Blocking CCR5 activity by maraviroc augmentation in post-stroke depression: a proof-of-concept clinical trial.

BACKGROUND: Post-stroke depression (PSD) is a significant impediment to successful rehabilitation and recovery after a stroke. Current therapeutic options are limited, leaving an unmet demand for specific and effective therapeutic options. Our objective was to investigate the safety of Maraviroc, a CCR5 antagonist, as a possible mechanism-based add-on therapeutic option for PSD in an open-label proof-of-concept clinical trial. METHODS: We conducted a 10-week clinical trial in which ten patients with subcortical and cortical stroke, suffering from PSD. were administered a daily oral dose of 300 mg Maraviroc. Participants were then monitored for an additional eight weeks. The primary outcome measure was serious treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. The secondary outcome measure was a change in the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: Maraviroc was well tolerated, with no reports of serious adverse events or discontinuations due to intolerance. The MADRS scores substantially reduced from baseline to week 10 (mean change: -16.4 ± 9.3; p < 0.001). By the conclusion of the treatment phase, a favorable response was observed in five patients, with four achieving remission. The time to response was relatively short, approximately three weeks. After the cessation of treatment, MADRS scores increased at week 18 by 6.1 ± 9.6 points (p = 0.014). CONCLUSIONS: Our proof-of-concept study suggests that a daily dosage of 300 mg of Maraviroc may represent a well-tolerated and potentially effective pharmacological approach to treating PSD. Further comprehensive placebo-controlled studies are needed to assess the impact of Maraviroc augmentation on PSD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05932550, Retrospectively registered: 28/06/2023.

Limbic self-neuromodulation as a novel treatment option for emotional dysregulation in premenstrual dysphoric disorder (PMDD); a proof-of-concept study.

AIM: To assess the efficacy of a novel neurofeedback (NF) method, targeting limbic activity, to treat emotional dysregulation related to premenstrual dysphoric disorder (PMDD). METHODS: We applied a NF probe targeting limbic activity using a functional magnetic resonance imaging-inspired electroencephalogram model (termed Amyg-EFP-NF) in a double-blind randomized controlled trial. A frontal alpha asymmetry probe (AAS-NF), served as active control. Twenty-seven participants diagnosed with PMDD (mean age = 33.57 years, SD = 5.67) were randomly assigned to Amyg-EFP-NF or AAS-NF interventions with a 2:1 ratio, respectively. The treatment protocol consisted of 11 NF sessions through three menstrual cycles, and a follow-up assessment 3 months thereafter. The primary outcome measure was improvement in the Revised Observer Version of the Premenstrual Tension Syndrome Rating Scale (PMTS-OR). RESULTS: A significant group by time effect was observed for the core symptom subscale of the PMTS-OR, with significant improvement observed at follow-up for the Amyg-EFP group compared with the AAS group [F(1, 15)=4.968, P = 0.042]. This finding was specifically robust for reduction in anger [F(1, 15) = 22.254, P < 0.001]. A significant correlation was found between learning scores and overall improvement in core symptoms (r = 0.514, P = 0.042) suggesting an association between mechanism of change and clinical improvement. CONCLUSION: Our preliminary findings suggest that Amyg-EFP-NF may serve as an affordable and accessible non-invasive treatment option for emotional dysregulation in women suffering from PMDD. Our main limitations were the relatively small number of participants and the lack of a sham-NF placebo arm.

Immune-related biomarkers and suicidal behaviors: A meta-analysis.

