A longitudinal study of the association between basal ganglia volumes and psychomotor symptoms in subjects with late life depression undergoing ECT.

Psychomotor dysfunction (PMD) is a core element and key contributor to disability in late life depression (LLD), which responds well to electroconvulsive therapy (ECT). The neurobiology of PMD and its response to ECT are not well understood. We hypothesized that PMD in LLD is associated with lower striatal volume, and that striatal volume increase following ECT explains PMD improvement. We analyzed data from a two-center prospective cohort study of 110 LLD subjects (>55 years) receiving ECT. Brain MRI and assessment of mood, cognition, and PMD was performed 1 week before, 1 week after, and 6 months after ECT. Volumetry of the caudate nucleus, putamen, globus pallidus, and nucleus accumbens was derived from automatically segmented brain MRIs using Freesurfer®. Linear multiple regression analyses were used to study associations between basal ganglia volume and PMD. Brain MRI was available for 66 patients 1 week post ECT and in 22 patients also six months post ECT. Baseline PMD was associated with a smaller left caudate nucleus. One week after ECT, PMD improved and volume increases were detected bilaterally in the caudate nucleus and putamen, and in the right nucleus accumbens. Improved PMD after ECT did not relate to the significant volume increases in these structures, but was predicted by a nonsignificant volume change in the right globus pallidus. No volume differences were detected 6 months after ECT, compared to baseline. Although PMD is related to lower striatal volume in LLD, ECT-induced increase of striatal volume does not explain PMD improvement.

'Big Five' personality characteristics are associated with loneliness but not with social network size in older adults, irrespective of depression.

OBJECTIVE: Loneliness and social isolation have negative health consequences and are associated with depression. Personality characteristics are important when studying persons at risk for loneliness and social isolation. The objective of this study was to clarify the association between personality factors, loneliness and social network, taking into account diagnosis of depression, partner status and gender. DESIGN: Cross-sectional data of an ongoing prospective cohort study, the Netherlands Study of Depression in Older Persons (NESDO), were used. SETTING AND PARTICIPANTS: 474 participants were recruited from mental health care institutions and general practitioners in five different regions in the Netherlands. MEASUREMENTS: NEO-Five Factor Inventory (NEO-FFI) personality factors and loneliness and social network were measured as well as possible confounders. Multinominal logistic regression analyses were performed to analyse the associations between NEO-FFI factors and loneliness and social network. Interaction terms were investigated for depression, partner status and gender. RESULTS: Higher neuroticism and lower extraversion in women and lower agreeableness in both men and women were associated with loneliness but not with social network size irrespective of the presence of depression. In the non-depressed group only, lower openness was associated with loneliness. Interaction terms with partner status were not significant. CONCLUSIONS: Personality factors are associated with loneliness especially in women. In men lower agreeableness contributes to higher loneliness. In non-depressed men and women, lower openness is associated with loneliness. Personality factors are not associated with social network size.

The tide has turned: incidence of depression declined in community living young-old adults over one decade.

AIMS: Studying birth-cohort differences in depression incidence and their explanatory factors may provide insight into the aetiology of depression and could help to optimise prevention strategies to reduce the worldwide burden of depression. METHODS: Data were used from the Longitudinal Aging Study Amsterdam, a nationally representative study among community dwelling older adults in the Netherlands. Cohort differences in depression incidence over a 10-year-period (score ⩾16 on the Center for Epidemiologic Studies Depression scale) were tested using a cohort-sequential-longitudinal-design, comparing two identically measured cohorts of non-depressed 55-64-year-olds, born 10-years apart. Baseline measurements took place in 1992/93 (early cohort, n = 794), and 2002/03 (recent cohort, n = 771). As indicated by the dynamic equilibrium model of depression, potential explanatory factors were distinguished in risk and protective factors. RESULTS: The incidence rates for depression in the early and recent cohort were 1.91 (95% confidence interval (CI) 1.59-2.27) and 1.60 (95% CI 1.31-1.94) per 100 person-years, respectively. A 29% risk reduction in depression incidence was observed in the recent cohort (HRcohort: 0.71, 95% CI 0.54-0.92, p = 0.011), as compared with the early cohort, even though average levels of risk factors such as chronic disease and functional limitations had increased. This reduction was primarily explained by increased levels of education, mastery and labour market participation. CONCLUSIONS: These findings suggest that favourable developments of protective factors have counterbalanced unfavourable effects of risk factors on the incidence of depression, resulting in a net reduction of depression incidence among young-old adults. However, maintaining a good physical health must be a priority to further decrease depression rates.

