Vascular risk factors, white matter microstructure, and depressive symptoms: a longitudinal analysis in the UK Biobank.

BACKGROUND: Cumulative burden from vascular risk factors (VRFs) has been associated with an increased risk of depressive symptoms in mid- and later life. It has been hypothesised that this association arises because VRFs disconnect fronto-subcortical white matter tracts involved in mood regulation, which puts older adults at higher risk of developing depressive symptoms. However, evidence for the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms from longitudinal studies is scarce. METHODS: This preregistered study analysed longitudinal data from 6,964 middle-aged and older adults from the UK Biobank who participated in consecutive assessments of VRFs, brain imaging, and depressive symptoms. Using mediation modelling, we directly tested to what extend white matter microstructure mediates the longitudinal association between VRF burden and depressive symptoms. RESULTS: VRF burden showed a small association with depressive symptoms at follow-up. However, there was no evidence that fractional anisotropy (FA) of white matter tracts mediated this association. Additional analyses also yielded no mediating effects using alternative operationalisations of VRF burden, mean diffusivity (MD) of single tracts, or overall average of tract-based white matter microstructure (global FA, global MD, white matter hyperintensity volume). CONCLUSIONS: Our results lend no support to the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms, while highlighting the relevance of using longitudinal data to directly test pathways linking vascular and mental health.

Retinal microvascular function and incidence and trajectories of clinically relevant depressive symptoms: the Maastricht Study.

BACKGROUND: Cerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is limited. We investigated the association of retinal microvascular function, a proxy for microvascular function in the brain, with incidence and trajectories of clinically relevant depressive symptoms. METHODS: Longitudinal data are from The Maastricht Study of 5952 participants (59.9 ± 8.5 years/49.7% women) without clinically relevant depressive symptoms at baseline (2010-2017). Central retinal arteriolar equivalent and central retinal venular equivalent (CRAE and CRVE) and a composite score of flicker light-induced retinal arteriolar and venular dilation were assessed at baseline. We assessed incidence and trajectories of clinically relevant depressive symptoms (9-item Patient Health Questionnaire score ⩾10). Trajectories included continuously low prevalence (low, n = 5225 [87.8%]); early increasing, then chronic high prevalence (early-chronic, n = 157 [2.6%]); low, then increasing prevalence (late-increasing, n = 247 [4.2%]); and remitting prevalence (remitting, n = 323 [5.4%]). RESULTS: After a median follow-up of 7.0 years (range 1.0-11.0), 806 (13.5%) individuals had incident clinically relevant depressive symptoms. After full adjustment, a larger CRAE and CRVE were each associated with a lower risk of clinically relevant depressive symptoms (hazard ratios [HRs] per standard deviation [s.d.]: 0.89 [95% confidence interval (CI) 0.83-0.96] and 0.93 [0.86-0.99], respectively), while a lower flicker light-induced retinal dilation was associated with a higher risk of clinically relevant depressive symptoms (HR per s.d.: 1.10 [1.01-1.20]). Compared to the low trajectory, a larger CRAE was associated with lower odds of belonging to the early-chronic trajectory (OR: 0.83 [0.69-0.99]) and a lower flicker light-induced retinal dilation was associated with higher odds of belonging to the remitting trajectory (OR: 1.23 [1.07-1.43]). CONCLUSIONS: These findings support the hypothesis that cerebral microvascular dysfunction contributes to the development of depressive symptoms.

Association of white matter hyperintensities and clinical vascular burden with depressive symptoms in Black older adults.

