Depressive Symptoms in Older Adults via Multimodal Markers on Magnetic Resonance Imaging: A Literature Review.

Depressive symptoms the most prevalent clinical condition in the field of mood disorders in older populations. Depressive symptoms are associated to poorer morbidity and mortality, and is considered a component of frailty and intrinsic capacity. Dementia could overlap with DS in clinical and brain abnormalities. Moreover, there are sex-differences in the field of Neuro- and Gero-science. To date, no review has addressed the neuro-anatomical basis of DS in older adults using magnetic resonance imaging (MRI), neither has investigated the discrimination of dementia nor sex-differences. This narrative review investigated studies about older adults; depressive symptoms evaluation via MRI, and published in English or Spanish over the past 7 years. Moreover, it evaluated dementia discrimination and sex-related differences. The most accurate evidence showed cerebral small vessel disease as a predictor of depressive symptoms worsening. Most studies were cross-sectional, with a coarse dementia screening and sex-unrepresentative samples. Cingulate cortex and hippocampus showed a negative association to depressive symptoms, and Precuneus cortex a positive association; although these inferences require further investigation. Additional research is needed to identify the brain imaging signature of depressive symptoms in older population (if any), and if this would be associated with sex and individuals'level of frailty and intrinsic capacity.

Sex-specifics of ECT outcome.

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 its predictors. METHODS: Clinical data from 20 independent sites participating in the Global ECT-MRI Research Collaboration (GEMRIC) were obtained for analysis, totaling 500 patients with MDD (58.6 % women) with a mean age of 54.8 years. Severity of depression before and after ECT was assessed with validated depression scales. Remission was defined as a HAM-D score of 7 points or below after ECT. Variables associated with remission were selected based on literature (i.e. depression severity at baseline, age, duration of index episode, and presence of psychotic symptoms). RESULTS: Remission rates of ECT were independent of sex, 48.0 % in women and 45.7 % in men (X2(1) = 0.2, p = 0.70). In the logistic regression analyses, a shorter index duration was identified as a sex-specific predictor for ECT outcome in women (X2(1) = 7.05, p = 0.01). The corresponding predictive margins did show overlapping confidence intervals for men and women. CONCLUSION: The evidence provided by our study suggests that ECT as a biological treatment for MDD is equally effective in women and men. A shorter duration of index episode was an additional sex- specific predictor for remission in women. Future research should establish whether the confidence intervals for the corresponding predictive margins are overlapping, as we find, or not.

[Use of antidepressants in unipolar depression in the elderly]. / L'utilisation des antidépresseurs dans l'épisode dépressif caractérisé unipolaire du sujet âgé.

OBJECTIVE: To study the ageing-related pharmacological modifications about major depressive episodes in the elderly and their impact on the efficiency and tolerability of antidepressants. METHODS: Research through Pubmed and the Cochrane Database of Systematic Reviews, using the following keywords "antidepressant" ; "treatment"; "late life depression"; "elderly"; up until July 2021. RESULTS: Antidepressants were found to be more efficient than a placebo in the elderly's response to and remission from major depressive episodes. Some depressive episode subtypes seem to be less responsive to antidepressants, such as depressive episodes of vascular origin, for which treating cardiovascular risk factors by statins, angiotensin receptor blockers or calcium channel blockers seems relevant. Two other depressive episode subtypes were highlighted : post-stroke depressive episodes and those induced by major neurocognitive disorders. Antidepressants showed an efficient response in the first case but not in the second. Even though antidepressants are known to stimulate cognitive performances in animals, as yet there is not sufficient evidence to prove they indeed improve cognitive functions, or reduce the risk of developing a neurocognitive disorder, or decelerate the cognitive decline in major neurocognitive disorders in humans. Ageing creates pharmacodynamical changes that increase older people's vulnerability to the side effects of antidepressants. Moreover, age-related pharmacokinetic modifications can also change every step in a drug's transformation process in the body, which leads to a high probability of having adverse effects. Since most antidepressants are eliminated using the P450 cytochrome system, their dosage must be adapted to changes of the P450 system. Somatic comorbidities can, in themselves, influence the pharmacokinetics of antidepressants. Many antidepressants interact with the P450 cytochrome and the P-GP protein, which puts them at a high risk of drug interactions. There is no proven efficiency difference between antidepressant classes. Some antidepressant adverse effects can be of particular importance in the elderly, like the risk of bleeding, cardiovascular episodes, hyponatremia, falling and fractures, anticholinergic effects, extrapyramidal syndrome, epilepsy, liver disease and death. Selective serotonin reuptake inhibitors have an indication as the first line of treatment, avoiding paroxetine and fluoxetine. Serotonin and norepinephrine re-uptake inhibitors are relevant if the patient presents psychomotor retardation or pain, while keeping in mind to check blood pressure. Tricyclics and monoamine oxidase inhibitors should be avoided because of their anticholinergic effects. Bupropion can be prescribed if the patient has extreme fatigue. Mirtazapine is useful when the patient presents sleep or appetite disturbance. Several molecules can be used in the case of drug-resistant depression, such as associating aripiprazole with small-dosage antidepressants, or electroconvulsive therapy, or repetitive Transcranial Magnetic Stimulation (rTMS). Ketamine and psychostimulants seem to have antidepressant effects, but complementary studies are needed to conclude. CONCLUSIONS: Unipolar major depressive episodes in the elderly are frequent and their medicinal treatment has specific features. Knowing the specificities of antidepressant use in the elderly allows to optimize its efficiency and to limit the risk of inappropriate prescription leading to harmful adverse effects.