Age modifies the association between apathy and recurrent falling in Dutch ambulant older persons with a high fall risk: Recurrent falling in Dutch outpatients, does apathy play a role?

Apathy, a common and disabling behavioural syndrome in older persons, has been associated with impaired physical performance and executive dysfunction. Both are fall risk factors and they share pathophysiological pathway. We cross-sectionally examined the association between apathy and recurrent falling (≥2 falls in the past 12 months) and number of falls in the past 12 months in 243 outpatients aged ≥65 years with ≥3 fall risk-factors visiting a fall-clinic after a fall. We calculated Odds Ratio's (ORs), Incidence Rate Ratio's (IRRs) and their 95% Confidential Intervals (CI95) using multivariable regression and negative binomial regression analyses. We adjusted for cognitive functioning, depression, the use of fall risk increasing drugs, visual impairment, urine incontinence, comorbidity, smoking, use of alcohol, body mass index (BMI), and the number of months between assessment of fall risk and of apathy. We assessed effect modification by age and gender. In our study, apathy was independently associated with recurrent falling in patients aged 65-75 years: OR 2.8 (CI95 1.0-7.7). Overall, patients with apathy experienced 1.46 times as many falls in the past 12 months compared to patients without apathy (IRR 1.46 (CI95 1.0-2.1). To conclude, in high fall-risk older outpatients, apathy was cross-sectionally associated with recurrent falling in patients aged 65-75 years and the number of falls. Apathy appeared to be especially relevant in relation to falling in this age group. Whether apathy predicts recurrent falling is yet to be determined.

Reliability of retrospective reports on childhood abuse and its determinants in older adults during a 6-year follow-up.

Controversy exists concerning the reliability of retrospective self-reports on childhood abuse since this method might be subject to under- or overreporting. Until now, no studies have been done in older adults, although reasons for under- or overreporting could be even more prominent in this age group. In this first study in older adults, test-retest reliability of retrospective measurements on childhood abuse and the influence of age, cognitive functioning and depression on this test-retest reliability was investigated. A longitudinal cohort study, the Netherlands Study of Depression in Older persons (NESDO), obtained information on childhood abuse at baseline and at a 6-year follow-up interview. Our sample consisted of 277 adults (mean age 68.5 years at baseline) of which 118 (42.6%) reported childhood abuse at baseline. The largest proportion of the answers was consistent (yes-yes or no-no) for every type of childhood abuse, varying from 85.2 to 93.5%. Looking more closely, 'yes' answers were more fluctuating than 'no' answers. Sexual abuse was most reliably reported in two separate interviews. There was no significant effect of age nor cognition on the test-retest reliability. Only test-retest reliability of emotional neglect was significantly associated with depression diagnosis and depression severity at baseline. In conclusion, test-retest reliability of retrospective self-reports on childhood abuse seems moderate to good, but slightly dependent on the type of abuse. The test-retest reliability was influenced neither by age nor cognition, only reporting of emotional neglect was associated with depression state.

The course of apathy in late-life depression treated with electroconvulsive therapy; a prospective cohort study.

