Poststroke Depression: An Update.

The presence of neuropsychiatric disorders after stroke has been recognized for more than 100 years, but controlled systematic studies did not begin until the 1970s. The most clinically important advances, however, have been in the treatment and prevention of poststroke depression (PSD). Recent meta-analyses of randomized controlled trials (RCTs) for the treatment of PSD have demonstrated the efficacy of antidepressants. Similarly, RCTs for the prevention of PSD have shown that antidepressants significantly decrease the incidence of PSD compared with placebo. Early treatment of PSD with antidepressants also appears to enhance both physical and cognitive recovery from stroke and may increase survival up to 10 years. Genetic and epigenetic variations, white matter disease, cerebrovascular deregulation, altered neuroplasticity, and changes in glutamate neurotransmission may be relevant etiological factors.

Rates and Predictors of Rapid Eye Movement Sleep Behavior Disorder Symptoms Among Post-9/11 Veterans.

OBJECTIVE: Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI), which are prevalent conditions among post-9/11 veterans, increase risks of rapid eye movement (REM) sleep behavior disorder (RBD) and degenerative synucleinopathy. Rates and predictors of RBD symptoms were investigated by screening post-9/11 veterans for RBD with a validated questionnaire. METHODS: In this cross-sectional analysis, consecutive patients in the Houston Translational Research Center for TBI and Stress Disorders (TRACTS) were screened with the English translation of the RBD Questionnaire-Hong Kong (RBDQ-HK). In addition to data from the standard TRACTS battery, systematic chart review was used to identify known sleep disorders mimicking or manifesting RBD. RESULTS: Of the 119 patients with available RBDQ-HK scores, 71 (60%) and 65 (55%) screened positive for RBD, when a total score ≥21 and a factor 2 score ≥8 were used as cutoff scores, respectively. Univariable analyses with both cutoffs showed consistent associations between a positive RBDQ-HK screen and global sleep quality, number of TBI exposures, and PTSD severity. Multivariable logistic regression with total score ≥21 as a cutoff indicated that PTSD severity (odds ratio=1.06, 95% CI=1.02-1.10) and number of TBIs (odds ratio=1.63, 95% CI=1.16-2.41) were independent predictors of a positive screen, whereas global sleep quality was no longer significant. Multivariable logistic regression with factor 2 score ≥8 as a cutoff showed similar results. CONCLUSIONS: Interdisciplinary parasomnia assessment, further validation of RBD screens, and standardized reporting of REM sleep without atonia could provide necessary information on the pathophysiological relationships linking PTSD, TBI, RBD symptoms, and ultimately synucleinopathy risk among post-9/11 veterans.

Post-Traumatic Stress Disorder and Risk of Degenerative Synucleinopathies: Systematic Review and Meta-Analysis.

OBJECTIVE: A systematic review was conducted to answer whether adult-onset post-traumatic stress disorder (PTSD) is associated with increased risk of Parkinson's disease (PD) and related synucleinopathies. DESIGN: A systematic search of Medline (Ovid), Embase (Elsevier), PsycInfo (Ovid), Cochrane Library (Wiley), and Web of Science (Clarivate) was performed using MeSH headings and equivalent terms for PTSD, PD, DLB, and related disorders. SETTING: No restrictions. PARTICIPANTS: Eligible articles were published in peer-reviewed journals, sampled adult human populations, and treated PTSD and degenerative synucleinopathies as exposures and outcomes, respectively. MEASUREMENTS: Extracted data included diagnostic methods, sample characteristics, matching procedures, covariates, and effect estimates. Bias assessment was performed with the Newcastle-Ottawa scale. Hazard ratios were pooled using the random effects model, and the Hartung-Knapp adjustment was applied due to the small number of studies. RESULTS: A total of six articles comprising seven unique samples (total n = 1,747,378) met eligibility criteria. The risk of PD was reported in three retrospective cohort studies and one case-control study. Risk of DLB was reported in one retrospective cohort, one case-control, and one prospective cohort study. No studies addressed potential relationships with multiple system atrophy or pure autonomic failure. Meta-analysis of hazard ratios from four retrospective cohort studies supported the hypothesis that incident PTSD was associated with PD and DLB risk (pooled HR 1.88, 95% C.I. 1.08-3.24; p = 0.035). CONCLUSIONS: The sparse literature to-date supports further investigations on the association of mid- to late-life PTSD with Parkinson's and related neurodegenerative disorders.