OBJECTIVES: Black older adults have a higher vascular burden compared to non-Hispanic White (NHW) older adults, which may put them at risk for a form of depression known as vascular depression (VaDep). The literature examining VaDep in Black older adults is sparse. The current study addressed this important gap by examining whether vascular burden was associated with depressive symptoms in Black older adults. METHODS: Participants included 113 Black older adults from the Healthy Brain Project, a substudy of the Health, Aging, and Body Composition Study. In multiple regression analyses, clinical vascular burden (sum of vascular conditions) and white matter hyperintensity (WMH) volume predicted depressive symptoms as measured by the Center for Epidemiologic Studies Depression Scale, controlling for demographic variables. Follow-up analyses compared the associations in the Black subsample and in 179 NHW older adults. RESULTS: Higher total WMH volume, but not clinically-defined vascular burden, predicted higher concurrent depressive symptoms and higher average depressive symptoms over 4 years. Similar associations were found between uncinate fasciculus (UF) WMHs and concurrent depressive symptoms and between superior longitudinal fasciculus WMHs and average depressive symptoms. The association between depressive symptoms and UF WMH was stronger in Black compared to NHW individuals. CONCLUSION: This research is consistent with the VaDep hypothesis and extends it to Black older adults, a group that has historically been underrepresented in the literature. Results highlight WMH in the UF as particularly relevant to depressive symptoms in Black older adults and suggest this group may be particularly vulnerable to the negative effects of WMH.

Functional, cognitive, and cerebrovascular aspects of depression before coronary artery bypass graft surgery: Testing the vascular depression hypothesis.

OBJECTIVE: Depression in patients undergoing coronary artery graft bypass (CABG) surgery is associated with morbidity and mortality, making its early identification and clinical management crucial. Vasculopathy and older age, hallmarks of patients requiring CABG, are also features of vascular depression. In this study, we assess for features of vascular depression in patients undergoing CABG surgery. METHODS: This is a cross-sectional analysis of a single-site prospective observational cohort study of patients undergoing CABG surgery. Subjects were assessed preoperatively using the Depression Interview and Structured Hamilton (DISH), depression scales, transcranial Doppler, neuropsychological testing, and clinical dementia rating (CDR). RESULTS: Of 161 subjects (mean age 66.2 ± 9.3, female 25%) who completed DISH, 18 had major or minor depression, 17 of whom had a past history of major or minor depression (mean age of onset 35.8 years-old). Pre-CABG depression was associated with greater functional impairment on CDR Sum of Boxes (OR = 3.7, 95% CI: 1.4, 9.7) and worse performance on letter fluency test (OR = 0.90, 95% CI: 0.81, 0.99) and trail-making tests (A: OR = 1.06, 95% CI: 1.01, 1.12; B: OR 1.02, 95% CI: 1.01, 1.04). Pre-CABG depression was not associated with middle cerebral artery (MCA) stenosis. CONCLUSIONS: Pre-CABG depression is associated with cognitive and functional impairment similar to vascular depression, but we did not find evidence of an association with older age of onset and MCA stenosis. Further studies on white matter disease in this population are needed to examine the vascular depression hypothesis for pre-CABG depression.

Occurrence of depression and assessment of functional capacity in patients with vascular diseases admitted to a Vascular Surgery Service.

Background: Vascular diseases are associated with significant sequelae and clinical repercussions for the lives of affected patients, which are more serious among the elderly. The consequences of vascular disease, such as limb loss, chronic pain, prolonged hospitalization, and polypharmacy, reduce these patients' autonomy and independence, influencing their wellbeing and quality of life. Objectives: To determine the prevalence of depression and assess functional capacity in patients with vascular diseases admitted to a Vascular Surgery Service. Methods: This is a descriptive, cross-sectional study, carried out at the Vascular Surgery Service of a tertiary hospital with a non-random sample of patients selected consecutively. The geriatric depression scale short form (GDS-15) was used to assess depression and the Katz scale was used for functional assessment. Results: The prevalence of depression in these patients was 60.6%. Associations were observed between depression and consultation with a family doctor in the last 12 months, alcoholism, claudication, diabetes, and individuals who had had an amputation. Individuals' Katz index functional capacity scores were significantly associated with sociodemographic variables, conditions related to vascular disease, and hospitalization. Conclusions: There was a high prevalence of depression in patients with vascular diseases admitted to a vascular surgery service and important reductions in functional capacity in some groups, such as individuals with low educational levels, those who had chronic pain in the lower limbs, patients with diabetes, and those who had had an amputation.

The enigma of vascular depression in old age: a critical update.