OBJECTIVES: Apathy, a lack of motivation, is frequently seen in older individuals, with and without depression, with substantial impact on quality of life. This prospective cohort study of patients with severe late-life depression treated with electroconvulsive therapy (ECT) aims to study the course of apathy and the predictive value of vascular burden and in particular white matter hyperintensities on apathy course. METHODS: Information on apathy (defined by a score of >13 on the Apathy Scale), depression severity, vascular burden, and other putative confounders was collected in at 2 psychiatric hospitals on patients with late-life depression (aged 55 to 87 years, N = 73). MRI data on white matter hyperintensities were available in 52 patients. Possible risk factors for apathy post-ECT were determined using regression analyses. RESULTS: After treatment with ECT, 52.0% (26/50) of the depression remitters still suffered from clinically relevant apathy symptoms. In the entire cohort, more patients remained apathetic (58.9%) than depressed (31.5%). Presence of apathy post-ECT was not associated with higher age, use of benzodiazepines, or severity of apathy and depression at baseline. Less response in depressive symptomatology after ECT predicted post-treatment apathy. The presence of vascular disease, diabetes mellitus and smoking, and white matter hyperintensities in the brain was not associated with post-treatment apathy. CONCLUSIONS: Apathy may perpetuate in individual patients, despite remission of depressive symptoms. In this cohort of patients with late-life depression, post-ECT apathy is not associated with white matter hyperintensities.

Inflammatory markers and cortisol parameters across depressive subtypes in an older cohort.

BACKGROUND: There is growing evidence that inflammatory and cortisol dysregulation are underlying pathophysiological mechanisms in the aetiology of major depressive disorder, particularly in younger adults. However, findings of biological disturbances in late-life depression have been divergent, probably due to the even greater heterogeneity of depression in older adults with aging processes influencing biological factors. Using empirically derived subtypes may enable the identification of biological disturbances underlying depression in older adults. METHODS: Data were used from the Netherlands Study of Depression in Older Persons (NESDO) of 359 persons aged 60 years or older, with a current diagnosis of major depressive disorder (MDD). Depressive subtypes (severe atypical, severe melancholic, and moderate severe subtype) that were previously identified through latent class analysis (LCA), were examined on differences in inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6), and neutrophil gelatinase-associated lipocalin (NGAL), as well as cortisol parameters. RESULTS: No differences in measures for inflammation and cortisol across subtypes were observed in uncorrected or for putative confounders corrected models. LIMITATIONS: Several subjects had missing cortisol and inflammatory data, decreasing the power. However, results did not change after imputation analysis. DISCUSSION: In this cohort of depressed older adults, no differences in inflammation and cortisol measures between depression subtypes were observed. This is probably due to the many (patho)physiological processes that are involved in aging, thereby clouding the results.

Prognostic significance of social network, social support and loneliness for course of major depressive disorder in adulthood and old age.

AIMS: Poor recovery from depressive disorder has been shown to be related to low perceived social support and loneliness, but not to social network size or frequency of social interactions. Some studies suggest that the significance of social relationships for depression course may be greater in younger than in older patients, and may differ between men and women. None of the studies examined to what extent the different aspects of social relationships have unique or overlapping predictive values for depression course. It is the aim of the present study to examine the differential predictive values of social network characteristics, social support and loneliness for the course of depressive disorder, and to test whether these predictive associations are modified by gender or age. METHODS: Two naturalistic cohort studies with the same design and overlapping instruments were combined to obtain a study sample of 1474 patients with a major depressive disorder, of whom 1181 (80.1%) could be studied over a 2-year period. Social relational variables were assessed at baseline. Two aspects of depression course were studied: remission at 2-year follow-up and change in depression severity over the follow-up period. By means of logistic regression and random coefficient analysis, the individual and combined predictive values of the different social relational variables for depression course were studied, controlling for potential confounders and checking for effect modification by age (below 60 v. 60 years or older) and gender. RESULTS: Multiple aspects of the social network, social support and loneliness were related to depression course, independent of potential confounders - including depression severity - but when combined, their predictive values were found to overlap to a large extent. Only the social network characteristic of living in a larger household, the social support characteristic of few negative experiences with the support from a partner or close friend, and limited feelings of loneliness proved to have unique predictive value for a favourable course of depression. Little evidence was found for effect modification by gender or age. CONCLUSIONS: If depressed persons experience difficulties in their social relationships, this may impede their recovery. Special attention for interpersonal problems, social isolation and feelings of loneliness seems warranted in depression treatment and relapse prevention. It will be of great interest to test whether social relational interventions can contribute to better recovery and relapse prevention of depressive disorder.

