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Kaohsiung Journal of Medical Sciences (2012) 28, 607e612

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ORIGINAL ARTICLE

Symptomatological and cognitive correlates of vascular comorbidity in older-elderly (at least 75 years old) men with major depressive disorder Yu-Yuan Wang a,e, Yun-Hsuan Chang b,c, Sheng-Yu Lee b,d, Chih-Chun Huang d, I-Hui Lee b,d, Tzung-Lieh Yeh b,d, Yen-Kuang Yang b,d, Yan-Chiou Ku f, Ru-Band Lu a,b,c,d,* a

Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan Department of Psychiatry, National Cheng Kung University Hospital & College of Medicine, National Cheng Kung University, Tainan, Taiwan c Division of Clinical Psychology, Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan d Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan e Yuli Veterans Hospital, Hualien, Taiwan f Department of Nursing, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan b

Received 21 October 2011; accepted 28 December 2011 Available online 21 July 2012

KEYWORDS Cognitive impairment; Elderly men; Major depression; Psychomotor retardation; Vascular comorbidity

Abstract Depression is a common geriatric psychiatric disorder increasing with age among elderly people ( 75 years old), especially those with medical comorbidities. They have higher suicide rates than younger men, but these are paid less attention. Elderly men (n Z 141) who were newly admitted residents of the Veterans’ Home in Tainan, Taiwan from 2004 to 2006 were recruited and screened for major depression. Specialist physicians obtained past histories of medical illnesses through chart reviews, interview, and health examinations. Fifty-nine of the 141 elderly people had major depression and participated in this study. Thirty-nine men in the group with vascular comorbidities (VC), and 20 in the group without (NVC) vascular comorbidities were compared. The VC group had more time-orientation impairment, greater psychomotor retardation, and diminished concentration/decision-making than did the NVC group. Psychomotor retardation and other cognitive function impairments (e.g., concentration and decision-making) are characteristic manifestations among patients with major depression and vascular comorbidity compared with those without vascular comorbidity. Copyright ª 2012, Elsevier Taiwan LLC. All rights reserved.

* Corresponding author. Institute of Behavioral Medicine, Institute of Allied Health Sciences, College of Medicine and Hospital, National Cheng-Kung University,138 Sheng-Li Road, Tainan 704, Taiwan. E-mail addresses: [email protected], [email protected] (R.-B. Lu). 1607-551X/$36 Copyright ª 2012, Elsevier Taiwan LLC. All rights reserved. doi:10.1016/j.kjms.2012.04.027

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Introduction Populations are growing older worldwide. Men of 65 years old and older have constituted more than 9.8% of the population in Taiwan since 2006. The number of older elderly (“older-old”:  75 years old) has almost doubled between 1994 and 2006 [1]. Compared with the younger elderly (60e74 years old), the older elderly have more medical disabilities and chronic diseases, get sick more often, and require more social support [2]. Moreover, the older elderly are more vulnerable to depressive disorders [3]. The deterioration of the mental and physical health of older elderly has become an important issue in geriatric psychiatry and a challenge to health care providers. However, only a limited number of studies of this burgeoning older elderly population have been done on residents of Asian veterans’ homes; the characteristics of older elderly men in Asian countries may differ from those of older elderly men in Western countries. Depression, a common geriatric psychiatric disorder [4], increased with age among a Swedish elderly population [5]; a similar trend was reported in a Han Chinese elderly population in Taiwan [6]. However, recognizing and treating major depression in older elderly persons with medical comorbidities is often challenging, even for the most experienced clinicians. Major depression is one of the most common psychiatric problems that may complicate the treatment and prognosis of medical patients [7]. Unfortunately, major depression often exacerbates coexisting medical conditions, ultimately accelerating the progression of the medical comorbidities [8]. Furthermore, older age, male gender, and medical illnesses are reported to be the three major risk factors for suicide [9]. Therefore, early differentiation between major depression with and without medical comorbidities among older elderly men is important. Some medical illnesses are believed to be associated with depression because of the higher prevalence of vascular comorbidities among older elderly patients with depression than among the general population of patients. The prevalence of depressive disorder is higher among patients with vascular comorbidities, including cerebrovascular accidents (CVA) [10], myocardial infarction, coronary artery disease [11], cancer, and diabetes mellitus (DM). Therefore, hypertension, DM, CVA, and heart disease were included in our study. Moreover, an early study [12] indicated that patients with late-onset depression have more frequent and severe patchy lesions in the frontal deep white matter and basal ganglia than do controls or patients with early-onset depression. We hypothesized that these specific cerebrovascular lesions could lead to characteristic symptoms. In this study, we compared the symptoms of major depression and cognitive correlates of vascular comorbidity among older-old men with major depression.

