Age at onset and vascular pathology in late-life depression.

OBJECTIVE: There is considerable evidence to suggest that late-onset depression may be etiologically distinct from early-onset depression. The aim of this study was to compare vascular function and magnetic resonance imaging-defined brain ischemic changes between early-onset depressed (EOD) and late-onset depressed (LOD) subjects. DESIGN: Case-control study. PARTICIPANTS: Twenty-five subjects with late-life depression recruited from secondary care were divided into groups with EOD (<60 years, 11 subjects) and LOD (>60 years, 14 subjects). MEASURES: All subjects underwent a variety of vascular assessments including pulse wave analysis, pulse wave velocity, carotid intima media thickness (IMT), and magnetic resonance imaging of the brain to assess white matter hyperintensities. RESULTS: The mean age of LOD subjects was 71.3 ± 4.0 years and EOD was 73.6 ± 4.7 years (p = NS). There were no baseline differences in vascular risk or sociodemographic variables. LOD subjects had significantly higher common carotid IMT (EOD: 0.06 [0.01]; LOD: 0.09 [0.02], p = 0.02), carotid plaques (EOD: 2.1 [1.1]; LOD: 5.4 [3.9], p = 0.02), and peripheral augmentation index (EOD: 81.7 [7.9]; LOD: 96.2 [21.6], p = 0.04) when compared with early-onset subjects, indicating more vascular pathology. There were no group differences in white matter hyperintensities. Age at onset of depression was positively correlated with peripheral augmentation index, common carotid IMT, and plaque index. CONCLUSION: This study suggests that elderly subjects with LOD have greater vascular impairment than those with an early-onset illness. Whether preventing vascular disease at an earlier age may decrease the risk of last onset depression is a potential area for future research.

Cerebrovascular damage in late-life depression is associated with structural and functional abnormalities of subcutaneous small arteries.

Late-life depression is increasingly viewed as a vascular illness because of patients exhibiting characteristic white matter brain lesions and in vivo large artery endothelial dysfunction. However, the "vascular depression" hypothesis pertains to the microvasculature, and this circulation has not been studied in this context. Our objective was to examine structure and function of small subcutaneous arteries in patients with late-life depression. Thus, 16 patients aged 71.8±4.0 years with late-life depression were compared with 15 control participants aged 72.1±5.9 years. There were similar cardiovascular profiles between the 2 groups. All of the participants underwent MRI brain scans and subcutaneous gluteal fat biopsy from which small arteries were isolated and studied using pressure myography. Cerebral microvascular damage in depressed patients was confirmed by assessment of basal ganglia Virchow-Robin space scores (depressed patients 3.9±1.7 versus controls: 2.5±1.6; P=0.01). Contractility to norepinephrine was equivalent in both groups, but relaxation of the small arteries to acetylcholine was significantly reduced in depressed patients (84.0±4.0%) compared with control participants (96.0±1.4%; P=0.012). This difference in arterial relaxation was reduced but not entirely eliminated when NO synthase was inhibited. Depressed patients also exhibited hypertrophic wall growth with an increase in medial cross-sectional area (P=0.035, multiple ANOVA and wall thickness; P=0.04, multiple ANOVA). In conclusion, despite similar cardiovascular profiles, depressed patients with cerebral microvascular damage show abnormalities of subcutaneous small artery structure and function.

Preventing late-life depression: a clinical update.

BACKGROUND: Achieving remission in late-life depressive disorder is difficult; it is far better to prevent depression. In the last ten years there have been a number of clinical studies of the feasibility of prevention. METHODS: A limited literature review was undertaken of studies from 2000 specifically concerning the primary prevention of late-life depressive disorder or where primary prevention is a relevant secondary outcome. RESULTS: Selective primary prevention (targeting individuals at risk but not expressing depression) has been shown to be effective for stroke and macular degeneration but not hip fracture. It may also prove effective for the depression associated with caregiving in dementia. Emerging evidence finds effectiveness for indicated prevention (in those identified with subthreshold depression often with other risk factors such as functional limitation). Despite a number of promising risk factors (for example, diet, exercise, vascular risk factors, homocysteine and insomnia), universal prevention of late-life depression (acting to reduce the impact of risk factors at the population level) has no current evidence base, although a population approach might mitigate suicide. CONCLUSION: Interventions which work in preventing late-life depression include antidepressant medication in standard doses and Problem-Solving Treatment. When integrated into a care model, such as collaborative care, prevention is feasible but more economic studies are needed.

