An atypical autopsy case of Lewy Body disease with clinically diagnosed major depression: A clinical,radiological and pathological study

We report an 84‐year‐old woman who was clinically diagnosed with late‐life major depression (LLMD) and having a diffuse type of dementia with Lewy bodies (DLB) neuropathologically. Clinically, this case showed depressive mood, anxiety, and irritation, but did not show cognitive dysfunction, visual hallucination, fluctuation of alertness and parkinsonism, which define the criteria for diagnosing DLB. Neuropathological examination demonstrated abundant Lewy‐related pathology including Lewy bodies and neurites in the hippocampal region and the cerebral cortex, and moderate levels in brain stem nuclei including the substantia nigra, locus ceruleus and dorsal raphe nucleus. These findings suggest the possibility that Lewy‐related pathology is associated with the depressive symptoms. Furthermore, it must be noted that some patients diagnosed with LLMD clinically may develop pathology of DLB without the typical or usual clinical symptoms.     

Dementia with Lewy bodies and depressive state

Depressive states are often observed in patients with dementia with Lewy bodies (DLB) during the clinical course and the prodromal stage. In the depressive state in patients with DLB, manifestations such as hallucinations, delusions, anxiety, hypochondria, agitation, and apathy are often found. As the differentiation of DLB and senile depression is often difficult, it is always necessary to consider the possibility of DLB for elderly patients with depression. In the pharmacotherapy for the depressive state of DLB, we should avoid using tricyclic antidepressants because of anticholinergic adverse effects. SSRIs and SNRIs are a better choice, with careful monitoring effects and side effects. Modified electro-convulsive therapy (mECT) or transcranial magnetic stimulation therapy (TMS) may be effective for pharmacotherapy-resistant cases.     

Dementia with Lewy Bodies is associated with higher scores on the Geriatric Depression Scale than is Alzheimer's disease

Background: Several reports suggest a higher morbidity of depression in patients with dementia with Lewy bodies (DLB) than in patients with Alzheimer's disease (AD). However, these results have not been duplicated consistently. The psychiatric symptoms of dementia, including depression, are important for its diagnosis and management. Thus, the aim of the present study was to clarify the characteristics of the depressive symptoms in DLB compared with AD using the Geriatric Depression Scale (GDS). Methods: We examined the GDS score for 86 patients with probable DLB (based on the Consensus Criteria for the clinical diagnosis of DLB) and 86 patients with probable AD (based on criteria of the National Institute for Neurological and Communicative Disorders and Stroke‐Alzheimer's Disease and Related Disorders Association), who were matched according to age, sex, education, and Mini‐Mental State Examination (MMSE) scores. We also examined correlations between GDS scores and age, sex, or MMSE scores in both groups. Correlations between GDS scores and metaiodobenzylguanidine (MIBG) scintigraphy were examined in patients with DLB. To characterize the GDS in DLB, its profile was examined using factor structures. Results: Scores for DLB patients were twice as high on the GDS as those for AD patients. There was no correlation between GDS score and age, sex, or MMSE scores in either group. Furthermore, there was no correlation between the results of MIBG scintigraphy and GDS scores in the DLB group. Using factor structures, the depression symptom profile of these diseases suggested that depression‐specific symptoms, such as mood, worry, or future outlook, were more frequent in the DLB group than non‐specific symptoms, such as lack of energy, decreased concentration, or apathy. Conclusions: The data suggest that depressive symptoms are highly specific symptoms of DLB, independent of other features of this disorder. The GDS could be used as a subsidiary tool in differentiating DLB from AD and is more useful than clinical observations of depression.     