[Definition, derogation and application of the professional secrecy within the frame of court ordered cares: A systematic review of the French legal and health literature since 1998]. / Définitions, dérogations et applications du secret professionnel dans le cadre des soins pénalement ordonnées : revue de la littérature médicale et juridique française depuis 1998.

INTRODUCTION: Guaranteed by several legal and deontological dispositions, professional secrecy is an essential aspect of medical care, especially concerning the therapeutic alliance. Since the creation in French law of court-ordered treatment, some information is likely to be shared between actors either from the field of healthcare or of justice. This questions the type of information that can be shared and the variances existing between the different types of court-ordered treatments, which are to be known by the professionals. METHODS: Following the methodology of the French Haute Autorité de Santé, a systematic review of the legal and health literature has been conducted. Different databases such as PubMed, Cairn and Legifrance have been reviewed with the following keywords « secret ¼, « injonction de soins ¼ (court-ordered treatment) and « obligation de soins ¼ (obligation of care). Only the French literature since 1998 has been retained and because it is often less pronounced by the courts, the case of the therapeutic injunction, which represents the third type of court-ordered care, has been excluded. RESULTS: Concerning the court-ordered treatment, on the one hand, the coordinating physician addresses the elements required in the control of measure to the Executive Magistrate. On the other hand, the Executive Magistrate sends a copy of the piece of the procedure to the coordinating physician, who transmits it to the general practitioner. The therapist can derogate from the medical secrecy in some circumstances as said in the law, either through the coordinating physician or the Executive Magistrate. In the case of obligation of care, where there is no coordinating physician, the general practitioner is still submitted to the classical rules of medical secrecy and only has to produce certificates of the follow-up with the patient. DISCUSSION: Some authors have expressed their reservations about these new laws of derogation, especially concerning the blurred lines of the exception to these laws. Others have underlined the astonishing differences between court-ordered treatment and the obligation of care for almost similar clinical situations. CONCLUSION: The rules of shared information must be known by the professionals and stated clearly to the patient at the beginning of treatment. Then, professionals are invited to remain thoughtful concerning the nature of this information. Finally, and as the public hearing of June 2018, promoted by the FFCRIAVS (Fédération Française des Centres Ressources pour les Intervenants auprès des Auteurs de Violences Sexuelles), said, it could be interesting to promote meeting spaces between the different actors of the management of people under court ordered cares, so as to better identify the limits of each one.

[Mood disorders and epilepsy surgery: A review]. / Troubles de l'humeur et chirurgie de l'épilepsie : une revue de la littérature.

