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BACKGROUND: Severe depression is associated with accelerated brain aging. BrainAge gap, the difference between predicted and observed BrainAge was investigated in patients with late-life depression (LLD). We aimed to examine BrainAge gap in LLD and its associations with clinical characteristics indexing LLD chronicity, current severity, prior to electroconvulsive therapy (ECT) and ECT outcome. METHODS: Data was analyzed from the Mood Disorders in Elderly treated with Electroconvulsive Therapy (MODECT) study. A previously established BrainAge algorithm (BrainAge R by James Cole, (https://github.com/james-cole/brainageR)) was applied to pre-ECT T1-weighted structural MRI-scans of 42 patients who underwent ECT. RESULTS: A BrainAge gap of 1.8 years (SD = 5.5) was observed, Cohen's d = 0.3. No significant associations between BrainAge gap, number of previous episodes, current episode duration, age of onset, depression severity, psychotic symptoms or ECT outcome were observed. LIMITATIONS: Limited sample size. CONCLUSIONS: Our initial findings suggest an older BrainAge than chronological age in patients with severe LLD referred for ECT, however with high degree of variability and direction of the gap. No associations were found with clinical measures. Larger samples including are needed to better understand brain aging and to evaluate the usability of BrainAge gap as potential biomarker of prognosis an treatment-response in LLD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02667353.

The risk of relapse following successful acute-phase treatment of late-life depression (LLD), including electroconvulsive therapy (ECT), is substantial. In order to improve reliable prediction of individuals' risk of relapse, we assessed the association between individual residual symptoms following a successful acute course of ECT for LLD and relapse at six-month follow-up. This prospective cohort study was part of the MODECT study, which included 110 patients aged 55 years and older with major depressive disorder. Participants who showed response to the index ECT course were monitored for relapse for six months. We used multivariable stepwise logistic regression models to assess the association between the scores on the 10 individual Montgomery-Asberg Depression Rating Scale (MADRS) items at the end of the acute ECT course and relapse at six-month follow-up. Of the 80 responders with available six-month follow-up data (58.75% of which had psychotic features at baseline), 36.25% had relapsed. Higher scores on the MADRS items 'reduced sleep' (odds ratio (OR) = 2.03, 95% confidence interval (CI) = 1.11-3.69, p = 0.0214) and 'lassitude' (OR = 1.62, 95% CI = 1.00-2.62, p = 0.0497) at the end of the acute ECT course were significantly associated with increased risk of relapse at six-month follow-up. In conclusion, some residual depressive symptoms, including sleep disturbance and lassitude, may help better identify patients vulnerable to relapse following a successful acute course of ECT for LLD. If these findings can be replicated, studies assessing interventions that target specific residual symptoms may further reduce post-ECT depressive relapse rates.

OBJECTIVE: Should we treat older, patients with depression with white matter hyperintensities (WMH) with electroconvulsive therapy (ECT)? WMH, inflammation, depression and cognitive functioning are suggested to be intertwined. Hence, this study investigates whether the association between inflammation and cognition is different in patients with depression with or without WMH. METHODS: Cognitive functioning was assessed using the Mini-Mental State Examination during and after a course of ECT in 77 older patients with depression. Serum samples (C-reactive protein [CRP], interleukin-6 [IL-6], interleukin-10 [IL-10] and tumour necrosis factor-alpha [TNF-α]) and 3T magnetic resonance imaging were obtained prior to ECT. RESULTS: An interaction effect was found for IL-10, but not for CRP, IL-6 or TNF-α. CONCLUSION: In general, the association between inflammatory markers and cognition in patients with depression treated with ECT is not different in patients with WMH compared to patients without WMH. ispartof: AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY vol:30 issue:4 pages:514-518 ispartof: location:England status: published

BACKGROUND: Although electroconvulsive therapy (ECT) is a safe and effective treatment for patients with severe late life depression (LLD), transient cognitive impairment can be a reason to discontinue the treatment. The aim of the current study was to evaluate the association between structural brain characteristics and general cognitive function during and after ECT. METHODS: A total of 80 patients with LLD from the prospective naturalistic follow-up Mood Disorders in Elderly treated with Electroconvulsive Therapy study were examined. Magnetic resonance imaging scans were acquired before ECT. Overall brain morphology (white and grey matter) was evaluated using visual rating scales. Cognitive functioning before, during, and after ECT was measured using the Mini Mental State Examination (MMSE). A linear mixed-model analysis was performed to analyze the association between structural brain alterations and cognitive functioning over time. RESULTS: Patients with moderate to severe white matter hyperintensities (WMH) showed significantly lower MMSE scores than patients without severe WMH (F(1,75.54) = 5.42, p = 0.02) before, during, and post-ECT, however their trajectory of cognitive functioning was similar as no time × WMH interaction effect was observed (F(4,65.85) = 1.9, p = 0.25). Transient cognitive impairment was not associated with medial temporal or global cortical atrophy (MTA, GCA). CONCLUSION: All patients showed a significant drop in cognitive functioning during ECT, which however recovered above baseline levels post-ECT and remained stable until at least 6 months post-ECT, independently of severity of WMH, GCA, or MTA. Therefore, clinicians should not be reluctant to start or continue ECT in patients with severe structural brain alterations. ispartof: American Journal Of Geriatric Psychiatry vol:29 issue:11 pages:1117-1128 ispartof: location:England status: accepted

