.16
SD: Standard deviation; CIRS: Cumulative Illness Rating Scale; IQCODE: Informant Questionnaire for Cognitive Decline in the Elderly.
other background variables, and no differences between cases and comparison group in gender and psychiatric history at one year. Self-Reported Outcome The TBI group reported substantially higher levels of difficulty on the self-report instruments compared with the comparison group, controlling for age, gen-
TABLE 2.
der, and MMSE (Table 2). The results for RPDQ were unchanged using the “somatic” subscale. Post hoc analysis indicated differences at baseline between mild TBI and comparison group and between moderate TBI and comparison group. By the six-month and one-year assessments, mild and moderate TBI differed from the comparison group on RPDQ and somatic subscales, but only moderate TBI differed
Self-Reported Outcome Cases Mean (SD)
General Health Questionnaire (GHQ) (range: 0–28) Baseline Six months One year Rivermead Head Injury Follow up (RHFQ) (range: 0–48) Baseline Six months One year Rivermead Postconcussive Symptoms (RPDQ) (range: 0–72) Baseline Six months One year
8.71 (7.6), N ⫽ 63 5.77 (6.6), N ⫽ 43 4.35 (5.8), N ⫽ 46
Comparison Group Mean (SD)
1.00 (2.3), N ⫽ 79 1.92 (3.8), N ⫽ 61 1.48 (3.4), N ⫽ 67
13.95 (11.7), N ⫽ 63 12.37 (11.1), N ⫽ 43 11.24 (11.7), N ⫽ 45
2.59 (3.8), N ⫽ 79 4.85 (6.3), N ⫽ 61 4.81 (7.0), N ⫽ 67
19.25 (16.2), N ⫽ 64 18.37 (16.2), N ⫽ 41 18.31 (19.6), N ⫽ 45
1.65 (4.8), N ⫽ 79 5.02 (8.7), N ⫽ 60 4.24 (8.9), N ⫽ 67
Repeated-Measures ANCOVA Controlling for Age, Gender, and MMSE TBI: F1,349 ⫽ 30.4, p ⬍0.0001 TBI ⫻ time: F2,349 ⫽ 9.45, p ⫽ 0.0001
TBI: F1,347 ⫽ 36.6, p ⬍0.0001 TBI ⫻ time: F2,347 ⫽ 3.02, p ⫽ 0.05
TBI: F1,345 ⫽ 59.7, p ⬍0.0001 TBI ⫻ time: F2,345 ⫽ 1.26, p ⫽ 0.29
SD: Standard deviation; ANCOVA: analysis of covariance; MMSE: Mini-Mental Status Examination; TBI: traumatic brain injury.
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Outcomes After TBI Sustained in Older Adulthood from the comparison group on RHFQ and GHQ. Thirteen of the 20 (65.0%) cases with moderate TBI, 12 of the 29 (41.4%) mild TBI cases, and only 12 of the 68 (17.3%) in the comparison group had subjective cognitive complaints at one year (2[1]⫽6.81, p⫽ 0.009). Depression At baseline, 11 of the 69 cases (15.9%) and none of the comparison group had an episode of major depression (2[1]⫽12.23 p⫽0.003). Fifteen cases (21.7%) and three in the comparison group (3.8%) had subsyndromal depression (2[1]⫽9.28, p⫽ 0.002). One year postinjury, six of the 49 patients with TBI (12.2%) (two mild TBI and four moderate
TABLE 3.
TBI) and only one of the 68 in the comparison group (1.5%) met criteria for a major depressive episode (2[1] ⫽4.03, p⫽ 0.04). Nine cases (18.8%) and two in the comparison group (2.9%) met criteria for subsyndromal depression (2[1] ⫽6.26, p⫽0.01). Five of the 11 patients with TBI with major depression at baseline also met criteria at one year, and conversely, five of the six patients with TBI with major depression at one year also had major depression at the baseline postinjury visit. Formal Cognitive Outcome. Patients with TBI had significantly worse performance than the comparison group at one year on the DRS, tests of processing speed and language, and on the COWAT (all p ⬍0.0045, see Table 3). The cases also had poorer
Cognitive Outcome Case
Comparison Group
Statistics
Statistics
Mean (SD) (N ⴝ 68)
Repeated-measures ANOVA
Repeated-measures ANCOVAa
135.38 (8.5) (N ⫽ 48) 28.19 (1.9) (N ⫽ 48)
139.0 (3.7)
F(1,42) ⫽ 9.61, p ⫽ 0.0035
F(1,42) ⴝ 10.82, p ⴝ 0.002
29.07 (1.2)
F(1,42) ⫽ 8.37, p ⫽ 0.006
F(1,42) ⴝ 9.33, p ⴝ 0.004
15.54 (4.7) (N ⫽ 48)
17.85 (4.4)
F(1,42) ⫽ 6.7, p ⫽ 0.01
F(1,42) ⫽ 7.04, p ⫽ 0.01
48.44 (19.4) (N ⫽ 45)
58.78 (13.7)
F(1,40) ⫽ 10.82, p ⫽ 0.002
F(1,40) ⫽ 14.97, p ⫽ 0.0004
25.20 (7.7) (N ⫽ 46)
29.31 (7.2)
F(1,40) ⫽ 8.71, p ⫽ 0.005
F(1,40) ⴝ 10.27, p ⴝ 0.003
9.68 (3.5) (N ⫽ 47)
11.48 (3.1)
F(1,41) ⫽ 5.8, p ⫽ 0.02
F(1,41) ⫽ 9.66, p ⫽ 0.003
13.36 (6.9) (N ⫽ 43)
13.63 (6.1)
F(1,38) ⫽ 0.15, NS
F(1,38) ⫽ 0.1, NS
47.19 (11.3) (N ⫽ 47)
54.87 (4.8)
F(1,41) ⫽ 24.60, p ⬍0.0001
F(1,41) ⫽ 24.68, p ⬍0.0001
33.02 (14.7) (N ⫽ 46) 3.98 (2) (N ⫽ 43) 31.33 (24.6) (N ⫽ 43)
42.72 (12.5)
F(1,40) ⫽ 11.2, p ⫽ 0.002
F(1,40) ⫽ 12.08, p ⫽ 0.001
4.84 (1.6)
F(1,37) ⫽ 7.02, p ⫽ 0.01
F(1,37) ⴝ 10.41, p ⴝ 0.003
20.75 (18.6)
F(1,37) ⫽ 7.5, p ⫽ 0.009
F(1,37) ⫽ 9.08, p ⫽ 0.005
Mean (SD) General cognitive tests Dementia Rating Scale Mini-Mental State Examination Attention/ working memory Digit span Processing speed Digit symbol Verbal memory Wechsler Memory Scale III CVLT long delay free recall Visual memory Rey-Osterrieth Complex Figure–delay Language Boston Naming Test Executive functioning COWAT WCST total categories completed WCST perseverative responses a
ANCOVA controlling for age, gender, education, and Cumulative Illness Rating Scale severity score. SD: Standard deviation; ANOVA: analysis of variance; ANCOVA: analysis of covariance; CVLT: California Verbal Learning Test; COWAT: Controlled Oral Word Association Test; WCST: Wisconsin Card Sort Test; NS: not significant.