AIMS: Historically, there is a strong link between depression and epilepsy. Patients with epilepsy are four to five times more likely to develop a depressive syndrome. It seems that the link between epilepsy and depression is bidirectional. There is little data on mood disorders secondary to epilepsy surgery. The goal of epilepsy surgery is to reduce the number and frequency of attacks, which in turn would allow improvements in mood disorders and cognitive impairment. METHODS: A systematic search of the international literature was performed using the bibliographic search engines PubMed and Embase. The following MESH terms were used: epilepsy surgery AND (depression OR depressive disorder OR mood disorder). We also used the "related articles" of PubMed, bibliography surveys, conference abstracts and Google Scholar to identify additional relevant papers. RESULTS: Of the 130 studies found by the systematic search, 112 are excluded because they did not take into account the mood disorders secondary to epilepsy surgery. Fifteen studies are included in this review of the literature with a case study. Depression is the psychopathological condition that is the most frequently studied. According to several studies, the prevalence of depression is approximately 30% with nearly 70% of cases diagnosed during the first three months following epilepsy surgery. The majority of patients presented depressive symptoms during the first 3 to 12months after epilepsy surgery. In these studies, the risk of developing depression is correlated with the existence of previous depressive elements relative to the epilepsy surgery. A small number of studies reported cases of de novo depression. Studies have shown a correlation between very good to excellent control of epileptic seizures and a persistent improvement of mood disorders. It would seem that depressive symptoms post-surgery are more common when the surgical intervention concerns the temporal lobe and in particular mesial resections. There are only very few cases of maniac episodes. Hamid et al. showed an increased risk of suicide waning after the epilepsy surgery over a period of 5years. CONCLUSION: Mood disorders are common psychiatric comorbidities in epilepsy surgery. The detection, prevention, and treatment of these symptoms in patients eligible for epilepsy surgery pose major challenges for psychiatrists and neurologists, requiring their close collaboration.

[Economic impact of consultation-liaison psychiatry in a French University Hospital Centre]. / Impact économique de la psychiatrie de liaison dans un CHU français.

BACKGROUND: In times of fiscal restraint for health structures, apart from the clinical input, it seems important to discuss the economic impact of liaison psychiatry. There are only a few studies on the economic added value provided by a liaison psychiatry team. In addition to this, only a few psychiatric pathologies are coded as they should be, hence we make the assumption of an additional development provided by a specialised team. METHODS: Over a short period of 4months, in three departments of the Toulouse University Hospital Centre, the added value to the general pricing system of liaison psychiatry was studied. The population was represented by all the consecutive requests for consultations from patients over 18years old, men and women, hospitalised at that time. These three departments frequently request consultations with the psychiatry liaison team. They set a diagnostic, and if this is associated with a higher Homogeneous Group of Patients (HGP), it provides added value. RESULTS: Fifty-two patients benefited from a psychiatric consultation over 4months. The results highlight a development of € 8630.43 for the traumatology department, € 3325.03 for the internal medicine department, and € 513.61 for the haematology department over the study period. The overall development over this period was € 12,469.07. CONCLUSION: To our knowledge, this approach is one of the first in France to highlight an economic impact of the intervention of liaison psychiatry in the claiming departments.

Adjustment disorder with anxiety in old age: comparing prevalence and clinical management in primary care and mental health care.

PURPOSE: Adjustment disorder with anxiety (AjD-A) is a common cause of severe anxiety symptoms, but little is known about its prevalence in old age. METHODS: This cross-sectional study examined the prevalence of AjD-A in outpatients over the age of 60 who consecutively consulted 34 general practitioners and 22 psychiatrists during a 2-week period. The diagnosis of AjD-A was obtained using the optional module for diagnostic of adjustment disorder of the Mini International Neuropsychiatric Interview (MINI). The study procedure also explored comorbid psychiatric conditions and documented recent past stressful life events, as well as social disability and current pharmacological and non-pharmacological management. RESULTS: Overall, 3651 consecutive subjects were screened (2937 in primary care and 714 in mental health care). The prevalence rate of AjD-A was 3.7% (n=136). Up to 39% (n=53) of AjD-A subjects had a comorbid psychiatric condition, mostly of the anxious type. The most frequently stressful life event reported to be associated with the onset of AjD-A was personal illness or health problem (29%). More than 50% of the AjD-A patients were markedly to extremely disabled by their symptoms. Compared to patients who consulted psychiatrists, patients who were seen by primary care physicians were older, had obtained lower scores at the Hamilton Anxiety Rating Scale, benefited less frequently from non-pharmacological management and received benzodiazepines more frequently. CONCLUSIONS: AjD-A appears to be a significantly disabling cause of anxiety symptoms in community dwelling elderly persons, in particular those presenting personal health related problems. Improvement of early diagnosis and non-pharmacological management of AjD-A would contribute to limit risks of benzodiazepine overuse, particularly in primary care settings.