Objective: Electroconvulsive therapy (ECT) is the most effective treatment for late-life depression (LLD). Research addressing long-term outcome following an acute course of ECT for LLD is limited. We aimed to describe relapse, cognitive impairment and survival 5 years after a treatment with ECT for severe LLD, and assess the association of clinical characteristics with all three outcome measures. Methods: This cohort study was part of the Mood Disorders in Elderly treated with ECT (MODECT) study, which included patients aged 55 years and older with major depressive disorder. Data regarding clinical course, cognitive impairment and mortality were collected 5 years after the index ECT course. We used multivariable Cox proportional hazards models and logistic regression models to assess the association of clinical characteristics with relapse and survival, and cognitive impairment, respectively. Results: We studied 110 patients with a mean age of 72.9 years. 67.1% of patients who showed response at the end of the index ECT course relapsed, and the included clinical characteristics were not significantly associated with the risk of relapse. 38.8% of patients with available data showed cognitive impairment at five-year follow-up. 27.5% were deceased; higher age and a higher number of previous psychiatric admissions were significantly associated with increased risk of mor-tality. Conclusions: Five-year outcome after a course of ECT for severe LLD seems to be in line with long-term outcome following other acute treatments for severe LLD in terms of relapse, cognitive impairment and survival. Additional studies aimed at improving long-term outcome in severe LLD are warranted. (Am J Geriatr Psychiatry 2022; 30:1283-1294)

Objective: Electroconvulsive therapy (ECT) is a safe and effective treatment, especially in psychotic late-life depression (LLD). However, it is not yet clear whether the greater efficacy seen in psychotic LLD is because of a shorter index episode duration. The first aim of this study was to substantiate the superior ECT remission rates in patients with psychotic LLD, as compared to patients with nonpsychotic LLD, and a second aim was to investigate whether this association is independent of the index duration. Methods: 186 patients with LLD treated with ECT were included in the study: 76 from the Valerius cohort (data collection from 2001 to 2006) and 110 from the Mood Disorders Treated with Electroconvulsive Therapy (MODECT) cohort (data collection from 2011 to 2013). The Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate depression severity, with remission defined as 2 consecutive MADRS scores

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 (β = 5.21, P = .04), while WMH in the left infratentorial region were associated with apathy symptoms (β 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.

Objective In the last decade, repetitive transcranial magnetic stimulation (rTMS) has been introduced as a non‐invasive neuromodulation therapy for depression. Little is known, however, about (serious) adverse events (AE) of rTMS in older adults with a depression. In this article, we want to study what is known about (serious) AE of rTMS in older adults (>60 years) with late‐life depression (LLD). Methods A systematic search has been performed according to the PRISMA guidelines in PubMed, EMBase and PsycInfo. We have screened 622 articles for eligibility. Eleven studies, evaluating 353 patients in total, were included in this review. Results AE were reported in 12.4% of the older adults with a LLD treated with rTMS, serious AE in 1.5%. Headache (6.9%) and discomfort at the stimulation site (2.7%) are the most commonly reported AE. Serious AE reported are: psychiatric hospitalization (three times), a combination of posterior vitreous detachment and retinal tear, and increased suicide ideation (both once). Conclusions rTMS in older adults with LLD was concluded overall to be safe due to the low frequency of AE reported in trials and observational studies. In case‐reports, however, more serious AE have been described. To tailor use of rTMS in older adults with LLD, more research is needed in larger samples to optimize tolerance., Highlights Little is known about (serious) AE of rTMS in older adults (>60 years) with LLD.A relatively low percentage of AE (12.4% in total) and serious AE (1.5% in total) in response to rTMS occurs in older adults with LLD.rTMS is a safe and well‐tolerated treatment option for older adults with LLD.

Psychotic major depression (PMD) is hypothesized to be a distinct clinical entity from nonpsychotic major depression (NPMD). However, neurobiological evidence supporting this notion is scarce. The aim of this study is to identify gray matter volume (GMV) differences between PMD and NPMD and their longitudinal change following electroconvulsive therapy (ECT). Structural magnetic resonance imaging (MRI) data from 8 independent sites in the Global ECT-MRI Research Collaboration (GEMRIC) database (n = 108; 56 PMD and 52 NPMD; mean age 71.7 in PMD and 70.2 in NPMD) were analyzed. All participants underwent MRI before and after ECT. First, cross-sectional whole-brain voxel-wise GMV comparisons between PMD and NPMD were conducted at both time points. Second, in a flexible factorial model, a main effect of time and a group-by-time interaction were examined to identify longitudinal effects of ECT on GMV and longitudinal differential effects of ECT between PMD and NPMD, respectively. Compared with NPMD, PMD showed lower GMV in the prefrontal, temporal and parietal cortex before ECT; PMD showed lower GMV in the medial prefrontal cortex (MPFC) after ECT. Although there was a significant main effect of time on GMV in several brain regions in both PMD and NPMD, there was no significant group-by-time interaction. Lower GMV in the MPFC was consistently identified in PMD, suggesting this may be a trait-like neural substrate of PMD. Longitudinal effect of ECT on GMV may not explain superior ECT response in PMD, and further investigation is needed. Funding Agencies|Keio University Medical Science Fund [99-095-0007]; AMED [JP20dm0307102h0003]; Research Foundation Flanders (FWO) grantFWO [G0C0319N]; KU Leuven Fund [C24/18/095]; Sequoia Fund for Research on Ageing and Mental Health; National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [MH125126, MH111826]; Carlos III Health InstituteInstituto de Salud Carlos III [CD20/00189]; Lundbeck FoundationLundbeckfonden; Western Norway Regional Health Authority [911986, 912238]