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Rapoport et al. performance on the MMSE, both tests of verbal memory, the digit span, and on the WCST, although these differences were of marginal significance (p between 0.05 and 0.0045, see Table 3). Post hoc comparisons indicated these cognitive differences to be present between patients with moderate TBI and the comparison group but not between mild TBI and the comparison group. Sample size precludes analysis comparing mild, complicated mild, and moderate TBI with control subjects. Once we controlled for age, gender, education, and severity of medical comorbidities, the cases still had significantly worse performance than the comparison group on processing speed, CVLT delayed recall, language, and COWAT (all p ⬍0.0045, see Table 3). Visual memory was not significant. The remaining tests were marginally worse in cases than the comparison group (p between 0.05 and 0.005, see Table 3). Because the measures of language, memory, and executive functioning are heavily reliant on the English language, these ANCOVAs were compared again in only those subjects fully fluent in English (39 cases and 68 of the comparison group). On controlling for age, gender, education, and medical comorbidities in this “English-fluent” subgroup, cases had significantly worse performance than controls on the MMSE and DRS, as well as on the digit symbol, both tests of verbal memory, the BNT, the COWAT, and the total score on the WCST (see Table 3). Relationship Between Self-Report and Cognitive Outcome. At one year, the self-reported instruments (GDS, GHQ, RPDQ, and RHFQ) were each correlated moderately (ranging from r ⫽0.243 to r ⫽0.49, p ⬍0.01) with all cognitive measures except MMSE, CVLT long delay free-recall, the Rey-Osterreith Complex Figure test, and the WCST subscales. The COWAT was only significantly associated with the RPDQ (r⫽0.25, p⫽0.01) and RHFQ (r ⫽0.24, p⫽ 0.01). Informant Ratings. At one year postinjury, informants rated the cases as having poorer performance in IADL than the comparison group (FAQ mean: 2.98; SD: 4.9 versus 0.38, SD: 1.5, respectively, t[59]⫽ 5.94, p ⬍0.0001. Post hoc comparison indicated that moderate TBI, but not mild TBI cases, were rated as having poorer IADLs.
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DISCUSSION The present report is the first one-year prospective cohort study of TBI sustained in older adulthood to examine detailed aspects of functioning and cognition. Older adults with TBI reported significantly higher levels of psychosocial dysfunction, psychologic distress, and postconcussive symptoms than those in the comparison group, and were more likely to subjectively report cognitive complaints and to meet criteria for major depression or subsyndromal depression than those in the comparison group. Although cognition was assessed in detail one year postinjury, a point at which most younger patients have improved, the cases had lower scores on verbal memory, language, processing speed, and frontal/ executive functioning than the comparison group, and informants rated them as having more difficulty with IADLs than the comparison group. Post hoc analyses indicated that most of the cognitive, selfreported, and informant-rated differences lay between those with moderate TBI and the comparison group. The presence of persisting differences in cognition after moderate TBI has been well-documented in younger patients.32 Memory and executive dysfunction have been previously demonstrated in older patients with moderate but not mild TBI as compared with the comparison group in a smaller sample of patients assessed within two months of injury.9 Severity of TBI is a significant factor in the development of cognitive deficits postinjury.33 Betaamyloid deposition has been shown after fatal severe TBI,34 a protein that may initiate the cascade of pathologic processes of AD,35 particularly in patients who are vulnerable to AD by virtue of advanced age. The demonstration of significant differences in cognition and functioning between patients with TBI and a comparison group at one year postinjury may be a harbinger of more significant decline in the years to come, and a longer duration of follow up is needed. Furthermore, cognitive outcome showed moderate correlations with self-reported outcome in this sample, highlighting the important interplay between cognitive and psychosocial functioning after TBI.
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Outcomes After TBI Sustained in Older Adulthood Although low levels of postconcussive symptoms, psychologic distress, and psychosocial dysfunction were reported by the patients with TBI in the present sample, their rates were higher than in the comparison group, and this difference was most robust for postconcussive symptoms among those with mild and moderate TBI compared with the comparison group. Postconcussive symptoms are a major cause of morbidity in the TBI population, and the pathophysiology has been elusive. In the present sample, older patients with TBI had higher rates of major depression than the comparison group. That the rate of major depression was much lower than the 33% incidence reported in the largest longitudinal evaluation of younger adults36 is consistent with our previous report of lower incidence of major depression among older than younger adults after TBI.37 TBI has been associated with serotonergic dysfunction,38 and this, together with the psychosocial impact of the injury and premorbid factors likely plays a role in the development of depression postTBI. The strengths of this investigation are that it is the largest prospective study to date of outcome after TBI in older adulthood. Subjects were all seen at baseline within two months of injury to ensure valid collection of injury, demographic, and previous illness history. Subjects with premorbid cognitive decline were carefully screened and excluded. A detailed cognitive examination was done at a set time one year postinjury using well-validated neuropsychologic tests assessing an array of cognitive skills. Domains of psychosocial dysfunction, psychologic distress, and postconcussive symptoms were similarly assessed at fixed time points postinjury, and informant report was elicited. Whereas previous studies of mood disturbance post-TBI in older adults have used continuous subjective rating scales, the present study incorporates a categorical assessment of mood was conducted by experienced clinicians using DSM criteria. We incorporated a comparison group matched for demographic variables and controlled for confounds of age, gender, education, and medical illness severity. Limitations of the study include potential for recruitment and attrition biases. The present sample of
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patients seen through the emergency department and trauma wards may not be representative of much of the mild TBI in the community, which is often unrecognized and for which patients do not often present to the hospital. It has been shown previously that those who consent to participation in TBI research may have subtly more severe injuries than those who refuse, even among “mild” TBI.39 Furthermore, the present “older” sample is much younger than the population of “elderly” in the community. Although an older sample may have been less likely to demonstrate resilience after such injuries, much research on TBI in older adults focuses on the age group of 50 plus,9,10 and as such, our research is comparable. Attrition may be a similar bias, like in the present sample, those who remained in the study were more likely to be female and have a psychiatric history than those who dropped out. However, the 71% follow-up rate in the present sample is higher than most longitudinal studies of TBI in younger adults.40 The potential limitation of the inclusion of patients who have English as a second language was addressed by excluding those not fluent from analysis of language-sensitive cognitive measures. When these subjects were excluded, the between-group differences remained. Also, although there were no differences between cases and the comparison group on overall severity of cardiorespiratory illness, data were not collected on cerebrovascular risk factors, and this remains a potential confound here. The present report shows TBI, particularly moderate TBI, in older adults to be related to major depression, informant- and self-rated difficulties, as well as cognitive difficulties relative to a comparison group. Cognitive and functional disruption from TBI may be at its initial peak shortly after injury, yet after the usual recovery period, older patients may be at a lower baseline threshold of “cognitive reserve,”35 and clinically significant differences may become even more evident as time passes. This study was supported by the Ontario Neurotrauma Foundation. Preliminary data from this investigation was presented at the American Psychiatric Association 157th Annual Meeting, May 1– 6, 2003, New York, NY, and the International Psychogeriatric Association 11th Annual Congress, August 18, 3003, Chicago.