Depression is common in older individuals and is associated with high disability and increased mortality, yet the factors predicting late-life depression (LLD) are poorly understood. The relationship between of depressive disorder, age- and disease-related processes have generated pathogenic hypotheses and provided new treatment options. LLD syndrome is often related to a variety of vascular mechanisms, in particular hypertension, cerebral small vessel disease, white matter lesions, subcortical vascular impairment, and other processes (e.g., inflammation, neuroimmune regulatory dysmechanisms, neurodegenerative changes, amyloid accumulation) that may represent etiological factors by affecting frontolimbic and other neuronal networks predisposing to depression. The "vascular depression" hypothesis suggests that cerebrovascular disease (CVD) and vascular risk factors may predispose, induce or perpetuate geriatric depressive disorders. It is based on the presence of various cerebrovascular risk factors in many patients with LLD, its co-morbidity with cerebrovascular lesions, and the frequent development of depression after stroke. Other findings related to vascular depression are atrophy of the medial temporal cortex or generalized cortical atrophy that are usually associated with cognitive impairment. Other pathogenetic hypotheses of LLD, such as metabolic or inflammatory ones, are briefly discussed. Treatment planning should consider there may be a modest response to antidepressants, but several evidence-based and novel treatment options for LLD exist, such as electroconvulsive therapy, transcranial magnetic stimulation, neurobiology-based psychotherapy, as well as antihypertension and antiinflammatory drugs. However, their effectiveness needs further investigation, and new methodologies for prevention and treatment of depression in older individuals should be developed.

Are Apathy and Depressive Symptoms Related to Vascular White Matter Hyperintensities in Severe Late Life Depression?

OBJECTIVE: Apathy symptoms are defined as a lack of interest and motivation. Patients with late-life depression (LLD) also suffer from lack of interest and motivation and previous studies have linked apathy to vascular white matter hyperintensities (WMH) of the brain in depressed and nondepressed patients. The aim of this study was to investigate the relationship between apathy symptoms, depressive symptoms, and WMH in LLD. We hypothesize that late-onset depression (LOD; first episode of depression after 55 years of age) is associated with WMH and apathy symptoms. METHODS: Apathy scores were collected for 87 inpatients diagnosed with LLD. Eighty patients underwent brain magnetic resonance imaging. Associations between depressive and apathy symptoms and WMH were analyzed using linear regression. RESULTS: All 3 subdomains of the 10-item Montgomery-Åsberg Depression Rating Scale correlated significantly with the apathy scale score (all P < .05). In the total sample, apathy nor depressive symptoms were related to specific WMH. In LOD only, periventricular WMH were associated with depression severity (ß = 5.21, P = .04), while WMH in the left infratentorial region were associated with apathy symptoms (ß coefficient = 5.89, P = .03). CONCLUSION: Apathy and depressive symptoms are highly overlapping in the current cohort of older patients with severe LLD, leading to the hypothesis that apathy symptoms are part of depressive symptoms in the symptom profile of older patients with severe LLD. Neither apathy nor depressive symptoms were related to WMH, suggesting that radiological markers of cerebrovascular disease, such as WMH, may not be useful in predicting these symptoms in severe LLD.

Pathomechanisms of Vascular Depression in Older Adults.

Depression in older individuals is a common complex mood disorder with high comorbidity of both psychiatric and physical diseases, associated with high disability, cognitive decline, and increased mortality The factors predicting the risk of late-life depression (LLD) are incompletely understood. The reciprocal relationship of depressive disorder and age- and disease-related processes has generated pathogenic hypotheses and provided various treatment options. The heterogeneity of depression complicates research into the underlying pathogenic cascade, and factors involved in LLD considerably differ from those involved in early life depression. Evidence suggests that a variety of vascular mechanisms, in particular cerebral small vessel disease, generalized microvascular, and endothelial dysfunction, as well as metabolic risk factors, including diabetes, and inflammation that may induce subcortical white and gray matter lesions by compromising fronto-limbic and other important neuronal networks, may contribute to the development of LLD. The "vascular depression" hypothesis postulates that cerebrovascular disease or vascular risk factors can predispose, precipitate, and perpetuate geriatric depression syndromes, based on their comorbidity with cerebrovascular lesions and the frequent development of depression after stroke. Vascular burden is associated with cognitive deficits and a specific form of LLD, vascular depression, which is marked by decreased white matter integrity, executive dysfunction, functional disability, and poorer response to antidepressive therapy than major depressive disorder without vascular risk factors. Other pathogenic factors of LLD, such as neurodegeneration or neuroimmune regulatory dysmechanisms, are briefly discussed. Treatment planning should consider a modest response of LLD to antidepressants, while vascular and metabolic factors may provide promising targets for its successful prevention and treatment. However, their effectiveness needs further investigation, and intervention studies are needed to assess which interventions are appropriate and effective in clinical practice.

