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Transient Ischemic Attack and Incidence of Depression in Old Age: Evidence From a Population-Based Analysis in Taiwan
REGULAR RESEARCH ARTICLES
Transient Ischemic Attack and Incidence of Depression in Old Age: Evidence From a Population-Based Analysis in Taiwan Kuan-Yi Wu, M.D., Chia-Yih Liu, M.D., Yeuk-Lun Chau, M.S., Chia-Ming Chang, M.D., Ph.D.
Objectives: The association between transient ischemic attack (TIA) and depression has not been investigated previously. This study was aimed to examine the relationship between TIA and depression in old age in Taiwan. Method: This cross-sectional analysis was performed using data from the nationwide 2002 Health Promotion Knowledge, Attitude, Performance Survey in Taiwan. Depressive symptoms were categorized using the Taiwanese Depression Questionnaire with a cutoff point of 18 of 19, and TIA was defined as the sudden or rapid onset of focal neurologic deficit that had fully resolved within 24 hours. Cerebrovascular risk factors (CVRFs) including age, cardiovascular disease, diabetes mellitus, hypertension, antihypertensive drugs, and smoking were used as covariates. Results: Of the total 3,613 subjects aged 65 years and older, 8.2% had previously experienced a TIA. Subjects with depressive symptoms were significantly more likely to have a previous TIA than those without depressive symptoms (17.1%:7.4%, odds ratio [OR] ⫽ 2.6, 95% confidence interval [CI] ⫽ 1.8 –3.8). After controlling of sex, education, functional disability, and CVRFs, TIA was still significantly associated with depression in old age (Adjusted OR ⫽ 2.1, 95% CI ⫽ 1.4 –3.2). Conclusion: Previous TIA was significantly increased risk of depression which cannot be explained by functional disability or CVRFs. This result supported the hypothesis of vascular depression. (Am J Geriatr Psychiatry 2010; 18:382–387) Key Words: Transient ischemic attack, depression, cerebrovascular factors
L
iteratures have long supported the existence of a strong association between stroke and depression.1,2 Some studies suggested a direct neurobiological mechanism caused by the structural brain damage (i.e., a direct disruption of brain circuits) of stroke.3,4 Other studies demonstrated an association
between deep white matter hyperintensities and depression.5– 8 Therefore, some studies proposed that small-vessel brain disease, which results from chronic ischemic changes in the brain over time, may be part of the pathogenetic mechanism of late-life depression.9 Most of these studies examining the association of
Received January 22, 2009; revised October 5, 2009; accepted October 6, 2009. From the Department of Psychiatry, Chang Gung Memorial Hospital at Linkou & College of Medicine, Chang Gung University, Taoyuan, Taiwan. Send correspondence and reprint requests to Chia-Ming Chang, M.D., Ph.D., Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, No. 5, Fu-Sing Street, Kweisan county, Taoyuan 333, Taiwan, ROC. e-mail: [email protected] © 2010 American Association for Geriatric Psychiatry
382
Am J Geriatr Psychiatry 18:5, May 2010
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Wu et al. stroke and depression have been mainly focused on fully manifested stroke. However, the association between depression and transient ischemic attack (TIA), a relevant subgroup of cerebrovascular diseases with the characteristic of no overt sequelae or residual complications, is still unclear.10 The vascular depression hypothesis was postulated that cerebrovascular disease can predispose, precipitate, or perpetuate a depressive syndrome in older adults.11,12 Cerebrovascular risk factors (CVRFs) have been identified as key risk factors for stroke.13 To test a small-vessel brain disease model, several studies have focused on the association between CVRFs and depression. Some of the results supported the existence of this association,7,14 –16 but other studies failed.1,17,18 Medical burden or psychological factors specific to TIA have less impact than a fully manifested stroke. To our knowledge, there have been a few studies examining the association between TIA and depression, whereas the majority of them involved mixed samples of stroke and TIA.19 –21 Therefore, the objective of this study is to focus exclusively on TIA and to examine whether TIA is independently associated with depressive symptoms in a large representative population-based sample of older people.
METHODS Sample This study was based on the 2002 Health Promotion Knowledge, Attitude, Performance Survey (HPKAP), a cross-sectional population-based nationwide survey conducted among Taiwanese residents in Taiwan aged 15 years or older. A total of 26,755 residents responded to HPKAP (response rate 81.9%). This nationwide survey consisted of a structured questionnaire, used to assess the current physical and mental health status, common medical illnesses, health knowledge and attitudes of the responders, and was supported by the Bureau of Health Promotion, Department of Health, Taiwan. HPKAP sought to obtain data from a nationally representative sample of households in Taiwan using three-stage stratified random sampling methods. The sampling process was based on the National Census Register, 2002: townships of cities and coun-
Am J Geriatr Psychiatry 18:5, May 2010
ties in Taiwan were randomly sampled as primary units; neighborhoods were randomly sampled as secondary units; and finally, eligible people aged 15 years and older were randomly sampled as project participants, with 26,755 participants in total completing the interview. Data were gathered in face-toface interviews conducted by 323 skillful interviewers employed by the Bureau of Health Promotion, who were trained in a 3-day workshop to ensure the standardization of interviews. To investigate the association between TIA and depression in old age, we used HPKAP data and focused on the 3,853 subjects aged 65 years or older. We excluded 235 subjects who had a history of fully manifested stroke and five subjects who provided incomplete responses to the TIA questionnaire; hence, the final sample size of this study was 3,613. This study was approved by the Institutional Review Board of Chang Gung Memorial Hospital. Measures Participants underwent an assessment at home by trained research interviewers. The measures described below were considered in this study, and some variables were newly categorized. Information was obtained using self- or informant reports. Previous Transient Ischemic Attacks TIA was defined as the sudden or rapid onset of focal neurologic deficit that had fully resolved within 24 hours. The ascertainment of TIA in this study was based on the responses of HPKAP participants to standardized questionnaires designed to gather information regarding lifetime occurrences of one or more focal neurologic symptoms with sudden onset and the mode of remission. A subject was considered to have TIA if he or she reported “yes” in the question—“Have you ever experienced of transient speech dysfunction, numbness/tingling, weakness/ paralysis and resolved within 24 hours, which people called it TIA or ‘mini stroke’?” To examine the effects of TIA on depression only, subjects who had suffered a fully manifested stroke were excluded. Information on CVRFs Framingham study12 had identified key risk factors—CVRFs—for completed stroke; these CVRFs con-
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Transient Ischemic Attack and Depression sisted of age, systolic blood pressure, use of antihypertensive therapy, cigarette smoking, the presence of diabetes mellitus or prior cardiovascular disease, atrial fibrillation, and left ventricular hypertrophy by electrocardiogram. Atrial fibrillation and left ventricular hypertrophy were not included in this study due to the limitations of the project data. Subjects were asked about a recalled physician diagnosis of specific illnesses of CVRFs in the standardized questionnaire. Based on the literature regarding cigarette smoking and stroke risk,22,23 subjects were divided into four smoking categories according to their baseline smoking habits: nonsmoker (had never smoked or had stopped smoking 5 or more years ago), exsmoker (had stopped smoking between 1 and 4 years ago), moderate smoker (smoked 1–20 cigarettes/day), and heavy smoker (smoked ⬎21 cigarettes/day).