Objective: Despite the effectiveness of electroconvulsive therapy (ECT), patients and practitioners are often reluctant to start it due to the risk of transient cognitive side effects, particularly in older patients. Inflammatory processes may be associated with the occurrence of these effects. This study assessed whether inflammatory markers prior to ECT are associated with cognitive functioning in depressed patients treated with ECT.Methods: Between 2011 and 2013, 97 older patients (mean [SD] age = 73.1 [8.1] years) with severe unipolar depression (according to DSM-IV) referred for ECT were included. Mini-Mental State Examination (MMSE) scores were used to determine cognitive functioning prior to, weekly during, and in the first week after a course of ECT. Serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) were assessed prior to ECT.Results: In fully adjusted models, there was an association between TNF-α and cognitive functioning (β = -1.05; 95% CI, -2.04 to -0.06; f2 = 0.06). An association was also found between baseline levels of IL-10 and TNF-α and lower MMSE scores during ECT (IL-10: β = -2.08; 95% CI, -3.22 to -0.95; TNF-α: β = -0.65; 95% CI, -1.07 to -0.22). In addition, an association was found between baseline CRP and lower MMSE scores directly after a course of ECT (β = -0.51; 95% CI, -0.93 to -0.09; f2 = 0.10). Associations with IL-6 did not reach significance.Conclusions: This study suggests that inflammatory processes are associated with lower cognitive functioning prior to ECT and predispose for further cognitive dysfunction during and after a course of ECT.Trial registration: ClinicalTrials.gov identifier: NCT02667353.

While brain-derived neurotrophic factor (BDNF) has been shown to predict response to pharmacotherapy in depression, studies in electroconvulsive therapy (ECT) are small and report conflicting results. This study assesses the association between pre-treatment BDNF levels and ECT outcome in severe late-life unipolar depression (LLD). The potential of BDNF as a clinical predictor of ECT outcome was subsequently evaluated. Characteristics associated with low and high BDNF subgroups were determined as well. Ninety-four patients diagnosed with LDD referred for ECT were included. Fasting serum BDNF levels were determined before ECT. Remission and response, measured with the Montgomery–Åsberg Depression Rating Scale, were the outcomes. The association between BDNF and ECT outcome was analysed with logistic regression and Cox regression. The clinical usefulness of BDNF was evaluated using the receiver operating characteristic (ROC) curve. Associations between clinical characteristics and low versus high BDNF levels were examined with T tests, chi-squared tests and Mann−Whitney tests. The odds of remission decreased with 33% for every five units increase of BDNF levels (OR 0.67, 95% confidence interval 0.47–0.96; p = 0.03); however, neither the association with time to remission nor the associations with response nor the adjusted models were significant. The area under the ROC (0.66) implied a poor accuracy of BDNF as a clinical test. Clinical characteristics associated with BDNF were inclusion site, physical comorbidities and duration of the index episode. To conclude, although there is an association between pre-treatment BDNF levels and ECT outcome, BDNF cannot be considered an eligible biomarker for ECT outcome in clinical practice.

BackgroundElectroconvulsive therapy (ECT) is the most effective intervention for patients with treatment resistant depression. A clinical decision support tool could guide patient selection to improve the overall response rate and avoid ineffective treatments with adverse effects. Initial small-scale, mono-center studies indicate that both structural magnetic resonance imaging (sMRI) and functional MRI (fMRI) biomarkers may predict ECT outcome, but it is not known whether those results can generalize to data from other centers.ObjectiveTo develop and validate neuroimaging biomarkers for ECT outcome in a multi-center setting.MethodsMultimodal data (i.e., clinical, sMRI and resting-state fMRI) was collected from seven centers of the Global ECT-MRI Research Collaboration (GEMRIC). We used data from 189 depressed patients to evaluated which data modalities or combinations thereof could provide the best predictions for treatment response (≥50% symptom reduction) or remission (HAM-D score ≤7) using a support vector machine classifier.ResultsRemission classification using a combination of gray matter volume and functional connectivity led to good performing models with average 0.82-0.83 area under the curve (AUC) when trained and tested on samples coming from the three largest centers, and remained acceptable when validated using leave-one-site-out cross-validation (0.70-0.73 AUC).ConclusionsThese results show that multimodal neuroimaging data is able to provide good prediction of remission with ECT for individual patients across different treatment centers, despite significant variability in clinical characteristics across centers. This suggests that these biomarkers are robust, indicating that future development of a clinical decision support tool applying these biomarkers may be feasible.

Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness.Methods: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R2) at the optimal p-value threshold is reported.Results: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R2 = 8.18%, p = .0013), Belgium (R2 = 6.83%, p = .016), and the Netherlands (R2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R2 = 4.42%, p = .0024) and unipolar MDE only (R2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold.Conclusions: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry.

OBJECTIVES: An association is found between changes in cytokine levels and antidepressant treatment outcome. Also, a proinflammatory profile is associated with a favourable electroconvulsive therapy (ECT) outcome. This paper investigates the pattern of inflammatory markers during a course of ECT in older depressed patients and whether this pattern is associated with ECT outcome. We hypothesised that ECT has an anti-inflammatory effect. METHODS: The pattern of CRP, IL-6, IL-10, and TNF-α during a course of ECT was examined using longitudinal mixed model analyses. Serum samples were collected in 99 older depressed patients (mean age: 72.8 ± 8.3 years, MADRS score 33.8 ± 9.0). RESULTS: After Bonferroni correction, there were no statistically significant alterations in levels of inflammatory markers during and after ECT. Effect sizes (Cohen's d) were -0.29 for CRP, -0.13 for IL-6, -0.06 for IL-10, and -0.07 for TNF-α. Changes in CRP or cytokine levels did not differ between remitters and non-remitters. Median baseline levels of CRP were significantly higher in remitters. CONCLUSIONS: A small to medium effect size towards decreased CRP and IL-6 levels was observed. An anti-inflammatory effect of ECT could not be confirmed. However, the findings may suggest that patients with an inflammatory profile benefit more from ECT than other patients. Further studies are needed to confirm these findings. ispartof: WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY vol:22 issue:10 pages:770-777 ispartof: location:England status: published

