Feasibility and Acceptability of Group Interpersonal and Social Rhythm Therapy for Recurrent Mood Disorders: A Pilot Study.

OBJECTIVE: Interpersonal and social rhythm therapy (IPSRT) was developed to empower patients with mood disorders by stabilizing underlying disturbances in circadian rhythms and by using strategies from interpersonal psychotherapy. Group IPSRT has not been studied with a transdiagnostic sample of patients across the life span with either major depressive disorder or bipolar disorder. METHODS: Thirty-eight outpatients, ages 26-80, with major depressive disorder or bipolar disorder in any mood state were recruited from clinics in the Netherlands and were treated with 20 sessions (two per week) of group IPSRT. Recruitment results, dropout rates, and session adherence were used to assess feasibility. The modified Client Satisfaction Questionnaire (CSQ) and a feedback session were used to measure treatment acceptability. Changes in mood symptoms, quality of life, and mastery were also measured. RESULTS: Participants' mean±SD age was 65.4±10.0 years. Participants were diagnosed as having major depressive disorder (N=14, 37%) or bipolar disorder (N=24, 63%). The dropout rate was relatively low (N=9, 24%). High CSQ scores (32.3±5.2 of 44.0 points) and low dropout rates indicated the acceptability and feasibility of group IPSRT for major depressive disorder and bipolar disorder. Quality of life 3 months after completion of treatment was significantly higher than at baseline (p<0.01, Cohen's d=-0.69). No significant differences were found between pre- and postintervention depressive symptom scores. CONCLUSIONS: Twice-weekly group IPSRT for older outpatients with major depressive disorder or bipolar disorder was feasible and acceptable. Future research should evaluate the short- and long-term efficacy of group IPSRT for major depressive disorder and bipolar disorder among patients of all ages.

Early life involvement in C9orf72 repeat expansion carriers.

OBJECTIVES: The chromosome 9 open reading frame 72 gene (C9orf72) hexanucleotide repeat expansion (C9orf72RE) is the most common genetic cause of behavioural variant frontotemporal dementia (bvFTD). Since the onset of the C9orf72RE-associated disease is sometimes hard to define, we hypothesise that C9orf72RE may cause a lifelong neuropsychiatric vulnerability. The first aim of our study was to explore lifelong behavioural and personality characteristics in C9orf72RE. Second, we aimed to describe distinctive characteristics of C9orf72RE during disease course. METHODS: Out of 183 patients from the Amsterdam Dementia Cohort that underwent genetic testing between 2011 and 2018, 20 C9orf72RE bvFTD patients and 23 C9orf72RE negative bvFTD patients were included. Patients and their relatives were interviewed extensively to chart their biography. Data analysis was performed through a mixed-methods approach including qualitative and quantitative analyses. RESULTS: Education, type of professional career and number of intimate partners were not different between carriers and non-carriers. Carriers were more often described by their relatives as having 'fixed behavioural patterns in daily life' and with limited empathy already years before onset of bvFTD symptoms. In carriers, disease course was more often characterised by excessive buying and obsessive physical exercise than in non-carriers. CONCLUSION: This is the first study thoroughly exploring biographies of bvFTD patients with C9orf72RE, revealing that subtle personality traits may be present early in life. Our study suggests that C9orf72RE exerts a lifelong neuropsychiatric vulnerability. This may strengthen hypotheses of links between neurodevelopmental and neurodegenerative diseases. Moreover, the presence of a distinct C9orf72RE -associated syndrome within the FTD spectrum opens doors for investigation of vulnerable neuronal networks.

Impact of Inflammation on Cognitive Functioning After Electroconvulsive Therapy in Older Patients with Depression with and Without White Matter Hyperintensities.

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.

The Association Between Loneliness and Psychiatric Symptomatology in Older Psychiatric Outpatients.

PURPOSE: Loneliness in adults increases with age. Although loneliness has been found to be associated with psychiatric disorders and dementia, no information is available on prevalence of loneliness in older psychiatric patients. The aims of this study were to examine prevalence of loneliness in older psychiatric outpatients, including gender differences and associations with psychiatric disorders and social isolation. METHODS: Cross-sectional study in an outpatient clinic for geriatric psychiatry between September 2013 and February 2018. Interviews were done in 181 patients. RESULTS: 80% of participants were lonely. Loneliness was associated with having contacts in less social network domains, in women but not in men. There were no associations with DSM-IV-TR-classifications. However, loneliness was associated with higher scores on questionnaires for depression and cognitive function. Intensity of treatment did not differ significantly between lonely and non-lonely participants. CONCLUSION: Loneliness is highly prevalent in older psychiatric outpatients, with men and women equally affected. Loneliness should be assessed in all older psychiatric patients, especially when they show high scores on symptom checklists or have a restricted social network.