Dementia with Lewy bodies: early diagnostic challenges

Dementia with Lewy bodies (DLB) is defined pathologically as neurodegeneration associated with Lewy bodies (LB). LB‐related symptoms, including olfactory dysfunction, dysautonomia, and mood and sleep disorders, are increasingly recognized as clinical signs that enable the early detection of DLB, because these symptoms often antedate dementia by years or even decades. It remains unknown if the clinical history of LB‐related symptoms is sufficient for the prodromal state of DLB to be suspected in memory clinics. We retrospectively investigated the clinical courses, including olfactory dysfunction, dysautonomia, depression, and rapid eye movement sleep behaviour disorder, of 90 patients with probable DLB. The timing of LB‐related symptoms that preceded or followed relative to the onset of memory loss was calculated. LB‐related symptoms were present in 79 of 90 patients (87.8%) with probable DLB before or at the time of memory loss onset. These symptoms preceded the onset of memory loss between 1.2 and 9.3 years. We also report on four non‐demented patients with a clinical history of LB‐related symptoms in our memory clinic. All four patients showed reduced cardiac [¹²³I]‐metaiodobenzylguanidine levels. Moreover, [¹⁸F]fluoro‐D‐glucose positron emission tomography scans revealed glucose hypometabolism in the occipital cortex in two patients. One patient converted to probable DLB with the development of parkinsonism 2 years after major depression was diagnosed. Based on a clinical history of LB‐related symptoms, we propose a conceptual framework to identify these symptomatic but non‐demented individuals that led us to suspect the underlying pathophysiology of Lewy body disease. Further prospective study is warranted to determine the clinical significance of LB‐related symptoms in non‐demented patients.     

The treatment of psychotic major depressive disorder with drugs and electroconvulsive therapy.

A retrospective chart review of 54 patients demonstrating depression with psychotic symptoms was accomplished with the use of Research Diagnostic Criteria (RDC) for diagnosis of psychotic major affective disorder. Patients received adequate trials of either tricyclic antidepressants alone, antipsychotics, the two in combination, or electroconvulsive therapy (ECT). Antidepressants alone were found to be ineffective or only partially effective in treating psychotic depression unless somatic or depressive declusions were the only psychotic symptoms. Antipsychotics alone were usually effective in providing at least a partial response, particularly with psychotic symptoms. Excellent responses of the depressive and psychotic elements were provided with ECT, ECT with antipsychotic medication, and the combination of antidepressant and antipsychotic medications. These latter treatments may be the most appropriate for depression with psychotic features.     

A comparative study of psychiatric symptoms in dementia with Lewy bodies and Parkinson's disease with and without dementia

OBJECTIVES: To compare the frequency and clinical correlates of neuropsychiatric symptoms in patients with Parkinson's disease (PD) with and without dementia and in those with dementia with Lewy bodies (DLB). METHODS: Neuropsychiatric symptoms during the month prior to assessment were assessed in clinically diagnosed PD patients with dementia (PDD; n = 48) and without dementia (PDND; n = 83) and in 98 DLB patients (33% autopsy confirmed) using standardized instruments. RESULTS: Delusions and hallucinations were significantly more common in DLB (57% and 76%) than PDD (29% and 54%) and PDND (7% and 14%) patients (p < 0.001). In all groups, auditory and visual hallucinations and paranoid and phantom boarder delusions were the most common psychotic symptoms. Frequency of major depression and less than major depression did not differ significantly between the three groups. Clinical correlates of hallucinations in PD were dementia (odds ratio (OR) = 3.9; 95% confidence interval (CI) 1.5-10.4) and Hoehn-Yahr stage 3 or more (OR 3.4; 95% CI 1.0-12.0), whereas no significant clinical correlates of hallucinations were found in DLB patients. CONCLUSIONS: Delusions and hallucinations occur with increasing frequency in PDND, PDD and DLB patients, but the presentation of these symptoms is similar. These findings support the hypothesis that psychiatric symptoms are associated with cortical Lewy bodies or cholinergic deficits in the two disorders.     

Dementia with Lewy Bodies (DLB) presenting with catatonic symptoms

In this report, we demonstrate through a putative case that Dementia with Lewy Bodies (DLB) can present with a catatonic syndrome which can pose diagnostic and management challenges. The patient was an 88‐year‐old gentleman presenting with acute psychotic and catatonic symptoms on a background of 5 months of functional decline. He showed good response of catatonic symptoms to Clonazepam and psychotic symptoms to Olanzapine. This led to resolution of behavioral problems and the establishment of a putative diagnosis of DLB. Patients with DLB may present with catatonic states; benzodiazepines help resolve catatonic symptoms and facilitate assessment in such patients; and Olanzapine effectively treats psychotic symptoms in DLB.     

