The Cortisol Awakening Response as a Biomarker for Cognitive Side-Effects of Electroconvulsive Therapy.

OBJECTIVE: To test whether the cortisol awakening response (CAR) could be a biomarker for cognitive decline during electroconvulsive therapy (ECT). METHODS: We studied 50 older patients with depression who were treated with ECT from the MODECT cohort. We used linear regression analyses to examine the association between CAR and cognitive change, assessed by the change in Mini Mental State Examination scores between baseline and 1 week after ECT course. CAR was assessed by the area under the curve of cortisol levels, according to Pruessner's-formula. Associations were adjusted for putative confounders, based on previous literature and availability. RESULTS: We found no significant associations between the CAR and cognitive change during the ECT course in (un)adjusted models. CONCLUSION: Our results indicate that the CAR is not usable as a biomarker for ECT-induced cognitive decline during ECT course. Further research in cohorts with larger samples is needed.

Pharmacological prevention of postictal agitation after electroconvulsive therapy-A systematic review and meta-analysis.

Background: Postictal agitation (PIA) after electroconvulsive therapy (ECT) is a serious clinical problem estimated to occur in 7-36% of patients and recur in 19-54% of patients. PIA has the potential to cause dangerous situations for the patient and staff members aside from the financial impact. To date, it is unclear which pharmacological interventions should be used in the management of PIA. This study aimed to systematically review the (preventative) pharmacological treatment options for PIA after ECT. Method: A systematic search was done in PubMed, EMBASE, PsycINFO, and Web of Science from inception until 10 November 2022. We included randomized trials with any pharmacological intervention or comparison and a predefined outcome measure on PIA. Studies that solely included patients with neurodegenerative disorders or stroke were excluded. Data quality was assessed with the RoB2 and GRADE. Meta-analysis was performed if possible. This study was registered on PROSPERO under CRD42021262323. Results: We screened 2,204 articles and included 14 studies. Dexmedetomidine was investigated in 10 studies. Alfentanil, lignocaine, esmolol, midazolam, propofol, ketamine, haloperidol, and diazepam were each studied in only one study. Meta-analysis revealed an OR of 0.45 (0.32-0.63), a moderate effect size, in favor of dexmedetomidine than placebo to prevent PIA with very low heterogeneity (I2 = 0%). The certainty of the evidence was moderate. The other interventions studied were all found to have low certainty of evidence. Conclusion: For clinical practice, we believe that our results indicate that dexmedetomidine should be considered for the prevention of PIA in patients that have previously experienced PIA.

Rivastigmine for ECT-induced cognitive adverse effects in late life depression (RECALL study): A multicenter, randomized, double blind, placebo-controlled, cross-over trial in patients with depression aged 55 years or older: Rationale, objectives and methods.

Background: Cognitive side-effects are an important reason for the limited use of electroconvulsive therapy (ECT). Cognitive side-effects are heterogeneous and occur frequently in older persons. To date, insight into these side-effects is hampered due to inconsistencies in study designs and small sample sizes. Among all cognitive side-effects, confusion and delirious states are especially troublesome for patients, relatives and clinicians. In particular inter-ictal delirium-like states are worrisome, since they may lead to premature treatment discontinuation. Besides a need for further insight into determinants of cognitive side-effects of ECT, there is a great need for treatment options. Methods and design: The Rivastigmine for ECT-induced Cognitive Adverse effects in Late Life depression (RECALL) study combines a multicenter, prospective cohort study on older patients with depression, treated with ECT, with an embedded randomized, placebo-controlled cross-over trial to examine the effect of rivastigmine on inter-ictal delirium. Patients are recruited in four centers across the Netherlands and Belgium. We aim to include 150 patients into the cohort study, in order to be able to subsequently include 30 patients into the trial. Patients are included in the trial when inter-ictal delirium, assessed by the Confusion Assessment method (CAM), or a drop in Mini Mental State Examination (MMSE) score of ≥4 during ECT, develops. In the cohort study, comprehensive measurements of ECT-related cognitive side-effects-and their putative determinants-are done at baseline and during the ECT-course. The primary outcome of the clinical trial is the effectiveness of rivastigmine on inter-ictal delirium-severity, assessed with a change in the Delirium Rating Scale-Revised-98. Secondary outcomes of the clinical trial are several ECT-characteristics and side-effects of rivastigmine. Discussion: This study is the first clinical trial with a focus on ECT-induced, inter-ictal delirium. The cohort provides the basis for recruitment of patients for the cross-over trial and additionally provides an excellent opportunity to unravel cognitive side-effects of ECT and identify putative determinants. This paper describes the rationale and study protocol. Clinical trial registration: EudraCT 2014-003385-24.

Clinical Phenotypes of Behavioral Variant Frontotemporal Dementia by Age at Onset.

BACKGROUND: Behavioral variant frontotemporal dementia (bvFTD) is generally considered a young-onset dementia, although age at onset is highly variable. While several studies indicate clinical differences regarding age at onset, no biomarker validated cohort studies with updated clinical criteria have been performed. OBJECTIVE: We aimed to examine behavior, cognition, and mortality over the full age spectrum in a cohort of bvFTD patients with neuroimaging, genetic, or histopathological confirmation and exclusion of positive Alzheimer's disease biomarkers or severe cerebrovascular damage. METHODS: In total, 315 patients with a clinical diagnosis of probable or definite bvFTD were included from the Amsterdam Dementia Cohort and grouped into quartiles by age-at-diagnosis. Neuropsychiatric symptoms and cognitive functioning were assessed with the neuropsychiatric inventory, the geriatric depression scale and a neuropsychological test battery. Data on mortality was obtained from the Dutch municipal register. Associations between age-at-diagnosis and clinical features and mortality risk were examined. RESULTS: Age-at-diagnosis ranged from 26 to 85 years and established quartiles with mean ages of 52±6, 61±2, 66±2, and 74±3 years. In the total sample, 44.4%exceeded an age of 65 years at time of diagnosis. Earlier age-at-diagnosis was associated with more severe behavioral symptoms, while later age-at-diagnosis was associated with more severe memory impairment. Unexpectedly, mortality risk was not associated with age-at-diagnosis. CONCLUSION: In bvFTD, symptom profile is associated with age-at-diagnosis. This should be taken into account with regard to diagnostics, patient management, and trial design. Additionally, based on our sample, the prevalence of late-onset bvFTD is higher than generally thought.