Annemiek Dols

• MD PhD
• psychiatrist and researcher at University Medical Center Utrecht

Purpose of Review Findings from the Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) project, including sociodemographic and clinical information from older age bipolar disorder (OABD) and healthy participants around the globe (approximately N = 5000) were reviewed. Data was collected in multiple waves to create a large integrated...

Objectives Shared decision making is used for reaching medical decisions, also in the management of major depressive disorder (MDD). Electroconvulsive therapy (ECT) is an effective treatment option for patients with severe MDD. However, the decision-making process, specifically the exchange of evidence-based information, for ECT may be hampered by...

Tijd Ik droomde, dat ik langzaam leefde… langzamer dan de oudste steen. Het was verschrikkelijk: om mij heen schoot alles op, schokte of beefde, wat stil lijkt. 'k Zag de drang waarmee de bomen zich uit de aarde wrongen terwijl ze hees en hortend zongen; terwijl de jaargetijden vlogen verkleurende als regenbogen… Ik zag de tremor van de zee, zijn z...

Background Patients with behavioral variant of frontotemporal dementia (bvFTD) initially may only show behavioral and/or cognitive symptoms that overlap with other neurological and psychiatric disorders. The diagnostic accuracy is dependent on progressive symptoms worsening and frontotemporal abnormalities on neuroimaging findings. Predictive bioma...

Major depressive disorder (MDD) is a complex psychiatric disorder that affects the lives of hundreds of millions of individuals around the globe. Even today, researchers debate if morphological alterations in the brain are linked to MDD, likely due to the heterogeneity of this disorder. The application of deep learning tools to neuroimaging data, c...

Electroconvulsive therapy (ECT) is an effective treatment for depression but is often associated with cognitive side effects. In patients, ECT-induced electric field (E-field) strength across brain regions varies significantly due to anatomical differences, which may explain individual differences in cognitive side effects. We examined the relation...

Introduction Unipolar and bipolar mood disorders in older adults are accompanied by cognitive impairment, including executive dysfunction, with a severe impact on daily life. Up and till now, strategies to improve cognitive functioning in late-life mood disorders (LLMD) are sparse. Therefore, we aimed to assess the efficacy of adaptive, computerize...

BACKGROUND Novel therapies are crucial for patients with major depressive disorder (MDD) since more than 33% of patients do not respond to first-line treatments. A promising novel treatment strategy is an intensive five-day course of Personalised functional connectivity guided Accelerated intermittent Theta burst stimulation (PAiT), modelled after...

Reliable predictors for electroconvulsive therapy (ECT) effectiveness would allow a more precise and personalized approach for the treatment of major depressive disorder (MDD). Prediction models were created using a priori selected clinical variables based on previous meta-analyses. Multivariable linear regression analysis was used, applying backwa...

Background Patients displaying clinical features of behavioural variant of frontotemporal dementia (bvFTD) but lacking both neuroimaging abnormalities and clinical progression are considered to represent the phenocopy syndrome of bvFTD (phFTD). Extensive clinical overlap between early phase bvFTD and phFTD hampers diagnostic distinction. We aimed t...

Background. Depression puts a great burden on both patients, relatives and society as a whole. Electroconvulsive therapy (ECT) is regarded as a safe and effective treatment for severe and chronic depressive episodes, even when other interventions such as psychotherapy or psychopharmacology have failed. Despite its superior efficacy, use of ECT for...

Background Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of...

Objectives The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE‐BD) project pools archival datasets on older age bipolar disorder (OABD). An initial Wave 1 (W1; n = 1369) analysis found both manic and depressive symptoms reduced among older patients. To replicate this finding, we gathered an independent Wave 2 (W2; n = 1232,...

Objects Studies of older age bipolar disorder (OABD) have mostly focused on “younger old” individuals. Little is known about the oldest OABD (OOABD) individuals aged ≥70 years old. The Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE‐BD) project provides an opportunity to evaluate the OOABD group to understand their characteristics...

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitat...

Background The C9orf72‐repeat expansion (C9RE) is the most prevalent genetic cause of frontotemporal dementia (FTD). Since its discovery, studies have shown that both family history (FH) and medical history of FTD patients carrying a C9RE are often not only positive for dementia, but also for psychiatric disorders and late‐onset behavioural change....

