[Neural networks in late life depression]. / Neurale netwerken bij depressie op latere leeftijd.

BACKGROUND: Major depression is associated with activity and connectivity changes of multiple neural networks that correlate to the clinical manifestation. The chronic and recurrent course of late -life depression (LLD) suggests a possible role for structural brain changes in these network alterations. Recent evolutions in brain imaging permits to investigate neural networks in LLD on multiple levels. AIM: To provide an overview of the structural, functional and molecular changes seen in imaging studies of LLD. METHOD: Narrative review. RESULTS: The neurobiology of LLD includes specific grey and white matter changes and dysfunctions in three neural networks that can be correlated to LLD symptomatology. Some patients show signs of accelerated or pathological brain aging. These provide a possible neurobiological underpinning for poor treatment response. CONCLUSION: Imaging studies show various neurobiological changes that contribute to neural network dysfunction in LLD.

PRECISION: the Belgian molecular profiling program of metastatic cancer for clinical decision and treatment assignment.

PRECISION is an initiative from the Belgian Society of Medical Oncology (BSMO) in collaboration with several stakeholders, encompassing four programs that aim to boost genomic and clinical knowledge with the ultimate goal to offer patients with metastatic solid tumors molecularly guided treatments. The PRECISION 1 study has led to the creation of a clinico-genomic database. The Belgian Approach for Local Laboratory Extensive Tumor Testing (BALLETT) and GeNeo studies will increase the number of patients with advanced cancer that have comprehensive genotyping of their cancer. The PRECISION 2 project consists of investigator-initiated phase II studies aiming to provide access to a targeted drug for patients whose tumors harbor actionable mutations in case the matched drug is not available through reimbursement or clinical trials in Belgium.

A longitudinal study of the association between basal ganglia volumes and psychomotor symptoms in subjects with late life depression undergoing ECT.

Psychomotor dysfunction (PMD) is a core element and key contributor to disability in late life depression (LLD), which responds well to electroconvulsive therapy (ECT). The neurobiology of PMD and its response to ECT are not well understood. We hypothesized that PMD in LLD is associated with lower striatal volume, and that striatal volume increase following ECT explains PMD improvement. We analyzed data from a two-center prospective cohort study of 110 LLD subjects (>55 years) receiving ECT. Brain MRI and assessment of mood, cognition, and PMD was performed 1 week before, 1 week after, and 6 months after ECT. Volumetry of the caudate nucleus, putamen, globus pallidus, and nucleus accumbens was derived from automatically segmented brain MRIs using Freesurfer®. Linear multiple regression analyses were used to study associations between basal ganglia volume and PMD. Brain MRI was available for 66 patients 1 week post ECT and in 22 patients also six months post ECT. Baseline PMD was associated with a smaller left caudate nucleus. One week after ECT, PMD improved and volume increases were detected bilaterally in the caudate nucleus and putamen, and in the right nucleus accumbens. Improved PMD after ECT did not relate to the significant volume increases in these structures, but was predicted by a nonsignificant volume change in the right globus pallidus. No volume differences were detected 6 months after ECT, compared to baseline. Although PMD is related to lower striatal volume in LLD, ECT-induced increase of striatal volume does not explain PMD improvement.

A European Academy of Neurology guideline on medical management issues in dementia.

BACKGROUND AND PURPOSE: Dementia is one of the most common disorders and is associated with increased morbidity, mortality and decreased quality of life. The present guideline addresses important medical management issues including systematic medical follow-up, vascular risk factors in dementia, pain in dementia, use of antipsychotics in dementia and epilepsy in dementia. METHODS: A systematic review of the literature was carried out. Based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework, we developed a guideline. Where recommendations based on GRADE were not possible, a good practice statement was formulated. RESULTS: Systematic management of vascular risk factors should be performed in patients with mild to moderate dementia as prevention of cerebrovascular pathology may impact on the progression of dementia (Good Practice statement). Individuals with dementia (without previous stroke) and atrial fibrillation should be treated with anticoagulants (weak recommendation). Discontinuation of opioids should be considered in certain individuals with dementia (e.g. for whom there are no signs or symptoms of pain or no clear indication, or suspicion of side effects; Good Practice statement). Behavioral symptoms in persons with dementia should not be treated with mild analgesics (weak recommendation). In all patients with dementia treated with opioids, assessment of the individual risk-benefit ratio should be performed at regular intervals. Regular, preplanned medical follow-up should be offered to all patients with dementia. The setting will depend on the organization of local health services and should, as a minimum, include general practitioners with easy access to dementia specialists (Good Practice statement). Individuals with dementia and agitation and/or aggression should be treated with atypical antipsychotics only after all non-pharmacological measures have been proven to be without benefit or in the case of severe self-harm or harm to others (weak recommendation). Antipsychotics should be discontinued after cessation of behavioral disturbances and in patients in whom there are side effects (Good Practice statement). For treatment of epilepsy in individuals with dementia, newer anticonvulsants should be considered as first-line therapy (Good Practice statement). CONCLUSION: This GRADE-based guideline offers recommendations on several important medical issues in patients with dementia, and thus adds important guidance for clinicians. For some issues, very little or no evidence was identified, highlighting the importance of further studies within these areas.