Methods Participants and procedures The Institutional Review Board of National Cheng Kung University Hospital approved this study. Participants were

Y.-Y. Wang et al. recruited from newly admitted residents of the Veterans’ Home in Tainan. They had voluntarily applied for residency in this home-care center because they were living alone, in poor health, lacking family and social support, or physically handicapped. The majority were ambulatory, physically capable, and able to provide for their own daily needs without assistance from others. Only a few were physically disabled and required a wheelchair, cane, or other ambulatory equipment, or needed other assistance. One hundred and forty-one new residents, who had completed health examinations between September 2004 and February 2006 at clinics affiliated with the Veterans’ Home, volunteered for this study. The study procedures were fully explained, and written informed consent was obtained from all. The inclusion criteria were: (1) a diagnosis of current major depressive disorder; (2) 75 years old or older; (3) male gender; (4) able to speak Mandarin or Taiwanese; and (5) capable of verbal communication. The exclusion criteria were factors that might interfere with the presentation of depressive symptoms: (1) a history of dementia or suspected dementia; (2) a current diagnosis of psychiatric disorders other than current major depressive disorder; (3) currently using antipsychotics or mood stabilizers; or (4) current substance abuse. Only participants with major depression were included in this study. Participants were divided into two groups: those with major depression and vascular comorbidities (VC); those with major depression without vascular comorbidities (NVC). The VC group contained those patients diagnosed with MDD and with evidence of having vascular comorbidity from reviewing their charts. The selective criteria of vascular comorbidity included hypertension, diabetes, history of stroke, heart diseases and peripheral vascular diseases. All volunteers were interviewed by an attending psychiatrist for an initial evaluation, and then by psychiatrists and psychologists using the Mini-Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Mini-International Neuropsychiatric Interview (MINI). The participants with major depression who were not in a depressive-symptom-free stage were given an antidepressant and a small dose of a benzodiazepine. To increase inter-rater reliability, all the interviewers were intensively trained in how to use the interview instruments and all the interviewers were closely supervised by two of the authors (RBL and YKY). All demographic data, medical charts, and histories of medical illnesses were reviewed, and then the results of the health examinations were analyzed. The short form of GDS [13] was developed specifically for geriatric use and all the questions require a “yes” or “no” answer.

Measures MMSE We used the Chinese version of the MMSE with a standardized norm to screen the participants. Those suspected of having dementia, i.e., those with scores lower than the two literacy-related cut-off scoresd23e24 for the literate and 13e14 for the illiterate (maximum possible score: 30) [14]dwere excluded.

Vascular comorbidity in elderly depression

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Diagnosis and severity of depression The Chinese version of the MINI was used to evaluate current major depressive episodes and other psychiatric diagnoses [15]. The diagnostic criteria of the MINI are based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The revised Chinese GDS was used to measure the severity of depression. The Chinese versions of the MINI and the GDS have been validated [16,17].

(mean age: 79.17  3.39 years; age range: 75e86 years) and were selected and divided into two groups based on whether they had vascular comorbidities: 39 men were in the VC group and 20 were in the NVC group. In the VC group, all participants had hypertension, 16 had DM, 16 had heart diseases, and three had hyperlipidemia.