The 5-year outcome of subjective quality of life in older schizophrenia patients.

PURPOSE: Subjective quality of life (SQOL) is increasingly valued as an important outcome in schizophrenia treatment. The current study aims to gain insight into changes in SQOL during 5-year follow-up in older persons with schizophrenia spectrum disorders (SSD). METHODS: The sample consisted of a catchment area-based group of 75 older Dutch patients (mean age 66.0 years) with schizophrenia or schizoaffective disorder. Factor analysis was used to identify subdomains of SQOL, measured with the Manchester Short Assessment of Quality of Life (MANSA). 5-Year course trajectories and putative predictors of changes in SQOL and subdomains were examined using multivariable regression analyses. RESULTS: 72% was stable in either a high or a low SQOL-status over time. When outcome was defined as change score, 36%, 20%, and 44% of participants, respectively, reported a clinically relevant improvement, deterioration, or no change of SQOL during follow-up. Three SQOL subdomains were identified with different course trajectories; 33% of participants reported an improvement in the subdomains satisfaction with 'daily life' and 'personal circumstances.' The largest number of declines (28%) was reported in the subdomain satisfaction with 'physical and mental health.' Predictors of positive total and subdomain SQOL-change scores were limited to a higher age of onset and higher baseline SQOL scores. CONCLUSION: In this cohort of older persons, it was demonstrated that SQOL might considerably change during 5-year follow-up. As course trajectories differed among subdomains, separate evaluation of these subdomains is clinically relevant. Improvement of SQOL is an attainable goal in older SSD patients despite deteriorating physical health.

Known in the nursing home: development and evaluation of a digital person-centered artistic photo-activity intervention to promote social interaction between residents with dementia, and their formal and informal carers.

BACKGROUND: To address the lack of social interaction and meaningful activities for persons with dementia (PWD) in nursing homes an artistic Photo-Activity was designed. The present study aims to develop a digital version of the Photo-Activity and to investigate its implementation and impact on nursing home residents with advanced dementia, and their (in)formal carers. METHODS: First, within a user-participatory design, a digital-app version of the Photo-Activity will be developed and pilot-tested, in co-creation with (in)formal carers and PWD. Next, the feasibility and effectiveness of the Photo-Activity versus a control activity will be explored in a randomized controlled trial with nursing home residents (N=90), and their (in)formal carers. Residents will be offered the Photo-Activity or the control activity by (in)formal carers during one month. Measurements will be conducted by independent assessors at baseline (T0), after one month (T1) and at follow up, two weeks after T1 (T2). Qualitative and quantitative methods will be used to investigate the effects of the intervention on mood, social interaction and quality of life of the PWD, sense of competence of informal carers, empathy and personal attitude of the formal carers, and quality of the relationship between the PWD, and their (in)formal carers. In addition, a process evaluation will be carried out by means of semi-structured interviews with the participating residents and (in)formal carers. Finally, an implementation package based on the process evaluation will be developed, allowing the scaling up of the intervention to other care institutions. DISCUSSION: Results of the trial will be available for dissemination by Spring 2023. The digital Photo-Activity is expected to promote meaningful connections between the resident with dementia, and their (in)formal carers through the facilitation of person-centered conversations. TRIAL REGISTRATION: Netherlands Trial Register: NL9219 ; registered (21 January 2021); NTR (trialregister.nl).

Transient Cognitive Impairment and White Matter Hyperintensities in Severely Depressed Older Patients Treated With Electroconvulsive Therapy.

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.

Neurocognitive functioning after electroconvulsive therapy in late-life depression: A 4-year prospective study.