A prospective naturalistic study of electroconvulsive therapy in late-life depression

We performed a prospective, naturalistic study using standardized clinical rating scales to characterize the effect of electroconvulsive therapy (ECT) on mood, cognition, and medical status in late-life depression. Over a 16-month period, 40 patients aged 60 years and over who fulfilled DSM-III criteria for a major depressive episode received a total of 42 ECT courses. Three patients (7%) developed significant medical complications: one had a syncopal episode due to arrhythmia, and two had symptomatic vertebral compression fractures. Confusion was noted during 13 courses (31%) and persisted at discharge in four (10%). More than half the patients were either psychotic or demented on admission, and all but three had been either unresponsive or intolerant to pharmacotherapy. All patients experienced a decrease in their depressive symptoms and more than two thirds were in complete or partial remission at discharge. Patients with psychotic depression experienced a greater improvement than patients with nonpsychotic depression, and patients with organic mental disorders experienced the same improvement as other patients. This study confirms that ECT is a safe and effective treatment of depression in late life.     

CASE REPORT: Psychotic symptoms complicate the clinical differentiation of Parkinson's disease with major depressive disorder from dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is diagnosed clinically according to the diagnostic criteria in the Third Report of the DLB Consortium. However, psychotic symptoms, such as visual hallucinations, delusions, and stupor, may complicate the clinical diagnosis of DLB. The present study reports on a patient with Parkinson's disease that was difficult to distinguish from DLB because of the presence of various psychotic symptoms. In making a diagnosis of DLB, it is important to assess essential psychiatric features and to observe patients for any changes in these features.     

Predicting efficacy of electroconvulsive therapy in major depressive disorder

The aim of this study was to investigate methods for predicting the efficacy of electroconvulsive therapy (ECT) in patients with major depressive disorder. Subjects comprised 24 inpatients with major depressive disorder diagnosed according to DSM-IV criteria who were resistant to antidepressant therapy or who, due to adverse reactions, could not undergo pharmacotherapy at adequate doses for sufficient durations. ECT was generally performed 12 times using a sinusoidal-wave device. Efficacy of ECT was evaluated using the 17-item Hamilton Rating Scale for Depression (HRSD). Multiple regression analysis was performed, using the final rate of improvement with ECT as the dependent variable, and improvement rate at completion of three ECT sessions and adequacy of pharmacotherapy before ECT as independent variables. Significant positive correlations were seen between final improvement rate with ECT and improvement rate at completion of three ECT sessions (partial correlation coefficient, 0.50, P<0.02), and significant negative correlations were seen between final improvement rate and adequacy of pharmacotherapy before ECT (partial correlation coefficient, -0.51, P<0.02). No significant differences were identified between responders and non-responders with respect to age, sex, duration of index episode, number of previous depressive episodes, whether depression was melancholia-type, whether depression was accompanied by psychotic features, total HRSD score immediately before ECT, and HRSD retardation or agitation scores. These results suggest that history of pharmacotherapy prior to ECT and improvement rate at completion of three ECT sessions may offer predictors for the final rate of improvement with ECT.     

A randomized controlled comparison of electroconvulsive therapy and repetitive transcranial magnetic stimulation in severe and resistant nonpsychotic major depression.

BACKGROUND: Studies published over the past few years suggest that transcranial magnetic stimulation (TMS) may have significant antidepressant actions. In a previous report, we compared electroconvulsive therapy (ECT) and repetitive TMS (rTMS) and found ECT to be superior for psychotic major depression (MD); however, ECT and rTMS had similar results in nonpsychotic MD. We now report on a controlled randomized comparison of ECT and rTMS in patients with nonpsychotic MD. METHODS: Forty patients with nonpsychotic MD referred for ECT were included. Electroconvulsive therapy was performed according to established protocols. Repetitive TMS was performed over the left dorsolateral prefrontal cortex at 90% motor threshold. Patients were treated with 20 sessions (five times per week for 4 weeks) of 10-Hz treatments (1200 pulses per treatment-day) at 90% motor threshold. Response to treatment was defined as a decrease of at least 50% in the Hamilton Rating Scale for Depression (HRSD) score, with a final HRSD equal or less than 10 points and a final Global Assessment of Function Scale rating of 60 or more points. RESULTS: The overall response rate was 58% (23 out of 40 patients responded to treatment). In the ECT group, 12 responded and eight did not; in the rTMS group, 11 responded and nine did not (chi2 =.10, ns). Thus, patients responded as well to either ECT or rTMS. CONCLUSIONS: This study adds to the growing literature supporting an antidepressant effect for rTMS. This study is particularly relevant because it suggests that rTMS and ECT reach similar results in nonpsychotic major depressive disorder.     