to provide unbiased population-based estimates of prevalence and associations between variables. The standardized weighted procedure was provided by the Health Promotion Bureau, Department of Health. We used clinically significant depression as the dependent variable (categorized by TDQ), and previous TIA, demographic factors, ADL disability and CVRFs as the independent variables. Univariate logistic analysis was carried out to investigate the association between depression and other variables. Multiple logistic regression was performed to determine the independent association between TIA and depression while controlling the covariates as confounding factors. Statistical significance was set at the level of p ⬍0.05.
Limitation in Activities of Daily Living
Characteristics of the Study Sample
Functional limitation was assessed in this study using a standard questionnaire of six basic activities of daily living (ADL) defined by similar variables from the Katz index.24 These activities included dressing, grooming, feeding, transferring, walking, and going to the toilet. In this study, ADL limitation was dichotomized as the presence of functional limitation (functionally dependent in one or more ADL by observation) and the absence of functional limitation (functionally independent in all ADL tasks by observation).25
RESULTS
The study sample had a mean age of 72.8 ⫾ 5.9 years and an even gender distribution (male, 51.5%). In total, 8.2% of subjects reported having experienced at least one TIA event before the HPKAP interview, and 8.6% of subjects were estimated as having some depressive symptoms, as classified using the TDQ total scores. Of these subjects, 34.7% had hypertension, 15.7% had diabetes mellitus, 21.5% had cardiovascular diseases, and 32.5% were undergoing antihypertensive treatment. Univariate Analysis
Depressive Symptoms Depressive symptoms were assessed using the Taiwanese Depression Questionnaire (TDQ), a reliable and validated scale that has been proved suitable for conducting epidemiologic surveys and screening for depression in Taiwanese people. The TDQ is an 18item, self-reported scale; each item is scored from 0 to 3, and the total score ranges from 0 to 54. A cutoff score of 19, which had a sensitivity of 0.89 and a specificity of 0.92,26 was used to indicate the presence of depressive disorder in this study. Statistical Analysis Given the stratified random sampling strategy used in the survey, weighted analyses of the data were used
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Subjects with depressive symptoms were significantly more likely to have previously experienced a TIA than those without depressive symptoms. Gender, education, ADL disability, cardiovascular diseases, and diabetes mellitus were also found to be significantly associated with depression. However, no substantial associations were noted in terms of living status, hypertension, or antihypertensive medication (Table 1). Multivariate Analyses The strength of the association between TIA and depression was reduced after adjustment for demographic data and ADL disability, but the association remained statistically significant. At finally, after con-
Am J Geriatr Psychiatry 18:5, May 2010
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Wu et al.
TABLE 1.
Univariate Associations Between Previous Occurrence of Transient Ischemia Attack (TIA), Demographic Factors, ADL Disability, CVRFs, and Depression in Old Age
Previous TIA Sex Male Female Age, years 65–69 70–74 75–79 80–84 ⱖ85 Education Formal None Living status With family With others Alone ADL disability Cardiovascular disease Hypertension Diabetes mellitus Antihypertensive drugs Smoking Nonsmoker Exsmoker Moderate smoker Heavy smoker
Depression, n ⴝ 263 (Weighted %)
No Depression, n ⴝ 3,350 (Weighted %)
OR (95% CI)
p
52 (17.1)
243 (7.4)
2.6 (1.8–3.8)
⬍0.001
87 (33.4) 176 (66.6)
1,717 (53.2) 1,633 (46.8)
1.0 2.3 (1.7–3.0)
⬍0.001
80 (30.1) 74 (26.7) 56 (23.2) 37 (11.4) 16 (8.6)
1,204 (35.1) 1,015 (29.8) 671 (21.3) 307 (9.2) 153 (4.7)
1.0 1.0 (0.7–1.5) 1.3 (0.9–1.9) 1.5 (0.9–2.4) 2.1 (1.2–3.7)
0.82 0.22 0.13 0.01
125 (49.4) 138 (50.6)
2,124 (66.5) 1,226 (33.5)
1.0 2.0 (1.5–2.7)
⬍0.001
224 (86.5) 5 (1.7) 34 (11.8) 83 (28.2) 89 (32.6) 111 (36.2) 62 (25.9) 100 (32.3)
2,911 (88.0) 40 (1.2) 399 (10.8) 244 (6.8) 615 (20.4) 1,154 (34.6) 484 (14.7) 1,080 (32.5)
1.0 1.5 (0.5–4.3) 1.1 (0.7–1.7) 5.4 (3.9–7.5) 1.9 (1.4–2.5) 1.1 (0.8–1.4) 2.0 (1.5–2.8) 1.0 (0.7–1.3)
0.49 0.64 ⬍0.001 ⬍0.001 0.63 ⬍0.001 0.96
220 (87.1) 7 (1.9) 20 (5.0) 16 (6.0)
2,617 (77.8) 39 (1.5) 369 (11.5) 325 (9.2)
1.0 1.1 (0.4–3.2) 0.4 (0.2–0.7) 0.6 (0.3–1.0)
0.80 ⬍0.001 0.06
Notes: p values are based on binary logistic regression; degrees of freedom for age was 4, for living status was 2, for smoking was 3, and for the other variables were equal to 1. OR: odds ratio; CI: confidence interval.