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 depr...

Electroconvulsive therapy (ECT) is an effective therapy for depression, but its cellular effects on the human brain remain elusive. In rodents, electroconvulsive shocks increase proliferation and the expression of plasticity markers in the hippocampal dentate gyrus (DG), suggesting increased neurogenesis. Furthermore, MRI studies in depressed patie...

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimu...

Objective The current literature on employment in older adults with bipolar disorder (OABD) is limited. Using the Global Aging and Geriatric Experiments in Bipolar Disorder Database (GAGE‐BD), we examined the relationship of occupational status in OABD to other demographic and clinical characteristics. Methods Seven hundred and thirty‐eight partic...

Background Two established staging models outline the longitudinal progression in bipolar disorder (BD) based on episode recurrence or inter-episodic functioning. However, underlying neurobiological mechanisms and corresponding biomarkers remain unexplored. This study aimed to investigate if global and (sub)cortical brain structures, along with bra...

Background: Major depressive disorder [MDD] is expected to be the leading cause of overall global burden of disease by the year 2030 [WHO]. Non-response to first line pharmacological and psychotherapeutic antidepressive treatments is substantial, with treatment-resistant depression [TRD] affecting approximately one third of depressed patients. The...

Background Behavioural symptoms and frontotemporal hypometabolism overlap between behavioural variant of frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD), hampering diagnostic distinction. Voxel-wise comparisons of brain metabolism might identify specific frontotemporal-(hypo)metabolic regions between bvFTD and PPD. We invest...

Background: Electroconvulsive therapy (ECT) is the most effective intervention for patients with treatment resistant depression. A clinical decision support tool could guide patient selection to improve the overall response rate and avoid ineffective treatments with adverse effects. Initial small-scale, monocenter studies indicate that both struct...

Objective: To test whether the cortisol awakening response (CAR) could be a biomarker for cognitive decline during electroconvulsive therapy (ECT). Methods: We studied 50 older patients with depression who were treated with ECT from the MODECT cohort. We used linear regression analyses to examine the association between CAR and cognitive change,...

Objectives: Despite the importance of psychosocial functioning impairment in Bipolar Disorder (BD), its role among Older Adults with BD (OABD) is not well known. The development of guidelines for the assessment of psychosocial functioning helps to facilitate a better understanding of OABD and can lead to better tailored interventions to improve th...

Background: Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depressive disorders. A recent multi-center study found no consistent changes in correlation-based (undirected) resting-state connectivity after ECT. Effective (directed) connectivity may provide more insight into the working mechanism of ECT. Objective...

Purpose of review: Older age bipolar disorder (OABD) refers to patients with bipolar disorder aged 50 years and over. There is a paucity of evidence-based guidelines specific to OABD, but in recent years, several studies have been published on OABD. The current review synthesizes previous literature (up to January 1, 2021) as well as most recent l...

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimu...

A 47-year-old highly educated man without psychiatric history was referred for psychiatric evaluation because of persistent subjective cognitive decline after repeated and extensive diagnostic evaluation in an outpatient memory clinic. The patient developed increasing preoccupation and anxiety with memory complaints and concerns, despite repetitive...

Introduction: Major depressive disorder (MDD) is a common psychiatric disorder. Despite several treatment options, a subgroup of patients will not respond to the commonly used antidepressant treatments and thus express treatment resistance (TRD). TRD can be quantified with the Dutch Measure for Treatment Resistance in Depression (DM-TRD). Electroc...

Background: Depression is reportedly associated with alterations in kynurenine pathway metabolites (kynurenines). Several kynurenines are involved in glutamate signaling, and some have potentially neurotoxic effects while others are considered neuroprotective. The pathway is upregulated under inflammatory conditions, which is associated with depres...

Background: Severe depression is associated with accelerated brain aging. BrainAge gap, the difference between predicted and observed BrainAge was investigated in patients with late-life depression (LLD). We aimed to examine BrainAge gap in LLD and its associations with clinical characteristics indexing LLD chronicity, current severity, prior to e...