Major depressive disorder with psychotic features may lead to misdiagnosis of dementia: a case report and review of the literature

Major depressive disorder (MDD) with psychotic features is relatively frequent in patients with greater depressive symptom severity and is associated with a poorer course of illness and greater functional impairment than MDD without psychotic features. Multiple studies have found that patients with psychotic mood disorders demonstrate significantly poorer cognitive performance in a variety of areas than those with nonpsychotic mood disorders. The Mini Mental State Examination (MMSE) and the Dementia Rating Scale, Second Edition (DRS-2) are widely used to measure cognitive functions in research on MDD with psychotic features. Established total raw score cut-offs of 24 on the MMSE and 137 on the DRS-2 in published manuals suggest possible global cognitive impairment and dementia, respectively. Limited research is available on these suggested cut-offs for patients with MDD with psychotic features. We document the therapeutic benefit of electroconvulsive therapy (ECT), which is usually associated with short-term cognitive impairment, in a 68-year-old woman with psychotic depression whose MMSE and DRS-2 scores initially suggested possible global cognitive impairment and dementia. Over the course of four ECT treatments, the patient's MMSE scores progressively increased. After the second ECT treatment, the patient no longer met criteria for global cognitive impairment. With each treatment, depression severity, measured by the 24-item Hamilton Rating Scale for Depression, improved sequentially. Thus, the suggested cut-off scores for the MMSE and the DRS-2 in patients with MDD with psychotic features may in some cases produce false-positive indications of dementia.     

Levodopa treatment and mood fluctuation in dementia with Lewy bodies: a case report

L‐3,4‐dihydroxyphenylalanine (L‐dopa) has been the gold standard for pharmacotherapy for parkinsonism in patients with dementia with Lewy bodies (DLB). While L‐dopa treatment is related to visual hallucinations, its relationship to mood fluctuation in DLB is poorly understood. Herein, we report the improvement of behavioural and psychological symptoms of dementia through the adjustment of L‐dopa treatment in a 78‐year‐old woman with probable DLB. Her marked mood swings were improved by changing L‐dopa administration from three to five times per day while maintaining the same total daily dosage. This observation suggests that there may be an association between plasmatic L‐dopa levels and mood fluctuation in patients with DLB. This pharmacological approach may be useful in the management of behavioural and psychological symptoms of dementia without the use of antipsychotic agents to avoid severe neuroleptic sensitivity, which is one of the suggestive clinical features in the Third Consortium on DLB clinical criteria.     

Antipsychotic effect of electroconvulsive therapy is related to normalization of subgenual cingulate theta activity in psychotic depression

OBJECTIVE: Electroconvulsive therapy (ECT) is one of the most effective options available for treating depressive and psychotic symptoms in a variety of disorders. While the exact mechanism of ECT is unclear, it is known to increase metabolism and blood flow specifically in the anterior cingulate cortex (ACC). The ACC is a cortical generator of theta rhythms, which are abnormal in patients with depression and psychotic disorders. Since patients with psychotic depression are known to respond particularly robustly to ECT, we investigated whether the therapeutic effect of ECT in this population was related to normalization of abnormal theta activity in the ACC. METHOD: We obtained 19-lead electroencephalography (EEG) data from 17 participants with psychotic depression before and 2-3 weeks after a full course of ECT. EEG data was analyzed with quantitative measures and low-resolution electromagnetic tomography (LORETA) compared to an age-adjusted normative database. RESULTS: Quantitative EEG analyses revealed that theta band (4-7 Hz) activity was the only frequency band that changed with ECT. LORETA analyses revealed that the primary site of theta activity change was within the subgenual ACC (Brodmann area 25). There was a positive association between increased subgenual ACC theta activity and decreased psychotic symptoms. The degree of low theta activity in the subgenual ACC prior to ECT predicted the antipsychotic response of ECT. CONCLUSIONS: The antipsychotic effect of ECT is related to normalization of subgenual ACC theta hypoactivity.     