OBJECTIVE: Despite the proven efficacy and safety of ECT, there is still concern about the possible cognitive side effects of ECT in older patients. In this study, we aimed to characterize the long-term cognitive effects of ECT in patients with late-life depression (LLD) from before the start until 4 years after the index ECT course. METHODS: Fourty one patients aged 55 years and older with a unipolar depression, referred for ECT, were included. The neuropsychological test battery was assessed prior to ECT, 6 months, 1 year, 2 years, 3 years, and 4 years after the last ECT session. RESULTS: We did not find any statistically significant cognitive changes from before the start to 4 years after ending the ECT course. Although we could not detect cognitive changes at group level, we found clinically important differences on an individual level. CONCLUSION: Cognitive performance in patients with LLD runs a stable course from before the start of ECT until 4 years after the index course. At an individual level, however, both cognitive decline and improvement can be witnessed. Older patients can tolerate ECT and most of them will not experience long-term cognitive side effects.

Cognitive performance in older-age bipolar disorder: Investigating psychiatric characteristics, cardiovascular burden and psychotropic medication.

OBJECTIVE: This study aimed to explore a large range of candidate determinants of cognitive performance in older-age bipolar disorder (OABD). METHODS: A cross-sectional study was performed in 172 BD patients aged ≥50 years. Demographics, psychiatric characteristics and psychotropic medication use were collected using self-report questionnaires and structured interviews. The presence of cardiovascular risk factors was determined by combining information from structured interviews, physical examination and laboratory assessments. Cognitive performance was investigated by an extensive neuropsychological assessment of 13 tests, covering the domains of attention, learning/ memory, verbal fluency and executive functioning. The average of 13 neuropsychological test Z-scores resulted in a composite cognitive score. A linear multiple regression model was created using forward selection with the composite cognitive score as outcome variable. Domain cognitive scores were used as secondary outcome variables. RESULTS: The final multivariable model (N = 125), which controlled for age and education level, included number of depressive episodes, number of (hypo)manic episodes, late onset, five or more psychiatric admissions, lifetime smoking, metabolic syndrome and current use of benzodiazepines. Together, these determinants explained 43.0% of the variance in composite cognitive score. Late onset and number of depressive episodes were significantly related to better cognitive performance whereas five or more psychiatric admissions and benzodiazepine use were significantly related to worse cognitive performance. CONCLUSION: Psychiatric characteristics, cardiovascular risk and benzodiazepine use are related to cognitive performance in OABD. Cognitive variability in OABD thus seems multifactorial. Strategies aimed at improving cognition in BD should include cardiovascular risk management and minimizing benzodiazepine use.

Are Apathy and Depressive Symptoms Related to Vascular White Matter Hyperintensities in Severe Late Life Depression?

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

The influence of social, psychological, and cognitive factors on the clinical course in older patients with bipolar disorder.

OBJECTIVES: Research on factors that contribute to recurrence in older adults with bipolar disorder (OABD) is sparse. Previous research showed that clinical factors (e.g., age of onset, lifetime psychotic features, and suicide risk) were not associated with the recurrence in OABD. In younger adults, worse social functioning, coping style, and worse cognitive functioning are found to be associated with an unfavorable course of bipolar disorder. Therefore, this study is focusing on social, psychological, and cognitive factors in OABD. More insight in these factors is essential in order to develop and further specify preventive and treatment interventions. METHODS: Data were used from the Dutch Older Bipolars (DOBi) cohort study. We included 64 patients for 3-year follow-up measurements, who were divided in a recurrent group and a nonrecurrent group. Logistic regression analyses were conducted to assess associations between social, psychological, and cognitive factors, and nonrecurrence. RESULTS: 39.1% reported at least one recurrence during the 3-year follow-up period. No significant associations were found between the social, psychological, and cognitive factors and having a recurrence during the follow-up period. DISCUSSION: Participants in the recurrent group were younger, more often female and less likely to have children. Our results suggest that results from the adult bipolar disorder population cannot be extrapolated to OABD patients, underlining the need for longitudinal studies in OABD.

Five-year outcome of clinical recovery and subjective well-being in older Dutch patients with schizophrenia.

