Vascular Depression Hypothesis Research Articles

Abstract TP39: Multi-Marker Cerebral Small Vessel Disease Score and Risk of Incident Depression: The Framingham Heart Study

Introduction: The vascular depression hypothesis postulates that cerebral small vessel disease (CSVD) contributes to the development of depression. A multi-marker CSVD score based on brain magnetic resonance imaging (MRI) could serve as a valuable tool for predicting the risk of developing vascular depression. This is important as depression can mimic cognitive impairment, dementia and is treatable. This study aimed to determine the relation of a MRI multi-marker CSVD score with incident depression in community-dwelling individuals. Methods: Framingham Heart Study participants from the Original and Offspring cohorts free of stroke, dementia and depression with available data on depression and CSVD ratings on MRI were included. Depression was defined as Center for Epidemiological Studies Depression scale score ≥16 or use of antidepressant medication. The multi-marker CSVD score was calculated by summing 1 point for individual CSVD markers present (covert brain infarcts, cerebral microbleeds, extensive white matter hyperintensities, high burden perivascular spaces, cortical superficial siderosis), ranging 0-5. Multivariable logistic regression models were used to relate the MRI-multi-marker CSVD score and incident depression in a primary analysis and individual CSVD biomarkers and depression in an exploratory analysis. Models were adjusted for age, sex, FHS cohort, time interval between MRI and clinic exam, body mass index, smoking, prevalent hypertension and diabetes. Results: In 1768 participants included (mean age 54.4±12.4 years, 54% male), the incidence of depression was 11% (median follow-up 6.0 years, IQR: 5.3-6.7). No CSVD score group had a statistically significant association with incident depression, however a CSVD score 3+ showed a trend towards increased odds of developing incident depression (OR 2.65 [0.87, 8.06], p =0.09). Among the individual CSVD markers, visible perivascular spaces had the highest odds for incident depression (OR 1.55 [0.96, 2.51] p =0.07). Conclusion: A higher multi-marker CSVD score might be associated with increased odds of incident depression. Further studies with a larger sample may help elucidate a potential association between this CSVD burden and onset of depression.

39 Relationships among Cardiovascular Risk Factors, White Matter Hyperintensities, and Depressive Symptoms in Black and White Older Adults

Objective:The vascular depression hypothesis posits that there is a relationship between vascular disease and geriatric depressive symptoms. Black Americans are at higher risk for cardiovascular disease (CVD) than their White counterparts. However, it is not fully understood whether risk for CVD or potentially related neurovascular changes have a differential relationship in Black and White Americans. We investigated differences in the relationships between white matter hyperintensities, risk for CVD, and depressive symptoms in Black and White older adults.Participants and Methods:Participants were derived from the National Alzheimer Coordinating Center database. Black (N = 120) and White (N = 120) participants were matched on age, sex, and education. White matter hyperintensity (WMH) and CVD burden data (sum of vascular conditions) on 320 individuals were analyzed (mean age = 75.9; 69.4% female). Age, sex, race, and education were included as covariates in separate regression models in which WMH and CVD burden predicted scores on the 15-item Geriatric Depression Scale (GDS-15). Follow-up stratified analyses were conducted to explore the relationship between WMH and CVD burden on GDS scores in the Black and White samples.Results:Lower WMH volume and higher CVD burden were associated with higher GDS scores in the total sample. Analyses stratified by race showed a positive effect of CVD burden on GDS scores only for the Black sample and a trend effect of WMH on GDS scores only for the White sample, with higher WMH volume associated with lower rather than higher GDS scores.Conclusions:These findings are consistent with previous research showing that WMH and CVD burden are related to depression in older adults. Contrary to expectation, WMH had a negative trend association with GDS scores in the White sample. Findings also suggest that different etiologies may play a role in the clinical presentation of depression in Black and White Americans. Additional research is needed to further explore the relationships among CVD, its neural correlates, and depressive symptoms in diverse samples.

