Diagnostic Instability Over Time in the Late-Onset Frontal Lobe Syndrome: When Can We Say it's FTD?

OBJECTIVES: Distinguishing sporadic behavioral variant of frontotemporal dementia (bvFTD) from late-onset primary psychiatric disorders (PPD) remains challenging with the lack of robust biomarkers. An early bvFTD misdiagnosis in PPD cases and vice-versa is common. Little is known about diagnostic (in)stability over longer period of time. We investigated diagnostic instability in a neuropsychiatric cohort up to 8 years after baseline visit and identified which clinical hallmarks contribute to diagnostic instability. DESIGN: Diagnoses of participants of the late-onset frontal lobe (LOF) study were collected from the baseline visit (T0) and the 2-year follow-up visit (T2). Clinical outcomes were retrieved 5-8 years after baseline visit (T final). Endpoint diagnoses were categorized into bvFTD, PPD and other neurological disorders (OND). We calculated the total amount of participants that switched diagnosis between T0-T2 and T2-T final. Clinical records of participants that switched diagnosis were assessed. RESULTS: Of the 137 patients that were included in the study, the final diagnoses at T final were bvFTD 24.1% (n = 33), PPD 39.4% (n = 54), OND 33.6% (n = 46) and unknown 2.9% (n = 4). Between T0 and T2, a total of 29 (21.2%) patients switched diagnosis. Between T2 and T final, 8 (5.8%) patients switched diagnosis. Prolonged follow-up identified few cases with diagnostic instability. Major contributors to diagnostic instability where a nonconverting diagnosis of possible bvFTD and a probable bvFTD diagnosis based on informant-based history and an abnormal FDG-PET scan whilst having a normal MRI. CONCLUSION: Considering these lessons, a FTD diagnosis remains stable enough to conclude that 2 years is sufficient to say if a patient with late-life behavioral disorder has FTD

Bipolarity in Older individuals Living without Drugs (BOLD): Protocol and preliminary findings

INTRODUCTION: Although clinical guidelines regard prophylactic medication as the cornerstone of treatment, it is estimated almost half of patients with bipolar disorder (BD) live without medication. This group is underrepresented in research but can provide indispensable knowledge on natural course, resilience and self-management strategies. We aim to describe the clinical phenotype of patients diagnosed with BD who have discontinued maintenance treatment. METHODS: The mixed-methods BOLD study included 58 individuals aged 50 years and over with BD that did not use maintenance medication in the past 5 years. A preliminary, quantitative comparison of clinical characteristics between BOLD and our pre-existing cohort of >220 older BD outpatients with medication (Dutch Older Bipolars, DOBi) was performed. RESULTS: BD-I, psychiatric comorbidities, number of mood episodes and lifetime psychotic features were more prevalent in BOLD compared to DOBi. BOLD participants had a younger age at onset and reported more childhood trauma. BOLD participants reported fewer current mood symptoms and higher cognitive, social, and global functioning. LIMITATIONS: Our findings may not be generalizable to all individuals diagnosed with BD living without maintenance medication due to selection-bias. CONCLUSION: A group of individuals exists that meets diagnostic criteria of BD and is living without maintenance medication. They appear to be relatively successful in terms of psychosocial functioning, although they do not have a milder clinical course than those on maintenance medication. The high prevalence of childhood trauma warrants further investigation. Future analyses will examine differences between BOLD and DOBi per domain (e.g. cognition, physical health, psychosocial functioning, coping)

Pre-treatment predictors of cognitive side-effects after treatment with electroconvulsive therapy in patients with depression: A multicenter study

Background: Electroconvulsive therapy (ECT) is a highly effective treatment for major depressive episodes (MDE). However, ECT-induced cognitive side-effects remain a concern. Identification of pre-treatment predictors that contribute to these side-effects remain unclear. We examined cognitive performance and individual cognitive profiles over time (up to six months) following ECT and investigated possible pre-treatment clinical and demographic predictors of cognitive decline shortly after ECT. Methods: 634 patients with MDE from five sites were included with recruitment periods between 2001 and 2020. Linear mixed models were used to examine how cognitive performance, assessed with an extensive neuropsychological test battery, evolved over time following ECT. Next, possible pre-treatment predictors of cognitive side-effects directly after ECT were examined using linear regression. Results: Directly after ECT, only verbal fluency (animal and letter; p < 0.0001; Cohen's d: −0.25 and −0.29 respectively) and verbal recall (p < 0.0001; Cohen's d: −0.26) significantly declined. However, during three and six months of follow-up, cognitive performance across all domains significantly improved, even outperforming baseline levels. No other pre-treatment factor than a younger age predicted a larger deterioration in cognitive performance shortly after ECT. Limitations: There was a substantial amount of missing data especially at 6 months follow-up. Conclusions: Our findings show that verbal fluency and memory retention are temporarily affected immediately after ECT. Younger patients may be more susceptible to experiencing these acute cognitive side-effects, which seems to be mostly due to a more intact cognitive functioning prior to ECT. These findings could contribute to decision-making regarding treatment selection, psychoeducation, and guidance during an ECT course