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Rapoport et al. References 1. Sosin DM, Sniezek JE, Thurman DJ: Incidence of mild and moderate brain injury in the United States, 1991. Brain Inj 1996; 10:47–54 2. Silver JM, Hales RE, Yudofsky SC: Neuropsychiatric aspects of TBI, in Synopsis of Neuropsychiatry. Edited by Yudofsky SC, Hales RE. Washington, DC, American Psychiatric Press, Inc, 1994, pp 279–306 3. Rothweiler B, Temkin NR, Dikmen SS: Aging effect on psychosocial outcome in TBI. Arch Phys Med Rehabil 1998; 79:881–887 4. Mosenthal AC, Livingston DH, Lavery RF, et al: The effect of age on functional outcome in mild TBI: 6-month report of a prospective multicenter trial. J Trauma 2004; 56:1042–1048 5. McCullagh S, Feinstein M: Cognitive impairment following TBI, in Neuropsychiatry of TBI. Edited by McAllistar T, Silver J. Washington, DC, APP Press, 2004 6. Fleminger S, Oliver DL, Lovestone S, et al: Head injury as a risk factor for Alzheimer’s disease: the evidence 10 years on; a partial replication. J Neurol Neurosurg Psychiatry 2003; 74:857–862 7. Goldstein FC, Levin HS, Goldman WP, et al: Cognitive and behavioral sequelae of closed head injury in older adults according to their significant others. J Neuropsychiatry Clin Neurosci 1999; 11:38–44 8. Aharon-Peretz J, Kliot D, Amyel-Zvi E, et al: Neurobehavioral consequences of closed head injury in the elderly. Brain Inj 1997; 11:871–875 9. Goldstein FC, Levin HS, Goldman WP, et al: Cognitive and neurobehavioral functioning after mild versus moderate TBI in older adults. J Int Neuropsychol Soc 2001; 7:373–383 10. Mazzucchi A, Cattelani R, Missale G, et al: Head-injured subjects aged over 50 years: correlations between variables of trauma and neuropsychological follow-up. J Neurol 1992; 239:256–260 11. Goldstein FC, Levin HS, Presley RM, et al: Neurobehavioural consequences of closed head injury in older adults. J Neurol Neurosurg Psychiatry 1994; 57:961–966 12. Kay T, Harrington DE, Adams R, et al: Definition of mild TBI. J Head Trauma Rehabil 1993; 8:86–87 13. Dikmen SS, Levin HS: Methodological issues in the study of mild head injury. J Head Trauma Rehabil 1993; 8:30–37 14. Jorm AF, Scott R, Cullen JS, et al: Performance of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a screening test for dementia. Psychol Med 1991; 21:785–790 15. Miller MD, Paradis CF, Houck PR, et al: Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale. Psychiatry Res 1992; 41:237–248 16. Crawford S, Wenden FJ, Wade DT: The Rivermead head injury follow up questionnaire: a study of a new rating scale and other measures to evaluate outcome after head injury. J Neurol Neurosurg Psychiatry 1996; 60:510–514 17. Goldberg DP, Hillier VF: A scaled version of the General Health Questionnaire. Psychol Med 1979; 9:139–145 18. King NS, Crawford S, Wenden FJ, et al: The Rivermead Post Concussion Symptoms Questionnaire: a measure of symptoms commonly experienced after head injury and its reliability. J Neurol 1995; 242:587–592 19. Ingebrigtsen T, Waterloo K, Marup-Jensen S, et al: Quantification of post-concussion symptoms 3 months after minor head injury in 100 consecutive patients. J Neurol 1998; 245:609–612 20. First MB, Spitzer RL, Gibbon M, et al: Structured Clinical Interview for DSM–IV Diagnoses (SCID): Clinician and Research Ver-
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sions. New York, Biometrics Research Department, Columbia University, 1996 21. Jorge RE, Robinson RG, Arndt S: Are there symptoms that are specific for depressed mood in patients with traumatic brain injury? J Nerv Ment Dis 1993; 181:91–99 22. Lavretsky H, Kumar A: Clinically significant non-major depression: old concepts, new insights. Am J Geriatr Psychiatry 2002; 10:239–255 23. Mattis S: Mental status examination for organic mental syndrome in the elderly patient, in Geriatric Psychiatry: A Handbook for Psychiatrists and Primary Care Physicians. Edited by Bellak L, Karasu T. New York, Grune & Stratton, 1976, pp 77–101 24. Folstein MF, Folstein SE, McHugh PR: ‘Mini-mental state.’ A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12:189–198 25. Psychological Corporation: Wechsler Adult Intelligence Scale: Technical Manual, 3rd ed. San Antonio, Harcourt Brace Jovanovich & Co, 1997 26. Delis DC, Kramer JH, Kaplan E, et al: California Verbal Learning Test: Adult Version Manual. San Antonio, TX, The Psychological Corp, 1987 27. Corwin J, Bylsma FW: Psychological examination of traumatic encephalopathy. Edited by Rey A, Osterrieth PA. The Complex Figure Copy Test. Clinical Neuropsychologist 1993; 7:3–21 28. Spreen O, Strauss E: A Compendium of Neuropsychological Tests. Administration, Norms and Commentary. New York, Oxford University Press, 1998 29. Heaton RK, Chelune GJ, Talley JL, et al: Wisconsin Card Sorting Test (WCST) Manual Revised and Expanded. Odessa, FL, Psychological Assessment Resources, 1993 30. Pfeffer RI, Kurosaki TT, Harrah CH, et al: Measurement of functional activities in older adults in the community. J Gerontol 1982; 37:323–329 31. Tabert