Publications by authors named "Sigfried Schouws"

33 Publications

Evaluating feasibility and satisfaction of a group intervention for mild cognitive impairment in older age bipolar disorder: "Brain train".

Bipolar Disord 2021 Sep 17. Epub 2021 Sep 17.

GGZ inGeest, Amsterdam, the Netherlands.

To date, no remediation treatment is available aimed at improving cognitive functioning in patients with older age bipolar disorder (OABD). Our pilot intervention (Brain train) included cognitive training, physical exercise, and social encounter with peers for OABD and was positively evaluated by the participants. However, its feasibility was limited as few patients fulfilled the inclusion criteria of cognitive and social impairment and retaining the physical ability to walk for a minimum of 30 min. OABD patients with cognitive impairment are a vulnerable group for which it is most challenging to design interventions aimed at improving daily functioning.
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http://dx.doi.org/10.1111/bdi.13126DOI Listing
September 2021

Inflammation and Cognitive Functioning in Depressed Older Adults Treated With Electroconvulsive Therapy: A Prospective Cohort Study.

J Clin Psychiatry 2021 Aug 10;82(5). Epub 2021 Aug 10.

GGZ inGeest Specialized Mental Health Care, Department of Old Age Psychiatry, Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.4088/JCP.20m13631DOI Listing
August 2021

Bipolar symptoms, somatic burden, and functioning in older-age bipolar disorder: Analyses from the Global Aging & Geriatric Experiments in Bipolar Disorder Database project.

Bipolar Disord 2021 Jul 27. Epub 2021 Jul 27.

Department of Psychiatry, University of California San Diego, San Diego, CA, USA.

Objective: Literature on older-age bipolar disorder (OABD) is limited. This first-ever analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated associations among age, BD symptoms, comorbidity, and functioning.

Methods: This analysis used harmonized, baseline, cross-sectional data from 19 international studies (N = 1377). Standardized measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Global Assessment of Functioning (GAF).

Results: Mean sample age was 60.8 years (standard deviation [SD] 12.2 years), 55% female, 72% BD I. Mood symptom severity was low: mean total YMRS score of 4.3 (SD 5.4) and moderate-to-severe depression in only 22%. Controlled for sample effects, both manic and depressive symptom severity appeared lower among older individuals (p's < 0.0001). The negative relationship between older age and symptom severity was similar across sexes, but was stronger among those with lower education levels. GAF was mildly impaired (mean =62.0, SD = 13.3) and somatic burden was high (mean =2.42, SD = 1.97). Comorbidity burden was not associated with GAF. However, higher depressive (p < 0.0001) and manic (p < 0.0001) symptoms were associated with lower GAF, most strongly among older individuals.

Conclusions: Findings suggest an attenuation of BD symptoms in OABD, despite extensive somatic burden. Depressive symptom severity was strongly associated with worse functioning in older individuals, underscoring the need for effective treatments of BD depression in older people. This international collaboration lays a path for the development of a better understanding of aging in BD.
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http://dx.doi.org/10.1111/bdi.13119DOI Listing
July 2021

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

Acta Psychiatr Scand 2021 10 21;144(4):392-406. Epub 2021 Jul 21.

Amsterdam UMC, Vrije Universiteit, Psychiatry, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1111/acps.13342DOI Listing
October 2021

Physical comorbidity in Older-Age Bipolar Disorder (OABD) compared to the general population - a 3-year longitudinal prospective cohort study.

J Affect Disord 2021 06 26;288:83-91. Epub 2021 Mar 26.

Amsterdam UMC, Vrije Universiteit, Psychiatry, Amsterdam Public Health Research Institute, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; GGZ inGeest Specialized Mental Health Care, Amsterdam, The Netherlands; Amsterdam UMC, Vrije Universiteit, Psychiatry, Amsterdam Neuroscience Research Institute, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

Background: The aim of this study was to examine the accumulation of chronic physical diseases in Older-Age Bipolar Disorder (OABD) as well as in individuals from the general aging population over a 3-year period.

Methods: This prospective longitudinal study compared 101 patients with OABD receiving outpatient care (DOBi cohort) with 2545 individuals from the general aging population (LASA cohort). The presence of eight major chronic diseases was asked at baseline and 3-year follow-up. Total number of diseases was the main outcome measure. Self-rated health (SRH, scale 1-5) was examined as a secondary outcome. Multilevel linear modelling of change was performed to estimate and test the observed change in both samples.

Results: At baseline, the number of chronic diseases was lower (b= -0.47, p<0.01) and self-rated health comparable (b=0.27, p=0.13) in DOBi than in LASA. Over 3 years the number of chronic diseases increased faster in DOBi than in LASA (b=0.51 versus b=0.35, p(interaction)=0.03). When corrected for employment, depressive symptoms, waist circumference, smoking, and alcohol use, this difference was no longer significant. SRH decreased faster in DOBi than in LASA (b=-0.24 versus b=-0.02, p(interaction)=0.04).

Limitations: Information on chronic diseases was collected using self-report.