Background: By 2030, over 50% of individuals living with bipolar disorder (BD) are expected to be aged ≥ 50 years. However, older age bipolar disorder (OABD) remains understudied. There are limited large-scale prospectively collected data organized in key dimensions capable of addressing several fundamental questions about BD affecting this subgro...

Objectives: Distinguishing sporadic behavioral variant of frontotemporal dementia (bvFTD) from late-onset primary psychiatric disorders (PPD) remains challenging with the lack of robust biomarkers. An early bvFTD misdiagnosis in PPD cases and vice-versa is common. Little is known about diagnostic (in)stability over longer period of time. We invest...

Objective: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and...

Electroconvulsive therapy (ECT) is an effective therapy for depression, but its cellular effects on the human brain remain elusive. In rodents, electroconvulsive shocks increase proliferation and the expression of plasticity markers in the hippocampal dentate gyrus (DG), suggesting increased neurogenesis. Furthermore, MRI studies in depressed patie...

Distinguishing the behavioural variant of Frontotemporal Dementia (bvFTD) from late‐onset primary psychiatric diseases (PPD) remains challenging with the lack of robust biomarkers for either disorder. Optimal duration of follow‐up of potential FTD cases remains elusive. Our aim was to determine whether a follow up duration of 5 years has added valu...

ECT is proposed to exert a therapeutic effect on WM microstructure, but the limited power of previous studies made it difficult to highlight consistent patterns of change in diffusion metrics. We initiated a multicenter analysis and sought to address whether changes in WM microstructure occur following ECT. Diffusion tensor imaging (DTI) data (n =...

Background The COVID-19 pandemic gives us the unique opportunity to study the course of psychiatric symptoms and resilience in older adults with bipolar disorder (OABD) whilst experiencing a collective long lasting stressor. The aim of this study was to investigate the course of depressive, manic and anxiety symptoms in OABD during the first six mo...

Background: Because the behavioral variant of frontotemporal dementia (bvFTD) shows major clinical overlap with primary psychiatric disorders (PPD) that affect similar neuroanatomical circuits, a common genetic vulnerability between FTD and PPD was hypothesized. Aims: We studied whether PPD are more prevalent in families of patients with sporadic...

Objectives: The distinction between bipolar I disorder (BD-I) and bipolar II disorder (BD-II) has been a topic of long-lasting debate. This study examined differences between BD-I and BD-II in a large, global sample of OABD, focusing on general functioning, cognition and somatic burden as these domains are often affected in OABD. Methods: Cross-...

Objectives: Late-onset bipolar disorder (LOBD) represents a significant subgroup of bipolar disorder (BD). However, knowledge for this group is mostly extrapolated from small studies in subjects with early/mixed age of illness onset. In this global sample of older adults with BD (OABD: ≥50 years old) we aim to characterize the sociodemographic and...

Objective Harmonizing different depression severity scales often requires creation of categorical variables that may decrease the sensitivity of the measure. Our aim was to compare the associations between categorical and continuous and harmonized measures of depression and global functioning in a large dataset of older age patients with bipolar di...

Objectives: The validity and applicability of two existing staging models reflecting illness progression have been studied in bipolar disorder (BD) in adults, but not in older adult populations. Staging model A is primarily defined by the number and recurrence of mood episodes, model B is defined by the level of inter-episodic functioning. This st...

Introduction Both older age bipolar disorder (OABD) and late life depression (LLD) have been associated with cognitive dysfunction. It is unclear how cognitive functioning differs between these disorders and what the influence of current depressive symptoms is. Methods We compared OABD (n = 148), LLD (n = 378) and healthy controls (HC) (n = 132) o...

Background: Adequate detection of symptoms and disease progression in behavioural variant frontotemporal dementia (bvFTD) is complex. Dementia cohorts usually utilize cognitive and functional measures, which fail to detect dominant behavioural and social cognitive deficits in bvFTD. Moreover, since patients typically have a loss of insight, caregi...

ECT is proposed to exert a therapeutic effect on WM microstructure, but the limited power of previous studies made it difficult to highlight consistent patterns of change in diffusion metrics. We initiated a multicenter analysis and sought to address whether changes in WM microstructure occur following ECT. Diffusion tensor imaging (DTI) data (n =...

