Robert G. Robinson

Poststroke depression : prevalence, diagnosis, treatment, and disease progression

In recent years, poststroke depression has attracted worldwide interest. This review focuses on the major research themes that have emerged. Pooled data from studies conducted throughout the world have found prevalence rates for major depression of 19.3% among hospitalized patients and 23.3% among outpatient samples. The diagnosis of poststroke depression is most appropriately based on a structured mental state exam and DSM-IV criteria for depression due to stroke with major depressive-like episode or depressive features. Rarely, poststroke patients may also develop bipolar mood disorder. The treatment of poststroke depression has been examined in several placebo-controlled randomized clinical trials with both nortriptyline and citalopram showing efficacy. The progression of recovery following stroke can be altered by treating depression, which has been shown to improve recovery in activities of daily living and cognitive impairment and to decrease mortality. In addition, two studies have demonstrated that poststroke depression can be prevented using antidepressant medication, which also decreases the frequency of associated physical illness. Furthermore, two studies have shown that premorbid depression can significantly increase the risk of stroke over the subsequent 10-15 years. The mechanisms underlying the association of cerebrovascular diseases and mood disorder are important areas for future investigation.

Effect of Antidepressants on the Course of Disability Following Stroke

OBJECTIVEnStroke often produces marked physical and cognitive impairments leading to functional dependence, caregiver burden, and poor quality of life. We examined the course of disability during a 1-year follow-up period after stroke among patients who were administered antidepressants for 3 months compared to patients given placebo for 3 months.nnnMETHODSnA total of 83 patients entered a double-blind randomized study of the efficacy of antidepressants to treat depressive disorders and reduce disability after stroke. Patients were assigned to either fluoxetine (N = 32), nortriptyline (N = 22) or placebo (N = 29). Psychiatric assessment included administration of the Present State Examination modified to identify DSM-IV symptoms of depression. The severity of depression was measured using the 17-item Hamilton Depression Rating Scale. The modified Rankin Scale was used to evaluate the disability of patients at initial evaluation and at quarterly follow-up visits for 1 year. Impairment in activities of daily living was assessed by Functional Independence Measure at the same time.nnnRESULTSnDuring the 1-year follow-up period, and after adjusting for critical confounders including age, intensity of rehabilitation therapy, baseline stroke severity, and baseline Hamilton Depression Rating Scale, patients who received fluoxetine or nortriptyline had significantly greater improvement in modified Rankin Scale scores compared to patients who received placebo (t [156] = -3.17, p = 0.002).nnnCONCLUSIONSnPatients treated with antidepressants had better recovery from disability by 1-year post stroke (i.e., 9 months after antidepressants were stopped) than patients who did not receive antidepressant therapy. This effect was independent of depression suggesting that antidepressants may facilitate the neural mechanisms of recovery in patients with stroke.

Apathy following stroke

Objective: We will review the available evidence on the frequency, clinical correlates, mechanism, and treatment of apathy following stroke. Methods: We have explored relevant databases (that is, PubMed, MEDLINE, and PsycINFO) using the following keywords and their combinations: apathy, motivation, abulia, stroke, cerebrovascular disease, basal ganglia, prefrontal cortex, anterior cerebral infarction, and thalamus. Results: The frequency of apathy following stroke has been consistently estimated between 20% and 25%. It appears to be associated with the presence of cognitive impairment, a chronic course characterized by progressive functional decline, and with disruption of neural networks connecting the anterior cingulate gyrus, the dorsomedial frontal cortex, and the frontal pole with the ventral aspects of the caudate nucleus, the anterior and ventral globus pallidus, and the dorsomedian and intralaminar thalamic nuclei. Published treatment studies have been mostly limited to anecdotal case reports, generally using dopamine agonists or stimulant medications. Cholinesterase inhibitors and nefiracetam may significantly reduce apathetic symptoms. However, their efficacy was examined in relatively small clinical trials that require replication. Conclusion: Apathy is a frequent neuropsychiatric complication of stroke that, although often associated with depression and cognitive impairment, may occur independently of both. Its presence has been consistently associated with greater functional decline. However, there is no conclusive evidence about which is the best treatment for this condition.