Frailty and Its Correlates in Adults With Late Life Depression.

OBJECTIVE: To investigate the rates of frailty and frailty characteristics and examine the clinical and neuropsychological correlates of frailty in adults with late life depression (LLD). METHODS: Data were used from the evaluation of 134 individuals over the age of 60 years (45 men, 89 women) with a depressive diagnosis who enrolled in studies for the treatment of their depression. Depression, neuropsychological functioning, white matter hyperintensity (WMH) burden via magnetic resonance imaging, and characteristics of frailty were assessed. RESULTS: Fried frailty burden (≥3 characteristics) was present in 25% of the sample, with this rate increasing to 45.5% when using clinically meaningful cut-scores for gait speed (<1 m/s) and physical activity levels (<1000 kcal/week). Moreover, 62% of the sample exhibited gait slowing (<1 m/s) or weakness (grip strength), with 29% demonstrating both. Greater frailty burden was associated with greater Hamilton Depression Rating Scale severity in covariate adjusted linear regression models (t127 = 2.41, p = 0.02). Greater frailty burden was not associated with neuropsychological dysfunction, nor was it associated with greater WMH burden. CONCLUSION: Findings from this study show that frailty, specifically physical frailty deficits in mobility and strength, is highly comorbid in adults with LLD, associated with greater depressive symptom severity, and does not appear to be associated with the vascular depression subtype of LLD. Future research should investigate the relationship between frailty and antidepressant treatment response as well as test whether there are age-related biological processes that result in the manifestation of the frail-depressed subtype of LLD.

Low-Grade Inflammation Is Associated with Apathy Indirectly via Deep White Matter Lesions in Community-Dwelling Older Adults: The Sefuri Study.

Low-grade inflammation is implicated in the pathogenesis of atherosclerosis, metabolic syndrome, and apathy as a form of vascular depression. We analyzed the brain magnetic resonance imaging findings in 259 community-dwelling older adults (122 men and 137 women, with a mean age of 68.4 years). The serum concentrations of high-sensitivity C-reactive protein (hsCRP) were measured by a quantitative enzyme-linked immunosorbent assay. Logistic regression analysis revealed that the log10 hsCRP value and the presence of a metabolic syndrome were independently associated with confluent but not punctate deep white matter lesions (DWMLs). Path analysis based on structural equation modeling (SEM) indicated that the direct path from the log10 hsCRP to the DWMLs was significant (ß = 0.119, p = 0.039). The direct paths from the metabolic syndrome to the log10 hsCRP and to the DWMLs were also significant. The direct path from the DWMLs to apathy (ß = -0.165, p = 0.007) was significant, but the direct path from the log10 hsCRP to apathy was not significant. Inflammation (i.e., elevated serum hsCRP levels) was associated with DWMLs independent of common vascular risk factors, while DWMLs were associated with apathy. The present analysis with SEM revealed the more realistic scheme that low-grade inflammation was associated with apathy indirectly via DWMLs in community-dwelling older adults.

Integrative Proteomics-Metabolomics Strategy for Pathological Mechanism of Vascular Depression Mouse Model.