Outcome of schizophrenia in later life can be evaluated from different perspectives. The recovery concept has moved forward this evaluation, discerning clinical-based and patient-based definitions. Longitudinal data on measures of recovery in older individuals with schizophrenia are scant. This study evaluated the five-year outcome of clinical recovery and subjective well-being in a sample of 73 older Dutch schizophrenia patients (mean age 65.9 years; SD 5.4), employing a catchment-area based design that included both community living and institutionalized patients regardless of the age of onset of their disorder. At baseline (T1), 5.5% of participants qualified for clinical recovery, while at five-year follow-up (T2), this rate was 12.3% (p = 0.18; exact McNemar's test). Subjective well-being was reported by 20.5% of participants at T1 and by 27.4% at T2 (p = 0.27; exact McNemar's test). Concurrence of clinical recovery and subjective well-being was exceptional, being present in only one participant (1.4%) at T1 and in two participants (2.7%) at T2. Clinical recovery and subjective well-being were not correlated neither at T1 (p = 0.82; phi = 0.027) nor at T2 (p = 0.71; phi = -0.044). There was no significant correlation over time between clinical recovery at T1 and subjective well-being at T2 (p = 0.30; phi = 0.122) nor between subjective well-being at T1 and clinical recovery at T2 (p = 0.45; phi = -0.088). These results indicate that while reaching clinical recovery is relatively rare in older individuals with schizophrenia, it is not a prerequisite to experience subjective well-being.

Evaluation of FindMyApps: protocol for a randomized controlled trial of the effectiveness and cost-effectiveness of a tablet-based intervention to improve self-management and social participation of community-dwelling people with mild dementia, compared to usual tablet use.

BACKGROUND: For the rising number of people living with dementia, cost-effective community-based interventions to support psychosocial care are needed. The FindMyApps intervention has been developed with and for people with dementia and their caregivers, to help them use tablets to facilitate self-management and engagement in meaningful social activities. A feasibility study and exploratory pilot trial evaluating FindMyApps have been carried out. This definitive trial further evaluates the effectiveness of the intervention and, for the first time, the cost-effectiveness. METHODS: A randomized controlled non-blinded single-center two-arm superiority trial will be conducted. Community-dwelling people with Mild Cognitive Impairment (MCI), or dementia with a Mini Mental-State Examination (MMSE) of > 17 and < 26, or Global Deterioration Scale 3 or 4, with an informal caregiver and access to a wireless internet connection will be included. In total, 150 patient-caregiver dyads will be randomly allocated to receive either usual care (control arm - tablet computer; n = 75 dyads) or usual care and the FindMyApps intervention (experimental arm - tablet computer and FindMyApps; n = 75 dyads). The primary outcomes are: for people with dementia, self-management and social participation; for caregivers, sense of competence. In addition to a main effect analysis, a cost-effectiveness analysis will be performed. In line with MRC guidance for evaluation of complex interventions a process evaluation will also be undertaken. DISCUSSION: Results of the trial are expected to be available in 2023 and will be submitted for publication in international peer-reviewed scientific journals, in addition to conference presentations and reporting via the EU Marie Sklodowska-Curie DISTINCT ITN network. By providing evidence for or against the effectiveness and cost-effectiveness of the FindMyApps intervention, the results of the trial will influence national implementation of FindMyApps. We hope that the results of the trial will further stimulate research and development at the intersection of technology and psycho-social care in dementia. We hope to further demonstrate that the randomized controlled trial is a valuable and feasible means of evaluating new digital technologies, to stimulate further high-quality research in this growing field. TRIAL REGISTRATION NUMBER: Netherlands Trial Register: NL8157 ; registered 15th November 2019.

Loneliness, social network size, and mortality in older adults and the role of cortisol.

BACKGROUND: Loneliness and social isolation have both been found to be associated with increased mortality in previous studies. One potential underlying mechanism is via the hypothalamic-pituitary-adrenal axis. OBJECTIVE: This study aimed to examine the association between social network size and cortisol, to analyze the associations between both loneliness and social network size and mortality, and to examine to what extent the association between network size and/or loneliness and mortality is mediated by cortisol. DESIGN: The study group consisted of 443 depressed and non-depressed participants of the Netherlands Study of Depression in the Elderly (NESDO). Cross-sectional analysis of the association between social network size and cortisol measures was followed by a survival analysis of the associations between both social network size and loneliness and mortality. RESULTS: There were no significant associations between social network size and cortisol measures. Loneliness and small social network size were not associated with mortality. Age and partner status were more important predictors of mortality. CONCLUSION: As people grow older the variety of factors that influence mortality risk increases, diminishing the effect of a single factor. Prevention of early morbidity and mortality in older adults should be tailored to specific needs and risks, instead of aiming at one specific factor.

Does cognitive function in older bipolar patients depend on recurrent or current mood symptoms?