Statistical analysis

There were no significant differences in the demographic data (mean age, VC: 78.69  2.90; NVC: 80.10  4.10, Z Z 1.12, p > 0.05) or in the severity of depression (Table 1) between the VC and NVC groups. There was only one significant difference in the MMSE subscores: time orientation (ManneWhitney Z Z 2.11; p < 0.05) (Table 1). For most of the depressive symptoms listed in DSM-IV, there were no significant differences between the groups, except for psychomotor retardation (Fisher exact p < 0.05) (Table 2). Binary logistic regression showed that psychomotor retardation (OR Z 6.88, 95% CI Z 1.27e37.29) and diminished concentration or decision-making (OR Z 3.76, 95% CI Z 1.03e13.67) were more common in the VC group than in the NVC group (Table 2).

The All data were analyzed using the Statistical Package for the Social Sciences 12.0 (SPSS Inc., Chicago, IL, USA). The mean scores for the GDS, the MMSE, and the comorbidity of depression with vascular disease were calculated separately to ensure comparability of the detailed scores. ManneWhitney U tests were used to analyze intergroup differences in age, education, GDS, and MMSE total scores and sub-scores [18] between the VC and NVC groups. A c2 test was used to analyze differences in the occurrence of depressive symptoms between the two groups. The Fisher exact test was used for any counts less than the expected five. Binary logistic regression was used to assess the odds ratios (OR) of the occurrence of depressive symptoms in the VC group compared with the NVC group. Statistical significance was set at p < 0.05.

Results Participant characteristics Of the 141 elderly men recruited for this study, 30 were excluded because of suspected dementia or a history of dementia, and seven were excluded for other psychiatric comorbidities: two with post-traumatic stress disorder, three with generalized anxiety disorder, and two with psychotic disorder. Finally, 104 participants (mean age: 79.55  4.21 years; age range: 75e95 years) were enrolled in the study, of which 59 screened with major depression

Characteristic symptoms of VC and NVC group members

Discussion Depression that occurs late in life is often considered to be an “organic model” of depression [19], and psychiatrists often pay more attention to this type of depression because it frequently is a secondary disorder associated with a treatable underlying medical illness. Identifying risk factors of VC in patients with depression may provide evidence of an organic etiology for depression; such symptoms should prompt psychiatrists to conduct additional examinations to check for possible vascular illnesses. Thus, by identifying the associated vascular comorbidities with depression in older-elderly men, we may be able to arrive at a clearer understanding of the nature of “organic depression”.

Table 1 Geriatric depression scale and Mini-Mental State Examination scores for major depression with vascular comorbidities and major depression without vascular comorbidities groups.

Mean scores of GDS Mean scores of MMSE Time orientation Place orientation Registration Attention/calculation Naming Repeating Obeying orders Reading Writing a sentence Construction ability Recall

VC (Mean  SD)

NVC (Mean  SD)

8.42  3.83 22.91  3.87 3.74  1.24 4.50  0.90 2.85  0.44 2.56  1.64 2.00  0.00 0.97  0.17 2.74  0.71 0.91  0.29 0.38  0.49 0.41  0.50 1.85  1.11

6.85  2.85 22.39  5.34 4.22  1.63 4.22  1.56 2.67  0.84 2.39  1.98 1.94  0.24 0.83  0.38 2.78  0.43 0.89  0.32 0.44  0.51 0.39  0.50 1.61  1.09

Z 1.47 0.35 2.11 0.10 0.58 0.30 1.37 1.75 0.50 0.26 0.43 0.16 0.82

p 0.142 0.728 0.035 0.923 0.559 0.762 0.169 0.080 0.619 0.792 0.667 0.874 0.411

GDS Z geriatric depression scale; MMSE Z Mini-Mental State Examination; NVC Z major depression without vascular comorbidities; SD Z standard deviation; VC Z major depression with vascular comorbidities; Z Z value from ManneWhitney test.