Elevated frequency and everyday functioning implications of vascular depression in persons with HIV disease

Depression and cardiovascular disease are common and associated with one another in HIV disease. This study aimed to determine the frequency and everyday functioning implications of the clinical syndrome of vascular depression among people living with HIV (PLWH). Participants in this cross-sectional study included 536 PLWH and 272 seronegative individuals who completed a biomedical and psychiatric research evaluation. Vascular depression was operationalized as the current presence of: 1) two or more vascular conditions; and 2) depression as determined by a normative elevation on the Depression/Dejection subscale of the Profile of Mood States or a diagnosis of Major Depressive Disorder per the Composite International Diagnostic Interview. Everyday functioning was measured by both self- and clinician-rated activities of daily living. A logistic regression model showed that HIV was associated with a three-fold increased risk of vascular depression, independent of potential confounding factors. A second logistic regression model within the PLWH sample showed that PLWH with vascular depression had significantly greater odds of dependence in everyday functioning as compared to PLWH with either vascular disease or depression alone. The elevated frequency of vascular depression in PLWH is consistent with the vascular depression hypothesis from the late-life depression literature. The high rate of functional dependence among PLWH with vascular depression highlights the clinical importance of prospective work on this syndrome in the context of HIV disease.

Treatment response in late-life depression: the absence of a relationship with white matter hyperintensity volume, executive functioning, and processing speed

Treatment response in late-life depression: the absence of a relationship with white matter hyperintensity volume, executive functioning, and processing speed

Depression, anxiety and motivation in arterial hypertension

The vascular depression hypothesis posits that cerebrovascular diseases are a major risk factor for emotional and behavioral disorders (EBD). Arterial hypertension (AH) is one of the main causes of cerebrovascular diseases. Objective: to assess the relationship between anxiety, depression and apathy in the patients with AH with case history, clinical features and neuroimaging. Patients and methods . 65 hypertensive outpatient were examined (mean age – 57.17±10.76 years). Cognitive status was evaluated with MiniMental State Examination, Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery. EBD was assessed with Beck Depression Scale, Spielberger Anxiety Questionnaire, and Robert's Apathy Scale. The Fazekas scale was used to determine the severity of leukoaraiosis. Results and discussion. Significant depression was present in 66.2%, anxiety – in 41.5%, and apathy – in 80% of hypertensive patients. Blood pressure level (p<0.05) and AH duration (p<0,05) were significantly associated with the severity of each EBD included in the analysis (anxiety, depression, apathy). Depression, anxiety, and apathy scores were significantly higher (p<0.01) in patients with hypertension-mediated organ damage or associated clinical conditions. A negative correlation was found between the severity of depression, anxiety and apathy and cognitive scores (p<0.01). Depression, anxiety and apathy were significantly (p<0.05) higher in patients with higher Fazecas score. Conclusion . Advanced AH is associated with an increased risk of EBD including depression, anxiety and apathy. These EBD develop together with cognitive impairment and vascular leukoencephalopathy. The study results can emphasize the pathogenetic impact of AH associated cerebral ischemia in EBD development.

RELATIONSHIP BETWEEN MOOD, THINKING AND WALKING: A SYSTEMATIC REVIEW EXAMINING DEPRESSIVE SYMPTOMS, EXECUTIVE FUNCTION, AND GAIT

Introduction Prior literature has proposed that the co-existence of late-life depression, executive dysfunction and impaired gait speed may constitute a specific phenotype in older adults with a possible shared brain mechanism. All three conditions are independently associated with negative health outcomes including impaired function, risk of falling and reduced quality of life. However, the existence, etiology, and implications of having all three conditions as a unitary triad remain unclear. This systematic review examined the literature to assess the consistency of this triad and to explore the possible role of frontal-subcortical circuitry in its etiology. Methods English language literature that assessed mood, executive function, and gait speed using a validated tool in human participants over age 65 were included for this review. Following the PRISMA guidelines, fifteen studies including 11,213 participants met criteria for inclusion in this study. Results The triad's existence was supported by 12 of the 15 studies (80%), including four longitudinal studies involving 368 participants. A prevalence of 17% was reported in one population study. The three included intervention studies provided mixed results regarding the benefit of pharmacological and exercise interventions. Two studies assessed the association between presence of white matter hyperintensities (WMH) and the triad, with one study finding a significant longitudinal relationship with periventricular WMH. Vascular risk factors were also commonly associated with this triad. Conclusions Taken together, the relationship between this triad, the vascular depression hypothesis and frontal subcortical pathology is suggested. Further longitudinal research is needed to further clarify the etiology and clinical relevance of this triad. This research was funded by: There are no sources of funding for the article. Prior literature has proposed that the co-existence of late-life depression, executive dysfunction and impaired gait speed may constitute a specific phenotype in older adults with a possible shared brain mechanism. All three conditions are independently associated with negative health outcomes including impaired function, risk of falling and reduced quality of life. However, the existence, etiology, and implications of having all three conditions as a unitary triad remain unclear. This systematic review examined the literature to assess the consistency of this triad and to explore the possible role of frontal-subcortical circuitry in its etiology. English language literature that assessed mood, executive function, and gait speed using a validated tool in human participants over age 65 were included for this review. Following the PRISMA guidelines, fifteen studies including 11,213 participants met criteria for inclusion in this study. The triad's existence was supported by 12 of the 15 studies (80%), including four longitudinal studies involving 368 participants. A prevalence of 17% was reported in one population study. The three included intervention studies provided mixed results regarding the benefit of pharmacological and exercise interventions. Two studies assessed the association between presence of white matter hyperintensities (WMH) and the triad, with one study finding a significant longitudinal relationship with periventricular WMH. Vascular risk factors were also commonly associated with this triad. Taken together, the relationship between this triad, the vascular depression hypothesis and frontal subcortical pathology is suggested. Further longitudinal research is needed to further clarify the etiology and clinical relevance of this triad.