MH, Albert SM, Borukhova-Milov L, et al: Functional deficits in patients with mild cognitive impairment: prediction of AD. Neurology 2002; 58:758–764 32. Rimel RW, Giordani B, Barth JT, et al: Moderate head injury: completing the clinical spectrum of brain trauma. Neurosurgery 1982; 11:344–351 33. Rapoport M, McCauley S, Levin H, et al: The role of injury severity in neurobehavioral outcome 3 months after TBI. Neuropsychiatry Neuropsychol Behav Neurol 2002; 15:123–132 34. Nicoll JA, Roberts GW, Graham DI: Apolipoprotein E epsilon 4 allele is associated with deposition of amyloid beta-protein following head injury. Nat Med 1995; 1:135–137 35. Lye TC, Shores EA: Traumatic brain injury as a risk factor for Alzheimer’s disease: a review. Neuropsychol Rev 2000; 10:115– 129 36. Jorge RE, Robinson RG, Moser D, et al: Major depression following traumatic brain injury. Arch Gen Psychiatry 2004; 61:42–50 37. Rapoport M, McCullagh S, Streiner D, et al: Age and major depression following mild traumatic brain injury. Am J Geriatr Psychiatry 2002; 11:365–369 38. Nayak AK, Mohanty S, Singh RK, et al: Plasma biogenic amines in head injury. J Neurol Sci 1980; 47:211–219 39. McCullagh S, Feinstein A: Outcome after mild traumatic brain injury: an examination of recruitment bias. J Neurol Neurosurg Psychiatry 2003; 74:39–43 40. McCullagh S, Kamkar K, Jardine A, et al: An examination of the high drop-out rate in studies of patients with mild traumatic brain injury. J Neuropsychiatry Clin Neurosci 2002; 14:116–117
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Objective: The objective of this study was to explore the effects of traumatic brain injury (TBI) on cognition and functioning in older adults in a one-year longitudinal study. Methods: Participants with mild-to-moderate TBI were compared with an age-, gender-, and education-matched healthy comparison group on aspects of cognition. Neuropsychologic tests were administered at one year. Self-reported measures of functioning were completed at baseline, six months, and one year. Informants rated instrumental functioning at one year. Results: Sixty-nine subjects aged 50 years and over (mean: 67 years; standard deviation: 7.9) and a comparison group of 79 participants were assessed. Patients with TBI had poorer processing speed, verbal memory, language, and executive function; they self-reported more psychologic distress, psychosocial dysfunction, and postconcussive symptoms; and they were rated as more impaired in functioning than the comparison group. TBI of moderate severity accounted for most of the between-group differences. Conclusion: TBI, particularly of moderate severity, led to poorer cognitive and psychosocial functioning one year postinjury among older adults. The clinical significance of this may become more evident with time in this vulnerable population. (Am J Geriatr Psychiatry 2006; 14: 456–465) Key Words: Traumatic Brain Injury, cognition, major depression
T
raumatic brain injury (TBI) occurs in roughly 1.5 million Americans1 annually. Although TBI is the most common neurologic cause of death in young adults, there is a second peak in TBI incidence in older adulthood,2 and TBI is often unrecognized
by clinicians. Older adults are more likely to have substantial disability and fatalities in the acute period compared with younger adults, even after milder injuries,3 although the age differences in outcome narrow by six months postinjury among those
Received February 8, 2005; revised October 27, 2005; accepted November 21, 2005. From Sunnybrook and Women’s College Health Sciences Centre, University of Toronto. Send correspondence and reprint requests to Mark Rapoport, MD, FRCPC, FG37-2075 Bayview Ave., Toronto, Ontario M4N 3M5, Canada. © 2006 American Association for Geriatric Psychiatry
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Rapoport et al. who survive.4 There are few prospective studies to date examining the consequences of TBI sustained in older adulthood. Cognitive deficits in the realms of attention, memory, and executive functioning have been well-documented in younger adults after TBI,5 and TBI has been linked in various epidemiologic studies to the later development of dementia.6 Prospective studies of cognitive sequelae of TBI in old age, however, have been limited by small sample sizes,7,8 shortterm follow up,9 sole reliance on informant report,7 variable length of follow up,7,10 absence of a control group,10 or failure to exclude those with premorbid cognitive decline.10 Prospective research into psychosocial outcome after TBI in older adults is similarly lacking. Nonetheless, there is some preliminary evidence in smaller samples that older adults have more mood disturbance and psychosocial dysfunction than agematched control subjects shortly after TBI.7,11 The purpose of the present study was to investigate the impact of mild and moderate TBI sustained in older adulthood on cognition, major depression, psychosocial dysfunction, psychologic distress, and postconcussive symptoms in the first year after TBI.