trolling of sex, education, functional disability, and all CVRFs, TIA continued to make a significant independent contribution to the risk of depression (Table 2).
DISCUSSION Our results showed that 8.2% of the study subjects had reported a lifetime occurrence of at least one TIA episode. In one epidemiologic study,22 6% of participants aged 45– 64 years were estimated as having a self-reported TIA. In another nationwide survey among participants aged 18 years or older, 2.3% reported being told by a physician that they had experienced a TIA, and an additional 3.2% recalled symptoms consistent with TIA but did not seek medical attention.23 One recent survey in the Asia elderly also revealed that the prevalence of physician diagnosis of TIA was 8.9%,19 which was consistent with our study.
Am J Geriatr Psychiatry 18:5, May 2010
The prevalence of depressive symptoms among community-dwelling elderly persons aged 65 years or older in Taiwan has been estimated at between 12.8% and 20.1%.27,28 In this study, the estimate of depressive disorder among elderly subjects as classified using the TDQ was calculated to be 8.6%. Such differences could be explained by the different screening instruments and study areas. A significant association was found between previous experience of a TIA and depression in old age independent of physical disability and other confounding covariates. The risk of current depression might remain increased over a considerably longer period of time after a TIA, which cannot fully be explained by the effects of functional limitation and other potential confounders. Because no overt physical complications result from a TIA, the medical disability and/or burden resulting from a TIA has less psychological impact on the development of depression than the same resulting from a fully mani-
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Transient Ischemic Attack and Depression
TABLE 2.
Multivariate Associations Between TIA and Depression in Old Age Model 1a
TIA Female Age, years 65–69 70–74 75–79 80–84 ⱖ85 Education ADL disability Cardiovascular disease Hypertension Diabetes mellitus Antihypertensive drugs Smoking Nonsmoker Exsmoker Moderate smoker Heavy smoker
Model 2b
Model 3c
OR (95% CI)
p
OR (95% CI)
p
OR (95% CI)
p
2.6 (1.8–3.9) 2.0 (1.5–2.8)
⬍0.001 ⬍0.001
2.2 (1.5–3.3) 1.8 (1.3–2.5)
⬍0.001 ⬍0.001
2.1 (1.4–3.2) 1.7 (1.2–2.3)
⬍0.001 0.005
1 1.0 (0.7–1.5) 1.3 (0.9–1.9) 1.3 (0.8–2.2) 1.8 (1.1–2.0) 1.5 (1.1–2.0)
0.875 0.217 0.238 0.044 0.011
1 0.9 (0.7–1.4) 1.1 (0.7–1.6) 1.0 (0.6–1.6) 1.2 (0.6–2.1) 1.4 (1.1–2.0) 4.2 (2.9–6.0)
0.78 0.766 0.927 0.618 0.021 ⬍0.001
1 0.9 (0.6–1.4) 1.1 (0.7–1.6) 1.0 (0.6–1.7) 1.3 (0.7–2.3) 1.5 (1.1–2.1) 3.9 (2.7–5.7) 1.6 (1.1–2.2) 1.6 (0.8–3.3) 1.8 (1.3–2.6) 0.5 (0.2–1.0)
0.757 0.793 0.937 0.436 0.012 ⬍0.001 0.009 0.19 0.001 0.037
1 1.6 (0.5–4.8) 0.5 (0.3–0.9) 1.0 (0.5–1.8)
0.383 0.028 0.893
Notes: p values are based on multivariate logistic regression. a Model 1 examined the multivariate effects of the demographic variables, degree of freedom was 3. b Model 2 examined the multivariate effects of the variables of Model 1 and ADL disability, degree of freedom was 5. c Model 3 examined the multivariate effects of the variables in Models 1 and 2 and the effects of cardiovascular disease, hypertension, diabetes mellitus, antihypertension drugs, and smoking, degree of freedom was 8.
fested stroke. This association between TIA and depression in old age independent of functional disability provides unique and alternative evidence for the involvement of cerebrovascular disease in the pathogenesis of late-life depression, which is different from the case of a fully manifested stroke. Interpretation and generalization of these findings must include acknowledgment of several potential limitations of this study. First, although we used standardized question to ascertainment of TIA, accurate diagnosis of TIA was a major limitation. For the nature of TIA, most epidemiologic ascertainment of occurrence of TIA is still limited to self-reported symptoms without any confirmatory laboratory abnormalities, as was the case in this study.29,30 Second, for the cross-sectional design, the temporal relationship between TIA and depression cannot be determined, which limits causal inference. Third, recall bias should also be considered. Nonetheless, this study used national random sampling data and found the
association between TIA and depression in old age independent of functional disability, which supported the vascular depression hypothesis, may be considered the strengths of this study. Future investigations may consider the analyses of the cumulative effect of CVRFs to explore the connection between clinical TIA and the pathophysiology of arthreosclerosis in the development of late-life depression and the performance of longitudinal design to elucidate the direction of causality between TIA and depression.
