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Psychosomatics 43:295-301, August 2002
© 2002 The Academy of Psychosomatic Medicine

Comparison of Cognitive Impairment Associated With Major Depression Following Stroke Versus Traumatic Brain Injury

Amane Tateno, M.D., Yuichi Murata, M.D., and Robert G. Robinson, M.D.

Received August 3, 2001; revised December 20, 2001; accepted January 17, 2002. From the Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA; and the Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan. Address correspondence and reprint requests to Dr. Robinson, Department of Psychiatry, University of Iowa, 200 Hawkins Drive, 2887 JPP, Iowa City, IA 52242-1057; robert-robinson{at}uiowa.edu (e-mail).


  ABSTRACT

 
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Several studies have reported an association between cognitive impairment and major depression following stroke but failed to find a similar association among patients with traumatic brain injury (TBI). This study examined the hypothesis that age differences between stroke and TBI patients would account for the differences in the effect of major depression on cognitive function. We examined subjects' cognitive function using the Mini-Mental State Examination and compared findings among patients with stroke or TBI. Results indicated that stroke patients with major depression (N = 73) were significantly older and more cognitively impaired than similar TBI patients (N = 35), even after matching patients for lesion volume and years of education. After matching for age, however, there was no association of major depression with cognitive impairment in this relatively young stroke population. These findings support the hypothesis that age, presumably related to physiological response to brain injury, accounts for differences in the effect of major depression on cognitive function between stroke and TBI patients.

Key Words: Cognitive Impairment • Traumatic Brain Injury

  INTRODUCTION

 
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Numerous studies have reported that mood disorders occur frequently following both stroke1–3 and traumatic brain injury (TBI).4–6 Depressive disorders following stroke, which include both major and minor depression, have been found in 23%–40% of patients depending on whether patients are identified in community surveys7 or in acute stroke or rehabilitation hospitals.8,9 Similarly depressive disorders following TBI have reported to occur in 7%–57% of patients depending on the population of patients being studied.5,10–12

The frequency and severity of cognitive impairment have been found by several investigators to be significantly more severe in patients with poststroke major depression compared to similar patients with minor depression or nondepressed patients.13–18 This cognitive impairment has been found to involve a wide range of intellectual functions, including orientation, memory, visual construction, executive function, and frontal lobe function.14 In addition, the association of major depression with cognitive impairment was found to be strongest during the acute stroke period but was present for up to 1 year.15 A recent study has also shown that patients with major depression who were treated successfully with nortriptyline showed significantly greater improvement in cognitive function compared to patients treated with placebo or nortriptyline whose mood did not improve.19

On the other hand, cognitive function as measured by the Mini-Mental State Examination (MMSE)20 was not significantly more impaired among patients with major depression following TBI compared with comparable nondepressed patients.11,12 Furthermore, cognitive dysfunction was no greater among TBI patients with major depression than comparable nondepressed at 3-, 6-, 9-, and 12-month follow-up evaluations.21

Since stroke and traumatic brain injury are both forms of brain injury that are associated with a greater prevalence of depression than non-brain-injured controls, one might question why patients with major depression following traumatic brain injury do not have a dementia of depression like patients with ischemic brain injury. In the present study, we compared cognitive function between patients with and without major depression following stroke or TBI and tested the hypothesis that age differences between the stroke and TBI patients would be related to the association of poststroke, but not post-TBI, major depression with greater cognitive impairment than no depression.


  METHODS

 
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patient Population
This study included patients with either stroke or TBI. All patients provided written consent to participate in these studies after they had been fully explained. The first group of stroke patients included 92 patients admitted to a rehabilitation hospital (Younkers Rehabilitation Center of Iowa Methodist Medical Center in Des Moines, Iowa) for the treatment of stroke who agreed to participate in a previously published treatment study of poststroke patients with and without depression and who were followed for 2 years.22 These patients had a mean age at enrollment of 67.5 ± 12.3 (SD) years; 96% were white, 63% were male, and 43% were from Hollingshead social class IV or V. The second group of stroke patients consisted of 309 consecutive admissions to the University of Maryland Hospital in Baltimore, Maryland, with a diagnosis of either acute intracerebral hemorrhage or cerebral infarction, 210 of which were followed for 2 years. The course of the cognitive impairment and the association with lesion hemisphere and major depression were previously published.15 These patients had a mean age at enrollment of 58.9 ± 13.4 (SD) years; 66% were African American, 43% were male, and 74% were from Hollingshead social class IV or V. Subjects were excluded only if their impairment in verbal comprehension precluded them from undergoing a verbal interview. Among these two groups of patients, 401 patients were examined for cognitive function using the MMSE.