METHODS Subject Selection Cases. A consecutive sample of patients age 50 years and over attendinga TBI clinic was assessed within two months of their injury and followed prospectively for one year. Although this age range represents a “younger” spectrum of older patients, it is consistent with other studies of TBI in older adults.9,10 Patients who were seen through the emergency room and trauma ward for possible TBI were screened for assessment in the TBI Clinic and then for participation in the study. Mild TBI is defined as loss or alteration of consciousness at the time of injury for 20 minutes or less, an initial Glasgow Coma Score (GCS) of 13–15, and posttraumatic amnesia of less than 24 hours (PTA).12 Subjects with moderate TBI had a GCS of 9 –12 and a PTA of less than one week13 or met criteria for mild TBI but had an intracranial complication of TBI (e.g., contusion). Exclusion criteria were a preinjury history of neuro-
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logic disease, serious acute medical illness, schizophrenia, or bipolar disorder. Subjects with preexisting cognitive decline were excluded based on history and a score of ⬎3.38 on the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE).14 The IQCODE assesses cognitive decline over time according to an informant who has known the subject for at least 10 years. For the present study, the IQCODE was modified to indicate cognitive changes over 10 years before the injury, and it was administered at the first visit, i.e., within two months of injury, to avoid further retrospective informant recall bias. Most cases brought an informant with them;those who did not provided a contact and the IQCODE was given over the telephone. Fifty-two percent of informants were a spouse, 33.3% an adult child, and 14.7% were others. Patients unable to provide an informant were not included in the study. Comparison Group. Cases were compared with a community comparison group who were recruited from newspaper advertisements. An orthopedic comparison group was not chosen because previous research suggests that such subjects may have preexisting cognitive impairment.8 Furthermore, TBI is difficult to exclude definitively in patients with orthopedic injuries, and 55% of our TBI sample had orthopedic trauma. The comparison group was matched to the TBI group by age decade (i.e., 50 –59, 60 – 69, 70 –79), education group (i.e., less than 13 years of education or greater than or equal to 13 years of education), and gender. Each case was matched, using the three previously mentioned variables, with one member of the comparison group or more when available. Exclusion criteria were the same as that for cases. Because the comparison group was not asked to bring an informant, they provided the name of one and the IQCODE was conducted over the telephone. Thirty-nine percent of the comparison group informants were a spouse, 30.4% an adult child, and 30.6% were others. Ethics. The institutional ethics board approved the study, and participants provided written informed consent. Data Collection Demographic, Medical/Psychiatric, and Injury Variables. These were collected from a clinician’s review of the chart and discussion with the patient and
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Outcomes After TBI Sustained in Older Adulthood informant. Demographic information included age, gender, marital status, living situation, employment, educational history, substance history, and the presence or absence of a prior diagnosis of psychiatric disorder or family psychiatric disorder in a first- or second-degree relative. Medical history was coded using the Cumulative Illness Rating Scale (CIRS)15– severity subscale. Injury data for the cases, namely the mechanism of accident, loss of consciousness (LOC), GCS score at the time seen by physicians in the emergency room, duration of PTA (based on the patient’s recollection of events after the injury), other musculoskeletal injuries, and results of the brain computed tomography (CT) scans reported on by a radiologist (coded as yes/no regarding focal abnormalities, i.e., contusions, subarachnoid hematomas, subdural hematomas, and so on), were recorded. Self-Reported Outcome Measures. Self-report measures included the Rivermead Head Injury Follow-up Questionnaire (RHFQ),16 a validated instrument that gives a detailed description of psychosocial functioning post-TBI encompassing relationships, work, and domestic activities. Psychologic distress was measured using the General Health Questionnaire (GHQ)17 with questions pertaining to somatic distress, social dysfunction, anxiety, and depression. The Rivermead Post Concussion Disorder Questionnaire (RPDQ)18 has been validated in mild TBI19 and was used to measure physical and emotional symptoms commonly seen after TBI. A “somatic” subscale was created to exclude those symptoms that overlap with major depression (e.g., insomnia, irritability) and only include those related to physical symptoms (e.g., headaches, dizziness). Additionally, at one year postinjury (or enrollment for control subjects), subjects were asked whether they were having memory problems that were worse than before the injury and worse than their age peers. Depression. Participants were assessed for the presence of a major depressive episode using the depression module of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) axis I disorders (SCID).20 DSM criteria are considered reliable and valid in TBI samples.21 Subsyndromal depression was also assessed using the criteria of a minimum of three DSM–IV symptoms of a major depressive episode, at least one of which is persistent depressed
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mood or anhedonia, lasting for at least two weeks.22 At baseline, 10 (14.5%) of the cases and three (4%) of the comparison group were taking an antidepressant; and one (1.5%) of the cases and two (2.6%) of the comparison group were taking a benzodiazepine. Formal Cognitive Outcome Measures. A cognitive battery was selected to demonstrate cognitive deficits consistent with TBI and/or dementia. The Mattis Dementia Rating Scale (DRS)23 and the Mini-Mental Status examination (MMSE)24 were used as overall measures of cognitive impairment. Attention and working memory were assessed using the WAIS-III (WAIS-III)24 Digit Span subtest. The WAIS III Digit Symbol subtest was used as an index of processing speed. Verbal memory was assessed using logical memory total delayed recall of both stories from the Wechsler Memory Scale-III (WMS-III)25 and the long-delay free recall score of the California Verbal Learning Test (CVLT).26 Visual memory was assessed using the delayed recall from the Rey-Osterrieth Complex Figure Test (RCFT).27 Language was assessed using the Boston Naming Test (BNT) total score.28 Executive function was assessed using the Controlled Oral Word Association Test (COWAT)28 and the Wisconsin Card Sort Test (WCST) total categories completed and perseverative responses.29 A WAIS-III vocabulary total score of greater than or equal to the 14th percentile was used as an index of fluency in English. Informant Ratings. Informant ratings of instrumental activities of daily living (IADLs) were provided using the Functional Activities Questionnaire (FAQ).30 The FAQ was developed to assess IADLs in early Alzheimer dementia (AD) and has been shown to predict conversion to AD among older adults with mild cognitive impairment.31 Timing of Outcome Assessments. Participants were first seen within two months of injury and had follow-up assessments one year (12 months⫾ 2) postinjury. Six months postinjury (⫾1), self-report questionnaires were mailed to all subjects for completion. The comparison group was enrolled at baseline and followed up at the same time points postenrollment as the cases. Demographic, medical/psychiatric, and injury variables were collected at the baseline visit. At baseline and one year, major depression was assessed and the MMSE administered. Self-reported measures of functioning were completed at baseline, six months, and one year. Neuropsychologic tests
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Rapoport et al. and IADL assessments were administered at one year. Baseline cognitive testing was limited to the MMSE because the goal of the study was to look at long-term implications of TBI. Furthermore, in the period after TBI, cognitive impact is common and patients may still exhibit PTA.