CONCLUSION This population-based study observed a significant association between TIA and depression in old age, independent of physical disability and CVRFs. The results may provide further support for the vascular depression hypothesis.
References 1. Stewart R, Prince M, Mann A, et al: Stroke, vascular risk factors and depression: cross-sectional study in a UK Caribbean-born population. Br J Psychiatry 2001; 178:23–28
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2. Whyte EM, Mulsant BH, Vanderbilt J, et al: Depression after stroke: a prospective epidemiological study. J Am Geriatr Soc 2004; 52:774 –778
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Wu et al. 3. Whyte EM, Mulsant BH: Post stroke depression: epidemiology, pathophysiology, and biological treatment. Biol Psychiatry 2002; 52:253–264 4. Kales HC, Maixner DF, Mellow AM: Cerebrovascular disease and late-life depression. Am J Geriatr Psychiatry 2005; 13:88 –98 5. Krishnan KR, Hays JC, Blazer DG: MRI-defined vascular depression. Am J Psychiatry 1997; 154:497–501 6. Lyness JM, Caine ED, Cox C, et al: Cerebrovascular risk factors and later-life major depression. Testing a small-vessel brain disease model. Am J Geriatr Psychiatry 1998; 6:5–13 7. Steffens DC, Krishnan KR: Structural neuroimaging and mood disorders: recent findings, implications for classification, and future directions. Biol Psychiatry 1998; 43:705–712 8. Chen CS, Chen CC, Kuo YT, et al: Carotid intima-media thickness in late-onset major depressive disorder. Int J Geriatr Psychiatry 2006; 21:36 – 42 9. Krishnan KR, Krishnan KR: Biological risk factors in late life depression. Biol Psychiatry 2002; 52:185–192 10. Rao R: Depression after transient ischemic attack: a clinically distinct subtype of vascular depression? Arch Gen Psychiatry 1998; 55:753–754 11. Alexopoulos GS, Meyers BS, Young RC, et al: ‘Vascular depression’ hypothesis. Arch Gen Psychiatry 1997; 54:915–922 12. Alexopoulos GS: The vascular depression hypothesis: 10 years later. Biol Psychiatry 2006; 60:1304 –1305 13. Wolf PA, D’Agostino RB, Belanger AJ, et al: Probability of stroke: a risk profile from the Framingham Study. Stroke 1991; 22:312–318 14. Mast BT, Azar AR, Murrell SA: The vascular depression hypothesis: the influence of age on the relationship between cerebrovascular risk factors and depressive symptoms in community dwelling elders. Aging Ment Health 2005; 9:146 –152 15. Mast BT, Neufeld S, MacNeill SE, et al: Longitudinal support for the relationship between vascular risk factors and latelife depressive symptoms. Am J Geriatr Psychiatry 2004; 12: 93–101 16. Mast BT, MacNeill SE, Lichtenberg PA: Post-stroke and clinicallydefined vascular depression in geriatric rehabilitation patients. Am J Geriatr Psychiatry 2004; 12:84 –92 17. Lyness JM, King DA, Conwell Y, et al: Cerebrovascular risk factors and 1-year depression outcome in older primary care patients. Am J Psychiatry 2000; 157:1499 –1501
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18. Lyness JM, Caine ED, King DA, et al: Cerebrovascular risk factors and depression in older primary care patients: testing a vascular brain disease model of depression. Am J Geriatr Psychiatry 1999; 7:252–258 19. Han MK, Huh Y, Lee SB, et al: Prevalence of stroke and transient ischemic attack in Korean elders: findings from the Korean Longitudinal Study on Health and Aging (KLoSHA). Stroke 2009; 40:966 –969 20. van Wijk I, Gorter JW, Lindeman E, et al: Mental status and health-related quality of life in an elderly population 15 years after limited cerebral ischaemia. J Neurol 2007; 254:1018 –1025 21. Brodaty H, Withall A, Altendorf A, et al: Rates of depression at 3 and 15 months poststroke and their relationship with cognitive decline: the Sydney Stroke Study. Am J Geriatr Psychiatry 2007; 15:477– 486 22. Wolf PA, D’Agostino RB, Kannel WB, et al: Cigarette smoking as a risk factor for stroke. The Framingham Study. JAMA 1988; 259:1025–1029 23. Ueshima H, Choudhury SR, Okayama A, et al: Cigarette smoking as a risk factor for stroke death in Japan: NIPPON DATA80. Stroke 2004; 35:1836 –1841 24. Katz S, Ford AB, Moskowitz RW, et al: Studies of illness in the aged. The index of ADL: a standardized measure of biological and psychosocial function. JAMA 1963; 185:914 –919 25. Kelly-Hayes M, Jette AM, Wolf PA, et al: Functional limitations and disability among elders in the Framingham Study. Am J Public Health 1992; 82:841– 845 26. Lee Y, Yang MJ, Lai TJ, et al: Development of the Taiwanese Depression Questionnaire. Chang Gung Med J 2000; 23:688 – 694 27. Chiu HC, Chen CM, Huang CJ, et al: Depressive symptoms, chronic medical conditions and functional status: a comparison of urban and rural elders in Taiwan. Int J Geriatr Psychiatry 2005; 20:635– 644 28. Liu CY, Wang SJ, Teng EL, et al: Depressive disorders among older residents in a Chinese rural community. Psychol Med 1997; 27: 943–949 29. Toole JF, Lefkowitz DS, Chambless LE, et al: Self-reported transient ischemic attack and stroke symptoms: methods and baseline prevalence. The ARIC Study, 1987–1989. Am J Epidemiol 1996; 144:849 – 856 30. Johnston SC, Fayad PB, Gorelick PB, et al: Prevalence and knowledge of transient ischemic attack among US adults. Neurology 2003; 60:1429 –1434
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Transient Ischemic Attack and Incidence of Depression in Old Age: Evidence From a Population-Based Analysis in Taiwan Kuan-Yi Wu, M.D., Chia-Yih Liu, M.D., Yeuk-Lun Chau, M.S., Chia-Ming Chang, M.D., Ph.D.