The TBI patients from Iowa included 59 consecutive patients admitted to the University of Iowa Hospitals and Clinics with acute head trauma and 32 consecutive patients admitted to the Younkers Rehabilitation Hospital of Iowa Methodist Medical Center who agreed to participate in a 2-year longitudinal observation study. The patients were included only if the trauma involved primarily the brain with no major damage to spinal cord or other organ systems. Patients were excluded if they had penetrating head injuries or secondary brain damage caused by hypovolemic shock or severe hypoxia (e.g., abdominal hemorrhages, lung collapse). Among both stroke and TBI groups, patients with delirium, decreased level of consciousness (drowsy, stuporous, or comatose), or significant comprehension deficit as determined by their inability to complete the first part of the Token Test were excluded. These patients had a mean age of 36.8 ± 15.4 (SD) years; 95% were white, 60% were male, and 56% were from Hollingshead social class IV or V. Data on the cognitive function of these patients has not been previously published. Another group of TBI patients was also included in the present study and consisted of 66 consecutive patients admitted to the Shock Trauma Center of the Maryland Institute of Emergency Medical Services System (MIEMSS) with an acute closed head injury who met the same inclusion criteria as the Iowa patients.11 These patients had a mean age of 28.5 ± 9.6 (SD) years; 76% were white, 86% were male, and 73% were from Hollingshead social class IV or V. Among these three groups of TBI patients, 154 patients were examined for cognitive function using the MMSE.

Psychiatric and Neurological Evaluations
After obtaining informed consent, patients were evaluated by a psychiatrist using a semistructured interview, the Present State Examination (PSE).23 Using the symptoms elicited from the PSE, a diagnosis of depression was made utilizing DSM-IV24 criteria. The Hamilton Depression Scale (HAM-D; 17 items)25 was used to measure the severity of depressive symptoms. Scores may range from 0 to 52 with higher scores indicating more severe depressive symptoms. Patients' cognitive functioning was assessed using the MMSE.

Neuroimaging
Computed tomography scans obtained as part of the patient's clinical care were evaluated by a neurologist or neuroradiologist who was blind to the psychiatric findings. Lesion volume was expressed as a percentage of total brain volume among the Iowa patients after three-dimensional reconstruction of the brain and automated calculation of brain volume. The Baltimore patients' lesion volume was determined by measuring the largest cross-sectional area of each lesion divided by the cross-sectional area of the brain taken at the level of the body of the lateral ventricles. We have shown the reliability and validity of this method in a prior publication.26

Statistical Analysis
Statistical analyses were performed using means and standard deviations, Student's t tests (two-tailed) for parametric data, and intergroup comparison. Frequency distributions were analyzed using {chi}2 tests (with Fisher's exact test, if sample sizes were prohibitively small).


  RESULTS

 
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Comparison of Characteristics of Stroke Patients With and Without Major Depression
Of the 401 acute stroke patients, the PSE was conducted and the presence or absence of a mood disorder was determined in 354. Of the 354 patients, 73 (20.6%) had major depression, 60 (16.9%) had minor depression, and 221 were nondepressed. Stroke patients with major depression were significantly younger (t352 = 1.996, P = 0.047) and had a significantly higher frequency of previous personal history of depression ({chi}2 = 13.715, P = 0.0002) and lower mean MMSE scores (t352 = 2.960, P = 0.003) than stroke patients without major depression (Table 1). There was no significant difference between stroke patients with major depression and stroke patients without major depression in mean days since stroke (30.9 ± 52.3 vs. 21.7 ± 33.7, t286 = -1.661, P = 0.10) and other characteristics (Table 1).


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TABLE 1. Characteristics of stroke patients and TBI patients



Comparison of Characteristics of TBI Patients With and Without Major Depression
Of 154 TBI patients, 35 (22.7%) had major depression, 12 (7.8%) had minor depression, and 107 were nondepressed. There were no significant differences between TBI patients with major depression and TBI patients without major depression in terms of mean MMSE scores, mean days since TBI (33.1 ± 22.3 vs. 31.2 ± 29.8, t147 = -0.344, P = 0.73), and other characteristics (Table 1).

