1. Introduction
Depression has become the largest contributor to burden of disease and non-fatal health loss due to its high prevalence, chronicity, and comorbidity with physical illness [
1,
2]. Depression is characterized by a state of low mood and loss of interest, as well as additional symptoms including but not limited to insomnia, fatigue, and difficulty to concentrate [
3]. Additionally, vascular disease and diabetes mellitus have been reported to significantly impact quality of life quality in elderly persons (i.e., persons > 65 years old) due to chronicity and poor prognosis [
4].
Extant research has reported that depression is strongly associated with vascular disease (i.e., hypertension, myocardial infarction, stroke), as well as diabetes mellitus [
5]. The vascular depression hypothesis posits that the phenomenology of depression may be subserved by cardiovascular abnormalities [
6]. It has hypothesized that vascular diseases may result in cerebral ischemia in select neurophysiological circuits that are relevant to depressive symptoms, which may partially explain the relationship between vascular diseases and depression [
7]. A separate line of evidence suggests that depression may increase the risk for vascular pathologies [
8,
9]. Multiple mechanisms mediating the preceding relationship include but are not limited to, cortisol dysregulation, arrhythmias, catecholamine signaling, and inflammation [
7]. However, the relationship between depression and vascular disease has not been fully characterized, and requires further investigation.
Extant evidence indicates that depression and vascular disease may both lead to functional impairment; the foregoing observation is especially pronounced in middle-aged (i.e., persons aged 45 to 60) [
10] and elderly adults who may experience concurrent, natural age-related functional decline [
11,
12]. Depression is a highly debilitating condition associated with significant functional impairment across multiple domains of psychosocial function, such as difficulty in Activity of Daily Living (ADL) and Instrumental Activity of Daily Living (IADL) [
13,
14]. It is separately reported that individuals who diagnosed with vascular diseases (e.g., stroke) exhibit greater susceptibility to dementia and cognitive decline due to potential neuropathological changes and vascular lesions in the brain [
15,
16,
17]. Moreover, vascular diseases such as cardiovascular diseases are associated with subsequent functional disability in middle-aged and elderly people [
18,
19,
20,
21]. The mechanisms that mediate the foregoing observations are not fully understood.
Notwithstanding, there is insufficient characterization of the potential combined effects of comorbid depression and vascular diseases on measures of functional impairment. Moreover, the effect of depression and comorbid vascular disease/diabetes mellitus on functional impairment in elderly adults has not been fully investigated. There is a need to elucidate the foregoing relationship among individuals with diabetes mellitus given that a substantial proportion of individuals with vascular disease have a comorbid diagnosis of diabetes mellitus [
4].
Herein, considering comorbidity with chronic diseases and depression has always been researching focuses, we adopted a cross-sectional design to investigate the associations between self-reported depression and three types of vascular diseases (i.e., hypertension, myocardial infarction and stroke) as well as diabetes mellitus, and the associations between depression and vascular diseases/diabetes mellitus and functional disability, by using a large sample of Chinese middle-aged and elderly population. According to “vascular depression” hypothesis [
6], we hypothesized that individuals with comorbid depression and vascular diseases/diabetes may experience worsening of symptoms in both conditions, which may mediate increased functional impairment. And those who have one of these two pathologies may have greater likelihood to develop the other.
3. Results
3.1. Sociodemographic Characteristics of Subjects
A total of 10531 participants were included in the analysis herein (
Figure 1).
Table 1 presents the baseline characteristics of all subjects. Excluding individuals who had missing data regarding diagnosis, the prevalence rates of hypertension, diabetes mellitus, myocardial infarction, and stroke were 14.6%, 5.8%, 7.9%, and 4.5%, respectively, and the participants who without all four diseases accounts for 42.9%. The average ages of patients with the five foregoing groups were 61.8 (SD = 9.4), 62.0 (SD = 8.8), 62.4 (SD = 9.0), 65.1 (SD = 8.2), 60.5 (SD = 9.3) years old, respectively. The prevalence of depression across each group was 42.0%, 42.4%, 46.5% and 50.1%, 42.0%, respectively.
3.2. The Association between Depression and Vascular Diseases/Diabetes Mellitus
A comparison of depressive scores according to whether participants had a codified diagnosis of vascular diseases is shown in
Table 2. Depressive severity scores were significantly higher in participants who had vascular diseases/diabetes mellitus when compared to participants without the foregoing diseases (
p < 0.001). Chi-square test results indicated that the prevalence rate of depression was also significantly higher in participants who were diagnosed with any type of the chronic diseases (i.e., Hypertension: OR = 1.39, 95% CI: 1.25, 1.54; Diabetes mellitus: OR = 1.32, 95% CI: 1.14, 1.52; Myocardial infarction: OR = 1.67, 95% CI: 1.48, 1.90; Stroke: OR = 1.80, 95% CI: 1.54, 2.10, Unexposed group: OR = 1.32, 95% CI: 1.18, 1.48, separately; all
p < 0.0001) (
Table 2).
3.3. Functional Impairment According to Groups
Table 3 shows descriptive statistics about functional ability as measured by the ADL scale and IADL scale.
Table 3 highlights the number of “functionally independent” people as well as the proportion of “functionally independent” people reported in each disease and unexposed category.