Incidence and predictive factors of depressive symptoms in Alzheimer's disease: the REAL.FR study.

BACKGROUND: Many patients develop psychiatric and behavioral disturbances in the course of Alzheimer's disease (AD). Among these disturbances, depressive symptoms are frequent and affect nearly 40% of patients. The natural history and course of such symptoms in AD, and in particular the predictive factors, are little known. We studied the incidence and risk factors for the development of the first depressive symptoms in AD. DESIGN: Multicenter prospective study. PARTICIPANTS: Three hundred twelve AD patients from the French Network on AD (REAL.FR) without depression and without antidepressant treatment at baseline were followed up and assessed every 6 months for 4 years. During follow-up, all events occurring between two visits were carefully recorded. MEASUREMENTS: We used the Neuropsychiatric Inventory (NPI) for comprehensive evaluation of behavioral and psychological symptoms and depressive symptoms in particular. A multivariate analysis was performed using a backward stepwise Cox proportional hazards model. RESULTS: The incidence of depressive symptoms was 17.45% person/years, 95%CI (13.88-21.02). Among non-time dependent variables, duration of disease (RR=0.51; 95%CI: 0.30-0.85, p=0.0102) and the number of comorbid conditions (RR=0.45; 95%CI: 0.24-0.83, p=0.0115) were protective factors against the development of depressive symptoms. Agitation/aggression (RR=1.96; 95%CI: 1.19-3.23, p=0.0078) and sleep disturbances (RR=2.65; 95%CI: 1.40-5.00, p=0.0026) were time-dependent variables predictive of depressive symptoms. CONCLUSION: Better knowledge of predictive factors of mood disturbances in AD will enable clinicians to set up appropriate management of their patients. As published longitudinal studies are few, further works should be carried out to improve knowledge of the pattern and course of depression and depressive symptoms in AD.

Sleep disorders and their impacts on healthy, dependent, and frail older adults.

BACKGROUND: Sleep disorders differ widely in the heterogeneous older adult population. Older adults can be classified into three groups based upon their overall level of disability: healthy, dependent, and frail. Frailty is an emerging concept that denotes older persons at increased risk for poor outcomes. OBJECTIVE: The aim of this consensus review is to describe the sleep disorders observed in healthy and dependent older adults and to discuss the potential sleep disorders associated with frailty as well as their potential consequences on this weakened population. METHODS: A review task force was created including neurologists, geriatricians, sleep specialists and geriatric psychiatrists to discuss age related sleep disorders depending on the three categories of older adults. All published studies on sleep in older adults on Ovid Medline were reviewed and 106 articles were selected for the purpose of this consensus. RESULTS: Many healthy older adults have complains about their sleep such as waking not rested and too early, trouble falling asleep, daytime napping, and multiple nocturnal awakenings. Sleep architecture is modified by age with an increased percentage of time spent in stage one and a decreased percentage spent in stages three and four. Insomnia is frequent and its mechanisms include painful medical conditions, psychological distress, loss of physical activity and iatrogenic influences. Treatments are also involved in older adults' somnolence. The prevalence of primary sleep disorders such as restless legs syndrome, periodic limb movements and sleep disordered breathing increases with age. Potential outcomes relevant to these sleep disorders in old age include mortality, cardiovascular and neurobehavioral co-morbidities. Sleep in dependent older adults such as patients with Alzheimer Disease (AD) is disturbed. The sleep patterns observed in these patients are often similar to those observed in non-demented elderly but alterations are more severe. Nocturnal sleep disruption and daytime sleepiness are the main problems. They are the results of Sleep/wake circadian rhythm disorders, environmental, psychological and iatrogenic factors. They are worsened by other sleep disorders such as sleep disordered breathing. Sleep in frail older adults per se has not yet been formally studied but four axes of investigation should be considered: i) sleep architecture abnormalities, ii) insomnia iii) restless legs syndrome (RLS), iv) sleep disordered breathing. CONCLUSION: Our knowledge in the field of sleep disorders in older adults has increased in recent years, yet some groups within this heterogeneous population, such as frail older adults, remain to be more thoroughly studied and characterized.