[ResPECT - a decade of Flemish-Dutch ECT research]. / ResPECT ­ een decennium Vlaams-Nederlands onderzoek naar elektroconvulsietherapie.

BACKGROUND: There is increasing clinical and scientific interest in electroconvulsive therapy (ECT). AIM: To provide an overview of the main research findings of the Flemish-Dutch research consortium ResPECT. METHOD: We report on our review of the relevant literature. RESULTS: Our studies confirm that ECT is one of the most efficient treatments for depression in later life and for depression with psychotic features. Older people with age-related brain pathology can respond well to ECT. It is still preferable to apply a standard pulse-width because this increases the efficacy of the treatment and minimises the cognitive impact. Even vulnerable older people can react favourably to ECT. CONCLUSION: Recent findings of the ResPECT consortium are providing new insights that are applicable in daily clinical practice. Research into mechanisms of action can also increase our understanding of the pathophysiology of severe depression.

Depressive subtypes in an elderly cohort identified using latent class analysis.

BACKGROUND: Clinical findings indicate heterogeneity of depressive disorders, stressing the importance of subtyping depression for research and clinical care. Subtypes of the common late life depression are however seldom studied. Data-driven methods may help provide a more empirically-based classification of late-life depression. METHODS: Data were used from the Netherlands Study of Depression in Older People (NESDO) derived from 359 persons, aged 60 years or older, with a current diagnosis of major depressive disorder. Latent class analysis (LCA) was used to identify subtypes of depression, using ten CIDI-based depression items. Classes were then characterized using various sociodemographic and clinical characteristics. RESULTS: The most prevalent class, as identified by LCA, was a moderate-severe class (prevalence 46.5%), followed by a severe melancholic class (prevalence 38.4%), and a severe atypical class (prevalence 15.0%). The strongest distinguishing features between the three classes were appetite and weight and, to a lesser extent, psychomotor symptoms and loss of interest. Compared with the melancholic class, the severe atypical class had the highest prevalence of females, the lowest mean age, the highest BMI, and highest prevalence of both cardiovascular disease, and metabolic syndrome. LIMITATIONS: The strongest distinguishing symptoms, appetite and weight, could be correlated. Further, only longitudinal studies could demonstrate whether the identified classes are stable on the long term. DISCUSSION: In older persons with depressive disorders, three distinct subtypes were identified, similar to subtypes found in younger adults. The strongest distinguishing features were appetite and weight; moreover, classes differed strongly on prevalence of metabolic syndrome and cardiovascular disease. These findings suggest differences in the involvement of metabolic pathways across classes, which should be considered when investigating the pathogenesis and (eventually) treatment of depression in older persons.

Loneliness in older adults is associated with diminished cortisol output.