BACKGROUND: Cognitive impairment in patients with bipolar disorder (BD) is viewed as an integral part of the disorder that seems to be rather stable and even present in euthymic state. Current mood symptoms influence cognition negatively and multiple mood episodes could lead to more severe psychopathology and cognitive impairment, resulting in a hypothesized neuroprogressive course of BD. The influence of current mood symptoms and recurrent mood episodes on cognitive functioning warrants further exploration. METHODS: Cohort 1 included 20 hypomanic and 21 depressed older adults with bipolar disorder (OABD) of which 20 were reassessed in the euthymic state and 50 healthy subjects. Cohort 2 included 27 OABD who had no recurrent mood episodes during 5 years and 29 who had recurrent mood episodes during 5 years. Neuropsychological examination including tests for memory, executive function, attention and verbal fluency was performed repeatedly in all subjects. RESULTS: In cohort 1 cross-sectional analyses showed that hypomanic, depressed and euthymic patients groups did not differ from each other with respect to their cognitive functioning, except for attention, which was poorer only in depressed patients. Regardless of mood state patients experienced significantly worse cognitive functioning compared to the healthy subjects. Within subject comparisons revealed that performance on memory tasks was worse in patients with current mood symptoms; depressed patients were more impaired in the learning condition and hypomanic patients were more impaired in delayed recall. In cohort 2 cognitive functioning was not different in patients with or without recurrence in 5 year follow-up. CONCLUSIONS: Although OABD had worse cognitive functioning than healthy subjects, there was a quite stable pattern of cognitive impairment, regardless of current or recurrent mood episodes. These results do not provide consistent support for the hypothesis of neuroprogression in BD.

Effectiveness of Pharmacological Interventions for Symptoms of Behavioral Variant Frontotemporal Dementia: A Systematic Review.

BACKGROUND: Clinical guidance on the symptomatic treatment of behavioral variant frontotemporal dementia (bvFTD) is limited. OBJECTIVE: To provide a systematic review of pharmacological interventions for symptomatic treatment of bvFTD, based on the International bvFTD Criteria Consortium clinical diagnostic criteria: apathy, disinhibition, lack of empathy or sympathy, hyperorality, stereotypical behavior, and executive dysfunction. METHODS: We systematically searched the PubMed, Embase, and PsycINFO databases for reports on pharmacological interventions for individuals with bvFTD, published between 1970 and 2018, using key indicators and relevant terms. Studies were included if the efficacy of the intervention in alleviating bvFTD symptoms was provided as an outcome. Due to the high prevalence of depressive symptoms in individuals with bvFTD, we also evaluated the effect of the interventions on depression. RESULTS: We included 23 studies-11 randomized controlled trials, eight open-label studies, one proof-of-concept study, and three case series-reporting on a total of 573 individuals. Of the 23 studies, 16 used pharmacological interventions that improved bvFTD symptoms. Based on the Neuropsychiatric Inventory, trazodone had the greatest significant reductive effect on the symptoms of bvFTD. Overall, citalopram, rivastigmine, paroxetine, and trazodone all reduced multiple symptoms, including disinhibition, hyperorality, and depression. CONCLUSIONS: This review provides an overview of the pharmacological interventions that can be used to treat the main bvFTD symptoms as well as a guideline for managing bvFTD. More research is needed to investigate the efficacy of pharmacological interventions for bvFTD through use of a validated outcome and a focus on the specific behavioral problems associated with bvFTD.

Effects of Pharmacogenetic Screening for CYP2D6 Among Elderly Starting Therapy With Nortriptyline or Venlafaxine: A Pragmatic Randomized Controlled Trial (CYSCE Trial).

PURPOSE/BACKGROUND: The duration of untreated depression is a predictor for poor future prognosis, making rapid dose finding essential. Genetic variation of the CYP2D6 isoenzyme can influence the optimal dosage needed for individual patients. The aim of this study was to determine the effectiveness of CYP2D6 pharmacogenetic screening to accelerate drug dosing in older patients with depression initiating nortriptyline or venlafaxine. METHODS/PROCEDURES: In this randomized controlled trial, patients were randomly allocated to one of the study arms. In the intervention arm (DG-I), the specific genotype accompanied by a standardized dosing recommendation based on the patients' genotype and the prescribed drug was directly communicated to the physician of the participant. In both the deviating genotype control arm (DG-C) and the nonrandomized control arm, the physician of the participants was not informed about the genotype and the associated dosing advise. The primary outcome was the time needed to reach adequate drug levels: (1) blood levels within the therapeutic range and (2) no dose adjustments within the previous 3 weeks. FINDINGS/RESULTS: No significant difference was observed in mean time to reach adequate dose or time to adequate dose between DG-I and DG-C. Compared with the nonrandomized control arm group, adequate drug levels were reached significantly faster in the DG-I group (log-rank test; P = 0.004), and there was a similar nonsignificant trend for the DG-C group (log-rank test; P = 0.087). IMPLICATIONS/CONCLUSIONS: The results of this study do not support pharmacogenetic CYP2D6 screening to accelerate dose adjustment for nortriptyline and venlafaxine in older patients with depression.