Biomarkers that can differentiate between psychiatric disorders with and without suicidal behavior history from each other and from healthy volunteers may explain part of the pathogenesis of suicidal behavior. We conducted the hitherto largest meta-analysis comparing immune biomarkers between subjects with and without suicide attempt history or death by suicide. The study protocol was registered with PROSPERO, CRD42020212841. Standardized mean differences (SMD) were pooled with random-effects models. Heterogeneity between studies was assessed with the I2-statistic and publication bias was evaluated by the Egger test and funnel plots. Data were based on 36 studies including 2679 persons with suicidal behaviors and 6839 comparison subjects, and four immune-related biomarkers (CRP, IL-6, TNF-α and IL-1ß). Suicidal behavior was associated with higher CRP blood levels compared with: healthy controls (SMD [95%CI] = 1.42[0.85-1.98]); patients with depression alone (SMD [95%CI] = 1.23[0.20-2.26]); and patients with any psychiatric disorders (SMD [95%CI] = 0.39[0.22-0.55]). IL-6 blood level was higher in patients with suicidal behaviors compared with healthy controls (SMD [95%CI] = 1.13[0.45-1.82]) and when compared with psychiatric patients without suicidal behaviors (SMD [95%CI] = 0.22 [0.11-0.33]). Meta-regression and subgroup analyses revealed that increased CRP in suicidal behavior is primarily driven by recent suicidal behavior. These results implicate the immune system and inflammatory response in suicidal behavior independent of a relationship to major psychiatric disorders, and that these biological measures are predominantly state-dependent markers. Future studies are needed to determine the cause-and-effect relationship of these immune system biomarkers with suicidal behavior, and their potential predictive properties.

CCR5-Δ32 polymorphism-a possible protective factor from gait impairment amongst post-stroke patients.

BACKGROUND AND PURPOSE: Stroke and small vessel disease cause gait disturbances and falls. The naturally occurring loss-of-function mutation in the C-C chemokine receptor 5 gene (CCR5-Δ32) has recently been reported as a protective factor in post-stroke motor and cognitive recovery. We sought to examine whether it also influences gait and balance measures up to 2 years after stroke. METHOD: Participants were 575 survivors of first-ever, mild-moderate ischaemic stroke or transient ischaemic attack from the TABASCO prospective study, who underwent a 3 T magnetic resonance imaging at baseline and were examined by a multi-professional team 6, 12 and 24 months after the event, using neurological, neuropsychological and mobility examinations. Gait rhythm and the timing of the gait cycle were measured by force-sensitive insoles. CCR5-Δ32 status and gait measures were available for 335 patients. RESULTS: CCR5-Δ32 carriers (16.4%) had higher gait speed and decreased (better) stride and swing time variability 6 and 12 months after the index event compared to non-carriers (p < 0.01 for all). The association remained significant after adjustment for age, gender, education, ethnicity and stroke severity. CONCLUSIONS: Significant associations were found between gait measurements and CCR5-Δ32 loss-of-function mutation amongst stroke survivors. This is the first study showing that genetic predisposition may predict long-term gait function after ischaemic stroke.

Preventing post-stroke dementia. The MARCH Trial. Protocol and statistical analysis plan of a randomized clinical trial testing the safety and efficacy of Maraviroc in post-stroke cognitive impairment.

Background: Current evidence suggest that 25%-33% of stroke-survivors develop post-stroke cognitive impairment (PSCI). The licensed drug Maraviroc, a CCR5-antagonist, is postulated to act via a neuroprotective mechanism that may offer the potential of preventing progression to vascular dementia. Our hypothesis: Maraviroc may have the potential to augment learning skills and cognitive performance by affecting synaptic plasticity, along with neuro-inflammatory modulation in patients with cerebral small vessel disease (SVD) and PSCI. Design: MARCH is a multi-center, double-blind randomized-control Phase-II trial of Maraviroc 150 or 600 mg/day versus placebo for 12-months in five stroke centers in Israel. Included are patients diagnosed with recent (1-24 months) subcortical stroke who experience mild PSCI and have evidence of white matter lesions and SVD on neuroimaging. Outcomes: Primary outcomes: 1. Change in cognitive scores. 2. Drug related adverse events. Secondary outcomes: change in functional and affective scores, MRI-derived measures, inflammatory markers, carotid atherosclerosis, cerebrospinal-fluid biomarkers in a sub-study. A sample size of 60 in each treatment group and 30 in the placebo group (total - 150 participants) provides 80% power between the treatment and the placebo groups. Conclusions: The results of this work could lead to a novel, readily available, therapeutic avenue to reduce PSCI, and possibly other pathologies. This study will test safety and effectiveness of Maraviroc in limiting cognitive deterioration and/or post stroke cognitive impairment in patients with cerebral small vessel disease. Schedule: First-patient first-visit was May 2021. Recruitment to complete in 2023, follow-up to complete in 2024.