OBJECTIVE: Loneliness in older adults has been associated with increased mortality and health problems. One of the assumed underlying mechanisms is dysregulation of the hypothalamic-pituitary-adrenocortical axis (HPA-axis). The purpose of this study was to investigate whether loneliness in older adults is associated with HPA-axis dysregulation and whether this association differs between depressed and non-depressed persons. METHODS: Cross-sectional data of 426 lonely and non-lonely older adults in the Netherlands Study of Depression in Older Persons (NESDO) were used. Linear regression analyses and multinominal logistic regression analyses were performed to examine the association between loneliness and morning cortisol, cortisol awakening response, diurnal slope and dexamethasone suppression ratio. In all analyses, confounders were introduced. In order to examine whether the association between loneliness and cortisol measures is different in depressed versus non-depressed persons, an interaction term for loneliness x depression diagnosis was tested. RESULTS: Cortisol output in the first hour after awakening and dexamethasone suppression ratio was lower in lonely participants. There were no significant interactions between loneliness and depression diagnosis in the association with the cortisol measures. CONCLUSION: This study is the first to investigate the association between the HPA-axis and loneliness in a large group of older adults aged 60-93years. We found lower cortisol output in the first hour after awakening and lower dexamethasone suppression ratio in lonely older depressed and non-depressed adults. Whether diminished cortisol output is the underlying mechanism that leads to health problems in lonely older adults is an interesting object for further study.

Big Five personality characteristics are associated with depression subtypes and symptom dimensions of depression in older adults.

OBJECTIVE: This study examined the associations of personality characteristics with both subtypes and symptom dimensions of depression in older adults. METHODS: Three hundred and seventy-eight depressed older adults participated in the Netherlands Study of Depression in Older Persons. Personality characteristics were assessed by the NEO-Five Factor Inventory. Subtypes and symptom dimensions of depression were determined using the Composite International Diagnostic Interview and the Inventory of Depressive Symptomatology (IDS). Multinomial logistic regression analyses were performed to examine the associations between personality and atypical, melancholic, and unspecified subtypes of major depression. Linear regression analyses examined the associations between personality and the IDS mood, somatic, and motivation symptom dimensions. The analyses were adjusted for confounders and additionally adjusted for depression severity. RESULTS: Neuroticism, Extraversion, Conscientiousness, and Agreeableness were associated with specified (atypical or melancholic) major depression compared with unspecified major depression in the bivariate analyses but lost their significance after adjustments for functional limitations and severity of depression. Neuroticism was positively associated with the IDS mood and motivation symptom dimensions, also in the adjusted models. Further, Extraversion and Agreeableness were negatively associated with the IDS mood symptom dimension, and Extraversion and Conscientiousness were negatively associated with the IDS motivation symptom dimension. None was associated with the IDS somatic symptom dimension. CONCLUSIONS: This study demonstrated the association of personality characteristics with mood and motivational symptoms of late-life depression. The lacking ability of personality to differentiate between melancholic and atypical depression seems to be largely explained by severity of depressive symptoms. Copyright © 2017 John Wiley & Sons, Ltd.

The long-term outcome of subthreshold depression in later life.

BACKGROUND: Subthreshold depression (SUBD) in later life is common and important as prodromal state and prominent risk factor in the development of major depressive disorder (MDD). Indicated prevention can reduce the incidence of MDD among people with SUBD substantially, but needs to be targeted to those that are truly at risk of developing MDD. METHOD: N = 341 eligible participants with SUBD were included from the first (1992/1993), second (1995/1996) and third (1998/1999) cycle from the Longitudinal Aging Study Amsterdam (LASA) by using a two-stage screening design. LASA is an ongoing prospective cohort study in The Netherlands among the older population (55-85 years). At baseline (1992/1993) N = 3107 participants were interviewed and follow-up cycles were conducted every 3 years until 2008/2009, resulting in maximal 17 years of observational period. The proportion of people that developed MDD, remained SUBD, or recovered from SUBD was measured and Cox proportional regression analyses were performed to investigate 29 putative predictors of MDD and recovery from SUBD. RESULTS: N = 153 (44.9%) recovered from SUBD, N = 138 (40.5%) remained chronically SUBD, and N = 50 (14.7%) developed MDD (incidence rate 15.1/1000 person-years). Women, high neuroticism, more chronic diseases, high body mass index, smoking and less social support predicted conversion to MDD. Men, low neuroticism and absence of pain predicted recovery from SUBD. CONCLUSIONS: Although older people with SUBD are clearly at risk of developing MDD, the majority did not, even after a long and thorough follow-up. Given the risk factors that were uncovered, targeting and prevention of MDD in those at very high risk is feasible.