BROODING MODERATES THE RELATIONSHIP BETWEEN CEREBROVASCULAR BURDEN AND VASCULAR DEPRESSION

Objective: The vascular depression hypothesis posits that cerebrovascular burden confers risk for late-life depression. Though neuroanatomical correlates of vascular depression (prefrontal white matter hyperintensities) are well established, little is known about cognitive correlates; the identification of which may suggest therapeutic targets. Aims of this study are to examine the hypothesis that the relationship between cerebrovascular burden and depressive symptoms is moderated by brooding, a type of rumination. Method: A sample of 52 community-dwelling, stroke-free, individuals over the age of 70, without history of severe mental illness or dementia completed the Ruminative Responses Scale, and provided self-report (cardiac disease, hypertension, diabetes, high cholesterol) CVB data. The Geriatric Depression Scale was used to assess depressive symptomatology. Results: Results of a bootstrapped model were that self-reported measures of CVB predicted depressive symptomatology. This relationship was significantly moderated by brooding. Among older adults, those who self-reported high CVB and medium to elevated levels of rumination experienced disproportionately more depressive symptomatology. Conclusions: These findings suggest that brooding rumination may be one correlate of the vascular depression syndrome. Future research should examine neuroanatomical correlates of rumination among older adults, and further explore brooding as a therapeutic target for those with late-life depression.

The role of neuroinflammation and neurovascular dysfunction in major depressive disorder.

Although depression has generally been explained with monoamine theory, it is far more multifactorial, and therapies that address the disease’s pathway have not been developed. In this context, an understanding of neuroinflammation and neurovascular dysfunction would enable a more comprehensive approach to depression. Inflammation is in a sense a type of allostatic load involving the immune, endocrine, and nervous systems. Neuroinflammation is involved in the pathophysiology of depression by increasing proinflammatory cytokines, activating the hypothalamus–pituitary–adrenal axis, increasing glucocorticoid resistance, and affecting serotonin synthesis and metabolism, neuronal apoptosis and neurogenesis, and neuroplasticity. In future, identifying the subtypes of depression with increased vulnerability to inflammation and testing the effects of inflammatory modulating agents in these patient groups through clinical trials will lead to more concrete conclusions on the matter. The vascular depression hypothesis is supported by evidence for the association between vascular disease and late-onset depression and between ischemic brain lesions and distinctive depressive symptoms. Vascular depression may be the entity most suitable for studies of the mechanisms of depression. Pharmacotherapies used in the prevention and treatment of cerebrovascular disease may help prevent vascular depression. In future, developments in structural and functional imaging, electrophysiology, chronobiology, and genetics will reveal the association between depression and brain lesions. This article aims to give a general review of the existing issues examined in the literature pertaining to depression-related neuroinflammatory and vascular functions, related pathophysiology, applicability to depression treatment, and directions for future research.

Association Between Cerebral Microbleeds and Depression in the General Elderly Population: A Meta-Analysis.