Dream Enactment Behaviors Associated With Posttraumatic Stress Disorder.

The investigators aimed to draw attention to current debates surrounding the etiologies of dream enactment behaviors in patients with posttraumatic stress disorder (PTSD). The phenomenological overlap between PTSD-related nocturnal symptoms, rapid eye movement sleep behavior disorder (RBD), and trauma-associated sleep disorder (TASD) is discussed. Strategies used to diagnose and manage dream enactment behaviors, whether due to RBD or another confounding sleep disorder, are considered. Finally, the need for further research on the pathophysiological overlap and integrated treatment of PTSD, RBD, and, possibly, TASD is highlighted.

Post-Traumatic Stress Disorder is Associated with further Increased Parkinson's Disease Risk in Veterans with Traumatic Brain Injury.

OBJECTIVE: Determining if traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for Parkinson's disease (PD). This constitutes a research priority for the Veterans Administration (VA) with implications for screening policy and prevention. METHODS: Population-based, matched case-control study among veterans using VA health care facilities from October 1, 1999, to September 30, 2013. We identified 176,871 PD cases and 707,484 randomly selected PD-free matched controls. PD, TBI, and PTSD were ascertained by validated International Classification of Disease 9th revision (ICD)-9 code-based algorithms. We examined the association between both risk factors and PD using race-adjusted conditional logistic regression. RESULTS: The overall study cohort prevalence for TBImild , TBInon-mild , and PTSD was 0.65%, 0.69%, and 5.5%, respectively. Both TBI and PTSD were significantly associated with PD in single-risk factor race-adjusted analyses (conditional odds ratio [cOR] = 2.99; 95% confidence interval [CI]: 2.69-3.32), 3.82 (95% CI: 3.67-3.97), and 2.71 (95% CI: 2.66-2.77) for TBImild , TBInon-mild , and PTSD, respectively). There was suggestive positive interaction observed with comorbid PTSD/TBI in dual-risk factor analyses, with significant 2.69-fold and 3.70-fold excess relative PD risk in veterans with TBImild and TBInon-mild versus those without TBI when PTSD was present versus 2.17-fold and 2.80-fold excess risk when PTSD was absent. INTERPRETATION: Our study was the first to demonstrate that both TBI and PTSD are independently associated with increased relative PD risk in a diverse nationwide cohort of military service veterans, and the first to suggest a potential modest synergistic excess risk in those with comorbid TBI/PTSD. Longitudinal research is needed to confirm these suggestive findings. ANN NEUROL 2020 ANN NEUROL 2020;88:33-41.

Clinical Correlates of Dream Enactment Behaviors in Previously Deployed OEF/OIF/OND Veterans: An Exploratory Analysis.

OBJECTIVE: Veterans with posttraumatic stress disorder (PTSD) frequently report dream enactment behavior (DEB). Although DEBs are associated with PTSD symptoms, their relationship with other sleep disorders, including REM behavior disorder, warrants reexamination of their clinical correlates. METHODS: The investigators used a cross-sectional, exploratory analysis to compare demographic and clinical characteristics of veterans endorsing regularly occurring DEB compared with those endorsing no or infrequent DEB. The participants comprised a convenience sample of servicemembers who were previously deployed to Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) and enrolled in an ongoing cohort study. RESULTS: Of the 78 eligible participants, 19 (24.4%) endorsed DEBs occurring at least once per week in the past month. Compared with participants who reported no or infrequent DEBs, participants with regularly occurring DEBs had poorer sleep quality, greater PTSD severity, a higher number of reported mild traumatic brain injuries (mTBI) with loss of consciousness, and a higher likelihood of being diagnosed with sleep disorders. After adjustment for global sleep quality, a significant association persisted between DEBs and the number of mTBI with loss of consciousness but not between DEBs and the severity of PTSD symptoms. CONCLUSIONS: These results suggest that mTBI may disrupt neural circuits regulating sleep among OIF/OEF/OND veterans. Prospective, polysomnographic assessment of muscle tone and behavioral events during REM sleep is needed to characterize the physiology of DEBs in this population.

Treating Alcohol Use Disorder in U.S. Veterans: The Role of Traumatic Brain Injury.