The association between ADL, IADL-related disability, and depression or vascular diseases/diabetes mellitus is separately presented in
Table 4,
Table 5 and
Table 6. On the whole, the diseased group had higher risk of functional impairment compared to not having diseases group (
Table 4). Stroke patients had higher Ors in both ADL and IADL-dependent assessments compared to unexposed participants; however, the foregoing associations were not observed in the diabetes mellitus subgroup. We also observed that myocardial infarction patients had higher Ors in ADL-dependent assessments compared to the unexposed group. Moreover, hypertension patients had higher Ors in IADL-dependent assessment. Furthermore, a strong association between depression and functional disability was identified; the foregoing association remained significant after controlling for extraneous variables including age, gender, education level, marital status and health behaviors (i.e., drinking and smoking). Detailed results are shown in
Table 5 and
Table 6.
Additionally, we observed that subjects who reported comorbid depression and vascular disease had significantly higher Ors with respect to higher scores of functional impairment in compared to those unexposed, and the association still remained after adjusted. (ADL: Hypertension: AOR = 3.863, 95% CI: 3.028, 4.927; Diabetes mellitus: AOR = 3.803, 95% CI: 2.844, 5.084; Myocardial infarction: AOR = 3.604, 95% CI: 2.787, 4.660; Stroke: AOR = 6.615, 95% CI: 4.914, 8.905, respectively; all p < 0.001; IADL: Hypertension: AOR = 4.295, 95% CI: 3.552, 5.194; Diabetes mellitus: AOR = 4.380, 95% CI: 3.441, 5.576; Myocardial infarction: AOR = 4.144, 95% CI: 3.367, 5.100; Stoke: AOR = 7.718, 95% CI: 6.003, 9.922, respectively; all p < 0.001).
4. Discussion
Herein, we explored the association between self-reported depression as well as vascular diseases (i.e., hypertension, myocardial infarction, and stroke)/diabetes mellitus and functional outcomes in middle-aged and older Chinese adults. We evaluated functional impairment as measured by the ADL scale and IADL scale and the fourth wave (2018) dataset from the CHARLS. Taken together, we observed greater functional impairment in subjects who had concurrent depression when compared with those unexposed.
Our findings are in accordance with published literature evaluating the effect of associations between comorbid medical disorders and mental disorders on functional outcomes. Extant literature has reported on the deleterious impact of vascular diseases/diabetes mellitus on cognition and functional abilities [
26]. For example, a previous meta-analysis revealed a significant increase in physical disability in individuals with diabetes [
27]. Moreover, it has been separately reported that individuals with hypertension, myocardial infarction, or stroke have an increased risk of functional impairment [
19,
20]. Furthermore, a separate retrospective cohort study reported on the increased risk of dementia in patients with comorbid depression and vascular disorders compared to individuals with a sole diagnosis of depression, especially for patients with stroke or hypertension [
15].
Available evidence indicates that elevated levels of C-reactive protein and albuminuria in people with cardiovascular diseases (CVD), which are biomarkers of CVD (e.g., myocardial infarction, stroke, coronary heart disease etc.), were independently correlated with functional disability in older adults [
28]. The preceding finding implies a close association of inflammation and albuminuria in persons with CVD and functional impairment. However, the mechanisms subserving the observed associations require further research.
It is also well described that depression adversely affects ADLs, with severe impairment in ADLs noted in geriatric populations [
29]. Previous evidence indicates that individuals with depression perform worse across disparate neuropsychological measures (e.g., executive function) when compared with non-depressed persons [
30,
31]. In our analysis, we did not identify a main effect of all the vascular diseases on functional impairment. It is likely that stroke is CVD with sudden onset and typically lead to direct damage to functional abilities, the extent of harm of diabetes depends more on the effect of covariates (e.g., duration of the disease, gender) [
21]. However, we found that the presence of depression had an association with functional impact of the mentioned above chronic disease.
Previous findings have implicated medical illnesses (e.g., CVD) with the onset of depression (i.e., “vascular depression” hypothesis) [
32,
33]. Mechanisms subserving the “vascular depression” hypothesis also have been published elsewhere [
34]. Among multiple factors reported, vascular diseases are reported to predict the increase of white matter hyperintensities (WMH) associated with depression, indicating a pathophysiologic nexus linking vascular and white matter pathology [
7]. The significant association between self-reported depression and vascular diseases/diabetes from our study was in accordance with the “vascular depression” hypothesis. Our findings herein highlight the importance of developing practical treatments for individuals with both depression and vascular diseases/diabetes.
Limitations
Several limitations need to be considered when interpreting the results of our study. First, the cross-sectional design precludes any statements about causation and cannot indicate a prediction of future events. Secondly, the measures of functional disability administered in our study were limited. Future studies should include a comprehensive multi-dimensional battery of functional ability assessments. Nonetheless, our study endeavors to extend knowledge further by documenting the additive effects of vascular disease in persons with depression on functional outcomes in elderly Chinese populations. The aging Chinese population along with rising rates of cardiovascular and metabolic disorders across China further underscores the relevance of our findings.
Taken together, future research should aim to implement a longitudinal design to explore causal relationships between depression, vascular disease/diabetes mellitus, and functional impairment. Furthermore, the biophysiological factors and mechanism underlying the foregoing associations need to be characterized in order to inform treatment approaches that endeavor to improve functional disability in individuals at risk.