The price of internship through COVID-19: 1st year physicians report substantial mental health symptoms during the pandemic.

OBJECTIVES: To examine the prevalence of mental health symptoms among medical interns working for the first time as physicians in a large tertiary hospital in Israel during the 1st COVID year. METHODS: All interns who worked for at least 2 months during the 1st COVID year (March 2020-February 2021) at the Tel-Aviv Sourasky Medical Center (TASMC), a large tertiary general hospital in Israel were approached simultaneously during April-May 2021, and were requested to fill in an online survey. In each questionnaire, the interns were asked to refer to the worst time they endured the symptoms described. Included were all medical. Depression and anxiety symptoms, post-traumatic stress symptoms and Burnout measures were evaluated using validated questionnaires. Depressive/anxiety symptoms were defined as primary end measures. We assessed the association between depression and anxiety symptoms, and demographic, post-traumatic and burnout measures. RESULTS: 145 out of 188 interns completed the study (77% overall response rate). The mean age was 30.36 ± 2.97. Almost half the interns (47%) reported depression/anxiety symptoms. The high depression/anxiety group was characterized by a lower mean age (29.87 ± 2.93 vs. 30.92 ± 2.91, p = 0.041), higher post-traumatic symptoms (15.62 ± 13.32 vs. 3.63 ± 5.59, p < 0.0001) and higher scores in 2/3 burnout subscales - emotional exhaustion (5.09 ± 1.29 vs. 3.61 ± 1.38, p = 0.000001) and depersonalization (3.83 ± 1.71 vs. 2.94 ± 1.46, p = 0.002). 11.4% of interns in the full sample reported they used cannabis or alcohol as "self-medication". CONCLUSIONS: medical interns serving for their first year as physicians during the COVID pandemic, developed mental symptoms in alarming numbers. The findings point to a crucial need to implement active interventions to protect these doctors, so that they can safely embark on their medical careers, specifically in times of global health crises.

Posttraumatic Stress Symptoms After Stroke: The Effects of Anatomy and Coping Style.

BACKGROUND: Posttraumatic stress disorder (PTSD) can be triggered by life-threatening medical emergencies, such as stroke. Data suggest that up to 25% of stroke survivors will develop PTSD symptomatology, but little is known about predisposing factors. We sought to examine whether neuroimaging measures and coping styles are related to PTSD symptoms after stroke. METHODS: Participants were survivors of first-ever, mild-moderate ischemic stroke, or transient ischemic attack from the TABASCO study (Tel Aviv Brain Acute Stroke Cohort). All participants underwent a 3T magnetic resonance imaging at baseline and were examined 6, 12, and 24 months thereafter, using neurological, neuropsychological, and functional evaluations. At baseline, coping styles were evaluated by a self-reported questionnaire. PTSD symptoms were assessed using the PTSD checklist. Data were available for 436 patients. RESULTS: Forty-eight participants (11%) developed probable PTSD (PTSD checklist ≥44) during the first year after the stroke/transient ischemic attack. Stroke was more likely to cause PTSD than transient ischemic attack. Stroke severity, larger white matter lesion volume, and worse hippocampal connectivity were associated with PTSD severity, while infarct volume or location was not. In a multivariate analysis, high-anxious and defensive coping styles were associated with a 6.66-fold higher risk of developing poststroke PTSD ([95% CI, 2.08-21.34]; P<0.01) compared with low-anxious and repressive coping styles, after adjusting for age, education, stroke severity, brain atrophy, and depression. CONCLUSIONS: In our cohort, PTSD was a common sequela among stroke survivors. We suggest that risk factors for PTSD development include stroke severity, white matter damage, and premorbid coping styles. Early identification of at-risk patients is key to effective treatment.

False-positive fentanyl screening kit results during treatment with long term injectable risperidone (Risperdal-Consta).

Fentanyl, a highly potent synthetic opioid, is a major cause of overdose deaths in the United States and worldwide. Urine drug immunoassay tests that include fentanyl in their drug panel are the common screening tool. However, false positive results may compromise test accuracy and cause grave clinical outcomes. In this preliminary report we describe 3 cases of patients with schizophrenia, who are treated with long-term injectable risperidone (Risperdal Consta) and were false positively screened for fentanyl by a rapid commercial screening kit. This finding warrants clinical attention to the possibility of inaccurate results regarding fentanyl misuse in multiple clinical settings.