Association between hippocampal volume change and change in memory following electroconvulsive therapy in late-life depression.

OBJECTIVE: Electroconvulsive therapy (ECT)-induced hippocampal volume change (HVC) has been repeatedly described in recent years. The similar time course of HVC and ECT-related cognitive effects suggest a relation, that is to date, understudied. This study investigates whether HVC following ECT predicts the change in memory performance six months after the end of the ECT treatment. METHODS: Hippocampal volume (HV) was measured via high-resolution 3D T1-weighted images in 88 patients with late-life depression, within 1 week before and after ECT. Memory performance was assessed before and six months after ECT. Multiple linear regression was used to examine whether change in memory performance could be predicted based on ECT-induced changes in HV. RESULTS: Larger right absolute HVC predicts less pronounced improvement on the VAT (visual memory) in the whole sample. For the 8-Word Test (verbal memory), Category Fluency Test (semantic memory), and MMSE, the effect is only present in patients who switched from right unilateral to bitemporal stimulation after six ECT sessions. Absolute HVC in the left hemisphere was not significantly related to cognitive change. CONCLUSION: A larger absolute change in right HV during ECT is associated with less improvement in memory performance up to 6 months post-ECT.

Long-term neurocognitive functioning after electroconvulsive therapy in patients with late-life depression.

OBJECTIVE: There is ongoing concern about the possible negative impact of ECT on neurocognitive functioning in older patients. In this study, we aimed to characterize the long-term cognitive effects of ECT in patients with late-life depression, using an extensive neuropsychological battery. METHODS: A total of 110 patients aged 55 years and older with unipolar depression, referred for ECT were included. The neuropsychological test battery was assessed prior to ECT and 6 months after the last ECT session. RESULTS: There were no statistically significant group-level changes from baseline to 6 months post-ECT in any of the neuropsychological measurements. Individual differences in cognitive performance were detected using the Reliable Change Index. CONCLUSION: Patients with late-life depression do not show deleterious cognitive effects 6 months following an ECT index course, although there are considerable differences at an individual level. Clinicians should not hesitate to prescribe ECT in older patients, as most of these patients will tolerate the treatment course and a small group will even experience a cognitive enhancement. However, clinicians should be aware that a small group of patients can experience cognitive side-effects. Further study is needed to predict which patients have a higher risk of developing cognitive side-effects.

The course of apathy in late-life depression treated with electroconvulsive therapy; a prospective cohort study.

OBJECTIVES: Apathy, a lack of motivation, is frequently seen in older individuals, with and without depression, with substantial impact on quality of life. This prospective cohort study of patients with severe late-life depression treated with electroconvulsive therapy (ECT) aims to study the course of apathy and the predictive value of vascular burden and in particular white matter hyperintensities on apathy course. METHODS: Information on apathy (defined by a score of >13 on the Apathy Scale), depression severity, vascular burden, and other putative confounders was collected in at 2 psychiatric hospitals on patients with late-life depression (aged 55 to 87 years, N = 73). MRI data on white matter hyperintensities were available in 52 patients. Possible risk factors for apathy post-ECT were determined using regression analyses. RESULTS: After treatment with ECT, 52.0% (26/50) of the depression remitters still suffered from clinically relevant apathy symptoms. In the entire cohort, more patients remained apathetic (58.9%) than depressed (31.5%). Presence of apathy post-ECT was not associated with higher age, use of benzodiazepines, or severity of apathy and depression at baseline. Less response in depressive symptomatology after ECT predicted post-treatment apathy. The presence of vascular disease, diabetes mellitus and smoking, and white matter hyperintensities in the brain was not associated with post-treatment apathy. CONCLUSIONS: Apathy may perpetuate in individual patients, despite remission of depressive symptoms. In this cohort of patients with late-life depression, post-ECT apathy is not associated with white matter hyperintensities.

[ResPECT - a decade of Flemish-Dutch ECT research]. / ResPECT ­ een decennium Vlaams-Nederlands onderzoek naar elektroconvulsietherapie.