It remains unclear whether cerebral microbleeds (CMBs) are associated with depression in the general elderly population. We thus performed a meta-analysis to evaluate the relationship between depression and CMBs. A systematic literature search was conducted in EBSCO, PubMed, and Web of Science for relevant studies that assessed the relationship between depression and the prevalence of CMBs. Five eligible studies including 7,328 patients were pooled in meta-analysis. The prevalence of CMBs was 18.0%. The prevalence of depression was 11.1%. The pooled analysis demonstrated odds ratio for CMBs and depression to be 1.187 (95% confidence interval 1.005-1.403; p = 0.043) with no evidence of statistical heterogeneity (I2 = 0.0%, p = 0.621). Our meta-analysis of available published data indicated an increased prevalence of depression in the subjects with pre-existing CMBs. This finding supports the vascular depression hypothesis. Further studies are needed to investigate the role of CMBs in the pathogenesis and progression of depression, which might provide a potential target for the prevention and treatment.

Vascular risk factors and depression in Parkinson's disease.

The aim of this study was to address the vascular depression hypothesis in Parkinson's disease (PD) from a large cohort of Chinese population. A cross-sectional analysis of 1784 Chinese patients with PD was conducted. Patients were divided into absence of depression (score ≤ 20) and presence of depression (score > 20) based on assessment of the Hamilton Depression Rating Scale. Other clinical assessments included the Unified PD Rating Scale (UPDRS), the Hamilton Anxiety Rating Scale, the frontal assessment battery (FAB) and the Montreal Cognitive Assessment (MoCA). Patients with depression showed a higher proportion of women, longer disease duration, higher UPDRS part III score, higher levodopa equivalent daily dose use, higher occurrences of motor fluctuation and dyskinesia, lower FAB score and lower MoCA score than those without depression (P < 0.05). The proportions of drinking and overweight/obesity in the depression group were significantly lower than those in the non-depression group (P < 0.05). A forward binary logistic regression model indicated that depression in PD was associated with female sex [odds ratio (OR) 1.376, P = 0.025], higher UPDRS part III score (OR 1.042, P < 0.001), lower FAB score (OR 0.937, P = 0.015), anxiety (OR 18.156, P < 0.001) and overweight/obesity (OR 0.700, P = 0.019), whereas no associations were found with hypertension, diabetes, smoking, drinking, hyperlipidaemia and heart disease. Our study failed to verify the vascular depression hypothesis in PD. On the contrary, it was demonstrated that overweight/obesity is negatively associated with the presence of depression in PD.

Microbleeds are associated with depressive symptoms in Alzheimer's disease

IntroductionCo-occurrence of cerebrovascular disease and depression led to the “vascular depression hypothesis”. White matter hyperintensities (WMHs) have been associated with depressive symptoms in population-based studies. We studied the association between small vessel disease and depressive symptoms in a memory clinic population. MethodsWe included >2000 patients with subjective cognitive decline (SCD), mild cognitive impairment, and Alzheimer's disease (AD). Magnetic resonance imaging was rated for WMHs, lacunes, and microbleeds. Depressive symptoms were assessed using the Geriatric Depression Scale. We performed logistic regression analysis. ResultsDepressive symptoms were present in AD: 17%; mild cognitive impairment: 25%; and SCD: 23%. SCD patients with WMHs showed higher propensity of depressive symptoms than AD patients with WMHs. AD patients with microbleeds were more likely to have depressive symptoms compared with AD patients without microbleeds (odds ratio = 1.70; 95% confidence interval: 1.08–2.68). DiscussionMicrobleeds are associated with depressive symptoms in AD, supporting a potential role of cerebral amyloid angiopathy in the occurrence of depressive symptoms in AD.