Vascular depression (VD), a subtype of depression, is caused by vascular diseases or cerebrovascular risk factors. Recently, the proportion of VD patients has increased significantly, which severely affects their quality of life. However, the current pathogenesis of VD has not yet been fully understood, and the basic research is not adequate. In this study, on the basis of the combination of LC-MS-based proteomics and metabolomics, we aimed to establish a protein metabolism regulatory network in a murine VD model to elucidate a more comprehensive impact of VD on organisms. We detected 44 metabolites and 304 proteins with different levels in the hippocampus samples from VD mice using a combination of metabolomic and proteomics analyses with an isobaric tags for relative and absolute quantification (iTRAQ) method. We constructed a protein-to-metabolic regulatory network by correlating and integrating the differential metabolites and proteins using ingenuity pathway analysis. Then we quantitatively validated the levels of the bimolecules shown in the bioinformatics analysis using LC-MS/MS and Western blotting. Validation results suggested changes in the regulation of neuroplasticity, transport of neurotransmitters, neuronal cell proliferation and apoptosis, and disorders of amino acids, lipids and energy metabolism. These proteins and metabolites involved in these dis-regulated pathways will provide a more targeted and credible direction to study the mechanism of VD. Therefore, this paper presents an approach and strategy that was applied in integrative proteomics and metabolomics for research and screening potential targets and biomarkers of VD, which could be more precise and credible in a field lacking adequate basic research.

Metabolic analysis of the antidepressive effects of Yangxinshi Tablet in a vascular depression model in mice.

In recent years, vascular depression has become the focus of international attention. Yangxinshi Tablet (YXST) is usually used in cthe linic for the treatment of arrhythmia and heart failure, but we found that it also has antidepressive effects. The objective of the study was to identify biomarkers related to vascular depression in hippocampus and explore the antidepressive effects of YXST on the mouse model. Untargeted metabolomics based on UHPLC-Q-TOF/MS was applied to identify significantly differential biomarkers between the model group and control group. Unsupervised principal component analysis (PCA) was used to scan the tendency of groups and partial least squares-discriminant analysis (PLS-DA) to distinguish between the vascular depressive mice and the sham. PCA stores showed clear differences in metabolism between the vascular depressive mice and sham groups. The PLS-DA model exhibited 38 metabolites as the biomarkers to distinguish the vascular depressive mice and the sham. Further, YXST significantly regulated 22 metabolites to normal levels. The results suggested that YXST has a comprehensive antidepressive effect on vascular depression via regulation of multiple metabolic pathways including amino acid, the tricarboxylic acid cycle and phosphoglyceride metabolisms. These findings provide insight into the pathophysiological mechanism underlying vascular depression and the mechanism of YXST.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Vascular depression consensus report - a critical update.

BACKGROUND: Vascular depression is regarded as a subtype of late-life depression characterized by a distinct clinical presentation and an association with cerebrovascular damage. Although the term is commonly used in research settings, widely accepted diagnostic criteria are lacking and vascular depression is absent from formal psychiatric manuals such as the Diagnostic and Statistical Manual of Mental Disorders, 5th edition - a fact that limits its use in clinical settings. Magnetic resonance imaging (MRI) techniques, showing a variety of cerebrovascular lesions, including extensive white matter hyperintensities, subcortical microvascular lesions, lacunes, and microinfarcts, in patients with late life depression, led to the introduction of the term "MRI-defined vascular depression". DISCUSSION: This diagnosis, based on clinical and MRI findings, suggests that vascular lesions lead to depression by disruption of frontal-subcortical-limbic networks involved in mood regulation. However, despite multiple MRI approaches to shed light on the spatiotemporal structural changes associated with late life depression, the causal relationship between brain changes, related lesions, and late life depression remains controversial. While postmortem studies of elderly persons who died from suicide revealed lacunes, small vessel, and Alzheimer-related pathologies, recent autopsy data challenged the role of these lesions in the pathogenesis of vascular depression. Current data propose that the vascular depression connotation should be reserved for depressed older patients with vascular pathology and evident cerebral involvement. Based on current knowledge, the correlations between intra vitam neuroimaging findings and their postmortem validity as well as the role of peripheral markers of vascular disease in late life depression are discussed. CONCLUSION: The multifold pathogenesis of vascular depression as a possible subtype of late life depression needs further elucidation. There is a need for correlative clinical, intra vitam structural and functional MRI as well as postmortem MRI and neuropathological studies in order to confirm the relationship between clinical symptomatology and changes in specific brain regions related to depression. To elucidate the causal relationship between regional vascular brain changes and vascular depression, animal models could be helpful. Current treatment options include a combination of vasoactive drugs and antidepressants, but the outcomes are still unsatisfying.