Psychiatric diagnoses underlying the phenocopy syndrome of behavioural variant frontotemporal dementia.

INTRODUCTION: The frontotemporal dementia (FTD) consortium criteria (2011) emphasise the importance of distinguishing possible and probable behavioural variant FTD (bvFTD). A significant number of possible patients with bvFTD do not show functional decline and remain with normal neuroimaging over time, thus exhibiting the bvFTD phenocopy syndrome. A neurodegenerative nature is unlikely but an alternative explanation is missing. Our aim was to detect psychiatric conditions underlying the bvFTD phenocopy syndrome after extensive evaluation. METHODS: We included patients with the bvFTD phenocopy syndrome whereby patients with probable bvFTD served as a control group. Patients had to have undergone both neurological and psychiatric evaluation. Their charts were reviewed retrospectively. Using both qualitative and quantitative methods, psychiatric and psychological conditions associated with the clinical syndrome were determined in both groups and their relative frequencies were compared. RESULTS: Of 181 suspected bvFTD cases, 33 patients with bvFTD phenocopy syndrome and 19 with probable bvFTD were included. Recent life events, relationship problems and cluster C personality traits were the most prevalent psychiatric/psychological conditions. The frequency of these conditions was higher in the group of patients with the bvFTD phenocopy syndrome (n=28) compared to the probable bvFTD group (n=9) (χ(2) p<0.05). CONCLUSIONS: This is the first study thoroughly exploring psychiatric causes of the bvFTD phenocopy syndrome, revealing that in most cases multiple factors played a contributory role. Our study gives arguments for neurological and psychiatric collaboration when diagnosing bvFTD. Prompt diagnosis of treatable psychiatric conditions is to be gained.

Childhood abuse, family history and stressors in older patients with bipolar disorder in relation to age at onset.

OBJECTIVES: The aim of this study is to explore the family history of psychiatric disorders, childhood abuse, and stressors in older patients with Bipolar Disorder (BD) and the association of these variables with the age at onset of BD. METHODS: The Questionnaire for Bipolar Disorder (QBP) and the Mini International Neuropsychiatric Interview (MINI-Plus) were obtained from 78 patients aged 60 and over to determine diagnosis, age at onset of the first affective episode, childhood abuse, family history of psychiatric disorders and past and recent stressful life events. RESULTS: Increased family history of psychiatric disorders was the only factor associated with an earlier age at onset of BD. Less family history of psychiatric disorders and more negative stressors were significantly associated with a later age at onset of the first (hypo)manic episode. LIMITATIONS: Age at onset, history of childhood abuse, and past stressful life events were assessed retrospectively. Family members of BD patients were not interviewed. CONCLUSIONS: Our findings suggest that age at onset can define distinct BD phenotypes. More specifically there was a stronger heredity of BD and other psychiatric disorders in patients with an early age of onset of BD. Negative stressors may play a specific role in patients with a late age at onset of a first (hypo)manic episode.

[Hashimoto encephalitis and depression]. / Hashimoto-encefalitis en depressie.

Hashimoto encephalitis (he) is an auto-immune disease, with 40-50% of patients developing psychopathology. This could require targeted treatment. HE and prednison could both cloud the identification of a concurrent depressive disorder. We saw a 78-year-old woman with he and a severe depression, and treated her succesfully with ect.

Tailored mental health care after nursing home admission: improving transfers of people with dementia with behavioral problems. An explorative study.