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Table 2 Occurrence and adjusted odds ratio of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition depressive symptoms in major depression with vascular comorbidities and major depression without vascular comorbidities groups. Individual symptom of depression Depressed mood Diminished interest or pleasure Appetite or weight change Sleep disturbance Psychomotor retardation Fatigue or loss of energy Feel worthless or guilty Diminished concentration or decision-making Suicidal thoughts

VC n (%) 30 36 22 27 36 37 33 28 22

(76.9) (92.3) (56.4) (69.2) (92.3) (94.9) (84.6) (71.8) (56.4)

NVC n (%) 13 (76.5) 15 (88.2) 10 (58.8) 11 (64.7) 12 (70.6) 13 (76.5) 13 (76.5) 8 (47.1) 7 (41.2)

c2

p a

0.03 0.11

3.16 1.10

1.000 0.634a 0.867 0.739 0.047a 0.062a 0.471a 0.076 0.294

ORa

95% CI

p

0.50 0.39 0.94 0.88 6.88 4.36 0.81 3.76 1.67

0.09e2.88 0.02e7.88 0.25e3.58 0.20e3.85 1.27e37.29 0.64e29.66 0.12e5.45 1.03e13.67 0.41e6.86

0.435 0.536 0.931 0.869 0.025 0.132 0.825 0.044 0.476

CI Z confidence interval; OR Z Odds ratiosa - adjusted for “psychomotor retardation” and “diminish concentration or decision-making”; NVC Z major depression without vascular comorbidities; VC Z major depression with vascular comorbidities. a Adjusted for Fisher exact test.

Usually in a health examination, the physical condition, rather than psychological and mental condition, is emphasized, which could lead to neglecting the symptoms of depression or some other mental disorders. Identifying the characteristic symptoms of VC could also provide useful information for primary care providers when evaluating major depression in medically ill patients. It could be helpful to reduce the possibility of overlooking the existence of underlying depression in older-elderly people. Our findings are practical for clinical use for primary health care providers because all the characteristic depressive symptoms were selected based on DSM-IV criteria. However, the risk factors identified in this study may serve only as reminders of possible underlying depression in the elderly. General medical practitioners could focus more on the physical illness and ignore the depressive symptoms, in older-elderly people, which not only accelerates both the depressive disorder and the medical illness, but also contributes to the underdiagnosis of the medical disorder. Therefore, we recommend that primary care providers evaluate carefully medically ill older-elderly patients and vigorously intervene when depression is suspected. In this study, the prevalence of major depression among the newly admitted older-elderly men in the Veterans’ Home was higher than that found in previous geriatric studies of a Western population [20], Chinese-American immigrants [21], and younger-elderly Han Chinese in Taiwan [22]. This disparity may be explained by several differences in the populations evaluated in these studies. Our study participants were older-elderly men, significantly older than the participants in the three other geriatric studies, and they may have had a higher prevalence of depression [23]. More than 60% of the study participants had at least one medical illness, and at least 75%, both with and without a vascular comorbidity, were diagnosed as depressed. Individuals with medical comorbidities, and especially the older-elderly, tend to have higher depressive symptom scores than do those without medical comorbidities [24]. The high prevalence of major depression among the older-elderly men newly admitted to the Veterans’ Home implied that a large number of undiagnosed cases could exist in the previously admitted population as well.

Additionally, our study participants were living alone, most of them unmarried or separated from their spouse and family because of the revolution in China in 1949. A lack of family support and a low level of formal education [25] are important risk factors for geriatric depression [21]. Although 51.9% of our study participants were illiterate, they had close peer-group relationships, and their living expenses were paid for by the Taiwan Ministry of Veterans’ Affairs. To what extent peer-group relationships may influence the physical and mental health of older-elderly men in similar environments requires additional studies.

Psychomotor retardation We found that psychomotor retardation is one of the risk factors for VC among older-elderly men with depression. Our finding is in line with a previous report [26] showing that psychomotor retardation is one specific symptom of vascular depression, but not of non-vascular depression. Psychomotor slowing is related to older age, depression, a smaller caudate nucleus volume, and mutation of the methylenetetrahydrofolate reductase enzyme [27]. Psychomotor slowing is significantly and inversely correlated with the volume of the caudate nucleus in depressed patients. A smaller caudate nucleus volume may be caused by a number of developmental, vascular, or neurodegenerative processes. Therefore, in the older-elderly, more severe psychomotor retardation may be the result of major depression with vascular comorbidities. More neuropsychological neuroimaging studies are needed to confirm this notion. The patients recruited in this study underwent a thorough historical interview and physical examination: no VC-group members had current stroke, nor did they showed obvious symptoms of a previous stroke. However, to a certain degree, the psychomotor retardation revealed in the patients in the VC group may have been contributed to by occult stroke rather than milder vascular conditions. Therefore, the types of vascular comorbidity often associated with psychomotor retardation need additional investigation. Furthermore, for psychiatric clinicians, such cardiovascular comorbidities should be taken into account