CCR5-Δ32 polymorphism: a possible protective factor for post-stroke depressive symptoms.

Background: A naturally occurring loss-of-function mutation in the gene for C-C chemokine receptor type 5 (CCR5-Δ32) has recently been reported as a protective factor in post-stroke motor and cognitive recovery. We sought to examine whether this mutation also prevented the development of depressive symptoms up to 2 years after a stroke. Methods: Participants were survivors of a first-ever mild to moderate ischemic stroke or transient ischemic attack from the TABASCO prospective study who underwent a 3 T MRI at baseline and were examined by a multiprofessional team 6, 12 and 24 months after the event, including an evaluation of depressive symptoms using the Geriatric Depression Scale. Results: CCR5-Δ32 status and a baseline depression evaluation were available for 435 patients. Compared with noncarriers, CCR5-Δ32 carriers (16.1%) had fewer depressive symptoms at admission (p = 0.035) and at 6 months (p < 0.001), 12 months (p < 0.001) and 24 months (p = 0.006) after the index event. This association remained significant at 6 and 12 months after adjustment for age, sex, education, antidepressant use, ethnicity and the presence of cortical infarcts. These findings were more robust in women. Compared to baseline, depressive symptoms in CCR5-Δ32 noncarriers tended to remain stable or grow worse over time, but in CCR5-Δ32 carriers, symptoms tended to improve. Limitations: A limitation of this study was the exclusion of patients who had a severe stroke or who had pre-stroke depression. Conclusion: Carriers of the CCR5-Δ32 allele had a lower tendency to develop depressive symptoms post-stroke, and this phenomenon was more prominent in women. These findings could have clinical implications; they suggest a mechanism-based treatment target for post-stroke depression. Drugs mimicking this loss-of-function mutation exist and could serve as a novel antidepressant therapy.

The Effects of the 1st National COVID 19 Lockdown on Emergency Psychiatric Visit Trends in a Tertiary General Hospital in Israel.

OBJECTIVE: To examine whether the 1st COVID-19 lockdown in Israel affected emergency psychiatric presentations in a general hospital. METHOD: We studied files of patients who underwent psychiatric consultation in the emergency-room (ER) at the Tel-Aviv Sourasky Medical Center during a lockdown imposed in 2020. Parallel data were obtained from 2017-2019, as control. RESULTS: The number of psychiatric consultations dropped during the lockdown period; an increased relative number of compulsory psychiatric hospitalizations was documented and a decreased rate of consented psychiatric hospitalizations. DISCUSSION: Less psychiatric patients approached the ER during the lockdown period, pointing to an urgent need to facilitate access to psychiatric care in future times of crisis.

Reducing Stigma Toward Psychiatry Among Medical Students: A Multicenter Controlled Trial.

OBJECTIVE: To examine the effect of a novel antistigma intervention curriculum (ASIC) in reducing stigma toward psychiatry among medical students. METHODS: Medical students from 8 hospitals in central Israel were divided into intervention (n = 57) and control (n = 163) arms. The students completed the 30-item Attitudes Toward Psychiatry (ATP-30) and the Attitudes Toward Mental Illness (AMI) scales at psychiatry rotation onset and conclusion. The ASIC was designed to target prejudices and stigma through direct informal encounters with people with serious mental illness (SMI) during periods of remission and recovery. Supervised small-group discussions followed those encounters to facilitate processing of thoughts and emotions that ensued and to discuss salient topics in psychiatry. The study was conducted between November 2017 and July 2018. RESULTS: Significant between-group differences were found at endpoint for attitudes toward psychiatry and psychiatric patients (P < .001). Although changing attitudes toward psychiatry as a career choice was not part of the ASIC, a significant between-group difference emerged by endpoint (P < .001). CONCLUSIONS: Implementation of an ASIC that includes contact with individuals with lived SMI experience followed by supervised small-group discussions is effective in reducing stigma in medical students' perceptions of people with mental illness and psychiatry. Further evaluation is warranted with regard to the long-term destigmatizing effects of an ASIC. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03907696.