BACKGROUND: There is increasing clinical and scientific interest in electroconvulsive therapy (ECT). AIM: To provide an overview of the main research findings of the Flemish-Dutch research consortium ResPECT. METHOD: We report on our review of the relevant literature. RESULTS: Our studies confirm that ECT is one of the most efficient treatments for depression in later life and for depression with psychotic features. Older people with age-related brain pathology can respond well to ECT. It is still preferable to apply a standard pulse-width because this increases the efficacy of the treatment and minimises the cognitive impact. Even vulnerable older people can react favourably to ECT. CONCLUSION: Recent findings of the ResPECT consortium are providing new insights that are applicable in daily clinical practice. Research into mechanisms of action can also increase our understanding of the pathophysiology of severe depression.

[Therapy for elderly family members and couples: concerning the viability of relationships in later life, the role reversal and 'finishing' amicably]. / Familie- en paartherapie bij ouderen: over leefbaarheid, rolomkering en finishing well.

BACKGROUND: Research shows that in most countries the number of elderly persons is increasing and that close relationships in late life are playing a more important role. Therefore, it is surprising that there have been so few publications about family therapy for the elderly. AIM: To formulate some guidelines for psychotherapy for family members in their later years and to make suggestions regarding further research. METHOD: We summarise the existing literature and focus on important themes about working with the elderly, supplementing major issues with our own clinical experience. RESULTS: Family therapy with the elderly differs from therapy for younger adults in some respects; for instance, the emphasis in the case of the elderly is more on strengthening the viability of a long/standing relationship. The reversal of roles that often accompanies the ageing process and leads to increasing dependency is another factor that affects the elderly more than the younger adults. If the last stage of life is to finish calmly and amicably, therapists need to tackle any tensions or injustices that patients have experienced in the course of their relationships. CONCLUSION: Psychotherapy for the elderly needs to provide clients with constant opportunities for reflection and should initiate discussions about partners' experiences of tensions and injustices in their earlier relationship. However, the increasing number of elderly persons means that more empirical research needs to be done into systematic psychotherapy.

[Obsessive-compulsive behaviour in two patients with right temporal variant frontotemporal dementia]. / Obsessief-compulsief gedrag bij de rechter temporale variant van frontotemporale dementie.

There is often a long delay before right temporal variant of frontotemporal dementia (rtlv) is correctly diagnosed. The late diagnosis is usually due to the occurrence of psychiatric symptoms as the first signs of disease and to the relatively young age of the patient. We report two patients who were initially treated for obsessive-compulsive disorder but were later diagnosed as having rtlv.

[Neurocognitive disorders in DSM-5: a critical review]. / Neurocognitieve stoornissen in de DSM-5: een kritische bespreking.

BACKGROUND: The APA published the DSM-5 in May, 2013. When compared to dsm-iv, the latest edition incorporates many changes, some relating to neurocognitive disorders. AIM: To review critically the new DSM-5 alterations and adjustments relating to neurocognitive disorders. METHOD: We compared the relevant chapters in DSM-IV-TR and DSM-5 and we searched the literature for articles involving discussions about cognitive disorders in DSM-5. RESULTS: With regard to differential diagnosis of neurocognitive disorders, DSM-5 has more in common with current clinical practice than does the DSM-IV. DSM-5 names ten etiological subtypes for which the diagnostic criteria are based on recent scientific research. However, some researchers and clinicians have reservations about using the term 'major neurocognitive disorder' instead of 'dementia', and are reluctant to make a distinction between 'mild' and 'major' cognitive disorders. CONCLUSION: The alterations and adjustments that appear in DSM-5 in relation to neurocognitive disorders may well mean progress for clinicians and researchers but they will inevitably require greater investment.

[Confusional arousal: a rare cause of self-injurious behaviour]. / Confusional arousal als zeldzame oorzaak van zelfverwonding.

Non-rapid eye movement (NREM) arousal sleep disorders (confusional arousal, somnambulism and sleep terror) are self-limiting and temporary phenomena which cannot be attributed to medical or psychiatric factors. However, very occasionally they can be the cause of unintentional injury to self or others. We describe the case of an 18-year-old who engaged in self-injurious behaviour while asleep. This behaviour could be attributed to confusional arousal.

[The impact of attachment on behavioral and psychological symptoms in dementia]. / Gehechtheid als beïnvloedende factor van gedrags- en psychologische symptomen bij dementie.

Contemporary research has increasingly acknowledged the importance of attachment on stress-related processes in ageing. Congruent with this, there has been much research on attachment in older adults over the past three decades. In this article, the main findings of this research are summarized, with a focus on attachment and dementia. Results show that, in general, the number of attachment figures decreases in old age. Moreover, their identity changes as adult children, deceased loved ones and God become more prominent. With relation to the quality of attachment, anxiety in close relations appears to diminish as people age, while attachment avoidance remains relatively stable. Individuals with high levels of attachment security also report greater well-being and a more positive attitude towards ageing compared to persons with low levels of attachment security. Furthermore, individuals characterized by insecure attachment show more behavioral and psychological problems in dementia. Also, caregiver burden, depression, as well as the quality of care giving and future caregiver commitment differ depending on the quality of attachment of the caregiver. There is preliminary evidence for the efficacy of attachment-based interventions in dementia. Finally, there is a need for greater methodological uniformity and the use of measures that are validated for an older population.