Vascular function in older adults with depressive disorder.

BACKGROUND: Cerebrovascular disease plays an important role in depressive disorder, especially in older adults. An understanding of vascular function in depression is important etiologically and to develop innovative treatments that may improve prognosis by ameliorating vascular damage. METHODS: This study assessed endothelial function, arterial stiffness, and atherosclerosis in a variety of vessel beds in 25 elderly subjects with depressive disorder compared with 21 nondepressed control subjects. Subjects underwent pulse wave velocity, pulse wave analysis, carotid intima media thickness analysis, and magnetic resonance imaging. A subset (16 patients and 15 control subjects) had assessment of biopsied small artery dilatation to acetylcholine to further assess endothelial function. RESULTS: The mean sample age was 72.4 years with an average age at onset for depression of 60 years. Mean carotid intima media thickness was significantly higher in depressed subjects (p < .01). Pulse wave velocity was 1.6 m/sec higher in depressed subjects (borderline significance). There was a significant reduction in the dilatation response to acetylcholine in preconstricted small arteries (p = .01). On magnetic resonance imaging, depressed subjects had significantly more dilated Virchow-Robin spaces in the basal ganglia (p = .01). Depressed subjects had greater volume of white matter lesions in all regions, but this did not reach statistical significance. There were no baseline differences in vascular risk. CONCLUSIONS: Depression in the elderly is associated with poorer endothelial function and more atherosclerosis. This is associated with a greater white matter hyperintensities lesion load and basal ganglia microangiopathy. The use of vasoprotective drugs to improve endothelial function or retard atherosclerosis as depression-modifying agents should be explored.

Recent understandings in geriatric affective disorder.

PURPOSE OF REVIEW: This article focuses on recent research into depression, bipolar disorder and anxiety in older people. RECENT FINDINGS: Many physical illnesses are associated with a high prevalence of depression but overall medical burden may largely account for this. The relationship between depression and vascular disease is two way. Frontal brain dysfunction may underlie depression both in cerebrovascular disease and neurodegenerative disorders. Besides antidepressants, psychological treatments, psychosocial interventions and enhanced primary care services are effective. Longer-term outcomes are poor but preventive strategies show promise. Medical and psychiatric comorbidity are also important themes in later-life anxiety and bipolar disorders. SUMMARY: Improving prognosis is a key concern and more research into novel pharmacological approaches (including vasoprotection), psychological interventions and prevention is needed.

Treatment of psychiatric syndromes due to cerebrovascular disease.

Neuropsychiatric syndromes are common in the setting of cerebrovascular disease. The most frequent psychiatric syndrome after stroke is depression. Emotionalism and apathy after stroke are also frequent and under-detected symptoms. Treatment principles are broadly similar to those currently used to treat non-organically ill patients. The evidence for pharmacological and psychological treatment for depression after stroke is scant, and of variable quality. Currently there is evidence of efficacy for both tricyclic antidepressants and SSRIs in the management of depression but the latter are better tolerated. Randomized controlled trials of antidepressants for post-stroke emotionalism are positive and this is encouraging. The current evidence base for psychological interventions either as first line or augmentative strategies is too limited and inconclusive to permit definite recommendations. Future studies might include multi-modal interventions using the principles of active case management and pharmacological studies which target both specific neuropsychiatric symptoms and underlying cerebrovascular disorder.

Abnormalities of CSF flow patterns in the cerebral aqueduct in treatment-resistant late-life depression: a potential biomarker of microvascular angiopathy.