Conclusions: A faster accumulation of chronic physical diseases and a faster decline in health perception was observed in OABD than in participants from the general population. The observed differences could partly be attributed to baseline differences in psychosocial, lifestyle, and health behaviour factors. Our findings urgently call for the use of integrated care in BD.
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http://dx.doi.org/10.1016/j.jad.2021.03.057DOI Listing
June 2021

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

Am J Geriatr Psychiatry 2021 Jan 8. Epub 2021 Jan 8.

GGZ inGeest Specialized Mental Health Care, Amsterdam, The Netherlands; Amsterdam UMC, Vrije Universiteit, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands; Amsterdam UMC, Vrije Universiteit, Psychiatry, Amsterdam Public Health (Research Institute), Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.jagp.2020.12.028DOI Listing
January 2021

Psychiatric symptoms during the COVID-19 outbreak in older adults with bipolar disorder.

Int J Geriatr Psychiatry 2021 06 23;36(6):892-900. Epub 2021 Jan 23.

Department of Old Age Psychiatry, GGZ inGeest, Amsterdam, the Netherlands.

Objectives: Older adults with bipolar disorder (OABD) are vulnerable for a COVID-19 infection via multiple pathways. It is essential for OABD to adhere to the COVID-19 measures, with potential consequences for the psychiatric symptoms. This situation offers the unique opportunity to investigate factors of vulnerability and resilience that are associated with psychiatric symptoms in OABD.

Methods: This study included 81 OABD patients aged over 50 years. Factors measured at baseline in patients that participated in 2017/2018 were compared with factors measured during the COVID-19 outbreak.

Results: Participants experienced less psychiatric symptoms during COVID-19 than (67.9% euthymic) than at baseline (40.7% euthymic). There was no difference in loneliness between COVID-19 and baseline. Not having children, more feelings of loneliness, lower mastery, passive coping style and neuroticism were associated with more psychiatric symptoms during COVID-19 measures.

Conclusions: Participants experienced less psychiatric symptoms during COVID-19 measures when compared to baseline. Our results indicate promising targets for psychological interventions aimed at curing and preventing recurrence in OABD and improving quality of life in this growing vulnerable group.
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http://dx.doi.org/10.1002/gps.5489DOI Listing
June 2021

Reliability and validity of the functioning assessment short test for older adults with bipolar disorder (FAST-O).

Int J Bipolar Disord 2020 Oct 2;8(1):28. Epub 2020 Oct 2.

Department of Old Age Psychiatry, GGZ inGeest, Amstelveenseweg 589, 1081JC, Amsterdam, The Netherlands.

Background: Many frequently used instruments fail to assess psychosocial functioning in patients with bipolar disorder. The Functioning Assessment Short Test (FAST) was developed in order to tackle this problem and to assess the main functioning problems experienced by patients with bipolar disorder. However, the original FAST is not fully applicable in older adults due to the domain of occupational functioning. The aim of our study was to validate an adapted version for Older adults (FAST-O) in a group of older adults with bipolar disorder (OABD).

Methods: 88 patients aged 50 years and over diagnosed with bipolar disorder were included. We adapted the items in the area of "work-related functioning" of the FAST into items assessing "societal functioning". Several measurements were conducted in order to analyse the psychometric qualities of the FAST-O (confirmatory factor analysis for internal structure, Cronbach's alpha for internal consistency, Spearman's rho for concurrent validity, Mann-Whitney U test for discriminant validity).

Results: Mean age in the study sample was 65.3 (SD = 7.5) and 57.3% was female. The internal structure was most similar to the internal structure of the original FAST. The internal consistency was excellent (Cronbach's alpha = .93). The concurrent validity when correlated with the Social and Occupational Functioning Assessment Scale was low, but significant. The FAST-O was also able to distinguish between euthymic and symptomatic OABD patients.

Conclusions: The FAST-O has strong psychometric qualities. Based on our results, we can conclude that the FAST-O is a short, efficient solution in order to replace global rating scales or extensive test batteries in order to assess daily functioning of older psychiatric patients in a valid and reliable manner.
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http://dx.doi.org/10.1186/s40345-020-00193-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532249PMC
October 2020

Admixture analysis of age at onset in older patients with schizophrenia spectrum disorders.

Int Psychogeriatr 2020 06 11;32(6):781-785. Epub 2020 Jun 11.

Amsterdam UMC, Vrije Universiteit, Psychiatry, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.

The nature of schizophrenia spectrum disorders with an onset in middle or late adulthood remains controversial. The aim of our study was to determine in patients aged 60 and older if clinically relevant subtypes based on age at onset can be distinguished, using admixture analysis, a data-driven technique. We conducted a cross-sectional study in 94 patients aged 60 and older with a diagnosis of schizophrenia or schizoaffective disorder. Admixture analysis was used to determine if the distribution of age at onset in this cohort was consistent with one or more populations of origin and to determine cut-offs for age at onset groups, if more than one population could be identified. Results showed that admixture analysis based on age at onset demonstrated only one normally distributed population. Our results suggest that in older schizophrenia patients, early- and late-onset ages form a continuum.
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http://dx.doi.org/10.1017/S104161022000085XDOI Listing
June 2020

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

Int J Geriatr Psychiatry 2020 10 8;35(10):1163-1170. Epub 2020 Jun 8.