Statistics Baseline Variables. Demographic and past illness variables were compared between patients with and without TBI. For continuous variables, a repeatedmeasures analysis of variance was used to compare the group differences accounting for the matched nature of the cases and control subjects, whereas for categorical variables, a generalized linear model was used to compare the group differences, once again accounting for the matched nature of cases and control subjects. t tests and chi-squared tests were used to compare the background variables between subjects who dropped out of the study before one year with those who remained. Self-Report and Informant-Report Measures. Repeated-measures analyses of covariance (ANCOVAs) were conducted to assess the relationship betweengroup (case versus comparison group) and the selfreport outcome measures as well as the interaction of group with time controlling for age, gender, and baseline MMSE. Paired comparisons were used to compare the informant ratings of cases and the comparison group on the FAQ at one year as well as to compare the presence of cognitive complaints between groups at one year. Because there were five self-/informant-report measures administered, a Bonferroni correction of 0.05/5 tests was applied, yielding a critical value of 0.01 for the self- and informant-report measures. Cognitive Evaluation. Cases and the comparison group were compared on performance on the individual cognitive tests using a repeated-measures analysis of variance accounting for the matched nature of the cases and control subjects. A Bonferroni correction of 0.05/11 tests was applied to the cognitive measures, yielding a critical p value of 0.0045 for the cognitive tests. Repeated-measures ANCOVA was then used to compare the performance of cases and comparison group on the individual cognitive tests controlling for age, sex, education, and severity
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of comorbid medical illnesses (CIRS severity index). Because the measures of language, memory, and executive dysfunction were strongly based on the English language, we repeated the ANCOVAs on those measures in a subgroup in whom English was their first language. Pearson’s correlation was conducted to investigate the relationship between self-reported and cognitive outcome measures. Role of Injury Severity. Post hoc Scheffe’s tests were used to examine whether the performance on cognitive tests, self-report measures, or ratings on the FAQ differences were between cases and mild TBI and between cases and moderate TBI. RESULTS Subjects. Seven hundred fifteen patients who were seen through the emergency room and trauma ward for possible TBI were screened for assessment in the TBI Clinic and then for participation in the study. After refusals and exclusions (Figure 1), 69 cases with TBI were included in the study at baseline. At baseline, 1.5% of cases were matched to three control subjects, 9% to two control subjects, and 89% to one control subject. There were three cases that were unmatched. Analysis included all cases but treated the matched ones as correlated observations. By one year, 20 of the subjects had been lost to attrition, and 49 (71.0%) remained (Figure 1). Ninetyfour control subjects were recruited through newspaper advertisements, and 78 were matched to the subjects and included in the study. Ten members of the comparison group dropped out by one year, whereas 68 (87.1%) remained (Figure 1). For the subjects with TBI, 37 (53.6%) had mild TBI. The remaining 32 (46.4%) of subjects had moderate TBI, 18 (26.1%) of whom would have met mild criteria but for intracranial abnormalities on CT. Of those subjects with “mild TBI,” 15 (40.5%) did not undergo a CT scan, 15 (40.5%) were found to have a negative CT, three (8%) had general atrophy, three (8%) had atrophy with incidental white matter changes, and one (2.7%) had incidental lacunar infarct. Of those with “complicated mild TBI,” CT scan results demonstrated two (11%) with subarachnoid hematomas, five (27.8%) with subdural hematomas, two (11%) with contusions, seven (38.9%) with injuries at multiple sites, one (5.6%) had general atrophy,
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Outcomes After TBI Sustained in Older Adulthood and one (5.6%) had epidural or sphenoid. Of the moderate TBI subjects, one (7%) had a negative CT scan, two (14.3%) had contusions, eight (57%) had injuries at multiple sites, two (14.3%) had general atrophy, and one (7%) had epidural or sphenoid hematomas. The mechanism of injury was related to falls in 35 (50.7%), motor vehicle accidents in 14 (20.3%), and “other” in 20 (29%). Thirty-eight (55.1%) had other significant injuries, either fractures or intraabdominal injuries. There were no differences in severity or mechanism of injury or of associated other injuries between those who remained in the study at one year (N⫽49) and those who were lost to attrition (N ⫽20).
FIGURE 1.
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Comparison of Background Variables There were no differences between cases and the comparison group in background variables (Table 1). Among those who remained in the study at one year, the comparison group had on average one year higher education than cases (mean: 14.07; standard deviation [SD]: 3.0 versus 12.53; SD: 4.0, respectively, F[1,116] ⫽5.73, p⫽0.019). Compared with those lost to attrition (N⫽ 31), subjects who remained in the study at one year (N ⫽117 cases and comparison group) were more likely to be female (57.3% versus 32.3%, 2[1] ⫽6.14, p ⬍0.05) and to have a psychiatric history (35.9% versus 6.5%, Fisher exact test, p ⬍0.001), but there were no other differences in the
Subject Flow Sheet
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TABLE 1.
Comparison of Baseline Variables
Age in years Male gender Unattached marital status (single, divorced widowed) IQCODE More than 13 years of education Mini-Mental Status Examination CIRS severity index CIRS cardiovascular respiratory illness severity Has had a mild traumatic brain injury in the remote past Has had a psychiatric history Has a family psychiatric history Time seen at one year postinjury
Cases (N ⴝ 69)
Comparison Group (N ⴝ 79)
Statistics, Significance
Mean: 67.00 (SD: 7.9) 33 (47.8%)
Mean: 68.04 (SD: 8.5) 38 (48.1%)
F(1,65) ⫽ 0.23, p ⫽ 0.63 2(1) ⫽ 0.14, p ⫽ 0.71
21 (30.4%) Mean: 2.98 (SD: 0.3) 35 (50.7%) Mean: 27.75 (SD: 2.2) Mean: 1.46 (SD: 0.6)
28 (35.4%) Mean: 3.00 (SD: 0.33) 46 (58.2%) Mean: 29.20 (SD: 1.1) Mean: 1.44 (SD: 0.6)
2(1) ⫽ 0.17, p ⫽ 0.68 F(1,65) ⫽ 0.25, p ⫽ 0.62 2(1) ⫽ 0.28, p ⫽ 0.59 F(1,64) ⫽ 26.23, p ⬍0.0001 F(1,65) ⫽ 0.01, p ⫽ 0.96
17 (24.6%)
13 (16.5%)
F(1,65) ⫽ 2.02, p ⫽ 0.16
8 (11.8%) 18 (26.1%) 18 (26.1%) Mean: 402.53 (SD: 57.3) (N ⫽ 49)
5 (6.3%) 26 (32.9%) 30 (38.0%) Mean: 386.47 (SD: 24.51) (N ⫽ 68)
2(1) ⫽ 2.94, p ⫽ 0.09 2(1) ⫽ 1.07, p ⫽ 0.30 2(1) ⫽ 3.52, p ⫽ 0.06 F(1,65) ⫽ 2.02, p ⫽ 0.16
SD: Standard deviation; CIRS: Cumulative Illness Rating Scale; IQCODE: Informant Questionnaire for Cognitive Decline in the Elderly.
other background variables, and no differences between cases and comparison group in gender and psychiatric history at one year. Self-Reported Outcome The TBI group reported substantially higher levels of difficulty on the self-report instruments compared with the comparison group, controlling for age, gen-
TABLE 2.