There is growing evidence that microvascular angiopathy (MVA) plays an important role in the development of dementia and affective disorders in older people. At currently available image resolutions it is not possible to image directly the vascular changes associated with MVA, but the effects on blood and cerebrospinal fluid (CSF) flow may be detectable. The aim of this study was to investigate a potential biomarker for MVA based on MRI of abnormalities in CSF flow. Since there is considerable indirect evidence that treatment resistance in late-onset depressive disorder is related to MVA, we assessed the method in a group of 22 normal volunteers and 29 patients with responsive (N=21) or treatment-resistant (N=8) late-onset depressive disorder. Single-slice quantified phase-contrast (PC) images of cerebral blood and CSF flow were collected at 15 points over a cardiac cycle, and the resulting flow curves were parameterized. Significant differences in the CSF flow (width of systolic flow peak and diastolic flow volume, both P<0.01) through the cerebral aqueduct were observed for the group of treatment-resistant patients when compared to age matched controls. No significant difference was observed for a group of 21 patients with treatment-responsive depression. The findings support the hypothesis that MR measurement of CSF flow abnormalities provides a biomarker of MVA, and thus could have application in a wide range of age-related diseases.

Prognosis of late life depression: a three-year cohort study of outcome and potential predictors.

BACKGROUND: Late-onset depression (LOD) has a poor prognosis which may be worsened by the presence of cerebrovascular disease. Few studies have explored prospectively the influence of vascular risk factors on longer term prognosis. METHODS: The original study involved 50 patients with LOD and 35 healthy age matched controls. Follow-up was at three years. Baseline measures included clinical, neuroradiological and neuropsychological variables. Outcome was assessed by mortality, progression to dementia and clinical course of depressive disorder. RESULTS: Sixty-two (73%) of the original cohort agreed to be re-interviewed. Seven participants had died (all from the depressed group) and six developed dementia, all but one from the depressed group. Vascular dementia predominated (although not significantly so) among those with dementia at follow-up. For 28 depressed patients with complete follow-up data (56% of the original sample), poor outcome was predicted by lower High Density Lipoprotein (HDL), raised Erythrocyte Sedimentation Rate (ESR) and a higher score on the Hachinski Index scale and one test of immediate memory. Initial response to treatment was not associated with later outcome. CONCLUSION: Late-onset depressive disorder is associated with a high rate of mortality and possibly dementia. Biochemical and inflammatory markers may be important in prognosis and their role should be confirmed in future studies.

Predictors of 1-year mortality in patients discharged from hospital following acute exacerbation of chronic obstructive pulmonary disease.

INTRODUCTION: acute exacerbation of COPD (AECOPD) is a major cause of hospital admission, and predicts subsequent medium-term mortality. We aimed to examine mortality predictors in patients discharged from hospital after AECOPD. METHODS: we obtained baseline demographic and clinical data from 100 patients (mean age (range)=73 (60-98) years; 48 males) admitted with AECOPD. All completed the following validated questionnaires: a quality of life questionnaire (Breathing Problems Questionnaire; BPQ); a screening questionnaire for depression (Brief Assessment Schedule Depression Cards; BASDEC); a disability questionnaire (Manchester Respiratory Activities of Daily Living questionnaire; MRADL). Following discharge all were prospectively followed and survival/mortality at 12 months confirmed from hospital notes and by contacting general practitioners. RESULTS: the prevalence of depression at recruitment was 56%. One-year mortality in the whole group was 36%. Odds ratios (95% confidence intervals) for mortality predictors (univariate logistic regression analysis) were: use of long-term oxygen therapy=2.72 (1.06-6.97); subsequent readmission=2.57 (1.08-6.12); MRADL score=0.87 (0.80-0.94) (disability predicting death); BASDEC score=1.13 (1.02-1.26) (depression predicting death); BPQ score=1.08 (1.04-1.12) (low quality of life predicting death); length of original hospital stay=1.03 (1.00-1.07). On multivariate logistic regression analysis the only mortality predictor was BPQ with an odds ratio (95% confidence limits) of 1.13 (1.04-1.22). In terms of mortality prediction for individuals, a threshold MRADL score of <12 gave a sensitivity of 86%, specificity of 55%, positive predictive value of 88% and negative predictive value of 52%, with similar predictive values using BPQ as an independent variable. CONCLUSIONS: 1-year mortality after AECOPD admission is high. The presence of depressive illness (which is extremely common), and levels of both disability and impairment of quality of life are univariate predictors of 1-year mortality in this patient group. This model may be useful in predicting prognosis for individuals and thus in guiding treatment decisions.