Department of Old Age, GGZ InGeest, Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1002/gps.5352DOI Listing
October 2020

The Value of Neuropsychological Assessment in the Differentiation Between Behavioral Variant Frontotemporal Dementia and Late-Onset Psychiatric Disorders.

J Clin Psychiatry 2020 02 4;81(1). Epub 2020 Feb 4.

Department of Old Age Psychiatry, GGZ inGeest, Amsterdam, The Netherlands.

Objective: To investigate which neuropsychological tests can discriminate between behavioral variant frontotemporal dementia (bvFTD) and psychiatric disorders presenting with similar late-onset frontal behavioral changes, such as apathy, disinhibition, reduced empathy, or compulsive behavior.

Methods: Patients presenting with frontal behavioral changes in middle or late adulthood received extensive baseline examinations, including neuropsychological assessment and brain imaging. After 2 years, examinations were repeated and patients were diagnosed according to DSM-IV or international bvFTD consensus criteria. The study period was April 2011-June 2015. Two groups were selected: 32 patients with bvFTD and 53 patients with a psychiatric or psychological diagnosis. Associations between neuropsychological test scores and diagnostic group were investigated with logistic regression analyses, and diagnostic accuracy was investigated with a receiver operating characteristic curve.

Results: BvFTD patients scored lower on tests for confrontational naming, gestalt completion, and verbal abstraction compared to psychiatric patients (P < .01). The confrontational naming test (Boston Naming Test) showed the strongest association with diagnostic group: a lower score indicated a higher probability for a bvFTD diagnosis (P < .001). This test could discriminate between the groups with good diagnostic accuracy (area under the curve = 0.81). Tests for attention, memory, and executive functions showed no discriminative ability between the groups.

Conclusions: Although one of the criteria of bvFTD is low performance on executive tests, these tests are not useful in differentiating bvFTD from psychiatric disorders. We recommend administering language tests, especially an extensive confrontational naming test, to aid differentiation between bvFTD and a psychiatric disorder in patients presenting with late-onset frontal behavioral changes.
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http://dx.doi.org/10.4088/JCP.19m12811DOI Listing
February 2020

Secondary mania as a possible presentation of a C9orf72 hexanucleotide repeat expansion.

Bipolar Disord 2019 02 12;21(1):90-92. Epub 2018 Dec 12.

Department of Old Age Psychiatry, GGZ inGeest/VU University Medical Center, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.

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http://dx.doi.org/10.1111/bdi.12724DOI Listing
February 2019

The relationship between cognitive and social functioning in older patients with bipolar disorder.

J Affect Disord 2018 11 24;240:177-182. Epub 2018 Jul 24.

Department of Old Age Psychiatry, GGZinGeest, Amstelveenseweg 589, 1081JC, Amsterdam, The Netherlands; Department of Psychiatry, Amsterdam Public Health research institute, VU University Medical Center, Amsterdam, The Netherlands; Neuroscience Campus VUmc, Amsterdam, The Netherlands.

Objectives: Patients with bipolar disorder (BD) show specific cognitive impairments, especially in the domains of attention, executive functioning and memory. Social and occupational problems seem to exist in 30-60% of BD patients. This study analysed the relationship between cognitive and social functioning in older age BD (OABD) patients.

Methods: This study included 63 OABD patients (aged > 60). Cognitive functioning was measured by an extensive neuropsychological assessment including global cognitive functioning, attention, learning and memory, executive functioning and verbal fluency. Social functioning, was obtained by clinical interview, including global social functioning, meaningful contacts and social participation. Linear regression analyses were conducted between cognitive performance and social functioning and the role of depression severity and disease duration was explored.

Results: Global social functioning, number of meaningful contacts and social participation were not interrelated. Global cognitive functioning, learning and memory and executive functioning were positively associated with global social functioning. No associations were found between cognitive functioning and social participation or meaningful contacts. Depression severity and disease duration were no effect modifiers.

Limitations: Limitations include the use of a sample with relatively low cognitive and social impairments and the use of a cross-sectional research design.

Conclusions: Global social functioning judged by the clinician was found to be independent of social functioning defined by the number of social contacts and social participation as reported by the patient. Global social functioning was related to cognitive functioning. An integrative treatment intervention including cognitive training and addressing social functioning may improve daily functioning in OABD patients.
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http://dx.doi.org/10.1016/j.jad.2018.07.055DOI Listing
November 2018

Associations between cognitive functioning, mood symptoms and coping styles in older age bipolar disorder.

J Affect Disord 2018 08 6;235:357-361. Epub 2018 Apr 6.

Department of Old Age Psychiatry, GGZ inGeest/VU University Medical Center, Amsterdam Public Health research institute, Amsterdam, The Netherlands.

Background: Older age patients with bipolar disorder (OABD) have often passive coping styles, generally considered as detrimental for functioning. The aim of the current study is to identify the contribution of cognitive functioning, subjective cognitive complaints and mood symptoms to passive and active coping styles in older age BD.