der, and MMSE (Table 2). The results for RPDQ were unchanged using the “somatic” subscale. Post hoc analysis indicated differences at baseline between mild TBI and comparison group and between moderate TBI and comparison group. By the six-month and one-year assessments, mild and moderate TBI differed from the comparison group on RPDQ and somatic subscales, but only moderate TBI differed
Self-Reported Outcome Cases Mean (SD)
General Health Questionnaire (GHQ) (range: 0–28) Baseline Six months One year Rivermead Head Injury Follow up (RHFQ) (range: 0–48) Baseline Six months One year Rivermead Postconcussive Symptoms (RPDQ) (range: 0–72) Baseline Six months One year
8.71 (7.6), N ⫽ 63 5.77 (6.6), N ⫽ 43 4.35 (5.8), N ⫽ 46
Comparison Group Mean (SD)
1.00 (2.3), N ⫽ 79 1.92 (3.8), N ⫽ 61 1.48 (3.4), N ⫽ 67
13.95 (11.7), N ⫽ 63 12.37 (11.1), N ⫽ 43 11.24 (11.7), N ⫽ 45
2.59 (3.8), N ⫽ 79 4.85 (6.3), N ⫽ 61 4.81 (7.0), N ⫽ 67
19.25 (16.2), N ⫽ 64 18.37 (16.2), N ⫽ 41 18.31 (19.6), N ⫽ 45
1.65 (4.8), N ⫽ 79 5.02 (8.7), N ⫽ 60 4.24 (8.9), N ⫽ 67
Repeated-Measures ANCOVA Controlling for Age, Gender, and MMSE TBI: F1,349 ⫽ 30.4, p ⬍0.0001 TBI ⫻ time: F2,349 ⫽ 9.45, p ⫽ 0.0001
TBI: F1,347 ⫽ 36.6, p ⬍0.0001 TBI ⫻ time: F2,347 ⫽ 3.02, p ⫽ 0.05
TBI: F1,345 ⫽ 59.7, p ⬍0.0001 TBI ⫻ time: F2,345 ⫽ 1.26, p ⫽ 0.29
SD: Standard deviation; ANCOVA: analysis of covariance; MMSE: Mini-Mental Status Examination; TBI: traumatic brain injury.
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Outcomes After TBI Sustained in Older Adulthood from the comparison group on RHFQ and GHQ. Thirteen of the 20 (65.0%) cases with moderate TBI, 12 of the 29 (41.4%) mild TBI cases, and only 12 of the 68 (17.3%) in the comparison group had subjective cognitive complaints at one year (2[1]⫽6.81, p⫽ 0.009). Depression At baseline, 11 of the 69 cases (15.9%) and none of the comparison group had an episode of major depression (2[1]⫽12.23 p⫽0.003). Fifteen cases (21.7%) and three in the comparison group (3.8%) had subsyndromal depression (2[1]⫽9.28, p⫽ 0.002). One year postinjury, six of the 49 patients with TBI (12.2%) (two mild TBI and four moderate
TABLE 3.
TBI) and only one of the 68 in the comparison group (1.5%) met criteria for a major depressive episode (2[1] ⫽4.03, p⫽ 0.04). Nine cases (18.8%) and two in the comparison group (2.9%) met criteria for subsyndromal depression (2[1] ⫽6.26, p⫽0.01). Five of the 11 patients with TBI with major depression at baseline also met criteria at one year, and conversely, five of the six patients with TBI with major depression at one year also had major depression at the baseline postinjury visit. Formal Cognitive Outcome. Patients with TBI had significantly worse performance than the comparison group at one year on the DRS, tests of processing speed and language, and on the COWAT (all p ⬍0.0045, see Table 3). The cases also had poorer
Cognitive Outcome Case
Comparison Group
Statistics
Statistics
Mean (SD) (N ⴝ 68)
Repeated-measures ANOVA
Repeated-measures ANCOVAa
135.38 (8.5) (N ⫽ 48) 28.19 (1.9) (N ⫽ 48)
139.0 (3.7)
F(1,42) ⫽ 9.61, p ⫽ 0.0035
F(1,42) ⴝ 10.82, p ⴝ 0.002
29.07 (1.2)
F(1,42) ⫽ 8.37, p ⫽ 0.006
F(1,42) ⴝ 9.33, p ⴝ 0.004
15.54 (4.7) (N ⫽ 48)
17.85 (4.4)
F(1,42) ⫽ 6.7, p ⫽ 0.01
F(1,42) ⫽ 7.04, p ⫽ 0.01
48.44 (19.4) (N ⫽ 45)
58.78 (13.7)
F(1,40) ⫽ 10.82, p ⫽ 0.002
F(1,40) ⫽ 14.97, p ⫽ 0.0004
25.20 (7.7) (N ⫽ 46)
29.31 (7.2)
F(1,40) ⫽ 8.71, p ⫽ 0.005
F(1,40) ⴝ 10.27, p ⴝ 0.003
9.68 (3.5) (N ⫽ 47)
11.48 (3.1)
F(1,41) ⫽ 5.8, p ⫽ 0.02
F(1,41) ⫽ 9.66, p ⫽ 0.003
13.36 (6.9) (N ⫽ 43)
13.63 (6.1)
F(1,38) ⫽ 0.15, NS
F(1,38) ⫽ 0.1, NS
47.19 (11.3) (N ⫽ 47)
54.87 (4.8)
F(1,41) ⫽ 24.60, p ⬍0.0001
F(1,41) ⫽ 24.68, p ⬍0.0001
33.02 (14.7) (N ⫽ 46) 3.98 (2) (N ⫽ 43) 31.33 (24.6) (N ⫽ 43)
42.72 (12.5)
F(1,40) ⫽ 11.2, p ⫽ 0.002
F(1,40) ⫽ 12.08, p ⫽ 0.001
4.84 (1.6)
F(1,37) ⫽ 7.02, p ⫽ 0.01
F(1,37) ⴝ 10.41, p ⴝ 0.003
20.75 (18.6)
F(1,37) ⫽ 7.5, p ⫽ 0.009
F(1,37) ⫽ 9.08, p ⫽ 0.005
Mean (SD) General cognitive tests Dementia Rating Scale Mini-Mental State Examination Attention/ working memory Digit span Processing speed Digit symbol Verbal memory Wechsler Memory Scale III CVLT long delay free recall Visual memory Rey-Osterrieth Complex Figure–delay Language Boston Naming Test Executive functioning COWAT WCST total categories completed WCST perseverative responses a
ANCOVA controlling for age, gender, education, and Cumulative Illness Rating Scale severity score. SD: Standard deviation; ANOVA: analysis of variance; ANCOVA: analysis of covariance; CVLT: California Verbal Learning Test; COWAT: Controlled Oral Word Association Test; WCST: Wisconsin Card Sort Test; NS: not significant.