Treatment of dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is known for its partial resistance and hypersensitivity to some treatments, but DLB is treatable with cholinesterase inhibitors, sometimes better than in Alzheimer's disease. Cholinesterase inhibitors have a symptomatic effect on cognition and behavior. Nevertheless, new antipsychotics are sometimes also useful to manage psychotic symptoms. Although DLB patients respond less well to levodopa than patients with Parkinson's disease, 75 percent of DLB patients improve with levodopa, which is the best-tolerated dopaminergic agent. Nonpharmacological strategies include speech therapy, physiotherapy, psychotherapy, and educational support groups for care givers.     

BDNF blood levels after electroconvulsive therapy in patients with mood disorders: A systematic review and meta-analysis

Objectives. To evaluate whether electroconvulsive therapy (ECT), a very effective non-pharmacological treatment for mood disorders, induces neurotrophic effects, indexed by the measurement of peripheral brain-derived neurotrophic factor (BDNF) levels. Methods. Systematic review and meta-analysis of clinical trials published in PubMed/Medline from the first date available to October 2013. We included studies measuring pre- and post-BDNF blood levels under ECT in patients with mood disorders in the acute depressive episode. Results. Eleven studies (n = 221 subjects) were eligible. These studies enrolled subjects with unipolar, bipolar and psychotic depression and varied regarding electrode placement (unipolar vs. bipolar) and previous use of pharmacotherapy. Nonetheless, BDNF significantly increased after ECT (Hedges’ g pooled, random-effects model of 0.354; 95% CI = 0.162–0.546). The results were robust according to sensitivity analysis and Begg's funnel plot did not suggest publication bias. Meta-regression results did not show association of the outcome with any clinical and demographic variable, including depression improvement. Conclusions. Our meta-analysis indicates that, similar to pharmacological interventions, peripheral BDNF increases after ECT treatment. The lack of correlation between BDNF increasing and depression improvement suggests that ECT induces neurotrophic effects regardless of clinical response in depression.     

Three and six-month outcome following courses of either ECT or rTMS in a population of severely depressed individuals--preliminary report.

BACKGROUND: Recent studies have strengthened the claim that repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depression. The longitudinal outcome of TMS-treated patients, however, has not been described. We report on the 3- and 6-month outcomes of a group of patients treated with either electroconvulsive therapy (ECT) (n = 20) or (rTMS) (n = 21). METHODS: Patients diagnosed with major depressive disorder with or without psychotic features referred for ECT were randomly assigned to receive either ECT or rTMS. Forty-one patients who responded to either treatment constituted the sample. Patients were followed on a monthly basis and outcomes were determined with the Hamilton Rating Scale for Depression-17 items (HRSD) and the Global Assessment of Functioning (GAF) scales. Medications were routinely prescribed. RESULTS: There were no differences in the 6-month relapse rate between the groups. Overall, 20% of the patients relapsed (four from the ECT group and four from the rTMS group). Patients reported equally low and not significantly different scores in the HRSD (ECT group 8.4 +/- 5.6 and TMS group 7.9 +/- 7.1) and the GAF (ECT group 72.8 +/- 12 and TMS group 77.8 +/- 17.1) at the 6-month follow up. CONCLUSIONS: Patients treated with rTMS do as well as those treated with ECT at the 3- and 6-month follow-up points. These data suggest that the clinical gains obtained with rTMS last at least as long as those obtained with ECT.     

Short-and Long-term Efficacy of Electroconvulsive Therapy for Late-life Depression: A Pilot Study