Methods: In 90 euthymic patients (age > 60) with BD I or II, we examined coping, neuropsychological profile including memory, attention, executive function and fluency, subjective cognitive complaints and mood symptoms.

Results: Better executive functioning and fewer depressive symptoms were associated with more active coping (p = .02 and p = .001 respectively). Associations between executive functioning and coping styles turned nonsignificant when combined with depressive symptoms in one model, indicating the importance of mood on coping styles. No associations were found between subjective cognitive complaints and coping styles.

Limitations: Cross-sectional data were used and no conclusions about causality can be made.

Conclusions: Even in euthymic patients, subclinical depressive symptoms may influence active coping negatively. Subjective cognitive complaints and objectified cognitive functioning seem to be of less importance for coping styles. Important implications are on the one hand optimizing treatment on reducing depressive symptoms and on the other hand focusing therapeutic interventions on coping in bipolar patients.
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http://dx.doi.org/10.1016/j.jad.2018.04.052DOI Listing
August 2018

Social Cognition Differentiates Behavioral Variant Frontotemporal Dementia From Other Neurodegenerative Diseases and Psychiatric Disorders.

Am J Geriatr Psychiatry 2018 05 1;26(5):569-579. Epub 2018 Feb 1.

Department of Old Age Psychiatry, GGZinGeest, VU University Medical Center, Amsterdam, The Netherlands; Alzheimer Centre & Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.

Objective: Although deficits in social cognition are established as core features in behavioral variant frontotemporal dementia (bvFTD), it remains unresolved if impaired social cognition distinguishes bvFTD from the broad differential diagnoses in clinical practice. Our aim was to study whether social cognition discriminates bvFTD from other neurodegenerative diseases and psychiatric disorders in patients presenting with late-onset frontal symptoms. Next, we studied the association of social cognition with frontal symptoms and cognitive functioning.

Methods: In this longitudinal multicenter study, besides clinical rating scales for frontal symptoms, social cognition was determined by Ekman 60 Faces test and Faux Pas in addition to neuropsychological tests for other cognitive domains in patients with probable and definite bvFTD (N = 22), other neurodegenerative diseases (N = 24), and psychiatric disorders (N = 33). Median symptom duration was 2.8 years, and patients were prospectively followed over 2 years.

Results: Total scores from Ekman 60 Faces test were significantly lower in bvFTD than in other neurodegenerative diseases and psychiatric disorders. Ekman 60 Faces test explained 91.2% of the variance of psychiatric disorders and other neurodegenerative diseases versus bvFTD (χ = 11.02, df = 1, p = 0.001) and was associated with all other cognitive domains. Faux Pas and the other cognitive domains did not differ between these diagnostic groups.

Conclusion: In this clinical sample Ekman 60 Faces test distinguished bvFTD successfully from other neurodegenerative diseases and psychiatric disorders. Although associated with social cognition, other cognitive domains were not discriminative. This study provides arguments to add the Ekman 60 Faces test to the neuropsychological examination in the diagnostic procedure of bvFTD.
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http://dx.doi.org/10.1016/j.jagp.2017.12.008DOI Listing
May 2018

The clinical course of late-life bipolar disorder, looking back and forward.

Bipolar Disord 2017 Dec 11. Epub 2017 Dec 11.

Department of Old Age Psychiatry, GGZinGeest, VUmc, Amsterdam, the Netherlands.

Objectives: Little is known about the course of late-life bipolar disorder (LLBD). First, we studied patients with LLBD retrospectively with regard to age at first mood episode, onset polarity, predominant polarity and episode density and its associations with other clinical variables. Next, we examined prospectively the clinical course and its associated factors.

Methods: Data were used from a dynamic cohort (Dutch Older Bipolars [DOBi]) including 101 patients with LLBD (mean age of 68.9 years) at baseline in 2012, with 3-year follow-up measurements available for 64 of these patients. Retrospective course was assessed by diagnostic interviews, and at follow-up polarity and duration for each consecutive episode were noted. Linear and logistic analyses were performed to assess associations between relevant factors and outcome.

Results: The mean age at the first episode was 33.0 years. Onset polarity was depression in 44.6% of patients, with a predominant polarity of depression in 47.5%. At 3-year follow-up, 37.5% of patients reported at least one mood episode, mainly depression. Life events, somatic illness, use of lithium and other factors were not associated with recurrence during the 3-year follow-up.

Discussion: A relapse rate of 37.5% in 3 years is high, considering that LLBD patients generally have a longer history of disease and were receiving care and medication. The course of LLBD can provide important information on which clinical factors are associated with recurrence. Further phenotyping may reveal unique predictors for outcome, and both course specifiers and clinical variables should be included.
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http://dx.doi.org/10.1111/bdi.12586DOI Listing
December 2017

The Pitfall of Behavioral Variant Frontotemporal Dementia Mimics Despite Multidisciplinary Application of the FTDC Criteria.

J Alzheimers Dis 2017 ;60(3):959-975

Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.