The Price of Stress: High Bedtime Salivary Cortisol Levels Are Associated with Brain Atrophy and Cognitive Decline in Stroke Survivors. Results from the TABASCO Prospective Cohort Study.

BACKGROUND AND OBJECTIVE: Previous studies suggest that excessive cortisol levels after stroke are associated with cognitive dysfunction. However, limited data exist regarding associations between post-stroke cortisol levels, brain abnormalities, genetic factors, and cognitive outcome. We sought to study these issues in a longitudinal stroke survivors cohort. METHODS: Data from 182 cognitively intact ischemic stroke patients from the TABASCO study were available. Saliva cortisol levels (bedtime and post-awakening) and cognitive assessments were obtained on admission, and 6, 12, and 24 months thereafter. During hospitalization, patients underwent 3T MRI scans and APOE genotyping. RESULTS: Higher bedtime cortisol levels immediately post-stroke were associated with larger neurological deficits (p < 0.001), brain atrophy (p = 0.025), worse white matter integrity (p = 0.003), and worse cognitive results up to 24 months post-stroke. These findings remained significant when adjusted for age, gender, education, smoking, stroke severity, apolipoprotein E4 (ApoE4) status, and body mass index. ApoE4 negatively modified the relation between cortisol and memory. As a group, participants who presented with high admission bedtime cortisol levels continued to present relatively elevated bedtime levels across all examined time-points, and this group had inferior memory and executive functioning scores compared to the lower cortisol group 24 months post-stroke (p = 0.05, p = 0.035, respectively). Post-awakening cortisol levels were not associated with neuroimaging findings or cognitive scores. CONCLUSIONS: High bedtime salivary cortisol levels post-stroke may provide information about dysregulation of diurnal HPA-axis activity under acute challenge conditions, and predict worse cognitive outcome. ApoE4 genotype might modify this association. These findings call for specific stress management interventions in stroke survivors.

Type 2 Diabetes Mellitus and Impaired Renal Function Are Associated With Brain Alterations and Poststroke Cognitive Decline.

BACKGROUND AND PURPOSE: Type 2 diabetes mellitus (T2DM) is associated with diseases of the brain, kidney, and vasculature. However, the relationship between T2DM, chronic kidney disease, brain alterations, and cognitive function after stroke is unknown. We aimed to evaluate the inter-relationship between T2DM, impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. METHODS: The TABASCO (Tel Aviv brain acute stroke cohort) is a prospective cohort of stroke/transient ischemic attack survivors. The volume and white matter integrity, ischemic lesions, and brain and hippocampal volumes were measured at baseline using 3-T MRI. Cognitive tests were performed on 507 patients, who were diagnosed as having mild cognitive impairment, dementia, or being cognitively intact after 24 months. RESULTS: At baseline, T2DM and impaired renal function (estimated creatinine clearance [eCCl] <60 mL/min) were associated with smaller brain and hippocampal volumes, reduced cortical thickness, and worse white matter microstructural integrity. Two years later, both T2DM and eCCl <60 mL/min were associated with poorer cognitive scores, and 19.7% of the participants developed cognitive decline (mild cognitive impairment or dementia). Multiple analysis, controlling for age, sex, education, and apolipoprotein E4, showed a significant association of both T2DM and eCCl <60 mL/min with cognitive decline. Having both conditions doubled the risk compared with patients with T2DM or eCCl <60 mL/min alone and almost quadrupled the risk compared with patients without either abnormality. CONCLUSIONS: T2DM and impaired renal function are independently associated with abnormal brain structure, as well as poorer performance in cognitive tests, 2 years after stroke. The presence of both conditions quadruples the risk for cognitive decline. T2DM and lower eCCl have an independent and additive effect on brain atrophy and the risk of cognitive decline. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01926691.

Vascular depression consensus report - a critical update.