OBJECTIVE: The authors examined the efficacy of valproate to reduce relapse to heavy drinking among veterans with alcohol use disorder (AUD) and neuropsychiatric comorbidities and whether antecedent traumatic brain injury (TBI) or posttraumatic stress disorder (PTSD) affected treatment response. METHODS: Participants were male veterans 18-60 years old with an AUD and no other substance use besides nicotine or cannabis. Sixty-two patients were randomly assigned to receive either valproate or naltrexone. Participants were evaluated at baseline and followed weekly for 24 weeks. All participants received standardized psychosocial interventions as well as treatment for coexistent psychiatric conditions. RESULTS: During the follow-up period, nine study subjects in the naltrexone group and 14 in the valproate group relapsed to heavy drinking, but the difference did not reach statistical significance. Participants with a history of moderate to severe TBI were more likely to relapse to heavy drinking compared with those with no TBI (hazard ratio=4.834, 95% CI=1.103-21.194, p=0.033). PTSD status did not significantly affect outcome. CONCLUSIONS: Intensive outpatient programs are efficacious alternatives to treat AUD in veterans, although the role of pharmacological treatment is not completely elucidated. Glutamatergic agents appear to be less effective than opiate antagonists to prevent relapse to heavy drinking and to increase cumulative abstinence. Future studies should examine novel pharmacological and nonpharmacological options.

Changes in motor function, cognition, and emotion-related behavior after right hemispheric intracerebral hemorrhage in various brain regions of mouse.

Intracerebral hemorrhage (ICH) is a detrimental type of stroke. Mouse models of ICH, induced by collagenase or blood infusion, commonly target striatum, but not other brain sites such as ventricular system, cortex, and hippocampus. Few studies have systemically investigated brain damage and neurobehavioral deficits that develop in animal models of ICH in these areas of the right hemisphere. Therefore, we evaluated the brain damage and neurobehavioral dysfunction associated with right hemispheric ICH in ventricle, cortex, hippocampus, and striatum. The ICH model was induced by autologous whole blood or collagenase VII-S (0.075 units in 0.5 µl saline) injection. At different time points after ICH induction, mice were assessed for brain tissue damage and neurobehavioral deficits. Sham control mice were used for comparison. We found that ICH location influenced features of brain damage, microglia/macrophage activation, and behavioral deficits. Furthermore, the 24-point neurologic deficit scoring system was most sensitive for evaluating locomotor abnormalities in all four models, especially on days 1, 3, and 7 post-ICH. The wire-hanging test was useful for evaluating locomotor abnormalities in models of striatal, intraventricular, and cortical ICH. The cylinder test identified locomotor abnormalities only in the striatal ICH model. The novel object recognition test was effective for evaluating recognition memory dysfunction in all models except for striatal ICH. The tail suspension test, forced swim test, and sucrose preference test were effective for evaluating emotional abnormality in all four models but did not correlate with severity of brain damage. These results will help to inform future preclinical studies of ICH outcomes.

Poststroke Depression: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association.

Poststroke depression (PSD) is common, affecting approximately one third of stroke survivors at any one time after stroke. Individuals with PSD are at a higher risk for suboptimal recovery, recurrent vascular events, poor quality of life, and mortality. Although PSD is prevalent, uncertainty remains regarding predisposing risk factors and optimal strategies for prevention and treatment. This is the first scientific statement from the American Heart Association on the topic of PSD. Members of the writing group were appointed by the American Heart Association Stroke Council's Scientific Statements Oversight Committee and the American Heart Association's Manuscript Oversight Committee. Members were assigned topics relevant to their areas of expertise and reviewed appropriate literature, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion. This multispecialty statement provides a comprehensive review of the current evidence and gaps in current knowledge of the epidemiology, pathophysiology, outcomes, management, and prevention of PSD, and provides implications for clinical practice.

Prevention of Poststroke Mortality Using Problem-Solving Therapy or Escitalopram.

OBJECTIVE: This study re-examined patients from a 1-year randomized controlled double-blind trial of escitalopram, problem-solving therapy (PST), or placebo to prevent depression among patients less than 3 months after a stroke. The objective of the current study was to determine if preventive treatment would predict time to death over 8-10 years of follow-up. Based on the importance of depression in poststoke mortality and a previous study of this population at 18 months' follow-up showing that stopping escitalopram but not PST led to a significant increase in depression, the authors hypothesized that PST would be associated with the longest time to death. METHODS: Of 129 eligible patients, 122 were contacted and 7 were lost to follow-up. Families and surviving patients were interviewed to determine current health status or the date and cause of death. RESULTS: Using the Weibull model of log time (years) to death, controlled for age, severity of physical illness, gender, severity of stroke, and history of depression after study entry, there was a significant independent effect of treatment. PST significantly and independently increased the time to mortality, whereas older age and major depression significantly and independently decreased the time to death. CONCLUSION: To the authors' knowledge, this is the first time a psychological antidepressant treatment administered for 1 year has been associated with increased survival among patients who have suffered a stroke.