Factors related to prevalence, persistence, and incidence of depressive symptoms in mild cognitive impairment: vascular depression construct.

OBJECTIVE: Depression is prevalent among elders with cognitive impairment. Cerebral white matter hyperintensities (WMH) have consistently been implicated in late-life depression and in cognitive impairment. This study aims to clarify the factors related to prevalence, persistence, and new onset of depressive symptoms in subjects with mild cognitive impairment (MCI). METHODS: As part of a multicenter prospective study, the Clinical Research Center for Dementia of South Korea (CREDOS) Study, we enrolled 590 subjects diagnosed with MCI and with no prior history of depression. Depressive symptoms were assessed by the Korean version of the Geriatric Depression Scale short form (SGDS-K) at baseline and at follow-up visits. Brain magnetic resonance imaging was performed at baseline to quantify WMH using a visual rating scale. RESULTS: The baseline prevalence of clinically significant depressive symptoms (SGDS-K ≥5) was 51.4%, and this feature was associated with younger age, lower educational achievement, and higher Clinical Dementia Rating Sum of Boxes (CDR-SB) scores. Persistence of depressive symptoms across the study period was significantly associated with baseline CDR-SB and depression scores. New onset of depression (SGDS-K ≥8; incidence 15.7%) among subjects free of depressive symptoms (SGDS-K <5) at baseline was associated with severe deep subcortical, but not periventricular, WMH. CONCLUSIONS: In patients with MCI aged 50 years or older, depressive symptoms were highly prevalent. Cognitive status was closely related to both prevalence and persistence of depressive symptoms, while new onset of depression was associated with deep subcortical WMH severity in this MCI cohort. Our findings provide prospective evidence consistent with the vascular depression hypothesis. Copyright © 2015 John Wiley & Sons, Ltd.

[Late-onset depression : Pathophysiology, diagnostics and treatment]. / Altersdepression : Pathophysiologie, Diagnostik und Therapie.

Late-onset depression (LOD) is defined as depression manifesting for the first time in later life. Up to now, there has been no exact definition of the lower age limit for LOD. Psychopathological symptoms of LOD do not fundamentally differ from depression in other phases of life; however, cognitive deficits are typically more pronounced. The LOD is associated with an increased risk of developing dementia. Imaging studies show reduction in gray matter volume and white matter lesions caused by vascular diseases. The occurrence of depression with vascular lesions of the brain is also referred to as "vascular depression". The diagnostic procedure includes a detailed medical history and the observation of psychopathological changes, physical examination, laboratory tests, electroencephalograph (EEG), electrocardiograph (ECG) and magnetic resonance imaging (MRI) of the head and neuropsychological tests to measure cognitive deficits. Psychotherapy is an effective treatment option. Selective serotonin reuptake inhibitors are the first-line pharmacological therapy.

Transcranial Parenchymal Sonographic Findings in Patients With Cerebral Small Vessel Disease: A Preliminary Study.