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 baseline was 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.
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http://dx.doi.org/10.3233/JAD-170608DOI Listing
May 2018

Cognitive Deficits in Patients With Neuropsychiatric Symptoms: A Comparative Study Between Behavioral Variant Frontotemporal Dementia and Primary Psychiatric Disorders.

J Clin Psychiatry 2017 Sep/Oct;78(8):e940-e946

Department of Old Age Psychiatry, GGZinGeest, Amsterdam, The Netherlands.

Objective: To compare neuropsychological profiles in behavioral variant frontotemporal dementia (bvFTD) with its most common primary psychiatric differential diagnoses, major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia, in older patients with active symptoms.

Methods: We included patients from different cohorts with MDD (DSM-IV-TR: 296.20-296.23, 296.30-296.33; n = 42; mean ± SD age, 72.0 ± 8.0 years; female = 57.1%) included from 2002 to 2007, noneuthymic BD (DSM-IV-TR: 296.00-296.06, 296.40-296.46, 296.50-296.56, 296.60-296.66, 296.7; DSM-IV-TR: 296.89; DSM-IV-TR: 296.80; n = 41; age, 71.7 ± 8.8 years; female = 53.7%) included from 2011 to 2015, nonremitted schizophrenia (DSM-IV-TR: 295.10, 295.20, 295.30, 295.60, 295.90; n = 47; age, 67.5 ± 7.1 years; female = 66%) included from 2006 to 2008, or probable/definite bvFTD (n = 173; age, 62.6 ± 8.0 years; female = 39.9%) (Frontotemporal Dementia Consensus criteria) included from 2000 to 2015 and healthy controls (n = 78; age, 71.9 ± 8.0 years; female = 71.8%) included from 2005 to 2007. Neuropsychological tests concerned the domains of attention and working memory, verbal memory, verbal fluency, and executive functioning. Analyses of variance were performed with age, gender, and education level as covariates. Post hoc Bonferroni tests were used to detail group differences.

Results: Compared to the healthy controls, both the bvFTD and primary psychiatric disorder groups showed significant impairment on all cognitive domains. Executive function was more disturbed in all primary psychiatric disorders compared to bvFTD (P < .001). Attention and working memory were significantly better in the bvFTD and schizophrenia groups compared to the MDD and BD groups (P < .001). For verbal memory, the bvFTD group scored significantly higher compared to patients with schizophrenia, BD, or MDD (P < .001). Patients with bvFTD had significantly lower scores on verbal fluency, especially due to Animal Naming, in comparison with the BD group (P < .001); however, these scores were not significantly different from those of MDD or schizophrenia patients.

Conclusions: Cognitive deficits in bvFTD are less severe than in primary psychiatric disorders with active symptoms. This indicates that in the differential diagnosis of bvFTD, disturbances on tests for cognitive performance do not rule out primary psychiatric diagnoses.
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http://dx.doi.org/10.4088/JCP.16m11019DOI Listing
November 2017

Early- and Late-Onset Depression in Late Life: A Prospective Study on Clinical and Structural Brain Characteristics and Response to Electroconvulsive Therapy.

Am J Geriatr Psychiatry 2017 Feb 22;25(2):178-189. Epub 2016 Sep 22.

Department of Old Age Psychiatry, GGZ inGeest, VU University Medical Center, Amsterdam, The Netherlands; EMGO+ Institute of Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.

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 <55 and ≥55 years).

Methods: Between January 2011 and December 2013, 110 patients aged 55 years and older with ECT-treated unipolar depression were included in The Mood Disorders in Elderly treated with ECT study. Clinical profile and somatic health were assessed. Magnetic resonance imaging (MRI) scans were performed before the first ECT and visually rated.

Results: Response rate was 78.2% and similar between the two sites but significantly higher in LOD compared with EOD (86.9 versus 67.3%). Clinical, somatic, and brain characteristics were not different between EOD and LOD. Response to ECT was associated with late age at onset and presence of psychotic symptoms and not with structural MRI characteristics. In EOD only, the odds for a higher response were associated with a shorter index episode.

Conclusion: The clinical profile, somatic comorbidities, and brain characteristics in LLD were similar in EOD and LOD. Nevertheless, patients with LOD showed a superior response to ECT compared with patients with EOD. Our results indicate that ECT is very effective in LLD, even in vascular burdened patients.
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http://dx.doi.org/10.1016/j.jagp.2016.09.005DOI Listing
February 2017

Comparison of social functioning in community-living older individuals with schizophrenia and bipolar disorder: a catchment area-based study.

Int J Geriatr Psychiatry 2017 05 27;32(5):532-538. Epub 2016 Apr 27.

GGZ inGeest, Amsterdam, The Netherlands.

Objective: Preserved social functioning is of utmost importance for older individuals living in the community to maintain independency. However, in patients with schizophrenia or bipolar disorder, it remains unclear which factors influence social functioning in later life.

Methods: In a catchment area-based study in Amsterdam, The Netherlands, 120 older (>60 years) community-living patients with schizophrenia (n = 73) and with bipolar disorder (n = 47) were included. Clinical interviews on social functioning and psychometric measurements were applied.