BACKGROUND: A substantial number of patients with late-life depression (LLD) that remitted after ECT experience relapse. Identifying risk factors for relapse may guide clinical management to devote attention to those at increased risk. Therefore the current study aims to evaluate which baseline clinical characteristics are related to relapse within six months after successful ECT in patients with severe LLD.METHODS: 110 patients with LLD from the prospective naturalistic follow-up Mood Disorders in Elderly treated with Electro-Convulsive Therapy (MODECT) study were included. A total of 73 patients (66.4%) remitted after ECT, six patients had missing information on relapse, rendering to a total sample size of 67 patients. Relapse within six months after ECT was defined as a Montgomery Åsberg Depression Scale (MADRS)-score > 15, readmission or restart of ECT. Logistic regression analyses were conducted to examine the association between baseline clinical characteristics and relapse.RESULTS: A total of 22 patients (32.8%) experienced a relapse. Patients with psychotic depression were less likely to relapse (odds ratio = 0.32, p = .047), corrected for prior admissions; 76.9% of patients with psychotic depression remained remitted.LIMITATIONS: Due to its naturalistic design, no firm conclusions can be drawn on the effect of post-ECT treatment.CONCLUSIONS: Patients with psychotic depression had a lower risk to experience relapse after successful ECT. This result strengthens the hypothesis that psychotic depression might be a specific depression subtype with a favorable ECT outcome up to six months after ECT.

Objectives: Electroconvulsive therapy (ECT) is the most effective treatment for depression; however, consensus on predictors for ECT outcome is lacking. We aim to examine the relation between pre-ECT salivary cortisol values and clinical characteristics and ECT outcome in depressed, older persons. Methods: A total of 102 inpatients meeting DSM-IV criteria for depression and referred for ECT were selected. Salivary cortisol was assessed at five time points during the day, providing insight into the cortisol awakening curve to the ground (AUCg) and to the increase (AUCi) and evening cortisol level. Depression severity was assessed using the Montgomery–Asberg Depression Rating Scale (MADRS). Remission was defined as MADRS

Objective The clinical profile of late-life depression (LLD) is frequently associated with cognitive impairment, aging-related brain changes, and somatic comorbidity. This two-site naturalistic longitudinal study aimed to explore differences in clinical and brain characteristics and response to electroconvulsive therapy (ECT) in early- (EOD) versus late-onset (LOD) late-life depression (respectively onset

Background: Increasing evidence suggests that glial mediated disruption of neuroplasticity contributes to depression. S100 calcium-binding protein B (S100B) promotes neuronal protection in nanomolar concentrations. Studies on its possible role as a treatment outcome marker in affective disorders are limited. Recent evidence suggests a putative role for S100B as a state marker of illness activity as it is found elevated in episodes of major depression. Aim: To investigate whether higher S100B is associated with favourable treatment outcome following electroconvulsive therapy (ECT) and to further explore whether S100B reflects a state marker of depression activity. Methods: Serum S100B samples, at baseline and post-ECT and clinical assessments including Montgomery Åsberg Rating scales were collected in 91 older depressed patients (mean age: 73.0 years), referred for ECT. Change in pre- and post-ECT S100B was compared between remitters and nonremitters. Logistic and Cox regression analyses were used to determine whether S100B was associated with remission of depression. Results: Patients with S100B levels in the intermediate tertile, that is, between 33 ng/L and 53 ng/L, had higher odds on remission, odds ratio: 5.5 (95%Confidence Interval (CI): 1.55–19.20, p =

BACKGROUND: Compelling evidence links elevated levels of C-reactive protein (CRP) and other inflammatory markers to poor treatment outcome of antidepressant medication. Little is known about the contribution of low-grade inflammation to treatment response to electroconvulsive therapy (ECT) in severely depressed patients.METHOD: Associations between serum levels of CRP, interleukin-6, interleukin-10, and tumour necrosis factor-α as well as remission of depression, time to remission, and speed of decline of depressive symptoms were examined in 95 older (mean age: 73.1 years) depressed patients treated with ECT.RESULTS: Moderately elevated levels of CRP at baseline (3 to 10 mg/L), but no other inflammatory markers, were associated with higher remission rates. In patients with moderately elevated CRP levels, the odds ratio for remission was 3.62 (95% confidence interval [CI], 1.09-11.97; p = 0.04). Time to remission was shorter in those with moderately elevated CRP levels (p = 0.05). Speed of decline was higher in patients with moderately elevated CRP levels as compared with those with low CRP levels (decline of 3.2 Montgomery Åsberg Depression Rating Scale points per administration vs. 2.3 points per administration, p = 0.03).LIMITATIONS: Because of the observational design, residual confounding through other lifestyle or demographic factors cannot be ruled out.CONCLUSIONS: Although earlier studies showed that low-grade inflammation contributes to poor treatment response in those treated with antidepressants, our study provides clues that low-grade inflammation does not have such a detrimental effect on the treatment response to ECT. This is underscored by our finding that moderately elevated CRP levels were associated with increased remission rates in depressed patients treated with ECT. Replication studies are warranted.