MMSE Changes During and After ECT in Late-Life Depression: A Prospective Study.

OBJECTIVE: There is ongoing concern about the impact of electroconvulsive therapy (ECT) on cognition in patients with late-life depression (LLD), especially in patients for whom pretreatment Mini-Mental State Exam (MMSE) scores are low. Our aim was to examine the evolution of cognitive effects of ECT, using the MMSE in a large group of patients with LLD. METHODS: One hundred nine patients aged 55 years and older with unipolar depression, referred for ECT, were included in our study. The MMSE was assessed before, during, immediately after, and 6 months after ECT. RESULTS: MMSE scores improved significantly during the course of ECT and remained stable during the 6-month period after ending ECT for the total group. In the group of patients with a low MMSE score (<24) at baseline, the MMSE score improved significantly during ECT, whereas in the group of patients with a normal MMSE score (≥24) at baseline, the score did not change significantly during ECT. In both groups, MMSE scores still increased slightly after ECT was discontinued. CONCLUSION: ECT does not cause deleterious cognitive effects, as measured with the MMSE, during and for 6 months after the ECT course in patients with LLD. In the event of a baseline cognitive impairment, MMSE scores tend to improve significantly during and for 6 months after the ECT course. The presence of pretreatment cognitive impairment should not lead clinicians to withhold ECT in older patients with severe depression.

Metabolic syndrome rates in older patients with severe mental illness after five years of follow-up and the association with mortality.

OBJECTIVES: To establish the course of metabolic syndrome (MS) rates in older patients with severe mental illness (SMI) after 5-year follow-up and evaluate whether MS at baseline is associated with mortality or diabetes at follow-up. METHODS: Patients (>60 years of age) with SMI (N = 100) were included at a specialized mental health outpatient clinic. Metabolic parameters were collected from patients' medical files at baseline and after 5-year follow-up. RESULTS: Follow-up data were available of 98 patients (98%); nine patients had died. Parameters of MS were available of 76 patients; 34.2% were diagnosed with MS. This was not significantly different compared with baseline (46.1%). MS at baseline was not significantly associated with mortality or development of diabetes at follow-up. CONCLUSIONS: In older patients with SMI, the rates of MS may reach a plateau. Screening for MS in older patients treated at a specialized mental health outpatient clinic may generate attention for their somatic health and treatment for the components of MS that may in turn have a positive effect on their outcome. However, further research with larger sample sizes is needed in order to confirm these findings.

Predicting progression in the late onset frontal lobe syndrome.

ABSTRACTA late onset frontal lobe syndrome (LOF) refers to a clinical syndrome with apathy, disinhibition, or stereotypical behavior arising in middle or late adulthood. Diagnostics are challenging, and both clinicians and patients need reliable predictors of progression to improve clinical guidance. In this longitudinal multicenter and genetically screened prospective study, 137 LOF patients with frontal behavior (FBI score≥11) and/or stereotypical behavior (SRI≥10) were included. Progression was defined as institutionalization, death, or progression of frontal or temporal atrophy at magnetic resonance imaging (MRI) after two years of follow up. Absence of progression at MRI in addition to stable or improved Mini Mental State Examination and Frontal Assessment Battery scores after two years was indicative for non-progression. The presence of stereotypy and a neuropsychological profile with executive deficits at baseline were found to be predictive for progression, while a history and family history with psychiatric disorders were predictors for non-progression. The combination of these clinical markers had a predictive value of 80.4% (p < 0.05). In patients presenting with late onset behavioral symptoms, an appraisal of the rate of deterioration can be made by detailed mapping of clinical symptoms. Distinction of progressive discourses from non-progressive or treatable conditions is to be gained.