Objectives: The association between transient ischemic attack (TIA) and depression has not been investigated previously. This study was aimed to examine the relationship between TIA and depression in old age in Taiwan. Method: This cross-sectional analysis was performed using data from the nationwide 2002 Health Promotion Knowledge, Attitude, Performance Survey in Taiwan. Depressive symptoms were categorized using the Taiwanese Depression Questionnaire with a cutoff point of 18 of 19, and TIA was defined as the sudden or rapid onset of focal neurologic deficit that had fully resolved within 24 hours. Cerebrovascular risk factors (CVRFs) including age, cardiovascular disease, diabetes mellitus, hypertension, antihypertensive drugs, and smoking were used as covariates. Results: Of the total 3,613 subjects aged 65 years and older, 8.2% had previously experienced a TIA. Subjects with depressive symptoms were significantly more likely to have a previous TIA than those without depressive symptoms (17.1%:7.4%, odds ratio [OR] ⫽ 2.6, 95% confidence interval [CI] ⫽ 1.8 –3.8). After controlling of sex, education, functional disability, and CVRFs, TIA was still significantly associated with depression in old age (Adjusted OR ⫽ 2.1, 95% CI ⫽ 1.4 –3.2). Conclusion: Previous TIA was significantly increased risk of depression which cannot be explained by functional disability or CVRFs. This result supported the hypothesis of vascular depression. (Am J Geriatr Psychiatry 2010; 18:382–387) Key Words: Transient ischemic attack, depression, cerebrovascular factors
L
iteratures have long supported the existence of a strong association between stroke and depression.1,2 Some studies suggested a direct neurobiological mechanism caused by the structural brain damage (i.e., a direct disruption of brain circuits) of stroke.3,4 Other studies demonstrated an association
between deep white matter hyperintensities and depression.5– 8 Therefore, some studies proposed that small-vessel brain disease, which results from chronic ischemic changes in the brain over time, may be part of the pathogenetic mechanism of late-life depression.9 Most of these studies examining the association of
Received January 22, 2009; revised October 5, 2009; accepted October 6, 2009. From the Department of Psychiatry, Chang Gung Memorial Hospital at Linkou & College of Medicine, Chang Gung University, Taoyuan, Taiwan. Send correspondence and reprint requests to Chia-Ming Chang, M.D., Ph.D., Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, No. 5, Fu-Sing Street, Kweisan county, Taoyuan 333, Taiwan, ROC. e-mail: [email protected] © 2010 American Association for Geriatric Psychiatry
382
Am J Geriatr Psychiatry 18:5, May 2010
Copyright © American Association for Geriatric Psychiatry. Unauthorized reproduction of this article is prohibited.
Wu et al. stroke and depression have been mainly focused on fully manifested stroke. However, the association between depression and transient ischemic attack (TIA), a relevant subgroup of cerebrovascular diseases with the characteristic of no overt sequelae or residual complications, is still unclear.10 The vascular depression hypothesis was postulated that cerebrovascular disease can predispose, precipitate, or perpetuate a depressive syndrome in older adults.11,12 Cerebrovascular risk factors (CVRFs) have been identified as key risk factors for stroke.13 To test a small-vessel brain disease model, several studies have focused on the association between CVRFs and depression. Some of the results supported the existence of this association,7,14 –16 but other studies failed.1,17,18 Medical burden or psychological factors specific to TIA have less impact than a fully manifested stroke. To our knowledge, there have been a few studies examining the association between TIA and depression, whereas the majority of them involved mixed samples of stroke and TIA.19 –21 Therefore, the objective of this study is to focus exclusively on TIA and to examine whether TIA is independently associated with depressive symptoms in a large representative population-based sample of older people.
METHODS Sample This study was based on the 2002 Health Promotion Knowledge, Attitude, Performance Survey (HPKAP), a cross-sectional population-based nationwide survey conducted among Taiwanese residents in Taiwan aged 15 years or older. A total of 26,755 residents responded to HPKAP (response rate 81.9%). This nationwide survey consisted of a structured questionnaire, used to assess the current physical and mental health status, common medical illnesses, health knowledge and attitudes of the responders, and was supported by the Bureau of Health Promotion, Department of Health, Taiwan. HPKAP sought to obtain data from a nationally representative sample of households in Taiwan using three-stage stratified random sampling methods. The sampling process was based on the National Census Register, 2002: townships of cities and coun-
Am J Geriatr Psychiatry 18:5, May 2010
ties in Taiwan were randomly sampled as primary units; neighborhoods were randomly sampled as secondary units; and finally, eligible people aged 15 years and older were randomly sampled as project participants, with 26,755 participants in total completing the interview. Data were gathered in face-toface interviews conducted by 323 skillful interviewers employed by the Bureau of Health Promotion, who were trained in a 3-day workshop to ensure the standardization of interviews. To investigate the association between TIA and depression in old age, we used HPKAP data and focused on the 3,853 subjects aged 65 years or older. We excluded 235 subjects who had a history of fully manifested stroke and five subjects who provided incomplete responses to the TIA questionnaire; hence, the final sample size of this study was 3,613. This study was approved by the Institutional Review Board of Chang Gung Memorial Hospital. Measures Participants underwent an assessment at home by trained research interviewers. The measures described below were considered in this study, and some variables were newly categorized. Information was obtained using self- or informant reports. Previous Transient Ischemic Attacks TIA was defined as the sudden or rapid onset of focal neurologic deficit that had fully resolved within 24 hours. The ascertainment of TIA in this study was based on the responses of HPKAP participants to standardized questionnaires designed to gather information regarding lifetime occurrences of one or more focal neurologic symptoms with sudden onset and the mode of remission. A subject was considered to have TIA if he or she reported “yes” in the question—“Have you ever experienced of transient speech dysfunction, numbness/tingling, weakness/ paralysis and resolved within 24 hours, which people called it TIA or ‘mini stroke’?” To examine the effects of TIA on depression only, subjects who had suffered a fully manifested stroke were excluded. Information on CVRFs Framingham study12 had identified key risk factors—CVRFs—for completed stroke; these CVRFs con-
383
Copyright © American Association for Geriatric Psychiatry. Unauthorized reproduction of this article is prohibited.