Background In electroconvulsive therapy (ECT), a generalized seizure is provoked under general anesthesia. Standard airway management is done by face mask ventilation, but this is difficult during generalized seizure. Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) is a method to increase apnea tolerance and permit apnea oxygenation. We hypothesize that THRIVE can oxygenate the patient during ECT and that it is comfortable for patients. Methods In this single-center feasibility study, 13 patients with a pharmacotherapy-resistant depressive disorder underwent 20 ECT sessions with the use of THRIVE. They received general anesthesia under standard monitoring and transcutaneous carbon dioxide monitoring. Afterward, they completed a survey comparing their prior experience with face mask oxygenation. Results There were no desaturations during the procedure, and patient comfort showed no difference in comparison to face mask. Compared with data from earlier ECT with face mask ventilation in the same patient, THRIVE did not seem to shorten seizure duration. Conclusions THRIVE is a novel, safe oxygenation method during ECT.

Introduction Electroconvulsive therapy (ECT) is an important and effective treatment for depression. However, research on course trajectories of depressive symptoms during ECT is limited. Insight into putative differences in speed of response of depressive symptom dimensions may enable clinicians to optimally inform patients and their relatives. Therefore, we aim to examine course trajectories of depressive symptom dimensions in depressed older persons during ECT.Methods Data were derived from the Mood Disorders in Elderly treated with Electro Convulsive Therapy study, including 110 persons, aged 55 years or more, with a current diagnosis of major depressive disorder and referred for ECT. Exploratory factor analysis was used to identify symptom dimensions, using the 10 depression items of the Montgomery-Åsberg Depression Rating Scale (MADRS). Differences in course trajectories of symptom dimension during 2 weeks were examined by multilevel analyses.Results Three symptom dimensions were identified: a “mood,” “melancholic,” and “suicidal” dimension. Mood showed a significantly greater severity decline as compared with melancholic and suicidal at the 1-week follow-up. At the 2-week follow-up, both mood and melancholic demonstrated a significantly greater decline as compared with suicidal. However, because scores on the suicidality item of the Montgomery-Asberg Depression Rating Scale were already lower at baseline compared with the other items, a floor effect cannot be ruled out.Discussion All symptom dimensions of depression showed a rapid response to ECT. Our findings did not support the general assumption that suicidal symptoms may be the first to improve. However, a floor effect on the suicidality item cannot be ruled out.

Objectives To examine the effects of an outreaching stepped care intervention program (Lust for Life) compared with usual care on depressive symptoms in older adults living in the community. Design Randomized clinical implementation trial. Setting 18 general practices and a home care organization in the Netherlands. Participants 263 community-dwelling 65+-year-olds with depressive symptoms according to the Patient Health Questionnaire-9 (PHQ-9). Intervention After three months of watchful waiting, participants could sequentially choose between the following evidence-based interventions: 1) guided self-help or an exercise program, 2) problem solving treatment or life review, and 3) a referral to their general practitioner. Measurements The outcome measure was depression severity (PHQ-9), measured every three months over 2 years. Results After the provision of the stepped care program, a significant short-term positive effect on depressive symptoms was found in the first three months after implementation, in which average PHQ-9 scores dropped from 9.34 (SE: 0.61, 95% CI: 8.14–10.5) to 7.83 (SE: 0.51, 95% CI: 6.84–8.81). Conclusions The Lust for Life program has a promising potential to relieve depressive symptoms of older adults in primary care in the short term. Providing one single clinical intervention in accordance with participants' choices instead of stepped care could be sufficient.

Background: Late-life depression is thought to differ in clinical presentation from early-life depression. Particularly, late-life depression is considered to be more characterized by apathy than is early-life depression. Lacking convincing evidence, this study examines the presence and associated socio-demographic/clinical characteristics of apathy in older compared to younger depressed persons.Methods: This cross-sectional study used data from two naturalistic cohort studies, i.e. the Netherlands Study of Depression in Older Persons (NESDO) and the Netherlands Study of Depression and Anxiety (NESDA). These studies included 605 persons (aged 18-93 years) with a major depressive disorder, divided into 217 early-life (= 60 years) depressed persons. Apathy was considered present if a score of >= 14 on the Apathy Scale.Results: Apathy was strongly associated with age: it was more frequently present in persons with late-life depression (74.5%) than in those with early-life depression (53.5%). Independent of age, the following characteristics were associated with the presence of apathy: male gender, low education, use of benzodiazepines, chronic diseases, and more severe depression. Of all potential risk factors, only former and current smoking was associated with the presence of apathy in older depressed persons but not in younger depressed persons (p-value for age interaction = 0.01).Limitations: No causal relationships can be drawn due to the cross-sectional design of the study.Conclusions: In depressed individuals, clinically relevant apathy was more frequently present in older compared to younger persons. Both age groups showed largely the same associated risk factors. Apathy was independently associated with older age, male gender and more severe depression.

Background: The behavioral variant of frontotemporal dementia (bvFTD) has a broad differential diagnosis including other neurological and psychiatric disorders. Psychiatric misdiagnoses occur in up to 50% of bvFTD patients. Numbers on misdiagnosis of bvFTD in psychiatric disorders are lacking. Objective: The aim of our study was to investigate the frequency and characteristics of bvFTD misdiagnoses in psychiatric disorders and other neurologic disorders. Methods: Thirty-five patients with a (possible or probable) bvFTD diagnosis made by specialized memory clinic neurologists were included. Change in diagnosis after consulting a psychiatrist at baselinewas recorded as well as change in diagnosis after two years of multidisciplinary neuropsychiatric follow-up. Differences in cognitive and behavioral profiles were investigated per diagnostic group after follow-up (bvFTD, psychiatry, other neurologic disorders). Clinical profiles are described in detail. Results: In 17 patients (48.5%), the bvFTD baseline diagnosis changed: Two at baseline after psychiatric consultation, and 15 after two years of multidisciplinary follow-up. Eleven (64.5%) of these 17 patients (31.5% of total) were reclassified with a psychiatric diagnosis. We found no differences for cognitive baseline profiles between patients with bvFTD versus psychiatric diagnoses. Conclusion: In almost half of cases, the initial bvFTD diagnosis was changed after follow-up, most often into a psychiatric disorder. A multidisciplinary neuropsychiatric approach in the diagnostic process of bvFTD results in the identification of treatable disorders. Our findings illustrate a limited specificity of the [18F]FDG-PET-scan and the bvFTD criteria in a neuropsychiatric cohort, especially combined with certain clinical symptoms, like disinhibition, apathy, or loss of empathy.