Results: Patients with schizophrenia scored lower on all social measures (social functioning, social participation, network size, availability of confidants) compared with their peers with bipolar disorder. In patients with schizophrenia, lower social functioning was associated with having more negative symptoms and depressive symptoms. Age of onset was also associated with social functioning in schizophrenia, with higher scores in very late-onset schizophrenia-like psychosis. Unfavourable social functioning in patients with bipolar disorder was associated with lower cognitive functioning. Furthermore, in both groups, social functioning was not related to age, having offspring or the presence of a partner.

Conclusions: In community-living older patients, schizophrenia has a more disruptive effect on social functioning than bipolar disorder, except in those with a very late-onset schizophrenia-like psychosis. Minimizing residual depressive symptoms and optimizing cognitive functioning may be targets for improving social functioning and independent-living in older patients with severe mental illness. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/gps.4490DOI Listing
May 2017

Five-year follow-up of cognitive impairment in older adults with bipolar disorder.

Bipolar Disord 2016 Mar 9;18(2):148-54. Epub 2016 Mar 9.

Department of Old Age Psychiatry, GGZ inGeest, Amsterdam, The Netherlands.

Objective: To date, cognitive impairment has been thought to be an integral part of bipolar disorder. In clinical staging models, cognitive impairment is one of the hallmarks to define the clinical stage and it plays an important role in identifying the risk factors for progression to later stages of the illness. It is important to examine neurocognitive performance over longer periods to test the hypothesis of neuroprogression of bipolar disorder.

Methods: A comprehensive neuropsychological test battery was applied at baseline and five years later to 56 euthymic older outpatients with bipolar disorder (mean age = 68.35 years, range: 60-90 years) and to a demographically matched sample of 44 healthy subjects. A group-by-time repeated measures multivariate analysis of variance was performed to measure changes over time for the two groups. The impact of baseline illness characteristics on the intra-individual change in neurocognitive performance within the bipolar disorder group was studied by using logistic regression analysis.

Results: At baseline and at follow-up, patients with bipolar disorder performed worse on all neurocognitive measures compared to the matched healthy subjects. However, there was no significant group-by-time interaction between the patients with bipolar disorder and the comparison group.

Conclusions: Although older patients with bipolar disorder had worse cognitive function than healthy subjects, they did not have greater cognitive decline over a five-year period. The change in acquired cognitive impairment of patients with bipolar disorder might parallel the cognitive development as seen in normal aging.
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http://dx.doi.org/10.1111/bdi.12374DOI Listing
March 2016

Impact of Imaging and Cerebrospinal Fluid Biomarkers on Behavioral Variant Frontotemporal Dementia Diagnosis within a Late-Onset Frontal Lobe Syndrome Cohort.

Dement Geriatr Cogn Disord 2016 17;41(1-2):16-26. Epub 2015 Oct 17.

Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.

Background: The criteria for behavioral variant frontotemporal dementia (bvFTD) incorporate MRI and [18F]-FDG-PET. Cerebrospinal fluid (CSF) analysis is merely advised for excluding Alzheimer's disease.

Aims: We aimed to assess the impact of biomarkers on diagnostic certainty and contingent changes of bvFTD diagnosis within the clinically relevant neuropsychiatric differential diagnosis of subjects with a late-onset frontal lobe syndrome (LOF).

Methods: We included 137 patients with LOF, aged 45-75 years, 72% males. Biomarker disclosure was considered contributing after any substantial difference in diagnostic certainty or a diagnostic change. Percentages of contributing biomarkers were compared between three major diagnostic groups (bvFTD, psychiatry, other neurological disorders). Certainty levels in stable diagnostic groups were compared to those with a diagnostic change.

Results: Biomarkers contributed in 53, 60 and 41% of the LOF patients for MRI, [18F]-FDG-PET and CSF, respectively. Biomarkers changed the diagnosis in 14% of cases towards bvFTD and in 13% from bvFTD into an alternative. Those that changed had a lower level of a priori diagnostic certainty compared to stable diagnoses.

Conclusion: Our study not only supports the widely accepted use of MRI and [18F]-FDG-PET in diagnosing or excluding bvFTD, but also shows that CSF biomarkers aid clinicians in the diagnostic process.
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http://dx.doi.org/10.1159/000441023DOI Listing
September 2016

A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force.

Bipolar Disord 2015 Nov 19;17(7):689-704. Epub 2015 Sep 19.

Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.

Objectives: In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the International Society for Bipolar Disorder (ISBD) Task Force on Older-Age Bipolar Disorder (OABD).

Methods: This task force report addresses the unique aspects of OABD including epidemiology and clinical features, neuropathology and biomarkers, physical health, cognition, and care approaches.

Results: The report describes an expert consensus summary on OABD that is intended to advance the care of patients, and shed light on issues of relevance to BD research across the lifespan. Although there is still a dearth of research and health efforts focused on older adults with BD, emerging data have brought some answers, innovative questions, and novel perspectives related to the notion of late onset, medical comorbidity, and the vexing issue of cognitive impairment and decline.