BACKGROUND: Vascular depression is regarded as a subtype of late-life depression characterized by a distinct clinical presentation and an association with cerebrovascular damage. Although the term is commonly used in research settings, widely accepted diagnostic criteria are lacking and vascular depression is absent from formal psychiatric manuals such as the Diagnostic and Statistical Manual of Mental Disorders, 5th edition - a fact that limits its use in clinical settings. Magnetic resonance imaging (MRI) techniques, showing a variety of cerebrovascular lesions, including extensive white matter hyperintensities, subcortical microvascular lesions, lacunes, and microinfarcts, in patients with late life depression, led to the introduction of the term "MRI-defined vascular depression". DISCUSSION: This diagnosis, based on clinical and MRI findings, suggests that vascular lesions lead to depression by disruption of frontal-subcortical-limbic networks involved in mood regulation. However, despite multiple MRI approaches to shed light on the spatiotemporal structural changes associated with late life depression, the causal relationship between brain changes, related lesions, and late life depression remains controversial. While postmortem studies of elderly persons who died from suicide revealed lacunes, small vessel, and Alzheimer-related pathologies, recent autopsy data challenged the role of these lesions in the pathogenesis of vascular depression. Current data propose that the vascular depression connotation should be reserved for depressed older patients with vascular pathology and evident cerebral involvement. Based on current knowledge, the correlations between intra vitam neuroimaging findings and their postmortem validity as well as the role of peripheral markers of vascular disease in late life depression are discussed. CONCLUSION: The multifold pathogenesis of vascular depression as a possible subtype of late life depression needs further elucidation. There is a need for correlative clinical, intra vitam structural and functional MRI as well as postmortem MRI and neuropathological studies in order to confirm the relationship between clinical symptomatology and changes in specific brain regions related to depression. To elucidate the causal relationship between regional vascular brain changes and vascular depression, animal models could be helpful. Current treatment options include a combination of vasoactive drugs and antidepressants, but the outcomes are still unsatisfying.

Is the time ripe for new diagnostic criteria of cognitive impairment due to cerebrovascular disease? Consensus report of the International Congress on Vascular Dementia working group.

BACKGROUND: Long before Alzheimer's disease was established as the leading cause of dementia in old age, cerebrovascular lesions were known to cause cognitive deterioration and associated disability. Since the middle of the last century, different diagnostic concepts for vascular dementia and related syndromes were put forward, yet no widely accepted diagnostic consensus exists to date. DISCUSSION: Several international efforts, reviewed herein, are ongoing to define cognitive impairment due to cerebrovascular disease in its different stages and subtypes. The role of biomarkers is also being discussed, including cerebrospinal fluid proteins, structural and functional brain imaging, and genetic markers. The influence of risk factors, such as diet, exercise and different comorbidities, is emphasised by population-based research, and lifestyle changes are considered for the treatment and prevention of dementia. CONCLUSION: To improve the diagnosis and management of vascular cognitive impairment, further progress has to be made in understanding the relevant pathomechanisms, including shared mechanisms with Alzheimer's disease; bringing together fragmented research initiatives in coordinated international programs; testing if known risk factors are modifiable in prospective interventional studies; and defining the pre-dementia and pre-clinical stages in line with the concept of mild cognitive impairment due to Alzheimer's disease.

Impaired renal function is associated with brain atrophy and poststroke cognitive decline.

OBJECTIVE: To evaluate the interrelationship among impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. METHODS: The Tel Aviv Brain Acute Stroke Cohort study is a prospective cohort of mild-moderate ischemic stroke/TIA survivors without dementia who underwent a 3T MRI and were cognitively assessed at admission and for 24 months following stroke. Renal function was evaluated at admission by creatinine clearance (CCl) estimation. The volumes of ischemic lesions and preexisting white matter hyperintensities (WMH), brain atrophy, and microstructural changes of the normal-appearing white matter tissue were measured using previously validated methods. RESULTS: Baseline data were available for 431 participants. Participants with a CCl <60 mL/min at baseline performed significantly worse in all cognitive tests over time (p = 0.001) than those with a CCl ≥60 mL/min and had larger WMH volume and cortical atrophy and smaller hippocampal volume (all p < 0.001). After 2 years, 15.5% of the participants were diagnosed with cognitive impairment. Multiple logistic regression analysis, controlling for traditional risk factors, suggested CCl <60 mL/min at baseline as a significant predictor for the development of cognitive impairment 2 years after the index stroke (odds ratio 2.01 [95% confidence interval 1.03-3.92], p = 0.041). CONCLUSIONS: Impaired renal function is associated with increased WMH volume and cortical atrophy, known biomarkers of the aging brain, and is a predictor for cognitive decline 2 years after stroke/TIA. Decreased renal function may be associated with cerebral small vessel disease underlying poststroke cognitive decline, suggesting a new target for early intervention.