Transient Ischemic Attack and Depression sisted of age, systolic blood pressure, use of antihypertensive therapy, cigarette smoking, the presence of diabetes mellitus or prior cardiovascular disease, atrial fibrillation, and left ventricular hypertrophy by electrocardiogram. Atrial fibrillation and left ventricular hypertrophy were not included in this study due to the limitations of the project data. Subjects were asked about a recalled physician diagnosis of specific illnesses of CVRFs in the standardized questionnaire. Based on the literature regarding cigarette smoking and stroke risk,22,23 subjects were divided into four smoking categories according to their baseline smoking habits: nonsmoker (had never smoked or had stopped smoking 5 or more years ago), exsmoker (had stopped smoking between 1 and 4 years ago), moderate smoker (smoked 1–20 cigarettes/day), and heavy smoker (smoked ⬎21 cigarettes/day).
to provide unbiased population-based estimates of prevalence and associations between variables. The standardized weighted procedure was provided by the Health Promotion Bureau, Department of Health. We used clinically significant depression as the dependent variable (categorized by TDQ), and previous TIA, demographic factors, ADL disability and CVRFs as the independent variables. Univariate logistic analysis was carried out to investigate the association between depression and other variables. Multiple logistic regression was performed to determine the independent association between TIA and depression while controlling the covariates as confounding factors. Statistical significance was set at the level of p ⬍0.05.
Limitation in Activities of Daily Living
Characteristics of the Study Sample
Functional limitation was assessed in this study using a standard questionnaire of six basic activities of daily living (ADL) defined by similar variables from the Katz index.24 These activities included dressing, grooming, feeding, transferring, walking, and going to the toilet. In this study, ADL limitation was dichotomized as the presence of functional limitation (functionally dependent in one or more ADL by observation) and the absence of functional limitation (functionally independent in all ADL tasks by observation).25
RESULTS
The study sample had a mean age of 72.8 ⫾ 5.9 years and an even gender distribution (male, 51.5%). In total, 8.2% of subjects reported having experienced at least one TIA event before the HPKAP interview, and 8.6% of subjects were estimated as having some depressive symptoms, as classified using the TDQ total scores. Of these subjects, 34.7% had hypertension, 15.7% had diabetes mellitus, 21.5% had cardiovascular diseases, and 32.5% were undergoing antihypertensive treatment. Univariate Analysis
Depressive Symptoms Depressive symptoms were assessed using the Taiwanese Depression Questionnaire (TDQ), a reliable and validated scale that has been proved suitable for conducting epidemiologic surveys and screening for depression in Taiwanese people. The TDQ is an 18item, self-reported scale; each item is scored from 0 to 3, and the total score ranges from 0 to 54. A cutoff score of 19, which had a sensitivity of 0.89 and a specificity of 0.92,26 was used to indicate the presence of depressive disorder in this study. Statistical Analysis Given the stratified random sampling strategy used in the survey, weighted analyses of the data were used
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Subjects with depressive symptoms were significantly more likely to have previously experienced a TIA than those without depressive symptoms. Gender, education, ADL disability, cardiovascular diseases, and diabetes mellitus were also found to be significantly associated with depression. However, no substantial associations were noted in terms of living status, hypertension, or antihypertensive medication (Table 1). Multivariate Analyses The strength of the association between TIA and depression was reduced after adjustment for demographic data and ADL disability, but the association remained statistically significant. At finally, after con-
Am J Geriatr Psychiatry 18:5, May 2010
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Wu et al.
TABLE 1.
Univariate Associations Between Previous Occurrence of Transient Ischemia Attack (TIA), Demographic Factors, ADL Disability, CVRFs, and Depression in Old Age
Previous TIA Sex Male Female Age, years 65–69 70–74 75–79 80–84 ⱖ85 Education Formal None Living status With family With others Alone ADL disability Cardiovascular disease Hypertension Diabetes mellitus Antihypertensive drugs Smoking Nonsmoker Exsmoker Moderate smoker Heavy smoker
Depression, n ⴝ 263 (Weighted %)
No Depression, n ⴝ 3,350 (Weighted %)
OR (95% CI)
p
52 (17.1)
243 (7.4)
2.6 (1.8–3.8)
⬍0.001
87 (33.4) 176 (66.6)
1,717 (53.2) 1,633 (46.8)
1.0 2.3 (1.7–3.0)
⬍0.001
80 (30.1) 74 (26.7) 56 (23.2) 37 (11.4) 16 (8.6)
1,204 (35.1) 1,015 (29.8) 671 (21.3) 307 (9.2) 153 (4.7)
1.0 1.0 (0.7–1.5) 1.3 (0.9–1.9) 1.5 (0.9–2.4) 2.1 (1.2–3.7)
0.82 0.22 0.13 0.01
125 (49.4) 138 (50.6)
2,124 (66.5) 1,226 (33.5)
1.0 2.0 (1.5–2.7)
⬍0.001
224 (86.5) 5 (1.7) 34 (11.8) 83 (28.2) 89 (32.6) 111 (36.2) 62 (25.9) 100 (32.3)
2,911 (88.0) 40 (1.2) 399 (10.8) 244 (6.8) 615 (20.4) 1,154 (34.6) 484 (14.7) 1,080 (32.5)
1.0 1.5 (0.5–4.3) 1.1 (0.7–1.7) 5.4 (3.9–7.5) 1.9 (1.4–2.5) 1.1 (0.8–1.4) 2.0 (1.5–2.8) 1.0 (0.7–1.3)
0.49 0.64 ⬍0.001 ⬍0.001 0.63 ⬍0.001 0.96
220 (87.1) 7 (1.9) 20 (5.0) 16 (6.0)
2,617 (77.8) 39 (1.5) 369 (11.5) 325 (9.2)
1.0 1.1 (0.4–3.2) 0.4 (0.2–0.7) 0.6 (0.3–1.0)
0.80 ⬍0.001 0.06
Notes: p values are based on binary logistic regression; degrees of freedom for age was 4, for living status was 2, for smoking was 3, and for the other variables were equal to 1. OR: odds ratio; CI: confidence interval.