Conclusions: Improving our understanding of the biological, clinical, and social underpinnings relevant to OABD is an indispensable step in building a complete map of BD across the lifespan.
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http://dx.doi.org/10.1111/bdi.12331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623878PMC
November 2015

Coping and personality in older patients with bipolar disorder.

J Affect Disord 2015 Sep 2;184:67-71. Epub 2015 Jun 2.

GGZ inGeest, Mental Health Institute, Amsterdam, The Netherlands.

Background: Little is known about coping styles and personality traits in older bipolar patients. Adult bipolar patients show a passive coping style and higher neuroticism scores compared to the general population. Our aim is to investigate personality traits and coping in older bipolar patients and the relationship between coping and personality.

Method: 75 Older patients (age > 60) with bipolar I or II disorder in a euthymic mood completed the Utrecht Coping List and the NEO Personality Inventory FFI and were compared to normative data.

Results: Older bipolar patients show more passive coping styles compared to healthy elderly. Their personality traits are predominated by openness, in contrast conscientiousness and altruism are relatively sparse. Neuroticism was related to passive coping styles, whereas conscientiousness was related to an active coping style.

Conclusions: Older bipolar patients have more passive coping styles. Their personality is characterized by openness and relatively low conscientiousness and altruism. Our sample represents a survival cohort; this may explain the differences in personality traits between older patients in this study and in adult bipolar patients in other studies. The association between coping styles and personality traits is comparable to reports of younger adult patients with bipolar disorder. Longitudinal studies are warranted to explore if coping and personality change with ageing in bipolar patients and to determine which coping style is most effective in preventing mood episodes.
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http://dx.doi.org/10.1016/j.jad.2015.05.045DOI Listing
September 2015

Identifying bvFTD Within the Wide Spectrum of Late Onset Frontal Lobe Syndrome: A Clinical Approach.

Am J Geriatr Psychiatry 2015 Oct 7;23(10):1056-66. Epub 2015 Apr 7.

Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands.

Objective: The behavioral variant of frontotemporal dementia (bvFTD) can be difficult to diagnose because of the extensive differential diagnosis, including many other diseases presenting with a frontal lobe syndrome. We aimed to identify the diagnostic spectrum causing a late onset frontal lobe syndrome and examine the quality of commonly used instruments to distinguish between bvFTD and non-bvFTD patients, within this syndrome.

Methods: A total of 137 patients fulfilling the criteria of late onset frontal lobe syndrome, aged 45 to 75 years, were included in a prospective observational study. Diagnoses were made after clinical and neuropsychological examination, and neuroimaging and cerebral spinal fluid results were taken into account. Baseline characteristics and the scores on the Mini-Mental State Exam (MMSE), frontal assessment battery (FAB), Frontal Behavioral Inventory (FBI), and Stereotypy Rating Inventory (SRI) were compared between the bvFTD and the non-bvFTD group.

Results: Fifty-five (40%) of the patients received a bvFTD diagnosis (33% probable and 7% possible bvFTD). Fifty-one patients (37%) had a psychiatric disorder, including 20 with major depressive disorder. Thirty-one patients received an alternative neurological, including neurodegenerative, diagnosis. MMSE and FAB scores were unspecific for a particular diagnosis. A score above 12 on the positive FBI subscale or a score above 5 on the SRI were indicative of a bvFTD diagnosis.

Conclusion: A broad spectrum of both neurological and psychiatric disorders underlies late onset frontal lobe syndrome, of which bvFTD was the most prevalent diagnosis in our cohort. The commonly used MMSE and the FAB could not successfully distinguish between bvFTD and non-bvFTD, but this could be achieved with the more specific FBI and SRI.
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http://dx.doi.org/10.1016/j.jagp.2015.04.002DOI Listing
October 2015

The prevalence and management of side effects of lithium and anticonvulsants as mood stabilizers in bipolar disorder from a clinical perspective: a review.

Int Clin Psychopharmacol 2013 Nov;28(6):287-96

aDepartment of Psychiatry, GGZ inGeest, VU University Medical Center, Amsterdam bDepartment of Old Age Psychiatry, GGZ Dijk en Duin, Castricum cDimence, Specialized Center Bipolar Disorders, Deventer, The Netherlands dDepartment of Mood Disorders, University Psychiatric Center - Catholic University Leuven, Kortenberg, Belgium.

Side effects are among the most frequent reasons preventing patients from taking their medication. Although the management of side effects is an important issue in clinical practice, particularly in patients with physical comorbidities, research on clinical management of side effects is rather scattered. The aim of this article was to provide an overview on the prevalence and management of various side effects of mood-stabilizing drugs. In December 2012, we carried out a PubMed search for publications reporting side effects in patients with bipolar disorder. Naturalistic studies describing the prevalence of side effects in treatment with mood stabilizers are sparse. We describe the prevalence of neurological, gastrointestinal, metabolic, thyroid, dermatological, nephrogenic, cognitive, sexual, hematological, hepatogenic, and teratogenic side effects of lithium, valproate, carbamazepine, and lamotrigine and discuss their clinical management. There are specific strategies that aim at reducing side effects, but, to date, studies on the efficacy of these interventions are lacking. With age, the renal elimination and hepatic metabolism of drugs reduce and comedication and somatic comorbidity increase, making elderly patients particularly susceptible to side effects. Most side effects can be managed by striving for the lowest possible dose without losing efficacy by lowering the dose below the therapeutic window. Specific measurements to limit certain side effects are available and may ameliorate treatment adherence.
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http://dx.doi.org/10.1097/YIC.0b013e32836435e2DOI Listing
November 2013

Building a new paradigm for the early recognition of behavioral variant frontotemporal dementia: Late Onset Frontal Lobe Syndrome study.