Social cognition differentiates phenocopy syndrome of behavioural variant frontotemporal dementia from behavioural variant frontotemporal dementia

Background: Patients displaying clinical features of behavioural variant of frontotemporal dementia (bvFTD) but lacking both neuroimaging abnormalities and clinical progression are considered to represent the phenocopy syndrome of bvFTD (phFTD). Extensive clinical overlap between early phase bvFTD and phFTD hampers diagnostic distinction. We aimed to assess the diagnostic value of clinician-rated, self-reported and caregiver-reported symptoms for clinical distinction between phFTD and bvFTD. Methods: There were 33 phFTD and 95 probable bvFTD patients included in the study (total N = 128). Clinician-rated, self-reported tests and caregiver-reported symptoms were compared between phFTD and bvFTD on social cognition, behaviour, mood and activities of daily living (ADL). Scores were compared between groups, followed by multiple logistic regression analysis, adjusted for age and sex. Receiver operating characteristic curves were plotted to assess diagnostic value. Results: Using clinician-rated and self-reported tests, phFTD patients performed better on facial emotion recognition and reported more depressive symptoms. Caregiver-reported behavioural symptoms indicated higher behavioural and ADL impairment in phFTD compared to bvFTD. Facial emotion recognition provided highest diagnostic accuracy for distinction of phFTD from bvFTD (area under the curve (AUC) 0.813 95% CI 0.735–0.892, P < 0.001, sensitivity 81%, specificity 74%) followed by depressive symptoms (AUC 0.769 95% 0.674–0.864, P < 0.001 sensitivity 81%, specificity of 63%). Conclusion: Social cognition tests are most suitable for distinction of phFTD from bvFTD. Caregiver-reported questionnaires and phFTD diagnosis seemed inversely correlated, showing more symptoms in phFTD. Further research is needed on phFTD aetiology and in caregivers taking into account disease burden to assess what explains this discrepancy between clinician-rated and caregiver-based tools

Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

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 (R 2) 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, R 2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R 2 = 8.18%, p = .0013), Belgium (R 2 = 6.83%, p = .016), and the Netherlands (R 2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R 2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R 2 = 4.42%, p = .0024) and unipolar MDE only (R 2 = 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

Demographic and clinical associations to employment status in older-age bipolar disorder: Analysis from the GAGE-BD database project

OBJECTIVE: The current literature on employment in older adults with bipolar disorder (OABD) is limited. Using the Global Aging and Geriatric Experiments in Bipolar Disorder Database (GAGE-BD), we examined the relationship of occupational status in OABD to other demographic and clinical characteristics. METHODS: Seven hundred and thirty-eight participants from 11 international samples with data on educational level and occupational status were included. Employment status was dichotomized as employed versus unemployed. Generalized linear mixed models with random intercepts for the study cohort were used to examine the relationship between baseline characteristics and employment. Predictors in the models included baseline demographics, education, psychiatric symptom severity, psychiatric comorbidity, somatic comorbidity, and prior psychiatric hospitalizations. RESULTS: In the sample, 23.6% (n = 174) were employed, while 76.4% were unemployed (n = 564). In multivariable logistic regression models, less education, older age, a history of both anxiety and substance/alcohol use disorders, more prior psychiatric hospitalizations, and higher levels of BD depression severity were associated with greater odds of unemployment. In the subsample of individuals less than 65 years of age, findings were similar. No significant association between manic symptoms, gender, age of onset, or employment status was observed. CONCLUSION: Results suggest an association between educational level, age, psychiatric severity and comorbidity in relation to employment in OABD. Implications include the need for management of psychiatric symptoms and comorbidity across the lifespan, as well as improving educational access for people with BD and skills training or other support for those with work-life breaks to re-enter employment and optimize the overall outcome

The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials

Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterized by diverse and prominent changes in behavior and personality. One of the greatest challenges in bvFTD is to capture, measure and predict its disease progression, due to clinical, pathological and genetic heterogeneity. Availability of reliable outcome measures is pivotal for future clinical trials and disease monitoring. Detection of change should be objective, clinically meaningful and easily assessed, preferably associated with a biological process. The purpose of this scoping review is to examine the status of longitudinal studies in bvFTD, evaluate current assessment tools and propose potential progression markers. A systematic literature search (in PubMed and Embase.com) was performed. Literature on disease trajectories and longitudinal validity of frequently-used measures was organized in five domains: global functioning, behavior, (social) cognition, neuroimaging and fluid biomarkers. Evaluating current longitudinal data, we propose an adaptive battery, combining a set of sensitive clinical, neuroimaging and fluid markers, adjusted for genetic and sporadic variants, for adequate detection of disease progression in bvFTD