MICROBLEEDS ARE ASSOCIATED WITH DEPRESSIVE SYMPTOMS IN ALZHEIMER’S DISEASE

The co-occurrence of cerebrovascular disease (CVD) and depression led to the ‘vascular depression hypothesis’. In particular white matter hyperintensities (WMH) have been found to be associated with depressive symptoms in population-based studies. We studied whether imaging markers of small vessel disease (SVD) were associated with depressive symptoms in a memory clinic population. We included 2136 patients from the Amsterdam Dementia Cohort: 810 subjective cognitive decline (SCD; 59±9yrs; 43%F; MMSE 28±1), 488 mild cognitive impairment (MCI; 66±7yrs; 36%F; MMSE 26±2) and 838 Alzheimer's disease (AD; 67±7yrs; 51%F; MMSE 20±4). Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS) and scored as absent (GDS<5) or present (GDS≥5). MRI was rated for presence of WMH (Fazekas, 0/1 vs. 2/3), lacunes (absent vs. present) and microbleeds (absent vs. present). We performed logistic regression analyses to investigate associations between WMH, lacunes and microbleeds (independent, in separate models) and depressive symptoms (dependent). All analyses were adjusted for age, gender and education (model 1) and additionally adjusted for MRI field strength, MMSE-score and vascular risk factors (model 2). We stratified for diagnosis. We observed depressive symptoms in 189 (23%) SCD-patients, 123 (25%) MCI-patients, and 143 (17%) AD-patients. Presence of SVD (WMH, lacunes and/or microbleeds) was found in 227 (28%) SCD-patients, 226 (46%) MCI-patients and 342 (40%) AD-patients. AD-patients with microbleeds were more likely to have depressive symptoms compared to AD-patients without microbleeds (odds ratio (OR)=1.75; 95%CI: 1.13–2.71, p<0.05). Microbleeds were not associated with depressive symptoms in SCD or MCI. AD-patients with WMH tended to show less often depressive symptoms compared to AD-patients without WMH (OR=0.64; 95%CI: 0.39–1.06, p=0.08). WMH were not associated with depressive symptoms in SCD and MCI (SCD: OR=1.46; 95%CI: 0.89–2.57;MCI: OR=0.91; 95%CI: 0.55–1.49, both p>0.05). We found no associations between lacunes and depressive symptoms in any group. We found that microbleeds are associated with depressive symptoms in AD. Contrary to our expectations, more severe WMH did not predispose for depressive symptoms in our memory clinic population. These findings suggest that depressive symptoms in AD may be related to underlying cerebral amyloid angiopathy.

PREDICTION OF FUNCTIONAL DISABILITY IN VASCULAR DEPRESSION

We compared the validity of models of subcortical ischemic depression and executive dysfunction syndrome in predicting functional disability in the elderly. We obtained data from elderly Korean subjects (n = 1356) aged 60 years or older at baseline from the CREDOS study from November 2005 to July 2014. A generalized estimating equation model was constructed to measure functional disability using instrumental activity of daily living as a primary outcome. A risk factor of interest was vascular depression evaluated by a visual rating scale of deep white matter hyperintensity in MRI, Stroop test and Geriatric Depression Scale score. ROC plots and area under the curve test were applied to examine the difference of the two definitions of vascular depression with predicted values of functional disability outcome. The mean follow-up duration of the participants was 1.7 years. The GEE model showed that presence of subcortical ischemic depression at baseline predicted functional disability compared to non-depressed subjects ([OR] 1.76; p = 0.002). The association was also statistically significant among the executive dysfunction syndrome group (OR 1.48; p = 0.003). There were no significant differences in predicting functional disability (p = 0.366) according to AUC differences between subcortical ischemic depression and executive dysfunction syndrome. under the curve test were applied to examine the difference of the two definitions of vascular depression with predicted values of functional disability outcome. The results will be useful in evaluating the cardinal features of the vascular depression hypothesis in predicting functional disability.

Discrete Time Survival Analysis Via Latent Variable Modeling: A Note on Lagged Depression Links to Stroke in Middle and Late Life

This article is concerned with a latent variable modeling approach to discrete time survival analysis that includes both time-invariant and time-varying covariates. The approach is illustrated with data from the Health and Retirement Study, which are utilized to study further the relationship of depression to stroke in middle and late life. Employing lag-1 depression scores as time-varying covariates, in addition to a set of relevant medical and demographic variables as time-invariant covariates collected at baseline, the article addresses a particular aspect of the prominent vascular depression hypothesis representing an important area in aging research, gerontology, geriatrics, and medicine. The results indicate considerable links of immediately prior depression levels to subsequent occurrences of stroke in middle-aged and older adults. The findings complement those reported by Raykov, Gorelick, Zajacova, and Marcoulides (2017), and are consistent with that hypothesis implying depression as a potential warning sign of an impending stroke.