Comparison of Characteristics of Stroke Patients With Major Depression and TBI Patients With Major Depression
Compared to TBI patients with major depression, stroke patients with major depression were significantly older (t106 = 9.330, P < 0.0001), less educated (t105 = -3.507, P = 0.0007), and had significantly lower mean MMSE scores (t106 = -4.692, P < 0.0001) and larger lesion volumes (t60 = 3.187, P = 0.002). There were no significant differences between stroke patients with major depression and TBI patients with major depression in terms of mean days since stroke or TBI (30.9 ± 52.3 vs. 33.1 ± 22.3, t100 = -0.241, P = 0.81), mean HAMD scores, and other characteristics (Table 1). Although it was not statistically significant, the percentage of white patients was lower in the stroke group compared to the TBI group. We therefore divided our group by race (i.e., white or nonwhite) and reanalyzed our data using only nonwhite patients. There were no differences, however, in our results. There was a significant difference in mean MMSE scores between stroke patients with major depression and without major depression (20.3 ± 6.4 vs. 22.8 ± 5.0, t172 = 2.417, P = 0.02), while there was no significant difference in mean MMSE scores between TBI patients with major depression and without major depression (26.7 ± 1.7 vs. 27.3 ± 2.1, t45 = -0.162, P = 0.87).

Controlling for Years of Education and Lesion Volume by Examining Matched Pairs
Since years of education and lesion volume were different between the stroke and TBI patients, and these factors were reported to be associated with cognitive impairment among patients with poststroke major depression,13,15 we matched patients with major depression following stroke or TBI (N = 28 pairs) for years of education (i.e., ±3 years) and lesion volume (i.e., ±2%). We also matched patients with TBI or stroke but without major depression for years of education and lesion volume (n = 56 pairs). Stroke patients with major depression were significantly older (t54 = 9.160, P < 0.0001) and had significantly lower mean MMSE scores (t54 = -3.162, P = 0.003) than TBI patients with major depression. There were no significant differences in mean HAMD scores between stroke and TBI patients with major depression (Table 2).


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TABLE 2. Characteristics of year of education- and lesion volume-matched pairs



Controlling for Age Differences Using Matched Pairs
Stroke patients were significantly different from TBI patients in terms of mean age (stroke patients 61.4 ± 13.8 vs. TBI patients 37.0 ± 15.4, t456 = 14.669, P < 0.0001). We therefore matched stroke and TBI patients for age (i.e., ±3 years) with major depression (N = 15 pairs) and without major depression (N = 30 pairs).

The characteristics of these pairs are shown in Table 3. There was no significant difference between stroke patients with and without major depression or between TBI patients with and without major depression or between stroke and TBI patients with major depression in terms of background characteristics. Stroke patients with major depression, however, had significantly larger lesion volume (t16 = 2.441, P = 0.03) than TBI patients with major depression. There were, however, no significant differences between TBI patients with major depression and stroke patients with major depression in mean MMSE scores and in the frequency of left-hemisphere lesions and subcortical lesions. Thus, after age matching stroke and TBI patients, there was no longer a cognitive impairment associated with major depression compared with no depression.


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TABLE 3. Characteristics of age-matched pairs




  DISCUSSION

 
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
This study demonstrated that patients with major depression following stroke were more cognitively impaired than patients with major depression following TBI or stroke patients without major depression. We found the same phenomenon when patients were matched by years of education and lesion volume. But when patients were age matched, stroke patients with major depression were not significantly different in the severity of cognitive impairment from TBI patients with major depression or stroke patients without major depression.

Before further discussion of our results, some methodological limitations need to be discussed. First, our measurement of cognitive function was only the brief, language-dominated examination, the MMSE. Patients were excluded if they were not able to undergo a verbal interview or had significant deficits in comprehension. Our findings, therefore, may not be applicable to all patients with stroke and TBI. Second, the use of patients from two demographically different patient populations may have led to greater generalizability of findings or may have led to findings influenced by cohort effects. Third, most of our TBI patients were young people (i.e., there was only one patient with major depression and six patients without major depression over 65), while more than half of our stroke patients were over age 65. We, therefore, examined age-matched pairs in this study. Finally, although there was no statistically significant difference, there was a difference of race (i.e., % white) between stroke patients and TBI patients. Therefore, we reanalyzed the data using only nonwhite patients. The results, however, were not altered. These data indicate that racial differences did not affect our results.