Preliminary Investigation of Cerebral Blood Flow and Amyloid Burden in Veterans With and Without Combat-Related Traumatic Brain Injury.

This study aimed to examine global and regional cerebral blood flow and amyloid burden in combat veterans with and without traumatic brain injury (TBI). Cerebral blood flow (in milliliters per minute per 100 mL) was measured by quantitative [(15)O]water, and amyloid burden was measured by [(11)C]PIB imaging. Mean global cerebral blood flow was significantly lower in veterans with TBI compared with non-TBI veterans. There were essentially no differences between groups for globally normalized regional cerebral blood flow. Amyloid burden did not differ between TBI and non-TBI veterans. Veterans who have suffered a TBI have significantly lower cerebral blood flow than non-TBI controls but did not manifest increased levels of amyloid, globally or regionally.

Prevention of post-stroke generalized anxiety disorder, using escitalopram or problem-solving therapy.

This study examined the efficacy of antidepressant treatment for preventing the onset of generalized anxiety disorder (GAD) among patients with recent stroke. Of 799 patients assessed, 176 were randomized, and 149 patients without evidence of GAD at the initial visit were included in this double-blind treatment with escitalopram (N=47) or placebo (N=49) or non-blinded problem-solving therapy (PST; 12 total sessions; N=53). Participants given placebo over 12 months were 4.95 times more likely to develop GAD than patients given escitalopram and 4.00 times more likely to develop GAD than patients given PST. Although these results should be considered preliminary, the authors found that both escitalopram and PST were effective in preventing new onset of post-stroke GAD.

Validation of electronic diagnostic codes for rapid eye movement sleep behavior disorder.

We investigated the accuracy of International Classification of Diseases (ICD) codes for the identification of Veterans with rapid eye movement (REM) sleep behavior disorder (RBD). The charts of 139 randomly sampled Veterans with ≥1 ICD-9 and ICD-10 code(s) for RBD were reviewed for documentation of a suspected, previous, or current diagnosis; clinical symptoms; and/or empiric treatments for this disorder. Notably, 71 (51.1%) of patients with RBD electronic diagnoses lacked polysomnography (PSG), and 29 (20.9%) had PSG reports without commentary on REM sleep without atonia (RSWA). Sleep centers are therefore encouraged to include a brief sentence in PSG report templates commenting on the presence/absence of RSWA.

STEP-Home transdiagnostic group reintegration workshop to improve mental health outcomes for post-9/11 Veterans: Design, methods, and rationale for a randomized controlled behavioral trial.

BACKGROUND: Many post-9/11 U.S. combat Veterans experience difficulty readjusting to civilian life after military service, including relationship problems, reduced work productivity, substance misuse, and increased anger control problems. Mental health problems are frequently cited as causing these difficulties, driven by unparalleled rates of mild traumatic brain injury, posttraumatic stress, and other co-occurring emotional and physical conditions. Given the high prevalence of multimorbidity in this cohort, acceptable, non-stigmatizing, transdiagnostic interventions targeting reintegration are needed. The STEP-Home reintegration workshop has the potential to significantly improve skills to foster civilian reintegration, increase engagement in VA services, and improve mental health outcomes in Veterans with and without diagnosed clinical conditions. METHODS/DESIGN: Ongoing from 2019, a prospective, two-site, randomized trial of 206 post-9/11 U.S. military Veterans randomized to receive either 12 sessions of the STEP-Home transdiagnostic reintegration workshop (SH; Active Intervention) or Present Centered Reintegration Group Therapy (PCRGT; Active Control Intervention). Primary outcomes are reintegration, anger, and emotional regulation post-intervention and at 3-months post-intervention. Secondary outcomes include measures of mental health, functional and vocational status, and cognition. CONCLUSION: This study addresses an important gap in transdiagnostic interventions to improve civilian reintegration in post-9/11 Veterans. STEP-Home is designed to promote treatment engagement and retention, opening the door to critically needed VA care, and ultimately reducing long-term healthcare burden of untreated mental health illness in U.S. Veterans. TRIAL REGISTRATION: Clinicaltrials.gov: D2907-R.