OBJECTIVES: In the Netherlands, many community-dwelling people with dementia and behavioral disturbances and their family caregivers receive mental health care from a community psychiatric nurse (CPN). To promote continuity of care for these persons after moving to a nursing home, a transfer intervention was developed. The aim of this explorative study was to evaluate this intervention and its implementation. METHOD: A qualitative explorative study design was used. CPNs visited professional nursing home carers, people with dementia and family caregivers six weeks after moving, advised on how to manage behavioral problems of their former clients and provided support to family caregivers. Twenty-two interviews were conducted with participants exposed to the intervention (5 CPNs, 5 family and 12 nursing home carers) and with 11 stakeholders (i.e., nursing home and mental health care managers, professional caregivers) to identify facilitators and barriers to the implementation. Data were collected in 2012 and 2013. RESULTS: The follow-up visit at six weeks met the need for background information of new admitted patients and helped family caregivers close off the period prior to the move. It did not meet the original purpose of providing nursing home staff with advice about problem behaviors on time: six weeks after the move was experienced as too late. CONCLUSION: The transfer intervention increased the awareness of nursing home staff about personal and behavioral characteristics of residents with dementia and supported caregivers in coping with the new situation. The timing of the intervention could be improved by scheduling it immediately after the move.

Hypothalamic-pituitary-adrenal axis activity in older persons with and without a depressive disorder.

BACKGROUND: Altered functioning of the hypothalamic-pituitary-adrenal axis (HPA-axis) has been associated with depression, but findings have been inconsistent. Among older depressed persons, both hyperactivity and hypo-activity of the HPA-axis were demonstrated. However, most studies were population-based studies, with single cortisol measurements, lacking insight into diurnal patterns of HPA-axis functioning. We aim to provide insight into functioning of the HPA-axis, assessed by various salivary cortisol samples, in depressed older adults and non-depressed controls. METHODS: Data were derived from the Netherlands Study of Depression in Older Persons. Cortisol levels of older persons without a lifetime diagnosis of depression and/or anxiety (n=109) were compared with older persons with a 6-month major depression diagnosis (n=311). ANCOVA analyses and random coefficient analysis on the four morning cortisol samples were performed. A possible U-shaped association between cortisol and depression status was examined. RESULTS: Depressed older persons showed higher morning cortisol levels at awakening (T1) and a less dynamic awakening response compared to non-depressed older persons. Dexamethasone suppression did not differ across groups. No U-shaped association between HPA-axis activity and depression was observed. CONCLUSION: We demonstrated a hypercortisolemic state and a diminished ability to respond to the stress of awakening among depressed older persons. Previously it was shown, that hypercortisolemic states may indicate a lifelong biological vulnerability for depression. Our findings expand on previous literature by demonstrating that in older persons the HPA-axis may become less responsive to stress, culminating in a further dysregulation of the diurnal cortisol-rhythm, superimposed on - possibly lifelong - hypercortisolemic states.

BDNF serum levels are not related to cognitive functioning in older depressed patients and controls.

BACKGROUND: Depression and cognitive decline are highly prevalent in older persons and both are associated with low serum brain derived neurotrophic factor (BDNF). Mutual pathways of depression and cognitive decline in older persons may explain the overlap in symptoms and low serum BDNF. We hypothesized that serum BDNF levels are lower in depressed elderly with poor cognitive performance (global or specifically in working memory, speed of information processing, and episodic memory) compared to depressed elderly without cognitive impairment or non-depressed controls. METHODS: BDNF Serum levels and cognitive functioning were examined in 378 depressed persons and 132 non-depressed controls from a large prospective study on late-life depression. The association between BDNF levels and each cognitive domain among the depressed patients was tested by four separate linear regression models adjusted for relevant covariates. An analysis of covariance (ANCOVA) was performed to compare BDNF serum levels in three groups (depression with cognitive impairment, depression without cognitive impairment, and non-depressed controls), when adjusted for potential confounders. RESULTS: No significant linear association was found between BDNF and any of the four cognitive domains tested. There are no differences in BDNF levels between controls and depressed patients with or without cognitive impairment global or in specific domains after controlling for confounders. CONCLUSIONS: BDNF serum levels in this cohort of older depressed patients and controls are not related to cognitive functioning. As BDNF is essential for the survival and functioning of neurons, its levels may remain normal in stages of disease where remission is achievable.