In spite of these caveats, there were some interesting findings. First, the severity of cognitive impairment associated with poststroke major depression was not present in our age-matched depressed and nondepressed, TBI and stroke groups. Because patients with TBI often suffer diffuse axonal injury, we did not detect many lesions in TBI patients on CT scans. This may have led to more general cognitive dysfunction27 in the TBI patients, while stroke patients may have had more focal cognitive deficits. A more detailed neuropsychological examination may have been able to identify a different pattern of cognitive dysfunction between the stroke and TBI patients.

Aging is one of the most important factors that influences cognitive function, and it has been demonstrated that elderly subjects without brain injury have more cognitive impairment on the MMSE than do younger subjects.28 Our results demonstrated the same association among brain-injured patients with major depression. This finding is consistent with the conclusion of Jorm et al.,29 who reported that only elderly patients with functional (i.e., no known brain injury) major depression show cognitive impairment. Our results suggested that the effect of major depression on cognitive function was absent in younger patients with stroke.

Is the younger age of the stroke patients sufficient to explain this loss of the cognitive impairment associated with major depression? One objection that might be raised is that the number of patients with TBI or stroke who were matched for age was too small to show a significant effect among 30 patients. The effect size of the difference in MMSE scores between patients with stroke versus TBI with major depression was 0.03. Thus, an 80% probability of finding a phenomenon with an {alpha} of 0.05 would require 62,000 patients. This result suggests that our failure to detect a difference in stroke and TBI patients was not a result of sample size. Another objection that might be raised is that we did not show the phenomenon of cognitive impairment associated with major depression in older TBI patients. Unfortunately, there was only one patient with major depression following TBI over age 60 and only six patients without depression over age 60. The ultimate proof of our age hypothesis would require that we show the phenomenon is present in TBI patients over age 60 or 65 but is absent in younger patients and that the cognitive impairment improves with treatment of depression. This kind of treatment trial, however, has never been conducted. Thus, at the present time, we can demonstrate that the phenomenon is not present in younger stroke patients and that this absence of cognitive impairment cannot be explained on the basis of the differences in lesion volume or years of education between the stroke and TBI patients. This is consistent with our original hypothesis that the dementia of depression in patients with brain injury, like functionally depressed patients, is a phenomenon that requires the normal loss of neurons associated with age as well as the regional cerebral hypometabolic effects such as frontal, temporal, or basal ganglia effects associated with depression.

In summary, this study has found that the association between major depression and cognitive impairment is present in elderly, but not young, stroke patients. This study is also consistent with the hypothesis that dementia of depression in both the brain-injured and the non-brain-injured population occurs only in the elderly. The ultimate proof of this hypothesis, however, will require further research.


  ACKNOWLEDGMENTS

 
This work was supported in part by the following NIMH grants: MH-40355, MH-52879, MH-53592, and Research Scientist Award MH-00163 (RGR) and a grant from the Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan (AT and YM). The authors thank James T. Kosier, B.S., for assistance on data management and analysis.