trolling of sex, education, functional disability, and all CVRFs, TIA continued to make a significant independent contribution to the risk of depression (Table 2).
DISCUSSION Our results showed that 8.2% of the study subjects had reported a lifetime occurrence of at least one TIA episode. In one epidemiologic study,22 6% of participants aged 45– 64 years were estimated as having a self-reported TIA. In another nationwide survey among participants aged 18 years or older, 2.3% reported being told by a physician that they had experienced a TIA, and an additional 3.2% recalled symptoms consistent with TIA but did not seek medical attention.23 One recent survey in the Asia elderly also revealed that the prevalence of physician diagnosis of TIA was 8.9%,19 which was consistent with our study.
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The prevalence of depressive symptoms among community-dwelling elderly persons aged 65 years or older in Taiwan has been estimated at between 12.8% and 20.1%.27,28 In this study, the estimate of depressive disorder among elderly subjects as classified using the TDQ was calculated to be 8.6%. Such differences could be explained by the different screening instruments and study areas. A significant association was found between previous experience of a TIA and depression in old age independent of physical disability and other confounding covariates. The risk of current depression might remain increased over a considerably longer period of time after a TIA, which cannot fully be explained by the effects of functional limitation and other potential confounders. Because no overt physical complications result from a TIA, the medical disability and/or burden resulting from a TIA has less psychological impact on the development of depression than the same resulting from a fully mani-
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Transient Ischemic Attack and Depression
TABLE 2.
Multivariate Associations Between TIA and Depression in Old Age Model 1a
TIA Female Age, years 65–69 70–74 75–79 80–84 ⱖ85 Education ADL disability Cardiovascular disease Hypertension Diabetes mellitus Antihypertensive drugs Smoking Nonsmoker Exsmoker Moderate smoker Heavy smoker
Model 2b
Model 3c
OR (95% CI)
p
OR (95% CI)
p
OR (95% CI)
p
2.6 (1.8–3.9) 2.0 (1.5–2.8)
⬍0.001 ⬍0.001
2.2 (1.5–3.3) 1.8 (1.3–2.5)
⬍0.001 ⬍0.001
2.1 (1.4–3.2) 1.7 (1.2–2.3)
⬍0.001 0.005
1 1.0 (0.7–1.5) 1.3 (0.9–1.9) 1.3 (0.8–2.2) 1.8 (1.1–2.0) 1.5 (1.1–2.0)
0.875 0.217 0.238 0.044 0.011
1 0.9 (0.7–1.4) 1.1 (0.7–1.6) 1.0 (0.6–1.6) 1.2 (0.6–2.1) 1.4 (1.1–2.0) 4.2 (2.9–6.0)
0.78 0.766 0.927 0.618 0.021 ⬍0.001
1 0.9 (0.6–1.4) 1.1 (0.7–1.6) 1.0 (0.6–1.7) 1.3 (0.7–2.3) 1.5 (1.1–2.1) 3.9 (2.7–5.7) 1.6 (1.1–2.2) 1.6 (0.8–3.3) 1.8 (1.3–2.6) 0.5 (0.2–1.0)
0.757 0.793 0.937 0.436 0.012 ⬍0.001 0.009 0.19 0.001 0.037
1 1.6 (0.5–4.8) 0.5 (0.3–0.9) 1.0 (0.5–1.8)
0.383 0.028 0.893
Notes: p values are based on multivariate logistic regression. a Model 1 examined the multivariate effects of the demographic variables, degree of freedom was 3. b Model 2 examined the multivariate effects of the variables of Model 1 and ADL disability, degree of freedom was 5. c Model 3 examined the multivariate effects of the variables in Models 1 and 2 and the effects of cardiovascular disease, hypertension, diabetes mellitus, antihypertension drugs, and smoking, degree of freedom was 8.
fested stroke. This association between TIA and depression in old age independent of functional disability provides unique and alternative evidence for the involvement of cerebrovascular disease in the pathogenesis of late-life depression, which is different from the case of a fully manifested stroke. Interpretation and generalization of these findings must include acknowledgment of several potential limitations of this study. First, although we used standardized question to ascertainment of TIA, accurate diagnosis of TIA was a major limitation. For the nature of TIA, most epidemiologic ascertainment of occurrence of TIA is still limited to self-reported symptoms without any confirmatory laboratory abnormalities, as was the case in this study.29,30 Second, for the cross-sectional design, the temporal relationship between TIA and depression cannot be determined, which limits causal inference. Third, recall bias should also be considered. Nonetheless, this study used national random sampling data and found the
association between TIA and depression in old age independent of functional disability, which supported the vascular depression hypothesis, may be considered the strengths of this study. Future investigations may consider the analyses of the cumulative effect of CVRFs to explore the connection between clinical TIA and the pathophysiology of arthreosclerosis in the development of late-life depression and the performance of longitudinal design to elucidate the direction of causality between TIA and depression.