OBJECTIVES: Patients with cerebral small vessel disease often present with various motor, cognitive, and emotional changes, including gait disturbances, parkinsonism, and depression. Substantia nigra hyperechogenicity, brain stem raphe hypoechogenicity, ventricle diameters, and sonographic characteristics of other brain structures on transcranial sonography have been increasingly used as biomarkers in a range of neurologic diseases. We aimed to explore the frequency and clinical correlates of transcranial sonographic findings in symptomatic patients with small vessel disease. METHODS: In a cross-sectional study, neurologic, cognitive, and emotional statuses and transcranial sonographic and magnetic resonance imaging findings were compared between 102 patients with small vessel disease and 45 healthy age- and sex-matched control participants. RESULTS: Compared to healthy controls, small vessel disease cases had more frequent brain stem raphe hypoechogenicity (55.9% versus 11.1%; P < .0001), substantia nigra hyperechogenicity (30.4% versus 11.1%; P = .022), and enlarged third ventricles (P < .0001). Substantia nigra hyperechogenicity correlated with gait disturbances, extrapyramidal features, and cognitive impairment. Brain stem raphe hypoechogenicity was associated with the diagnosis of depression. Enlargement of the third and lateral ventricles was more frequent in patients with cognitive impairment. Pathologic substantia nigra hyperechogenicity and enlarged ventricles were associated with the severity of cerebral ischemic lesions. CONCLUSIONS: Transcranial sonography shows pathologic findings in a substantial number of patients with small vessel disease, probably reflecting disruption of frontostriatal pathways.

Frequencies of apolipoprotein E alleles in depressed patients undergoing hemodialysis--a case-control study.

OBJECTIVE: To explore the relation between the frequencies of apolipoprotein E (ApoE) alleles and the occurrence of depression in patients undergoing hemodialysis in a Chinese population. METHODS: We examined the ApoE alleles in a sample of 288 subjects: 72 patients with depression under hemodialysis, 74 patients without depression under hemodialysis, 75 patients with depression under nondialytic treatment and 67 patients without depression under nondialytic treatment. The depression state was assessed using the Center for Epidemiological Studies Depression (CES-D) scale. Associations between the occurrence of depression and the frequencies of ApoE alleles were examined using multinomial logistic regression models with adjustment of relevant covariates. Information about sociodemographics, clinical data, vascular risk factors and cognitive function was also collected and evaluated. RESULTS: The frequencies of ApoE-ɛ2 were significantly different between depressed and non-depressed patients irrespective of dialysis (p < 0.05), but no significant difference was found in the frequencies of ApoE-ɛ4 (p > 0.05). Serum ApoE levels were significantly different between depressed and non-depressed patients in the whole sample (p < 0.05). Multinomial logistic regression models showed significant association between the frequency of ApoE-ɛ2 and the occurrence of depression in the Chinese population after control of relevant covariates, including age, sex, educational level, history of smoking and drinking, vascular risk factors and cognitive function. CONCLUSIONS: No association between the frequency of ApoE-ɛ4 and the occurrence of depression was found in patients undergoing hemodialysis. Further research is needed to find out if ApoE-ɛ2 acts as a protective factor in Chinese dialysis population since it might decrease the prevalence of depression and delay the onset age.

Leisure-Time Physical Inactivity Associated with Vascular Depression or Apathy in Community-Dwelling Elderly Subjects: The Sefuri Study.

BACKGROUND: Although physical inactivity is a major public health problem, the causative factors for physical inactivity per se are poorly understood. To address this issue, we investigated the relationship between deep white matter lesions (DWMLs) on magnetic resonance imaging, apathy, and physical activities using structural equation modeling (SEM). METHODS: We examined 317 community-dwelling elderly subjects (137 men and 180 women with a mean age of 64.5 years) without dementia or clinically apparent depression. Physical activity was assessed with a questionnaire consisting of 3 components (leisure-time, work, and sport activities). RESULTS: The mean score from the apathy scale (a visual analogue version of Starkstein's apathy scale) of the Grades 2-3 DWML group was 420 (95% confidence interval [CI] 379-461), which was lower (more apathetic) than the Grade 0 DWML group score of 478 (95% CI 463-492) after adjustment for education as a covariate. SEM showed that the direct paths from DWMLs or education to apathy were significant, and the direct path from apathy to leisure-time activity was highly significant (ß = .25, P < .001). The degree of apathetic behavior was negatively associated with sport activity in female subjects and positively associated with TV watching in male subjects. CONCLUSIONS: The results of the study show that DWMLs are one of the major factors that cause apathetic behavior and that apathy has significant negative effects on leisure-time physical activity in community-dwelling elderly subjects. Even a minor level of apathy without major depression would have a significant impact on activities of daily living and quality of life.