Rapid cognitive decline in Alzheimer's disease. Consensus paper.

The rate of cognitive decline in Alzheimer's disease (AD) varies considerably between individuals, with some subjects showing substantial deterioration and others showing little or no change over the course of the disease. These wide variations support the relatively new concept of Rapid Cognitive Decline (RCD). Patients with an accelerated rate of cognitive decline have showed to present a worse evolution in terms of mortality, loss of autonomy and institutionalisation. The conclusions from RCD studies conducted in the past years remain very heterogeneous and sometimes contradictory. This is possibly due to methodological differences, mainly the different "a priori" definitions of RCD used to identify rapid decliners. Consequently of this, there is considerable variation in reported frequency of patients with RCD which may vary from 9.5% to 54%. The lack of both consensus definition and consensual clinical assessment tools is one of the major barriers for establishing an appropriated management of rapid decliners in clinical practice. Presently, management of rapid decliners in AD remains to be a challenge waiting to better know predictive factors of a RCD. To date no specific guidelines exist to follow-up or to treat patients with this condition. This consensus paper proposes the loss of 3 points or greater in Mini-Mental State Examination (MMSE) during six months as an empirical definition of rapid cognitive decline to be used in routine medical practice and to be relevant for clinical-decision making in patients with mild to moderately-severe AD.

Prevention of progression to dementia in the elderly: rationale and proposal for a health-promoting memory consultation (an IANA Task Force).

Alzheimer's disease (AD) is the most frequent form of dementia and according to the most recent estimation it affects nearly 27 million people in the world. The onset of the disease is generally insidious. It is becoming increasingly evident that the underlying pathophysiological mechanisms are active long before the appearance of the clinical symptoms of the disease. In the current context, it is important to develop strategies to delay the onset of cognitive decline. Delaying the onset by 5 years would reduce the prevalence by half at term, and a delay of 10 years would reduce it by three-quarters. The effectiveness of currently suggested preventive approaches remains to be confirmed, but certain strategies could be applied straight away to at-risk subjects. We propose that a health-promoting memory consultation should be set up for elderly persons who have attended a specialized memory consultation and in whom the diagnosis of dementia and of AD in particular, has not been established by standardized tools. Through this consultation, they would be offered full multidimensional investigation of all aspects of their health status, follow-up could be organized, general practitioners in private practice could be made more conscious of this population and the elderly could be made more aware of the risk factors to which they are exposed. The development of an information policy for the elderly would meet a present need. In our reflection, we must take into account the question of how to give this preventive consultation its due place in the healthcare pathway of the elderly person in order to ensure coordinated follow-up with all the other health professionals involved. The principle of the health-promoting memory consultation is undergoing validation in a large French multicentre preventive trial in 1200 frail elderly persons aged 70 years followed for three years, the Multidomain Alzheimer Preventive Trial (MAPT).

[Safety and efficacy of oral escitalopram as continuation treatment of intravenous citalopram, in patients with major depressive disorder--the navigade switch study]. / Tolérance et efficacité de l'escitalopram per os, en relais de la forme intraveineuse du citalopram chez des patients présentant un episode dépressif majeur.