Blood Vessel Function and Cognition in Elderly Patients With Atherosclerosis

Background and Purpose— Although a strong relationship has been established between vascular disease and cognitive decline, the current challenge is to identify vascular risk factors and mechanisms that are associated with cognitive function before the development of severe dysfunction (eg, vascular dementia). This study was conducted to determine the relationship between blood vessel function and cognition in elderly patients with atherosclerosis. Methods— Participants were 14 elderly individuals with atherosclerotic vascular disease, who had no history of stroke, cardiac surgery, or dementia diagnosis. Forearm blood flow was measured before and after brachial artery infusion of 3 vasoactive agents (verapamil, acetylcholine, nitroprusside), and these measures of vessel function were then correlated with neuropsychological performance (total scale score on the Repeatable Battery for the Assessment of Neuropsychological Status). Results— Positive correlations were found between neuropsychological performance and vasodilation in response to all 3 agents, with 2 reaching statistical significance (verapamil: &rgr;=0.78, P=0.001; nitroprusside: &rgr;=0.56, P=0.038) and the third showing a strong trend toward significance (acetylcholine: &rgr;=0.49, P=0.076). Correlations between neuropsychological performance and more conventional vascular-related variables were much weaker. Conclusions— These data provide preliminary evidence of a relationship between resistance vessel function and neuropsychological performance. With further research, measures of vessel dysfunction may be useful in identifying individuals at risk for cognitive decline and vascular dementia.

Altered Neural Activity and Emotions Following Right Middle Cerebral Artery Stroke

Stroke of the right MCA is common. Such strokes often have consequences for emotional experience, but these can be subtle. In such cases diagnosis is difficult because emotional awareness (limiting reporting of emotional changes) may be affected. The present study sought to clarify the mechanisms of altered emotion experience after right MCA stroke. It was predicted that after right MCA stroke the anterior cingulate cortex (ACC), a brain region concerned with emotional awareness, would show reduced neural activity. Brain activity during presentation of emotional stimuli was measured in 6 patients with stable stroke, and in 12 age- and sex-matched nonlesion comparisons using positron emission tomography and the [(15)O]H(2)O autoradiographic method. MCA stroke was associated with weaker pleasant experience and decreased activity ipsilaterally in the ACC. Other regions involved in emotional processing including thalamus, dorsal and medial prefrontal cortex showed reduced activity ipsilaterally. Dorsal and medial prefrontal cortex, association visual cortex and cerebellum showed reduced activity contralaterally. Experience from unpleasant stimuli was unaltered and was associated with decreased activity only in the left midbrain. Right MCA stroke may reduce experience of pleasant emotions by altering brain activity in limbic and paralimbic regions distant from the area of direct damage, in addition to changes due to direct tissue damage to insula and basal ganglia. The knowledge acquired in this study begins to explain the mechanisms underlying emotional changes following right MCA stroke. Recognizing these changes may improve diagnoses, management and rehabilitation of right MCAxa0strokexa0victims.

Prevention of Poststroke Apathy Using Escitalopram or Problem-Solving Therapy

OBJECTIVEnApathy 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.nnnMETHODSnPatients 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.nnnRESULTSnUsing 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]).nnnCONCLUSIONnEscitalopram or PST was significantly more effective in preventing new onset of apathy following stroke compared with placebo.

Decreased heart rate variability is associated with poststroke depression.