Vascular comorbidity in elderly depression while interviewing or caring for the older-elderly with depression to confirm the risk of vascular conditions.

Cognitive deficits among in older-elderly men with vascular comorbidities Chong et al. (2001) found a high prevalence of depressive disorders among the elderly in Taiwan, especially in an urban widow with low level of education, and elderly with physical illness were generally more vulnerable to depression [22]. Geriatric depression is known to be associated with specific cognitive deficits, including visuospatial impairment, poor attention and concentration, slower mental processing speed, and executive dysfunction [28]. Lockwood et al. (2002) reported that participants with late life depression would have worse performance in both attention and executive tasks, regardless of age. In addition, the depressed elderly would have greater impairment in executive measures [29]. In Asia, Lee et al. (2005) did not only find the prevalence of cognitive impairment in older adults, but also suggested the factors related to cognitive impairment, whereas socio-behavioral factor and hospitalization experience were significant for elderly in Japan [30]. We found that participants in the VC group had more time-orientation impairments than did those in the NVC group. Additional neuropsychological examinations to verify our results are warranted. Regular follow-ups are necessary to search for additional organic and structural changes, such as Parkinson’s disease, dementia, and other neurodegenerative diseases, in the brains of depressed and non-depressed older-elderly men. This study controlled only for hypertension, DM, CVA, and heart disease, because most older-elderly men complain about uncertain discomfort in the whole body, such as gastrointestinal disturbances, joint pain, frequent urination, chest tightness, etc. These complaints, however, may be caused by hypochondriasis rather than actual physical or mental illness. All the residents at the Veterans’ Home receive regular annual physical check-ups for hypertension, DM, CVA, and heart disease. This may be helpful for clinical practitioners to differentiate those with major depression with vascular comorbidities from those without vascular comorbidities. Based on a more precise differentiation, these two distinctive pathologic entities can be managed appropriately. However, further study is still needed to prove the clinical value of differentiating between them.

Limitations The small population of participants in this study might have caused a Type II error; therefore, the results should be carefully considered. In addition, our study participants were recruited from a veterans’ home, an institution in which most residents have the same background, which may also limit generalizing our findings to the elderly in the community. Moreover, we could not control for the possible influence of antidepressants or night time benzodiazepine sedatives in patients with major depression. Using the MMSE as a cognitive assessment tool was a limitation in the present study, because the MMSE may not be sensitive enough to assess mild cognitive changes [31] or

611 executive dysfunctions. In addition, the comparisons of MMSE scores and sub-scores may be flawed because some participants in each group might have been differentially excluded owing to their low scores on the MMSE. Although the Chinese version of the MINI has been well validated, only the PTSD module is used in the literature. It could be one of the limitations of this study that we used the Chinese version of the MINI to evaluate the patients.

Conclusions Higher occurrences of psychomotor retardation and diminished concentration and decision-making abilities were found in the VC group than in the NVC group. These symptoms may be characteristic of major depression with vascular comorbidity in the older-elderly with depression. To identify the risk factors for the older-elderly with major depression and vascular comorbidities should motivate psychiatrists to look for additional symptomatic evidence of organic depression when treating the depressed olderelderly with these symptoms and to introduce prompt treatment for these vascular comorbidities.

Acknowledgments This study was supported in part by a Department of Health grant DOH 95-TD-M-113-055 (R-BLu) and by the National Cheng Kung University Project to Promote Academic Excellence and Develop World Class Research Centers, Tainan, Taiwan. The financial sponsors played no role in this study. We thank Yu-Shan Wang for administrative assistance.

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