Is vascular depression a distinct sub-type of depressive disorder? A review of causal evidence.

BACKGROUND: Vascular depression is an important conceptual and clinical concept. OBJECTIVE: To apply criteria which, in an ideal world, should be satisfied before an association between depression and vascular disease can be considered robust. METHOD: A literature review with discussion of findings in the light of recently suggested guidelines for the development of new psychiatric disorders. RESULTS: There is considerable evidence linking depression in later life with vascular brain disease but the interaction is bi-directional. Depression and vascular disease could be mediated by factors other than traditional vascular risk factors. There is increasing interest in mechanisms such as inflammatory processes which may mediate both depression and vascular disease. CONCLUSIONS: Vascular depression provides a useful framework with which to remind the clinician of important interactions between depression and vascular disease but conceptually it may be too restrictive.

Guideline for the management of late-life depression in primary care.

OBJECTIVE: To develop a guideline for the primary care management of depression in later life based on best practice. METHOD: Source material included relevant guidelines, literature reviews and consensus documents coupled with an updated literature review covering 1998-October, 2001. This material was summarised as a series of evidence-based statements and recommendations agreed by consensus. RESULTS: Good quality evidence exists for the pharmacological and psychological treatment of depressive episode (major depression), although not specifically in primary care. There is some evidence of efficacy of antidepressants in late-life dysthymia and minor depression associated with poor functional status. In depressive episode, current evidence suggests acute treatment for at least six weeks and a continuation period of at least 12 months. Both tricyclic antidepressants and Selective Serotonin Re-uptake Inhibitors are effective in longterm prevention. There is less data on how to manage patients who do not respond in the acute treatment phase. More data is needed on sub-groups of patients with specific co-morbid medical conditions and those who are frail. Collaborative care is effective in older depressed primary care patients. CONCLUSIONS: There are effective treatments for depression in primary care. More research is needed to address the optimum treatment of depression with medical co-morbidity and to elucidate the role of newer psychological interventions. Collaborative care between primary care and specialist services is a promising new avenue for management.

Prevalence of sub-threshold depression in elderly patients with chronic obstructive pulmonary disease.

OBJECTIVES: We hypothesized that COPD patients with sub-threshold depression would have levels of disability and impaired quality of life approaching that for major depression and significantly greater than for non-depressed COPD patients. SETTING: A university teaching hospital METHOD: 137 outpatients (69 men), with a mean age of 73 years (range 60-89 years) with symptomatic irreversible, moderate to severe COPD were recruited. Subjects were interviewed using the Geriatric Mental State Schedule (GMS), a structured psychiatric interview schedule, along with its diagnostic algorithm AGECAT. A GMS/AGECAT score of 3 or more is indicative of a case-level of depression, a GMS/AGECAT score of 1-2 indicates sub-threshold depression and GMS/AGECAT of 0, no depression. Physical disability was measured by the Manchester Respiratory Activities of Daily Living questionnaire (MRADL) and quality of life was assessed by the Breathing Problems Questionnaire (BPQ). RESULTS: Mean (SD) one second forced expiratory volume was 0.89 (0.33) litres. The prevalence of GMS/AGECAT case-level depression (>or= 3) was 57 cases (42%); of GMS/AGECAT sub-threshold depression (1-2) 34 (25%); and GMS/AGECAT non-depression (0) 46 (33%). Comparison of MRADL score in the three groups (mean, 95% confidence intervals) revealed [GMS >or= 3 = 9.9 (8.4 to 11.3) vs GMS = 1-2, 12.9 (11.2 to 14.4) vs GMS = 0, 15.6 (14 to 16.6) p < 0.0001]. BPQ scores (mean, 95% confidence intervals) showed [GMS >or= 3 = 54 (50 to 57) vs GMS = 1-2, 40 (36.3 to 44) GMS = 0, 33 (30.6 to 36.7) p < 0.0001]. There was no significant difference in FEV(1) between the three groups. CONCLUSION: Sub-threshold depression accounted for 25% of the sample. In this study disability associated with sub-threshold depression in patients with COPD was intermediate to that associated with case-level depression and no with depression and significantly worse than in the latter group. Sub-threshold depression is associated with substantial morbidity in COPD.