OBJECTIVEnAlthough decreased heart rate variability (HRV) has been well-documented in association with depression after myocardial infarction, this phenomenon has not been studied in patients with stroke. The present study was designed to prospectively assess heart rate in relationship to depression among patients with acute stroke.nnnDESIGNnUsing 24-hour Holter monitoring, HRV was assessed.nnnSETTINGnA large university rehabilitation hospital.nnnPARTICIPANTSnPatients with first ever stroke and no other severe physical illness, cigarette smoking, or drug therapy that could affect HRV were evaluated over 24 hours for HRV.nnnMEASUREMENTSnPatients were evaluated using the Structured Clinical Interview for depression diagnosis. Severity was assessed by the Hamilton Depression Rating Scale. Stroke severity was assessed by the National Institutes of Health Stroke Scale, the Barthel Index, and the Mini- Mental State Exam. The standard deviation (SD) of time in milliseconds of normal to normal beats (SDNN) was the primary measure of HRV.nnnRESULTSnAmong patients with poststroke major or minor depression (N = 33), the SDNN was 109 +/- 32.6 SD compared with nondepressed patients (N = 16) whose SDNN was 133.9 +/- 40.1 SD (Wilcoxon rank test S = 492, p = 0.048). The SDNN was significantly and independently related to the existence of depression, but no other intergroup differences.nnnCONCLUSIONSnThese findings, for the first time, have provided some evidence that both major and minor poststroke depression may lead to decreased HRV. Future research in larger groups of patients should determine whether other measures of HRV more specific to sympathetic-parasympathetic tone are decreased in patients with poststroke depression.

Is Family History of Depression a Risk Factor for Poststroke Depression? Meta-Analysis

OBJECTIVEnTo determine whether family history of psychiatric disorder constitutes a risk factor for the development of poststroke depression.nnnDESIGNnA meta-analysis setting: patients examined for depression following stroke seen in acute care, rehabilitation hospital, or outpatient care settings.nnnPARTICIPANTSnAll patients who were reported in the worlds literature in English language publications in which information was provided about the existence or not of poststroke depression and the presence or absence of a family history of psychiatric disorder.nnnMEASUREMENTSnThe frequency of family history of psychiatric disorder was determined for each study as well as the relationship of family history to the presence of poststroke depression.nnnRESULTSnBased on data obtained from 903 patients with stroke, the fixed model analysis found a risk ratio of 1.51 and the random model a risk ratio of 1.46 for the existence of poststroke depression if there is a positive family history of psychiatric disorder compared with a negative family history.nnnCONCLUSIONSnThe existence of a positive family history of psychiatric disorder constitutes a risk factor for development of poststroke depression. The role of family history in poststroke depression, however, appears to be substantially lower than among elderly depressed patients without evidence of vascular disease.

Treatment of late-life depression: A role of non-invasive brain stimulation techniques

Late-life depression (LLD) is a frequent complication of the ageing process, occurring in up to 5% of community-dwelling elderly and in a higher proportion of subjects with coexistent medical illnesses. Its presence has been consistently associated with cognitive impairment, greater disability and increased mortality. Approximately half of patients with LLD have evidence of subcortical ischaemic damage in prefrontal circuits revealed by MRI. This might constitute the biological substrate of the cardinal symptoms of depression and of executive dysfunction. An important proportion of patients with LLD do not achieve remission of their depressive symptoms in spite of adequate pharmacological and psychotherapeutic treatment. In addition, a group of LLD patients progress to further impairment and disability in the form of a dementing disorder. There is an imperative need to develop new treatment strategies for LLD. Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are safe and efficacious interventions that might be used in combination with other therapeutic options to improve treatment outcomes. However, there are still questions regarding the optimal way in which rTMS and dTCS should be delivered as well as to the way in which we may identify the subjects who will benefit the most from these interventions.

Incident Apathy During the First Year After Stroke and Its Effect on Physical and Cognitive Recovery

OBJECTIVEnThis prospective study examined the course of cognitive, physical, and social impairment among patients who developed apathy during the first year after stroke.nnnMETHODSnPatients 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.nnnRESULTSnA 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.nnnCONCLUSIONnApathy is common after stroke and leads to less recovery in cognition and ADLs over the first year after stroke compared with similar nonapathic patients.