Am J Geriatr Psychiatry 2014 Jul 25;22(7):735-40. Epub 2013 Jun 25.

Alzheimer Centre and Department of Neurology, VU University Medical Centre, Amsterdam, the Netherlands.

Objective: To describe the aims and design of the ongoing Late Onset Frontal Lobe Syndrome study (LOF study), a study on the spectrum of neurodegenerative and psychiatric etiologies causing behavioral changes in later life, and on the role of magnetic resonance imaging (MRI), [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET), and cerebrospinal fluid (CSF) biomarkers in predicting and identifying the different underlying pathologies with a special focus on the behavioral variant of frontotemporal dementia.

Methods: The LOF study is an observational cross-sectional and prospective follow-up study. Patients aged 45-75 years with a frontal behavioral change consisting of apathy, disinhibition, or compulsive/stereotypical behavior were included (April 2011-2013). Patients underwent a multidisciplinary assessment by a neurologist and psychiatrist and MRI, CSF, and PET measurements at inclusion and after 2 years of follow-up.

Results: The diagnostic added value of MRI, PET, and CSF results and their predictive value will be measured after 2 years of follow-up.

Conclusion: This is the first large-scale prospective follow-up study of patients with late-onset behavioral disorders.
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http://dx.doi.org/10.1016/j.jagp.2013.02.002DOI Listing
July 2014

Cognitive decline in elderly bipolar disorder patients: a follow-up study.

Bipolar Disord 2012 Nov 21;14(7):749-55. Epub 2012 Sep 21.

GGZ inGeest, Amsterdam, The Netherlands.

Objective: Older individuals with bipolar disorder may exhibit greater cognitive decline over time compared to mentally healthy elderly individuals. We aimed to investigate neurocognitive performance in bipolar disorder over a period of two years.

Methods: A comprehensive neuropsychological test battery was applied at baseline and two years later to 65 euthymic elderly outpatients with bipolar disorder (mean age = 68.35, range: 60-90 years) and to a demographically comparable sample of 42 healthy elderly controls. A general linear model was used to measure changes over time for the two groups. The impact of baseline illness characteristics on intra-individual change in neurocognitive performance within the bipolar group was studied by using logistic regression analysis.

Results: At baseline and at follow up, bipolar disorder patients performed worse on all neurocognitive measures compared to the healthy elderly group. However, there was no significant group-by-time interaction between the bipolar disorder patients and the comparison group.

Conclusions: Although older bipolar disorder patients have worse cognitive function than normal controls, they did not have greater cognitive decline over a period of two years.
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http://dx.doi.org/10.1111/bdi.12000DOI Listing
November 2012

Cognitive impairment in late life schizophrenia and bipolar I disorder.

Int J Geriatr Psychiatry 2013 Jan 12;28(1):82-90. Epub 2012 Mar 12.

GGZ inGeest, VU University Medical Center, Amsterdam, The Netherlands.

Objective: Evidence in younger populations suggests quantitative but not categorical differences in cognitive impairments between schizophrenia and bipolar disorder. It is uncertain whether a similar distinction applies to patients in later life.

Methods: We compared the cognitive abilities of older, community-living schizophrenia patients, controlling for their state of symptomatic remission, with those of older euthymic patients with bipolar I disorder. The study included 67 patients with schizophrenia (20 in symptomatic remission, 47 not in symptomatic remission; mean age 68 years) and 74 euthymic bipolar I patients (mean age 70 years), who were compared using analysis of covariance on clinical and neuropsychological variables (e.g., attention/working memory, verbal memory, executive function and verbal fluency) and contrasted with 69 healthy controls.

Results: Remitted (SR) and non-remitted (SN) schizophrenia patients and bipolar I (BP) patients were impaired relative to healthy controls, with mostly large effect sizes for verbal memory (Cohen's d: SR 1.34, SN 1.48, BP 1.09), executive function (Cohen's d: SR 0.87, SN 1.29, BP 0.71) and verbal fluency (Cohen's d: SR 1.09, SN 1.25, BP 0.88), but smaller effect sizes for the domain of attention/working memory (Cohen's d: SR 0.26, SN 0.18, BP 0.52). Differences in cognitive performance between the remitted schizophrenia patients and the bipolar I patients were not significant.

Conclusions: In both older patients with schizophrenia and with bipolar disorder, serious and pervasive cognitive deficits can be demonstrated. Trait-related cognitive deficits in schizophrenia and bipolar disorder may share major phenotypic similarity in later life.
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http://dx.doi.org/10.1002/gps.3793DOI Listing
January 2013
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