Mortality predictors in disabling chronic obstructive pulmonary disease in old age.

OBJECTIVE: prospectively to evaluate predictors of mortality in elderly patients with disabling chronic obstructive pulmonary disease. METHODS: 137 (69 men) outpatients, aged 60-89 (mean 73) years with symptomatic disabling chronic obstructive pulmonary disease. We collected baseline demographic and physiological data. Subjects completed the Manchester Respiratory Activities of Daily Living Questionnaire, the Brief Assessment Schedule Depression Cards a screening questionnaire for depression, the Breathing Problems Questionnaire measuring quality of life, and the Montgomery Asberg Depression Rating Scale measuring severity of depression. All subjects were followed prospectively and survival and mortality data were confirmed by contacting general practitioners and scrutinising hospital notes at 30 months. RESULTS: the mean (standard deviation) of one second forced expiratory volume was 0.89 (0.3) litres. At 30 months, 44 patients (21 men, aged 61-89 [mean 75] years: 32% of the total) had died. Mean (standard deviation) baseline one second forced expiratory volume of those dying was 0.71 (0.2) litres. On logistic regression analysis, predictors of mortality were: Manchester Respiratory Activities Of Daily Living Questionnaire score (odds ratio=0.88, 95% confidence interval=0.80-0.97); pre-bronchodilator one second forced expiratory volume (odds ratio=0.04, confidence interval=0.005-0.32); body mass index (odds ratio=0.87, confidence interval=0.79-0.97); and long term oxygen therapy (odds ratio=3.17, confidence interval=1.04-8.36). Current smoking status, pack-years smoked, depression scores, quality of life scores, co-morbid diseases and social class did not predict mortality. CONCLUSION: disability, use of long-term oxygen therapy, pre-bronchodilator lung function and body-mass index were independent predictors of mortality in elderly patients with severe chronic obstructive pulmonary disease.

Vascular basis of late-onset depressive disorder.

BACKGROUND: Growing evidence suggests that there may be a subtype of depression arising in later life that is characterised by a distinct clinical presentation and an association with cerebrovascular disease. This has been termed 'vascular depression'. AIMS: To review the evidence for associations between cardiovascular disease and depression and between cerebrovascular disease and depression, and to examine implications for clinical practice and research. METHOD: The authors reviewed the medical literature covering the past 5 years. RESULTS: There is strong evidence for an association between cardiovascular disease and depression, but this is not confined to older people. The causal pathway may be bi-directional. There is also a convergence of evidence suggesting a causal link between cerebrovascular disease and depression, especially that occurring later in life. The major focus has been on neuroradiological findings thought to be due to vascular disease, although the pathology may be heterogeneous. CONCLUSIONS: Although there are gaps in the evidence there is strong support for the concept of vascular depression, characterised by reduced depression ideation, subcortical neurological dysfunction, apathy and psychomotor change. This has implications for both treatment and prevention.

Research into depressive disorder in later life: who is doing what? A literature search from 1998-2001.

AIMS AND BACKGROUND: The International Psychogeriatric Association (IPA) aims to improve the mental health care of older people globally. With regard to depression, a number of key publications over the past decade have highlighted areas of progress and areas requiring further research. In order to help clarify what progress has been made, the author conducted a literature review of original research subsequent to three recent major reviews. METHOD: A literature search of four databases over the period 1998-October 2001. Publications with an abstract in English were studied to ascertain number of relevant publications; type of research methodology; topics; and where the research originated. RESULTS: A total of 1,002 publications meeting predefined criteria were located. Fifty-nine percent were cross-sectional studies; less than 10% were randomized controlled studies. The most common themes were depression with comorbidity and etiology, accounting for almost half the papers, with stroke and Parkinson's disease the most frequently researched comorbid medical disorders, although interest in Alzheimer's disease, heart disease, hip fracture, and chronic lung disease appears to be increasing. There were comparatively few studies of psychological and psychosocial interventions. A quarter of the publications concerned major depressive disorder. There were striking variations in the origin of publications with two regions, North America and Northern Europe, accounting for two thirds of all publications but only 13.7% of the world's population aged 65 and over. CONCLUSIONS: Progress is being made but it might occur more rapidly and with greater scope with more international and cross-center collaboration.