CONCLUSION This population-based study observed a significant association between TIA and depression in old age, independent of physical disability and CVRFs. The results may provide further support for the vascular depression hypothesis.
References 1. Stewart R, Prince M, Mann A, et al: Stroke, vascular risk factors and depression: cross-sectional study in a UK Caribbean-born population. Br J Psychiatry 2001; 178:23–28
386
2. Whyte EM, Mulsant BH, Vanderbilt J, et al: Depression after stroke: a prospective epidemiological study. J Am Geriatr Soc 2004; 52:774 –778
Am J Geriatr Psychiatry 18:5, May 2010
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Wu et al. 3. Whyte EM, Mulsant BH: Post stroke depression: epidemiology, pathophysiology, and biological treatment. Biol Psychiatry 2002; 52:253–264 4. Kales HC, Maixner DF, Mellow AM: Cerebrovascular disease and late-life depression. Am J Geriatr Psychiatry 2005; 13:88 –98 5. Krishnan KR, Hays JC, Blazer DG: MRI-defined vascular depression. Am J Psychiatry 1997; 154:497–501 6. Lyness JM, Caine ED, Cox C, et al: Cerebrovascular risk factors and later-life major depression. Testing a small-vessel brain disease model. Am J Geriatr Psychiatry 1998; 6:5–13 7. Steffens DC, Krishnan KR: Structural neuroimaging and mood disorders: recent findings, implications for classification, and future directions. Biol Psychiatry 1998; 43:705–712 8. Chen CS, Chen CC, Kuo YT, et al: Carotid intima-media thickness in late-onset major depressive disorder. Int J Geriatr Psychiatry 2006; 21:36 – 42 9. Krishnan KR, Krishnan KR: Biological risk factors in late life depression. Biol Psychiatry 2002; 52:185–192 10. Rao R: Depression after transient ischemic attack: a clinically distinct subtype of vascular depression? Arch Gen Psychiatry 1998; 55:753–754 11. Alexopoulos GS, Meyers BS, Young RC, et al: ‘Vascular depression’ hypothesis. Arch Gen Psychiatry 1997; 54:915–922 12. Alexopoulos GS: The vascular depression hypothesis: 10 years later. Biol Psychiatry 2006; 60:1304 –1305 13. Wolf PA, D’Agostino RB, Belanger AJ, et al: Probability of stroke: a risk profile from the Framingham Study. Stroke 1991; 22:312–318 14. Mast BT, Azar AR, Murrell SA: The vascular depression hypothesis: the influence of age on the relationship between cerebrovascular risk factors and depressive symptoms in community dwelling elders. Aging Ment Health 2005; 9:146 –152 15. Mast BT, Neufeld S, MacNeill SE, et al: Longitudinal support for the relationship between vascular risk factors and latelife depressive symptoms. Am J Geriatr Psychiatry 2004; 12: 93–101 16. Mast BT, MacNeill SE, Lichtenberg PA: Post-stroke and clinicallydefined vascular depression in geriatric rehabilitation patients. Am J Geriatr Psychiatry 2004; 12:84 –92 17. Lyness JM, King DA, Conwell Y, et al: Cerebrovascular risk factors and 1-year depression outcome in older primary care patients. Am J Psychiatry 2000; 157:1499 –1501
Am J Geriatr Psychiatry 18:5, May 2010
18. Lyness JM, Caine ED, King DA, et al: Cerebrovascular risk factors and depression in older primary care patients: testing a vascular brain disease model of depression. Am J Geriatr Psychiatry 1999; 7:252–258 19. Han MK, Huh Y, Lee SB, et al: Prevalence of stroke and transient ischemic attack in Korean elders: findings from the Korean Longitudinal Study on Health and Aging (KLoSHA). Stroke 2009; 40:966 –969 20. van Wijk I, Gorter JW, Lindeman E, et al: Mental status and health-related quality of life in an elderly population 15 years after limited cerebral ischaemia. J Neurol 2007; 254:1018 –1025 21. Brodaty H, Withall A, Altendorf A, et al: Rates of depression at 3 and 15 months poststroke and their relationship with cognitive decline: the Sydney Stroke Study. Am J Geriatr Psychiatry 2007; 15:477– 486 22. Wolf PA, D’Agostino RB, Kannel WB, et al: Cigarette smoking as a risk factor for stroke. The Framingham Study. JAMA 1988; 259:1025–1029 23. Ueshima H, Choudhury SR, Okayama A, et al: Cigarette smoking as a risk factor for stroke death in Japan: NIPPON DATA80. Stroke 2004; 35:1836 –1841 24. Katz S, Ford AB, Moskowitz RW, et al: Studies of illness in the aged. The index of ADL: a standardized measure of biological and psychosocial function. JAMA 1963; 185:914 –919 25. Kelly-Hayes M, Jette AM, Wolf PA, et al: Functional limitations and disability among elders in the Framingham Study. Am J Public Health 1992; 82:841– 845 26. Lee Y, Yang MJ, Lai TJ, et al: Development of the Taiwanese Depression Questionnaire. Chang Gung Med J 2000; 23:688 – 694 27. Chiu HC, Chen CM, Huang CJ, et al: Depressive symptoms, chronic medical conditions and functional status: a comparison of urban and rural elders in Taiwan. Int J Geriatr Psychiatry 2005; 20:635– 644 28. Liu CY, Wang SJ, Teng EL, et al: Depressive disorders among older residents in a Chinese rural community. Psychol Med 1997; 27: 943–949 29. Toole JF, Lefkowitz DS, Chambless LE, et al: Self-reported transient ischemic attack and stroke symptoms: methods and baseline prevalence. The ARIC Study, 1987–1989. Am J Epidemiol 1996; 144:849 – 856 30. Johnston SC, Fayad PB, Gorelick PB, et al: Prevalence and knowledge of transient ischemic attack among US adults. Neurology 2003; 60:1429 –1434
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