Depressive symptoms following stroke and transient ischemic attack: is it time for a more intensive treatment approach? results from the TABASCO cohort study.

OBJECTIVE: To examine whether depressive symptoms after a stroke or a transient ischemic attack (TIA) increase the risk of cognitive impairment and functional deterioration at 2-year follow-up. METHODS: Participants were survivors of first-ever, mild-to-moderate ischemic stroke or TIA from the TABASCO prospective cohort study who underwent 3T magnetic resonance imaging and were examined by a multiprofessional team 6, 12, and 24 months after the event using direct interviews, depression scales, and neurologic, neuropsychological, and functional evaluations. The main outcome was the development of cognitive impairment, either mild cognitive impairment (MCI) or dementia. MCI was diagnosed by a decline on at least 1 cognitive domain (≥ 1.5 SD) of the Montreal Cognitive Assessment score and/or on the computerized neuropsychological battery, as compared with age- and education-matched published norms. Dementia was diagnosed by a consensus forum that included senior neurologists specializing in memory disorders and a neuropsychologist. RESULTS: Data were obtained from 306 consecutive eligible patients (mean age: 67.1 ± 10.0 years) who were admitted to the department of emergency medicine at the Tel Aviv Medical Center from April 1, 2008, to December 1, 2011, within 72 hours from onset of symptoms of TIA or stroke. Of these patients, 51 (16.7%) developed cognitive impairment during a 2-year follow-up. Multivariate regression analysis showed that a Geriatric Depression Scale (GDS) score ≥ 6 at admission and at 6 months after the event was a significant independent marker of cognitive impairment 2 years after the stroke/TIA (OR = 3.62, 95% CI, 1.01-13.00; OR = 3.68, 95% CI, 1.03-13.21, respectively). A higher GDS score at 6 months was also related to a worse functional outcome (P < .001). CONCLUSIONS: Our results support depression screening among stroke and TIA survivors as a tool to identify patients who are prone to have a worse cognitive and functional outcome. These patients may benefit from closer medical surveillance and a more intensive treatment approach. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01926691.

The clock-drawing test as a possible indicator of acute psychosis.

The clock-drawing test (CDT) is used widely to evaluate cognitive disorders, but its role in the assessment of psychotic disorders has not been studied. We sought to examine whether the CDT plays a role as an indicator of psychosis and to establish its sensitivity to clinical improvement of psychosis. The CDT was administered twice to 53 hospitalized patients without dementia but with psychosis: once at admission and again before discharge. The CDT scores were calculated in a random order by two independent senior psychiatrists who were blinded to the patients' status (admission or discharge). The inter-rater reliability was high (0.89 at admission, 0.85 at discharge, P<0.01 for both). The severity of psychosis was assessed by the Positive and Negative Syndrome Scale (PANSS). Patients had significantly lower CDT scores at admission than at discharge (2.87±1.39 vs. 3.91±1.08, respectively, P<0.01). The PANSS-total score of the patients showed a significant improvement (84.90±17.77 vs. 69.18±16.23, P<0.01). An inverse correlation was found between CDT performance and psychosis severity, as reflected by the PANSS-positive symptom subscale at admission (R=-0.279, P<0.05). Our findings suggest that the CDT may aid in the assessment of psychotic states and in their clinical monitoring.

Ten Years of Abstinence in Former Opiate Addicts: Medication-Free Non-Patients Compared to Methadone Maintenance Patients.

Fifty-five former opioid addicts who have been methadone maintained patients for 10 or more years and whose urine has tested negative for drugs for 2 or more years were compared to 99 former opioid addicts who have been medication-free for 10 or more years. Groups were comparable in age and education, but the medication-free subjects were younger when having started opioids with more severe addiction scores. Methadone maintained patients presented with a higher proportion of psychiatric comorbidity and chronic pain. Their scores of perceived sleep quality and cognitive state were poorer than the medication-free individuals. Possible explanations of the differences are discussed in this article.