Electroconvulsive therapy (ECT) is the treatment of choice in severe geriatric depression. High remission rates may be influenced by specific brain morphology characteristic of geriatric depression. Our objective was to identify the relationship between brain structure, symptom profile, and ECT response. In a naturalistic cohort of 55 patients with a major depressive disorder, structural magnetic resonance imaging (MRI) was performed before ECT. Voxel-based morphometry was applied to determine regional differences in gray matter (GM) volume between patients and 23 matched healthy controls. Depressed patients with psychotic symptoms showed significantly higher remission rates and smaller regional GM volume of the left inferior frontal gyrus (IFG). Patients with late onset depression showed smaller regional GM volume of the bilateral lateral temporal cortex. Larger size of response in the whole patient group was related to smaller pretreatment regional GM volume of the right lateral temporal cortex, whereas faster speed of response was related to smaller pretreatment regional GM volume of the right IFG. ECT is most effective in depressed patients with psychotic symptoms. In this study the presence of psychotic symptoms was related to pretreatment smaller GM volume of the left IFG and bilateral temporal cortex. Smaller volume of the IFG pretreatment was related to faster treatment response, and smaller volume of the right lateral temporal cortex pretreatment was related to larger response to ECT. These results are possibly explained by the connectivity between these brain regions and an interconnected network that is particularly activated by the ECT-induced seizures.

Background: Little is known about the role of childhood abuse in late-life depression. The aim of the study is therefore to study whether childhood abuse is associated with late-life depression according to its onset, and which clinical characteristics play a role in this association.Methods: Data were used from 378 depressed and 132 non-depressed persons, aged 60-93 years, from the Netherlands Study of Depression in Older persons (NESDO). Childhood abuse included psychological, physical and sexual abuse and emotional neglect.Results: 53% of the depressed older adults reported childhood abuse, compared to 16% of the non-depressed older adults (p Limitations: Age of depression onset and childhood abuse were asked retrospectively, which may have biased the results.Conclusions: Childhood abuse is strongly related to late-life depression and its comorbidities, even in the case of late-onset depression. This might suggest that psychological wellbeing can be maintained throughout middle age, but may be disturbed in later life. (c) 2012 Elsevier B.V. All rights reserved.

BackgroundDepressive disorders in older persons are associated with an altered functioning of the Hypothalamic–Pituitary–Adrenal (HPA)-axis. In adults, a lower cortisol awakening response is a predictor of a worse prognosis of depression, but to date longitudinal studies in older depressed persons are lacking. We hypothesised that a lower cortisol awakening response is also associated with poorer course of depression in later life.MethodsData were derived from the Netherlands Study of Depression in Older Persons (NESDO). Participants with a 6-month Major Depressive Disorder (MDD), who provided 2-year follow-up data, were included (n = 246). Logistic regression analyses were conducted to examine the association between diurnal cortisol levels and depressive status at 2-year follow-up.ResultsBoth lower (OR = 3.54; 95% CI = 1.59–7.89) and higher evening cortisol levels (OR = 2.41; 95% CI = 1.09–5.35) at baseline were associated with poorer prognosis of MDD. Low dexamethasone suppression was associated with poorer course (OR = 2.37; 95% CI = 1.09–5.16), but failed to reach significance after additional adjustment for severity and chronicity of MDD (OR = 1.98; 95% CI = 0.89–4.42). Cortisol awakening response was not significantly associated with course. Since smoking has a great impact on cortisol levels, we conducted post-hoc analyses including non-smokers only, indicating that lower evening cortisol levels (OR = 2.83, 95% CI = 1.31–6.13) predicted unfavourable course.ConclusionsThis first longitudinal study on cortisol and prognosis of depression in older persons demonstrates that in particular lower evening cortisol levels may predict poorer course in MDD. This finding may have clinical implications. Evening cortisol values may serve as a marker to identify persons at risk for an unfavourable course.

The Dutch dementia guideline has been extended to include recommendations in the area of psychosocial interventions for patients, caregivers and professionals.- The diagnostic recommendations in the revised directive are based on a stepwise work-up with the aim of establishing the cause of the dementia. This is guided by the recent diagnostic criteria, evidence of the diagnostic value of additional investigations, and the patient's wishes.- Although there have been no major breakthroughs in the treatment of patients with Alzheimer's disease in recent years, the revised guideline also contains important new recommendations in this area. For example, it includes recommendations on administration routes (first-choice use of patches or preparations with slow release of cholinesterase inhibitors), the use of combination therapy (not prescribing memantine in combination with cholinesterase inhibitors) and regular monitoring of the effectiveness of antipsychotics and cholinesterase inhibitors.- The guideline (in Dutch) can be found at www.richtlijnendatabase.nl (search for 'dementie') and will be actively implemented.