  REFERENCES

 
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Ebrahim S, Barer D, Nouri F: Affective illness after stroke. Br J Psychiatry 1987; 151:52-56[Abstract/Free Full Text]
  2. Wade DT, Legh-Smith J, Hewer RA: Depressed mood after stroke, a community study of its frequency. Br J Psychiatry 1987; 151:200-205[Abstract/Free Full Text]
  3. Eastwood MR, Rifat SL, Nobbs H, et al: Mood disorder following cerebrovascular accident. Br J Psychiatry 1989; 154:195-200[Abstract/Free Full Text]
  4. Tyerman AL, Humphrey M: Changes in self concept following severe head injury. Int J Rehabil Res 1984; 7:11-23[Medline]
  5. Brooks N, Campsie L, Symington C, et al: The five year outcome of severe blunt head injury: A relative's view. J Neurol Neurosurg Psychiatry 1986; 49:764-770[Abstract/Free Full Text]
  6. Silver JM, Yudofsky SC, Hales RE: Depression in traumatic brain injury. Neuropsychiatr Neuropsychol Behav Neurol 1991; 4:12-23
  7. Burvill PW, Johnson GA, Jamrozik KD, et al: Prevalence of depression after stroke: The Perth Community Stroke Study. Br J Psychiatry 1995; 166:320-327[Abstract/Free Full Text]
  8. Robinson RG, Price TR: Post-stroke depressive disorders: A follow-up study of 103 outpatients. Stroke 1982; 13:635-641[Abstract/Free Full Text]
  9. Sinyor D, Jacques P, Kaloupek DG, et al: Post-stroke depression and lesion location: An attempted replication. Brain 1986; 109:539-546
  10. Rutherford WH, Merrett JD, McDonald JR: Sequelae of concussion caused by minor head injuries. Lancet 1977; 1:1-4[Medline]
  11. Fedoroff JP, Starkstein SE, Forrester AW, et al: Depression in patients with acute traumatic brain injury. Am J Psychiatry 1992; 149:918-923[Abstract/Free Full Text]
  12. Fann JR, Katon WJ, Uomoto JM, et al: Psychiatric disorders and functional disability in outpatients with traumatic brain injuries. Am J Psychiatry 1995; 152:1493-1499[Abstract/Free Full Text]
  13. Robinson RG, Bolla-Wilson K, Kaplan E, et al: Depression influences intellectual impairment in stroke patients. Br J Psychiatry 1986; 148:541-547[Abstract/Free Full Text]
  14. Bolla-Wilson K, Robinson RG, Starkstein SE, et al: Lateralization of dementia of depression in stroke patients. Am J Psychiatry 1989; 146:627-634[Abstract/Free Full Text]
  15. Downhill JE Jr,, Robinson RG: Longitudinal assessment of depression and cognitive impairment following stroke. J Nerv Ment Dis 1994; 182:425-431[Medline]
  16. House A, Dennis M, Warlow C, et al: The relationship between intellectual impairment and mood disorder in the first year after stroke. Psychol Med 1990; 20:805-814[Medline]
  17. Andersen G, Vestergaard K, Riis JO, et al: Dementia of depression or depression of dementia in stroke?. Acta Psychiatr Scand 1996; 94:272-278[Medline]
  18. Kauhanen M, Korpelainen JT, Hiltunen P, et al: Poststroke depression correlates with cognitive impairment and neurological deficits. Stroke 1999; 30:1875-1880[Abstract/Free Full Text]
  19. Murata Y, Kimura M, Robinson RG: Does cognitive impairment cause post-stroke depression?. Am J Geriatr Psychiatry 2000; 8:310-317[CrossRef][Medline]
  20. 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[CrossRef][Medline]
  21. Jorge RE, Robinson RG, Arndt SV, Starkstein SE, et al: Depression following traumatic brain injury: A 1 year longitudinal study. J Affect Disord 1993; 27:233-243[CrossRef][Medline]
  22. Robinson RG, Schultz SK, Castillo C, et al: Nortriptyline versus fluoxetine in the treatment of depression and in short term recovery after stroke: A placebo controlled, double-blind study. Am J Psychiatry 2000; 157:351-359[Abstract/Free Full Text]
  23. Wing JK, Cooper JE, Sartorius N: The Measurement and Classification of Psychiatric Symptoms: An Instructional Manual for the PSE and CATEGO Programs. New York, Cambridge University Press, 1974
  24. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition: Washington, DC, American Psychiatric Press, 1994
  25. Hamilton MA: A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23:56-62
  26. Starkstein SE, Robinson RG, Price TR: Comparison of cortical and subcortical lesions in the production of post-stroke mood disorders. Brain 1987; 110:1045-1059[Abstract/Free Full Text]
  27. Taylor CA, Price TRP: Neuropsychiatric assessment, in Neuropsychiatry of Traumatic Brain Injury: Edited by Silver JM, Yudofsky SC, Hales RE. Washington, DC, American Psychiatric Press, 1994, pp 81-132
  28. Rapoport MJ, Feinstein A: Outcome following traumatic brain injury in the elderly: A critical review. Brain Inj 2000; 14:749-761[CrossRef][Medline]
  29. Jorm AF.: Cognitive deficit in the depressed elderly: A review of some basic unresolved issues. Aust N Z J Psychiatry 1986; 20:11-22[Medline]




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