Physical Violence and Aggression in Parkinson's Disease: A Systematic Review.

BACKGROUND: Physical violence and aggression (PVA), defined as behaviors with the potential to cause bodily injury, are unfortunate risks in the management of all-cause neurodegenerative dementias. While dementia in Parkinson's disease (PD) may not be evident for many years after clinical onset, neuropsychiatric disturbances occur at all stages of the disease. At issue is whether PVA in PD is associated with clinical factors that can be targets for prevention and management in the absence of a prevailing dementia syndrome. OBJECTIVE: This systematic review examined the extent to which PVA in PD without dementia is a clinically significant concern and whether it is associated with factors that could warrant proactive management. METHODS: A systematic search of 9 electronic databases used MeSH headings and equivalent terms for PD, aggression, and violence. Eligible manuscripts were original articles that were published in peer-reviewed journals and reported on adults with PD in the awake state with PVA as possible outcomes. Extracted data included study design, PD ascertainment methods and characteristics, PVA assessment methods, subject demographics, psychiatric and medical comorbidities, and pertinent results. Inciting and confounding factors were extracted from case reports. Quality assessment tools were applied in accordance with the study design (e.g., observational, qualitative, or case report). RESULTS: The search identified 10 manuscripts: 2 observational quantitative studies (total n with PD = 545), 1 qualitative study (n with PD = 20), and 7 case reports (n = 7). The observational studies suggested that PVA is less common than other neuropsychiatric disturbances, but heterogeneous methods and quality concerns prevented further conclusions. In the case reports, all patients were male, and most were early onset. In 6 of the reports, PVA occurred in the context of bilateral subthalamic nucleus deep brain stimulation. CONCLUSIONS: PVA, while relatively rare in PD, can be a significant management issue that is associated with select premorbid characteristics and antiparkinsonian motor treatments. As PVA may be under-reported, further understanding of its frequency, causes, risk factors, and outcomes would benefit from its systematic assessment, ideally using self-report and informant-based questionnaires.

Incident apathy during the first year after stroke and its effect on physical and cognitive recovery.

OBJECTIVE: This prospective study examined the course of cognitive, physical, and social impairment among patients who developed apathy during the first year after stroke. METHODS: Patients diagnosed with apathy (N = 23) were compared with patients who had no apathy (N = 33) at initial, 3, 6, 9, and 12 months after stroke for severity of global cognitive impairment as measured by Mini-Mental State Examination, severity of impairment in activities of daily living (ADLs) as measured by Functional Independence Measure, and severity of impairment in social functioning as measured by Social Functioning Exam. RESULTS: A total of 41.1% of patients met diagnostic criteria for apathy during the first year after stroke. The mean time from stroke to onset of apathy was 3.8 (3.3 SD) months and the mean duration was 5.6 (2.3 SD) months. Using a linear mixed model, after controlling for age, initial severity of impairment, and major depression, patients in the apathy group had significantly less recovery in cognition (t(149) = -2.06; p = 0.0411) and ADLs (t(104) = -3.37; p = 0.0011) during the first year after stroke compared with nonapathic patients. CONCLUSION: Apathy is common after stroke and leads to less recovery in cognition and ADLs over the first year after stroke compared with similar nonapathic patients.

Prevention of poststroke apathy using escitalopram or problem-solving therapy.

OBJECTIVE: Apathy occurs frequently following stroke and prior studies have demonstrated the negative effect of apathy on recovery from stroke. This study was a secondary analysis examining the efficacy of escitalopram, problem-solving therapy (PST), or placebo administered for 1 year to prevent the onset of apathy among patients with recent stroke. METHODS: Patients within 3 months of an index stroke who did not meet DSM-IV diagnostic criteria for major or minor depression and who did not have a serious comorbid physical illness were enrolled. Patients were recruited from three sites: University of Iowa, University of Chicago, and Burke Rehabilitation Hospital. One hundred fifty-four patients without evidence of apathy at initial evaluation were included in the randomized controlled trial using escitalopram (10 mg patients ≤65 years; 5 mg patients >65 years) (N = 51) or placebo (N = 47) or non-blinded PST (12 total sessions) (N = 56) over 1 year. At 3, 6, 9, and 12 months, patients were assessed for diagnosis and severity of apathy using the Apathy Scale. RESULTS: Using a Cox proportional hazards model of time to onset of apathy, participants given placebo were 3.47 times more likely to develop apathy than patients given escitalopram and 1.84 times more likely to develop apathy than patients given PST after controlling for age, sex, cognitive impairment, and diabetes mellitus status (adjusted hazard ratio: 3.47, 95% CI: 1.79-6.73 [escitalopram group]; adjusted hazard ratio: 1.84, 95% CI: 1.21-2.80 [PST group]). CONCLUSION: Escitalopram or PST was significantly more effective in preventing new onset of apathy following stroke compared with placebo.