BACKGROUND: Disability in activities of daily living (ADL) might be more prevalent among elderly with low income due to higher prevalence of chronic diseases and impairments, as well as stronger associations of these factors with ADL-disability. METHODS: In the Leiden 85-plus Study, we defined disability as being unable to perform one or more basic ADL activities. Presence of chronic diseases was obtained from medical records, impairments were assessed with performance-tests. RESULTS: Elderly with low income had higher prevalence of ADL-disability (23% versus 12%; odds ratio 2.0; 95% confidence interval 1.3-3.2), higher prevalence of impairments and equal prevalence of chronic diseases, except for dementia and co-morbidity. Associations of these factors with ADL-disability were not stronger. CONCLUSIONS: We conclude that ADL-disability is more prevalent in elderly with low income. Neither prevalence of chronic diseases nor the association with disability could explain this.

CONTEXT: Despite the equivocal outcomes of randomized controlled trials, general clinical opinion favors screening and treatment of elderly individuals with subclinical thyroid disorders.OBJECTIVES: To determine whether subclinical thyroid dysfunction should be treated in old age and the long-term impact of thyroid dysfunction on performance and survival in old age.DESIGN, SETTING, AND PARTICIPANTS: A prospective, observational, population-based follow-up study within the Leiden 85-Plus Study of 87% of a 2-year birth cohort (1912-1914) in the municipality of Leiden, the Netherlands. A total of 599 participants were followed up from age 85 years through age 89 years (mean [SD] follow-up, 3.7 [1.4] years).MAIN OUTCOME MEASURES: Complete thyroid status at baseline; disability in daily life, depressive symptoms, cognitive function, and mortality from age 85 years through 89 years.RESULTS: Plasma levels of thyrotropin and free thyroxine were not associated with disability in daily life, depressive symptoms, and cognitive impairment at baseline or during follow-up. Increasing levels of thyrotropin were associated with a lower mortality rate that remained after adjustments were made for baseline disability and health status. The hazard ratio (HR) for mortality per SD increase of 2.71 mIU/L of thyrotropin was 0.77 (95% confidence interval [CI], 0.63-0.94; P = .009). The HR for mortality per SD increase of 0.21 ng/dL (2.67 pmol/L) of free thyroxine increased 1.16-fold (95% CI, 1.04-1.30; P = .009).CONCLUSIONS: In the general population of the oldest old, elderly individuals with abnormally high levels of thyrotropin do not experience adverse effects and may have a prolonged life span. However, evidence for not treating elderly individuals can only come from a well-designed, randomized placebo-controlled clinical trial.

OBJECTIVES: To compare the value of dual tasking in predicting falling in the general population of oldest old with that of easy-to-administer single tasks. DESIGN: Prospective population-based follow-up study. SETTING: Municipality of Leiden, the Netherlands. PARTICIPANTS: Representative cohort of 380 individuals, all aged 85 at baseline. MEASUREMENTS: During enrollment, walking time over a 12-meter distance was measured, as well as the verbal fluency to recite names of animals or professions during a 30-second period. In the dual task, performance was assessed when participants combined walking with reciting names. Incidence of falls and fractures was assessed by interviewing participants and checking their medical histories. RESULTS: After 1 year of follow-up, 42% of the participants reported one or more falls, and 4% suffered a fracture. Total walking time, number of steps, and verbal fluency were all strongly related to incident falls (P for trend for all

Low high-density lipoprotein cholesterol is associated with an increased risk for cardiovascular disease and stroke. At the same time, cardiovascular disease and stroke are important risk factors for dementia. We assessed the association between total and fractionated cholesterol and cognitive impairment and explored whether observed associations were dependent on or independent of atherosclerotic disease. In a population-based study, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were measured in 561 subjects 85 years old and grouped in three equal strata representing decreasing serum concentrations. History of cardiovascular disease and stroke was determined. All subjects completed the Mini-Mental State Examination (MMSE), and the presence of dementia was determined. Median MMSE scores were significantly lower in subjects with low high-density lipoprotein cholesterol (25 points vs 27 points, p < 0.001). No differences in MMSE scores were found for other lipids and lipoproteins. MMSE scores in subjects with and without cardiovascular disease were 26 and 27 points (p = 0.007), respectively, and in subjects with and without stroke were 21 and 26 points (p < 0.001), respectively. The associations between low MMSE scores and low high-density lipoprotein cholesterol remained significant after subjects with cardiovascular disease or stroke were excluded. In a comparison of subjects with low high-density lipoprotein cholesterol with subjects with high high-density lipoprotein cholesterol, the odds ratio for dementia was 2.3 (95% confidence interval, 1.2-4.3), and in subjects without cardiovascular disease or stroke, it was 3.7 (95% confidence interval, 1.3-10.1). All odds ratios were unaffected by education, low-density lipoprotein cholesterol, triglycerides, and survival. Low high-density lipoprotein cholesterol is associated with cognitive impairment and dementia. At least part of the association between high-density lipoprotein cholesterol and cognitive function is independent of atherosclerotic disease.

It has been suggested that the metabolic syndrome and type 2 diabetes are manifestations of the inflammatory host response. This host response is orchestrated by the production of pro- and anti-inflammatory cytokines that are under genetic control. We therefore hypothesized that a low production capacity of interleukin-10 (IL-10), a centrally operating cytokine with strong anti-inflammatory properties, associates with the metabolic syndrome and type 2 diabetes in old age. In the current study, 599 inhabitants of the city of Leiden, age 85 years, were visited at their place of residence. The production capacity of the anti-inflammatory cytokine IL-10 was assessed in a whole-blood assay in which lipopolysaccharide was used as a stimulus. Serum concentrations of lipids, lipoproteins, glucose, and HbA1c were determined, and a history of type 2 diabetes was obtained. Serum concentrations of total cholesterol, LDL cholesterol, triglycerides, glucose, and HbA1c gradually decreased over strata representing higher IL-10 production capacity, whereas the concentration of HDL cholesterol gradually increased (all P < 0.01). The odds ratio for type 2 diabetes was 2.7 (95% confidence interval 1.5–4.9) when subjects with the lowest IL-10 production capacity were compared with those with the highest IL-10 production capacity. These findings showed that low IL-10 production capacity (i.e., a pro-inflammatory response) is associated with the metabolic syndrome and type 2 diabetes.