On the Potential of Discrete Time Survival Analysis Using Latent Variable Modeling: An Application to the Study of the Vascular Depression Hypothesis

Analysis and modeling of time to event data have been traditionally associated with nonparametric, semiparametric, or parametric statistical frameworks. Recent advances in latent variable modeling have additionally provided unique analytic opportunities to methodologists and substantive researchers interested in survival time modeling. As a consequence, discrete time survival analyses can now be readily carried out using latent variable modeling, an approach that offers substantively important extensions to conventional survival models. Using data from the Health and Retirement Study, the discussed approach is applied to the study of the increasingly prominent vascular depression hypothesis in gerontology, geriatrics, and aging research, allowing examination of the unique predictive power of depression with respect to time to stroke in middle-aged and older adults.

CADASIL as a Useful Medical Model and Genetic Form of Vascular Depression

The main magnetic resonance imaging (MRI) findings of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are white matter hyperintensities (WMHs), lacunar infarctions, and cerebral microbleeds (CMBs). The purpose of this study was to investigate the effects of these three neuroimaging markers of CADASIL on depression to determine whether CADASIL is a useful medical model supporting the vascular depression hypothesis. Eighty-four subjects with CADASIL, aged 34-86 years, participated in this study. They underwent comprehensive clinical evaluation, including 3T MRI and genotyping of NOTCH3. The effects of WMH, lacunar infarctions, and CMBs were analyzed by path analyses and multivariate logistic regression analyses. Patients with CADASIL exhibited frequencies of 17.9% for major depressive disorder (MDD) and 10.7% for minor depressive disorder. The frequency of MDD increased from 5.0% to 46.2% as WMH volume increased from first quartile to fourth quartile. WMH volume (OR: 1.03, 95% CI: 1.003-1.06) in patients with CADASIL was associated with the current depressive disorder. Path analyses demonstrated that only WMH volume was associated with the Korean version of the short form Geriatric Depression Scale score, Center for Epidemiologic Studies Depression Scale score, and 17-item Hamilton depression scale score. The effects of lacunar infarctions and CMBs on depression were not significant in path analyses and multivariate logistic regression analyses. This study demonstrates that WMHs are closely associated with depression in patients with CADASIL. This supports that CADASIL might be a useful medical model and genetic form of vascular depression.

Cardiovascular risk factors and risk of incident depression throughout adulthood among men: The Johns Hopkins Precursors Study

BackgroundModifiable cardiovascular risk factors elevate risk of subsequent depression in older adults, but the effect of their onset before or after age 65 on incident depression is unclear. MethodsParticipants were 1190 male medical students without a diagnosis of depression, who matriculated in 1948–1964 and followed through 2011. Cox proportional hazards models were used to assess associations of vascular risk-factor burden, diabetes, hypertension, hyperlipidemia, smoking status, and overweight/obese status with onset of incident depression. Adjustment covariates were race, enrollment wave, baseline age, physical activity, and heavy alcohol use. ResultsThe analysis included 44,175 person-years of follow-up. Among participants depression-free until age 65, vascular risk-factor burden after age 65 (Hazard Ratio, [HR]: 2.13, 95% Confidence Interval, [CI]: 1.17, 3.90) was associated with incident depression risk after age 65. The magnitude of vascular risk-factor burden after age 65 on depression risk after age 65 is comparable to the effect of 8.2 additional years of age. Diabetes (HR: 2.79, 95% CI: 1.25, 6.26), hypertension (HR: 2.72, 95% CI: 1.52, 4.88), and hyperlipidemia (HR: 1.88, 95% CI: 1.05, 3.35) before age 65 were associated with incident depression risk after age 65. Men diagnosed with diabetes after age 65 had 2.87 times the risk of incident depression after age 65 (95% CI: 1.24, 6.62). LimitationsOur findings are restricted to male former medical students, which may affect study generalizability. ConclusionsResults support the vascular depression hypothesis. Depression screening in older adults with vascular risk-factor burden may provide an avenue for prevention of late-onset depression.

Cerebrovascular burden and depressive symptomatology interrelate over 18years: support for the vascular depression hypothesis.