Background : Electroconvulsive therapy (ECT) is often administered among the elderly, who are particularly likely to have concurrent medical conditions and medication intolerance. Objective : To examine the short‐and long‐term efficacy of ECT for late‐life depression, we performed a two‐phase, prospective, naturalistic follow‐up study that compared treatment outcome in old‐aged with that in middle‐aged subjects. Methods : Phase I study: Twenty‐one subjects who were consecutively referred for ECT, aged at least 50 years, and met the DSM‐IV criteria for a major depressive episode were enrolled. Before ECT, severity of concurrent medical conditions was assessed with the cumulative illness rating scale (CIRS). Before and after a course of ECT, the severity of depressive symptoms was evaluated with the 17‐item Hamilton rating scale for depression (HAM‐D). Phase II study: Seventeen subjects who responded to an acute ECT course in the phase I study were enrolled. Various continuation medications were administered, and symptoms were monitored and evaluated with the HAM‐D for 24 weeks or until relapse. Results : Overall the subjects had an 81 % short‐term response rate and a 47% relapse rate within 24 weeks after ECT. Response and relapse rates were not significantly different between the middle‐and old‐aged groups (response rates: 91% vs. 70%; relapse rates: 40% vs. 57%). However, the old‐aged patients had higher post‐ECT HAM‐D scores than the middle‐aged patients did (P<0.05), and CIRS scores positively correlated with post‐ECT HAM‐D scores (P<0.05). Relapsers tended to have higher CIRS scores than non‐relapsers did (P=0.06). Conclusion : In late‐life depression, the short‐term response rate to ECT is considerably good, but the relapse rate was relatively high. Clinicians need to take into consideration the age of patient and any concurrent medical conditions, when planning long‐term management of residual depressive symptoms and prevention of relapse after an initial good response to ECT.     

Practice of electroconvulsive therapy at the research and training hospital in Turkey

Objective  We sought to obtain an overview of electroconvulsive therapy (ECT) practice in Bakirkoy Research and Training Hospital for Psychiatric and Neurological Diseases, which is the biggest hospital for psychiatry in Turkey. Method  From 1st January 2006 to 30th June 2007, a form enquiring about evaluation of ECT was filled retrospectively. Results  The total number of patients, admitted for psychiatry during the survey period was 265,283. A total of 1,531 patients (12.4% among inpatients and 0.58% in all psychiatric admissions) received 13,618 sessions (including multiple hospitalizations) of ECT from 12,341 psychiatric inpatients during the survey period. Ninety-eight patients had multiple hospitalizations. The male-to-female ratio was 1.26–1. Patients with bipolar affective disorder, current episode manic with or without psychotic symptoms received ECT most frequently (30.3%), followed by patients with schizophrenia (29.5%), severe depressive episode with or without psychotic symptoms (include bipolar affective disorder current episode severe depression) (15.2%), other non-organic psychotic disorders (14.4%), schizoaffective disorders (6.3%), mental and behavioral disorders due to psychoactive substance abuse with psychotic disorders (3.5%) and catatonic schizophrenia (0.7%). Patients who received ECT were in age group of 25–44 years (64.7%), followed by 45–64 years (17.7%), 18–24 years (15.4%), 65 years and older (1.4%), and younger than 18 years (0.8%). All patients received modified ECT. There were no ECT-related deaths during the survey. Conclusion  The rate of ECT among all psychiatric inpatients during the survey period was 12.4%. The majority of patients who received ECT were diagnosed with bipolar affective disorder-current episode manic and schizophrenia. ECT training programs for psychiatry residents and specialists should be planned, and conducted systematically.     

Classification of psychotic symptoms in dementia with Lewy bodies.

OBJECTIVE: The aim of this study is to determine empirically a possible classification of psychotic symptoms, and identify the frequency of such symptoms in dementia with Lewy bodies (DLB). METHODS: This was a clinical study of prospectively observed patients from the memory clinic at Shiga Medical Center. The authors conducted a factor analysis of psychotic symptoms in 96 probable DLB and 4 possible DLB patients, clinically diagnosed according to the consensus criteria, were included. RESULTS: Four factors were obtained. Factor 1 was closely akin to misidentifications, including Capgras syndrome, phantom boarder, and reduplication of people and places. Factor 2 consisted of reduplication of people, the belief that deceased relatives are still alive, and the belief that absent relatives are in the house, which was classified as a type of misidentification or paramnesia. Factor 3 was akin to visual hallucinations of nonhuman objects, and factor 4 mirrored the hallucination of people and feeling of presence. Delusions were independent of these factors. Following the results of factor analysis, the rates of each symptom group were identified. Hallucinations were the most frequent psychotic symptom in DLB (78%), followed by misidentifications (56%) and delusions (25%). CONCLUSION: This study suggested that hallucinations, misidentifications, and delusions should be separately considered in understanding of underlying pathophysiology or psychopathology of DLB.