Background:The consequences of co-occurring persistent loneliness and late life depression are yet unknown. The aim of this study was to get a deeper insight into the mental health consequences of loneliness in older persons with depressive symptoms and their perspectives of emotional distress by using a mixed-methods study design.Methods:Two hundred and forty nine community-dwelling older persons with depressive symptoms according to the Patient Health Questionnaire-9 (≥6) were included. A validated cut-off score on the Loneliness Scale was used to distinguish lonely elders from elders who were not lonely. Quantitative and qualitative data were used to examine differences in mental health and perspectives on emotional distress between lonely and not lonely older persons with depressive symptoms.Results:Loneliness was highly prevalent among older persons with depressive symptoms (87.8%). Lonely people suffered from worse mental ill-health (e.g., more severe depressive symptoms, more often a depressive disorder and a lower quality of life) compared to not lonely individuals. Depressive symptoms were regarded as a logical consequence of loneliness. Lonely people perceived little command over their situation: causes of loneliness were attributed externally to perceived deficits in their social networks and they mainly expressed the need to be listened to.Conclusion:Our findings underline the importance of paying considerable attention to (severe) loneliness in older adults with depressive symptoms given its high prevalence and serious mental health consequences. Future studies should look into whether addressing loneliness when discussing depressive symptoms in clinical practice may provide an opportunity to better adjust to older persons’ depression perceptions and might therefore improve care utilization.

Next to outer hair cell dysfunction, age-related hearing loss may be explained by apolipoprotein E (APOE) genotype. In the Leiden 85-plus Study, a population-based study, the participants were 85 years old. We measured hearing loss by pure-tone audiometry in 435 participants in relation to APOE. Results demonstrated that those with the APOE-e4/e4 genotype had the highest levels of hearing loss (n = 6; 56.1 dB), those with the APOE-e3/e4 or e2/e4 genotype (n = 89) had intermediate levels of hearing loss (51.0 dB), and those without the APOE-e4 allele (n = 340) had the lowest levels of hearing loss (48.9 dB), p for trend = 0.02. Eighty percent of participants had hearing loss of 35 dB and more, that is, hearing impairment. The APOE-e4 allele was associated with a 2.0-fold increased risk of hearing impairment (confidence interval [CI 95%], 1.0–4.0), compared with those without the APOE-e4 allele. The risk for hearing impairment in subjects with the APOE-e4 allele remained similar after adjustment for cardiovascular disease, stroke, and cognitive impairment. Our results suggest that the APOE-e4 allele contributes to age-related hearing loss.

Neuropathological studies have revealed the presence of a broad variety of inflammation-related proteins (complement factors, acute-phase proteins, pro-inflammatory cytokines) in Alzheimer's disease (AD) brains. These constituents of innate immunity are involved in several crucial pathogenic events of the underlying pathological cascade in AD, and recent studies have shown that innate immunity is involved in the etiology of late-onset AD. Genome-wide association studies have demonstrated gene loci that are linked to the complement system. Neuropathological and experimental studies indicate that fibrillar amyloid-beta (A beta) can activate the innate immunity-related CD14 and Toll-like receptor signaling pathways of glial cells for pro-inflammatory cytokine production. The production capacity of this pathway is under genetic control and off spring with a parental history of late-onset AD have a higher production capacity for pro-inflammatory cytokines. The activation of microglia by fibrillar A beta deposits in the early preclinical stages of AD can make the brain susceptible later on for a second immune challenge leading to enhanced production of pro-inflammatory cytokines. An example of a second immune challenge could be systemic inflammation in patients with preclinical AD. Prospective epidemiological studies show that elevated serum levels of acute phase reactants can be considered as a risk factor for AD. Clinical studies suggest that peripheral inflammation increases the risk of dementia, especially in patients with preexistent cognitive impairment, and accelerates further deterioration in demented patients. The view that peripheral inflammation can increase the risk of dementia in older people provides scope for prevention

Objective Transient cognitive impairment during electroconvulsive therapy (ECT) can be a reason to discontinue ECT in depressed elderly patients. We hypothesized that both white matter hyperintensities and medial temporal lobe atrophy contribute to transient cognitive impairment during ECT. Methods In 81 elderly patients with depression, magnetic resonance images (MRI) were recorded before ECT. We rated white matter hyperintensities (WMH) with the Age-Related White Matter Changes scale (ARWMC). Cognitive impairment during ECT was measured weekly with the Mini Mental State Examination (MMSE), 2 days after each session. Results The mean MMSE score at baseline for all patients was 25.5 points, the lowest MMSE score during ECT was 23.3 points, and the mean MMSE score after ECT was 26.3 points. Stratification for the ECT method showed no significant difference in the lowest MMSE scores of patients with or without WMH, receiving unilateral ECT (22.5 points versus 23.9 points). There was a difference in the lowest MMSE scores in patients who switched from unilateral ECT to bilateral ECT (18.7 points in patients with WMH versus 22.0 points in patients without WMH). Conclusion Depressed elderly patients with WMH who receive bilateral ECT are at increased risk of transient cognitive impairment. Our findings show, however, that cognitive impairment improves when ECT is continued. This implies that ECT does not have to be discontinued when patients experience transient cognitive impairment during ECT.