Despite the equivocal outcomes of randomized controlled trials, general clinical opinion favors screening and treatment of elderly individuals with subclinical thyroid disorders.
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.
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).
Complete thyroid status at baseline; disability in daily life, depressive symptoms, cognitive function, and mortality from age 85 years through 89 years.
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).
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.
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.
Between 2011 and 2013, 97 older patients (mean SD age = 73.1 8.1 years) with severe unipolar depression (according to
) 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.
In fully adjusted models, there was an association between TNF-α and cognitive functioning (β = -1.05; 95% CI, -2.04 to -0.06;
= 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;
= 0.10). Associations with IL-6 did not reach significance.
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.
ClinicalTrials.gov identifier: NCT02667353.
•The odds of remission are higher for depressed patients with CRP levels >3 mg/L.•Time to remission is shorter in depressed patients with CRP levels >3 mg/L.•Low-grade inflammation contributes to a ...better outcome with electroconvulsive therapy.
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.
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.
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).
Because of the observational design, residual confounding through other lifestyle or demographic factors cannot be ruled out.
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.
Apathy in early and late-life depression Groeneweg-Koolhoven, Isis; Ploeg, Merel; Comijs, Hannie C. ...
Journal of affective disorders,
12/2017, Letnik:
223
Journal Article
Recenzirano
Odprti dostop
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.
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) and 388 late-life (≥ 60 years) depressed persons. Apathy was considered present if a score of ≥14 on the Apathy Scale.
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).
No causal relationships can be drawn due to the cross-sectional design of the study.
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.
•Apathy, as clinical syndrome, was significantly more often present in older compared to younger depressed persons.•In both older and younger depressed persons higher severity of depression was associated with more apathy.•Smoking was associated with the presence of apathy in older but not in younger depressed persons.•Age, male gender and severeness of depression were independently associated with presence of apathy in depressed persons.
Electroconvulsive 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, monocenter 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. The objective of this study was to develop and validate neuroimaging biomarkers for ECT outcome in a multicenter setting.
Multimodal data (i.e. clinical, sMRI and resting-state fMRI) were collected from seven centers of the Global ECT-MRI Research Collaboration (GEMRIC). We used data from 189 depressed patients to evaluate which data modalities or combinations thereof could provide the best predictions for treatment remission (HAM-D score ⩽7) using a support vector machine classifier.
Remission 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 (
= 109), and remained acceptable when validated using leave-one-site-out cross-validation (0.70-0.73 AUC).
These results show that multimodal neuroimaging data can be used to predict remission with ECT for individual patients across different treatment centers, despite significant variability in clinical characteristics across centers. Future development of a clinical decision support tool applying these biomarkers may be feasible.
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.
Obesity is a frequent somatic comorbidity of major depression, and it has been associated with worse clinical outcomes and brain structural abnormalities. Converging evidence suggests that ...electroconvulsive therapy (ECT) induces both clinical improvements and increased subcortical grey matter volume in patients with depression. However, it remains unknown whether increased body weight modulates the clinical response and structural neuroplasticity that occur with ECT.
To address this question, we conducted a longitudinal investigation of structural MRI data from the Global ECT-MRI Research Collaboration (GEMRIC) in 223 patients who were experiencing a major depressive episode (10 scanning sites). Structural MRI data were acquired before and after ECT, and we assessed change in subcortical grey matter volume using FreeSurfer and Quarc.
Higher body mass index (BMI) was associated with a significantly lower increase in subcortical grey matter volume following ECT. We observed significant negative associations between BMI and change in subcortical grey matter volume, with pronounced effects in the thalamus and putamen, where obese participants showed increases in grey matter volume that were 43.3% and 49.6%, respectively, of the increases found in participants with normal weight. As well, BMI significantly moderated the association between subcortical grey matter volume change and clinical response to ECT. We observed no significant association between BMI and clinical response to ECT.
Because only baseline BMI values were available, we were unable to study BMI changes during ECT and their potential association with clinical and grey matter volume change.
Future studies should take into account the relevance of body weight as a modulator of structural neuroplasticity during ECT treatment and aim to further explore the functional relevance of this novel finding.
The apolipoprotein-ε4 allele (APOE-ε4) is strongly associated with detrimental outcomes in affluent populations including atherosclerotic disease, Alzheimer's disease, and reduced lifespan. Despite ...these detrimental outcomes, population frequencies of APOE-ε4 are high. We hypothesize that the high frequency of APOE-ε4 was maintained because of beneficial effects during evolution when infectious pathogens were more prevalent and a major cause of mortality. We examined a rural Ghanaian population with a high pathogen exposure for selective advantages of APOE-ε4, to survival and or fertility.
This rural Ghanaian population (n = 4311) has high levels of mortality from widespread infectious diseases which are the main cause of death. We examined whether APOE-ε4 was associated with survival (total follow-up time was 30,262 years) and fertility after stratifying by exposure to high or low pathogen levels. Households drawing water from open wells and rivers were classified as exposed to high pathogen levels while low pathogen exposure was classified as those drawing water from borehole wells. We found a non-significant, but positive survival benefit, i.e. the hazard ratio per APOE-ε4 allele was 0.80 (95% confidence interval: 0.69 to 1.05), adjusted for sex, tribe, and socioeconomic status. Among women aged 40 years and older (n = 842), APOE-ε4 was not associated with the lifetime number of children. However, APOE-ε4 was associated with higher fertility in women exposed to high pathogen levels. Compared with women not carrying an APOE-ε4 allele, those carrying one APOE-ε4 allele had on average one more child and those carrying two APOE-ε4 alleles had 3.5 more children (p = 0.018).
Contrary to affluent modern-day populations, APOE-ε4 did not carry a survival disadvantage in this rural Ghanaian population. Moreover, APOE-ε4 promotes fertility in highly infectious environments. Our findings suggest that APOE-ε4 may be considered as evolutionarily adaptive. Its adverse associations in affluent modern populations with later onset diseases of aging further characterize APOE-ε4 as an example of antagonistic pleiotropy.
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.
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