Intravenous (iv) administration of an antidepressant is a common practice in some European countries, particularly in France, Spain, and Italy in the initial treatment phase of hospitalised, severe depressed patients. After a beneficial response is observed, patients are switched to an oral formulation. The approved treatment period of the iv form of citalopram is limited to 8-10 days. The high bioavailability of citalopram permits the use of identical iv and oral doses. Citalopram is a racemate, consisting of a 1:1 mixture of the S- and R-enantiomers. The therapeutically active component is the S-enantiomer (escitalopram). Pharmacokinetic single dose administration studies in healthy subjects have demonstrated that daily oral administration of 20 mg of escitalopram or 40 mg citalopram results in similar plasma concentrations of the S-enantiomer of citalopram. This open-label multicentre French prospective study investigated the tolerability and efficacy of oral escitalopram 10 and 20 mg/day, administered for a 6-week period as continuation treatment of citalopram (20 mg or 40 mg daily) intravenous (iv), in patients with Major Depressive Disorder. A total of 171 patients were enrolled, of whom 147 (85%) completed the study. The mean MADRS score at inclusion (last citalopram dose) was 31.6 +/- 9.9. The total MADRS score decreased after 3 days of oral treatment with escitalopram. Escitalopram demonstrated a continuous effect in treating depressive symptoms throughout the study. The decrease in MADRS mean total score from baseline was statistically significant to each visit (day 3, 15; p < 0.0001). At final visit (J42), the decrease was - 18.9 +/- 11.7 (p < 0.0001) and the MADRS mean total score was 12.7 +/- 9.3. There were no differences seen in the patient response comparing gender, age, and the single or recurrent episodes. The changes of Clinical Global Impression scores (CGI-S, CGI-I, PGE-Patient Global Evaluation) were also indicative of an improvement of the patients' depression. The CGI-I and PGE scores were significantly correlated indicating good agreement between investigator and patient in rating the degree of improvement. At the end of the study, 67% of patients were classified as responders (decrease of MADRS score from baseline > or = 50%), and the majority of them were considered remitters (final MADRS score < or = 12). Overall, the switch from intravenous citalopram to oral escitalopram was well tolerated in the study population. In all, 57 patients (33%) reported at least one adverse event (AE) during the study (21 patients in the 10 mg group and 36 patients in the 20 mg group); of these, 7 patients (4%) withdrew from the study. The most frequently reported AEs were suggestive of residual symptoms of depression (anxiety, 9%; insomnia, 5% of patients). In conclusion, in this study oral escitalopram (10 mg or 20 mg) was well tolerated as continuation treatment after switching from intravenous citalopram (20 mg or 40 mg). From the efficacy and safety data of this study, it can be concluded that the switch from citalopram iv to oral escitalopram (10 and 20 mg/day) is effective in decreasing depressive symptoms, and could be safely proposed in patients with major depressive disorder.

[Depressive symptoms in Alzheimer's disease: preliminary results of the REAL.FR study]. / Symptômes dépressifs dans la maladie d'Alzheimer: résultats préliminaires de l'étude REAL.FR.

UNLABELLED: The Alzheimer's disease (AD) is today regarded as a degenerative pathology with a serious and common complication: occurrence of mental and behavioral disturbances. Among this neuropsychiatrics symptoms, the depressive symptoms occupy a significant place by their frequency and their consequences on the caregiver's burden. The prevalence of such disorders is very variously appreciated in the literature. OBJECTIVE: To assess with precision depressive symptoms in a population with Alzheimer's disease rated on neuropsychiatric inventory NPI. METHOD: Cross-sectional study of patients with AD presenting at the consultation of psycho-geriatic, geriatric or neurologic services in 16 french university hospitals. The frequency of the depression was evaluated with the NPI on a population of 578 subjects with AD. We studied the association existing between these symptoms and the antecedents of depression and we studied the gravity of these disorders according to the cognitive status. RESULTS: Caregivers describe less one depressive symptom for approximately 40% of the subjects included in the study n = 229. The average score of gravity is close to 4 and is thus clinically significant. More the stage of dementia is severe more the number of subjects presenting a clinically significant score is important. Scores of depression evolve parallel to the stage of dementia. The antecedents of depression are a risk factor for depressive symptoms in the AD p < 0.001. DISCUSSION: These results confirm those of primary studies. In our study, more than the prevalence of depressive symptoms it seems that is the severity of the disorder which is associated with the dementia severity. The continuation of this work will allow a prospective evaluation of depressive symptoms in the AD.