Introduction Electroconvulsive therapy (ECT) is proposed to exert an effect on white matter (WM) microstructure, but the limited power of previous studies made it difficult to highlight consistent patterns of change in diffusion metrics. Objectives We initiated a multi-site mega-analysis and sought to address whether changes in WM microstructure o...

Introduction Introduction : Residual depressive symptoms are common after a successful acute treatment of late-life depression (LLD), and their presence predicts increased risk of relapse. While electroconvulsive therapy (ECT) is the most effective treatment for LLD, little is known about which particular symptoms remain and impact long-term outcom...

Background: Developing treatments for cognitive impairment is key to improving the functioning of people with mood disorders. Neuroimaging may assist in identifying brain-based efficacy markers. This systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force examines the evidence from neu...

Objective: Electroconvulsive therapy (ECT) is a safe and effective treatment, especially in psychotic late-life depression (LLD). However, it is not yet clear whether the greater efficacy seen in psychotic LLD is because of a shorter index episode duration. The first aim of this study was to substantiate the superior ECT remission rates in patients...

Background Cognitive side-effects are an important reason for the limited use of electroconvulsive therapy (ECT). Cognitive side-effects are heterogeneous and occur frequently in older persons. To date, insight into these side-effects is hampered due to inconsistencies in study designs and small sample sizes. Among all cognitive side-effects, confu...

Objectives: There is limited information on the characteristics of older adults with bipolar disorder (OABD) treated with lithium, along with safety concerns about its use by older adults. The aim of the present study is to describe the demographic and clinical characteristics of OABD receiving lithium therapy, using data from the Global Aging & G...

The risk of relapse following successful acute-phase treatment of late-life depression (LLD), including electroconvulsive therapy (ECT), is substantial. In order to improve reliable prediction of individuals' risk of relapse, we assessed the association between individual residual symptoms following a successful acute course of ECT for LLD and rela...

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders based on brain patterns. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, w...

Objectives: Antipsychotic drugs (APS) are widely used to treat patients with bipolar disorder (BD), but there is limited information in older-age bipolar disorder (OABD). This analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated characteristics of OABD patients prescribed APS vs. those not prescr...

Objective Electroconvulsive therapy (ECT) is the most effective treatment for late-life depression (LLD). Research addressing long-term outcome following an acute course of ECT for LLD is limited. We aimed to describe relapse, cognitive impairment and survival five years after a treatment with ECT for severe LLD, and assess the association of clini...

Objective Some individuals with bipolar disorder (BD) experience manic and depressive symptoms concurrently, but data are limited on symptom mixity in older-age bipolar disorder (OABD). Using the Global Aging & Geriatric Experiments in Bipolar Disorder Database, we characterized mixity in OABD and associations with everyday function. Methods The s...

Een grote groep mensen met een bipolaire stoornis stopt uit eigen beweging met medicatie of gebruikt de medicijnen nooit. Deze patiënten zijn vaak niet in zorg binnen de ggz, maar mogelijk wel bij de huisarts. Het BI-zonder-onderzoek moet meer inzicht geven in het welbevinden van deze groep mensen.

Background: Cognitive impairments are an emerging treatment target in mood disorders but currently there are no evidence-based pro-cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provid...

Objectives We aim to characterize the cognitive performance in euthymic older adults with bipolar disorder (OABD) through a comprehensive neuropsychological assessment to obtain a detailed neuropsychological profile. Methods We conducted a systematic search in MEDLINE/Pubmed, Cochrane, and PsycInfo databases. Original studies assessing cognitive f...

Objective Previous research showed impairments in non-affective cognition, affective cognition, and social functioning in adult patients with bipolar disorder (BD). Only 37% of adult BD patients recovers in social functioning, and both aspects of cognition are important constructs of influence. The role of affective cognition in older age bipolar d...

Objectives : To compare the prevalence of physical morbidities among men and women with older adult bipolar disorder (OABD), and men with and without OABD. Methods : Cross-sectional analysis of the collaborative Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) database and non-OABD data from the Health In Men Study. OABD defined...