The NIHSS supplementary motor scale: a valid tool for multidisciplinary recovery trials.

BACKGROUND: There is a growing interest in therapies that may augment motor recovery that could be initiated in the acute stroke unit and maintained through the rehabilitation period. Homogenization of the currently fragmented stroke clinicometrics is necessary before such multidisciplinary trials can be conducted. The supplementary motor scale of the NIH Stroke Scale (SMS-NIHSS) is a simple and reliable scale for assessing proximal and distal motor function in the upper and lower extremities. We hypothesized that the currently underutilized SMS-NIHSS is a valid tool for assessing motor recovery with prognosticative value. METHODS: We performed an analysis of SMS-NIHSS scores recorded in 1,281 patients enrolled in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST). We plotted the probability of a favorable outcome (FO) and very favorable outcome (VFO) at 3 months based on the baseline SMS-NIHSS scores. In order to better study the relationship between SMS-NIHSS and 3-month functional outcome, we performed multivariate logistic regression analyses using both FO and VFO as outcome measures. Analyses were adjusted for potential confounders such as age, sex, side of the lesion, time from symptom onset to emergency room arrival, temperature, systolic blood pressure, blood glucose level and treatment group assignment (ORG 10172 vs. placebo). We also calculated the Spearman correlation coefficient between the SMS-NIHSS, Barthel Index (BI) and Glasgow Outcome Score (GOS) obtained at the 3-month visit. RESULTS: The mean SMS-NIHSS scores were 8.18 at baseline and 4.68 at 3 months. The SMS-NIHSS scores showed a gradual improvement during the first 3 months after stroke. There was a linear relationship between the baseline SMS-NIHSS scores and the probability of an FO or VFO at 3 months. The SMS-NIHSS baseline score was an independent predictor of FO (OR = 0.86; 95% CI 0.84-0.87; p < 0.0001) and VFO (OR = 0.85; 95% CI 0.84-0.87; p < 0.0001) at 3 months after adjusting for confounders. The degree of improvement in the SMS-NIHSS scores from baseline to 3 months was also independently associated with FO and VFO (p < 0.0001). At 3 months, SMS-NIHSS scores showed a strong correlation with the BI (r = -0.70; p < 0.0001) and GOS (r = 0.73; p < 0.0001). CONCLUSIONS: The SMS-NIHSS is a valid scale for assessing motor recovery with prognosticative value, and may be sensitive to changes during recovery. Given that the SMS-NIHSS is an extension of the widely accepted NIHSS, it could be easily implemented in trials conducted in a variety of clinical research settings, including acute stroke hospitals and rehabilitation units.

Donepezil alone and combined with intensive language-action therapy on depression and apathy in chronic post-stroke aphasia: A feasibility study.

This study explored the feasibility and effectiveness of a short-term (10-week) intervention trial using Donepezil administered alone and combined with intensive language action therapy (ILAT) for the treatment of apathy and depression in ten people with chronic post-stroke aphasia. Outcome measures were the Western Aphasia Battery and the Stroke Aphasia Depression Questionnaire-21. Structural magnetic resonance imaging and 18fluorodeoxyglucose positron emission tomography were acquired at baseline and after two endpoints (Donepezil alone and Donepezil-ILAT). The intervention was found to be feasible to implement. Large treatment effects were found. Donepezil alone and combined with ILAT reduced aphasia severity, while apathy and depression only improved with Donepezil-ILAT. Structural and functional neuroimaging data did not show conclusive results but provide hints for future research. Given these overall positive findings on feasibility, language and behavioral benefits, further studies in larger sample sizes and including a placebo-control group are indicated.