[The use of clozapine and levodopa for the treatment of persistent visual hallucinations and parkinsonism in Lewy body dementia]. / Clozapine en levodopa als behandeling van persisterende visuele hallucinaties en motorische symptomen bij dementie met lewylichaampjes.

Visual hallucinations (VH) are sometimes difficult to treat in patients with Lewy body dementia (LBD). We describe the concurrent use of clozapine and levodopa for the treatment of persistent VH and parkinsonism in a patient with LBD and severely increased sensitivity to antipsychotics.

[Imaging of language and communication in dementia]. / Beeldvorming van taal en communicatie bij dementie.

BACKGROUND: Social interaction in patients with dementia is compromised by language problems and impairment of other cognitive domains involved in communication. AIM: To describe language and communication problems in patients with dementia and to provide insight into the neurological basis of these problems. METHOD: Our study is based on some of our own research findings and on relevant literature concerning the imaging of language and communication in patients with Alzheimer's disease and frontotemporal degeneration. RESULTS: Imaging revealed that the clinical expression of communicative disorders in patients with cortical neurodegeneration depends on regional brain atrophy and a possible functional reorganisation triggered by neuropathological changes. CONCLUSION: Brain imaging increases our knowledge about the pathogenesis of communicative disorders in dementia.

Alzheimer dementia caused by a novel mutation located in the APP C-terminal intracytosolic fragment.

Since the first report showing that Alzheimer disease (AD) might be caused by mutations in the amyloid precursor protein gene (APP), 20 different missense mutations have been reported. The majority of early-onset AD mutations alter processing of APP increasing relative levels of Abeta42 peptide, either by increasing Abeta42 or decreasing Abeta40 peptide levels or both. In a diagnostic setting using direct sequence analysis, we identified in one patient with familial early-onset AD a novel mutation in APP (c.2172G>C), predicting a K724N substitution in the intracytosolic fragment. The mutation is located downstream of the epsilon-cleavage site of APP and is the furthermost C-terminal mutation reported to date. In vitro expression of APP K724N cDNA showed an increase in Abeta42 and a decrease in Abeta40 levels resulting in a near three-fold increase of the Abeta42/Abeta40 ratio. Further, in vivo amyloid positron emission tomography (PET) imaging revealed significantly increased cortical amyloid deposits, supporting that in human this novel APP mutation is likely causing disease.

Attentional responses to unattended stimuli in human parietal cortex.

Right-sided parietal lesions lead to lateralized attentional deficits which are most prominent with bilateral stimulation. We determined how an irrelevant stimulus in the unattended hemifield alters attentional responses in parietal cortex during unilateral orienting. A trial consisted of a central spatial cue, a delay and a test phase during which a grating was presented at 9 degrees eccentricity. Subjects had to discriminate the orientation of the grating. The unattended hemifield was either empty or contained a second, irrelevant grating. We carried out a series of functional MRI (fMRI) studies in 35 healthy volunteers (13 men and 22 women, aged between 19 and 30 years) as well as a behavioural and structural lesion mapping study in 17 right-hemispheric lesion patients, 11 of whom had neglect. In the patients with but not in those without neglect, the addition of a distractor in the unattended hemifield significantly impaired performance if attention was directed contralesionally but not if it was directed ipsilesionally. In the healthy volunteers, we discerned two functionally distinct areas along the posterior-anterior axis of the intraparietal sulcus (IPS). The posterior, descending IPS segment in both hemispheres showed attentional enhancement of responses during contralateral attentional orienting and was unaffected by the presence of an irrelevant stimulus in the ignored hemifield. In contrast, the right-sided horizontal IPS segment showed a strong attentional response when subjects oriented to a stimulus in the relevant hemifield and an irrelevant stimulus was simultaneously present in the ignored hemifield, compared with unilateral stimulation. This effect was independent of the direction of attention. The symmetrical left-sided horizontal IPS segment showed the highest responses under the same circumstances, in combination with a contralateral bias during unilateral stimulation conditions. None of the six patients without neglect had a lesion of the horizontal IPS segment. In four of the 11 neglect patients, the lesion overlapped with the horizontal IPS activity cluster and lay in close proximity to it in another four. The remaining three patients had a lesion at a distance from the parietal cortex. Our findings reconcile the role of the IPS in endogenous attentional control with the clinically significant interaction between direction of attention and bilateral stimulation in right parietal lesion patients. Functional imaging in neglect patients will be necessary to assess IPS function in those cases where the structural lesion spares the middle IPS segment.