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Rapoport et al. performance on the MMSE, both tests of verbal memory, the digit span, and on the WCST, although these differences were of marginal significance (p between 0.05 and 0.0045, see Table 3). Post hoc comparisons indicated these cognitive differences to be present between patients with moderate TBI and the comparison group but not between mild TBI and the comparison group. Sample size precludes analysis comparing mild, complicated mild, and moderate TBI with control subjects. Once we controlled for age, gender, education, and severity of medical comorbidities, the cases still had significantly worse performance than the comparison group on processing speed, CVLT delayed recall, language, and COWAT (all p ⬍0.0045, see Table 3). Visual memory was not significant. The remaining tests were marginally worse in cases than the comparison group (p between 0.05 and 0.005, see Table 3). Because the measures of language, memory, and executive functioning are heavily reliant on the English language, these ANCOVAs were compared again in only those subjects fully fluent in English (39 cases and 68 of the comparison group). On controlling for age, gender, education, and medical comorbidities in this “English-fluent” subgroup, cases had significantly worse performance than controls on the MMSE and DRS, as well as on the digit symbol, both tests of verbal memory, the BNT, the COWAT, and the total score on the WCST (see Table 3). Relationship Between Self-Report and Cognitive Outcome. At one year, the self-reported instruments (GDS, GHQ, RPDQ, and RHFQ) were each correlated moderately (ranging from r ⫽0.243 to r ⫽0.49, p ⬍0.01) with all cognitive measures except MMSE, CVLT long delay free-recall, the Rey-Osterreith Complex Figure test, and the WCST subscales. The COWAT was only significantly associated with the RPDQ (r⫽0.25, p⫽0.01) and RHFQ (r ⫽0.24, p⫽ 0.01). Informant Ratings. At one year postinjury, informants rated the cases as having poorer performance in IADL than the comparison group (FAQ mean: 2.98; SD: 4.9 versus 0.38, SD: 1.5, respectively, t[59]⫽ 5.94, p ⬍0.0001. Post hoc comparison indicated that moderate TBI, but not mild TBI cases, were rated as having poorer IADLs.
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DISCUSSION The present report is the first one-year prospective cohort study of TBI sustained in older adulthood to examine detailed aspects of functioning and cognition. Older adults with TBI reported significantly higher levels of psychosocial dysfunction, psychologic distress, and postconcussive symptoms than those in the comparison group, and were more likely to subjectively report cognitive complaints and to meet criteria for major depression or subsyndromal depression than those in the comparison group. Although cognition was assessed in detail one year postinjury, a point at which most younger patients have improved, the cases had lower scores on verbal memory, language, processing speed, and frontal/ executive functioning than the comparison group, and informants rated them as having more difficulty with IADLs than the comparison group. Post hoc analyses indicated that most of the cognitive, selfreported, and informant-rated differences lay between those with moderate TBI and the comparison group. The presence of persisting differences in cognition after moderate TBI has been well-documented in younger patients.32 Memory and executive dysfunction have been previously demonstrated in older patients with moderate but not mild TBI as compared with the comparison group in a smaller sample of patients assessed within two months of injury.9 Severity of TBI is a significant factor in the development of cognitive deficits postinjury.33 Betaamyloid deposition has been shown after fatal severe TBI,34 a protein that may initiate the cascade of pathologic processes of AD,35 particularly in patients who are vulnerable to AD by virtue of advanced age. The demonstration of significant differences in cognition and functioning between patients with TBI and a comparison group at one year postinjury may be a harbinger of more significant decline in the years to come, and a longer duration of follow up is needed. Furthermore, cognitive outcome showed moderate correlations with self-reported outcome in this sample, highlighting the important interplay between cognitive and psychosocial functioning after TBI.
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Outcomes After TBI Sustained in Older Adulthood Although low levels of postconcussive symptoms, psychologic distress, and psychosocial dysfunction were reported by the patients with TBI in the present sample, their rates were higher than in the comparison group, and this difference was most robust for postconcussive symptoms among those with mild and moderate TBI compared with the comparison group. Postconcussive symptoms are a major cause of morbidity in the TBI population, and the pathophysiology has been elusive. In the present sample, older patients with TBI had higher rates of major depression than the comparison group. That the rate of major depression was much lower than the 33% incidence reported in the largest longitudinal evaluation of younger adults36 is consistent with our previous report of lower incidence of major depression among older than younger adults after TBI.37 TBI has been associated with serotonergic dysfunction,38 and this, together with the psychosocial impact of the injury and premorbid factors likely plays a role in the development of depression postTBI. The strengths of this investigation are that it is the largest prospective study to date of outcome after TBI in older adulthood. Subjects were all seen at baseline within two months of injury to ensure valid collection of injury, demographic, and previous illness history. Subjects with premorbid cognitive decline were carefully screened and excluded. A detailed cognitive examination was done at a set time one year postinjury using well-validated neuropsychologic tests assessing an array of cognitive skills. Domains of psychosocial dysfunction, psychologic distress, and postconcussive symptoms were similarly assessed at fixed time points postinjury, and informant report was elicited. Whereas previous studies of mood disturbance post-TBI in older adults have used continuous subjective rating scales, the present study incorporates a categorical assessment of mood was conducted by experienced clinicians using DSM criteria. We incorporated a comparison group matched for demographic variables and controlled for confounds of age, gender, education, and medical illness severity. Limitations of the study include potential for recruitment and attrition biases. The present sample of
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patients seen through the emergency department and trauma wards may not be representative of much of the mild TBI in the community, which is often unrecognized and for which patients do not often present to the hospital. It has been shown previously that those who consent to participation in TBI research may have subtly more severe injuries than those who refuse, even among “mild” TBI.39 Furthermore, the present “older” sample is much younger than the population of “elderly” in the community. Although an older sample may have been less likely to demonstrate resilience after such injuries, much research on TBI in older adults focuses on the age group of 50 plus,9,10 and as such, our research is comparable. Attrition may be a similar bias, like in the present sample, those who remained in the study were more likely to be female and have a psychiatric history than those who dropped out. However, the 71% follow-up rate in the present sample is higher than most longitudinal studies of TBI in younger adults.40 The potential limitation of the inclusion of patients who have English as a second language was addressed by excluding those not fluent from analysis of language-sensitive cognitive measures. When these subjects were excluded, the between-group differences remained. Also, although there were no differences between cases and the comparison group on overall severity of cardiorespiratory illness, data were not collected on cerebrovascular risk factors, and this remains a potential confound here. The present report shows TBI, particularly moderate TBI, in older adults to be related to major depression, informant- and self-rated difficulties, as well as cognitive difficulties relative to a comparison group. Cognitive and functional disruption from TBI may be at its initial peak shortly after injury, yet after the usual recovery period, older patients may be at a lower baseline threshold of “cognitive reserve,”35 and clinically significant differences may become even more evident as time passes. This study was supported by the Ontario Neurotrauma Foundation. Preliminary data from this investigation was presented at the American Psychiatric Association 157th Annual Meeting, May 1– 6, 2003, New York, NY, and the International Psychogeriatric Association 11th Annual Congress, August 18, 3003, Chicago.
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