Potentially incongruent research literatures suggest three divergent hypotheses about depressive symptomatology: (1) symptoms are recurrent; (2) later-life depression results from high cerebrovascular burden (CVB); and (3) depressive symptoms contribute to comorbidities causing vascular burden. Past vascular depression research assumes that later-life depressive symptoms relate uniquely to high CVB and not to prior, recurrent depression. This study examines these divergent hypotheses. Data include 5175 participants across 18years from the Wisconsin Longitudinal Study (mean age at 1993 baseline was 53years; follow-ups in 2004 and 2011). Depressive symptomatology was measured using the Center for Epidemiological Studies Depression. CVB was operationalized as hypertension, high blood sugar, diabetes, and other heart problems. Hypotheses were examined via a cross-lagged structural equation model and logistic regression. Model fit was acceptable (root mean square error of approximation (RMSEA)=0.047; comparative fit index=0.963). Hypotheses 1 and 2 were supported. Depressive symptomatology at 2004 and 2011 follow-ups was predicted by earlier depressive symptomatology and prior CVB. Hypothesis 3 was partially supported; depressive symptomatology in 2004 predicted subsequent CVB. Logistic regression results were that CVB predicted clinically significant depressive symptoms based on the Center for Epidemiological Studies Depression clinical cutoff. Cerebrovascular burden in midlife predicts depressive symptomatology in later-life, even after accounting for prior depressive symptomatology, supporting a fundamental assumption of the vascular depression hypothesis. Midlife depressive symptomatology also predicted escalation of CVB in later-life. Results suggest a process model of later-life depressive symptom development that interrelates CVB and depressive symptoms throughout the life span and have clinical implications for the interruption of this process through the integration of primary care and behavioral health specialists. Copyright © 2017 John Wiley & Sons, Ltd.

Markers of cerebral small vessel disease and severity of depression in the general population

The vascular depression hypothesis postulates that cerebral small vessel disease can cause or exacerbate depression in elderly persons. Numerous studies explored the association of imaging markers of cerebral small vessel disease including white matter lesions (WMLs) and lacunar infarcts with depressive symptoms or disorders. However, cerebral microbleeds have not been tested in depression. In the current study, we aimed to explore the association of WMLs, lacunar infarcts and cerebral microbleeds with depression continuum in a large population-based sample, the Rotterdam Study. Study population consisted of 3799 participants (aged 45 or over) free of dementia. WML volumes, lacunar infarcts and cerebral microbleeds were measured with brain magnetic resonance imaging. Depressive symptoms, depressive disorders and co-morbid anxiety disorders were assessed with validated questionnaires and clinical interview. WML volumes and lacunar infarcts were associated with depressive symptoms and disorders. Cerebral microbleeds, especially in deep or infratentorial brain regions, were related to depressive disorders only. Our results indicate that WMLs and lacunar infarcts might be non-specific vascular lesions seen in depressive symptoms and disorders. Association of cerebral microbleeds with more severe forms of depression may indicate impaired brain iron homeostasis or minor episodes of cerebrovascular extraversion, which may play a role in depression etiology.

MRI-defined versus clinically-defined vascular depression; comparison of prediction of functional disability in the elderly

BackgroundWe compared the validity of models of subcortical ischemic depression (SID) and depression-executive dysfunction syndrome (DED) in predicting functional disability in the elderly. MethodsWe obtained data from elderly Korean subjects (n=1356) aged 60 years or older at baseline from the CREDOS study from November 2005 to July 2014. A generalized estimating equation (GEE) model was constructed to measure functional disability using instrumental activity of daily living as a primary outcome. A risk factor of interest was SID and DED evaluated by a visual rating scale of deep white matter hyperintensity in MRI, Stroop test and Geriatric Depression Scale (GDS) score. Receiver-operating-characteristic plots and area under the curve (AUC) test were applied to examine the difference of the two definitions of vascular depression with predicted values of functional disability outcome. ResultsThe mean (SD) follow-up duration of the participants was 1.7 (0.9) years. The GEE model showed that presence of SID at baseline predicted functional disability compared to non-depressed subjects (GDS score: Odds ratio [OR] 1.76; 95% CI 1.23, 2.53; p=0.002). The association was also statistically significant among the DED group (OR 1.48; 95% CI 1.15, 1.92; p=0.003). There were no significant differences in predicting functional disability (95% CI: −0.003 to 0.009, p=0.366) according to AUC differences between SID and DED. ConclusionsThe results will be useful in evaluating the cardinal features of the vascular depression hypothesis in predicting functional disability.