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.

Intensive aphasia therapy improves low mood in fluent post-stroke aphasia: Evidence from a case-controlled study.

Introduction: Depressive symptoms are a major drawback of aphasia, negatively impacting on functional outcomes. In a previous study, Intensive Language-Action Therapy (ILAT) was effective in improving depression and low mood in persons with chronic non-fluent aphasia. We present a proof-of-concept case-control study that evaluates language and mood outcomes amongst persons with fluent post-stroke aphasia.Participants: Thirteen Spanish speaking persons with fluent aphasia due to chronic stroke lesions in the left hemisphere participated in the study.Intervention: Five participants (intervention group) received ILAT for 3 h/day during two consecutive weeks, for an overall of 30 h, and 8 participants (control group) entered a waiting-list no-treatment arm.Results: The main finding was that participants receiving active treatment showed significant improvements on depression and aphasia severity scores, whereas no significant changes were found in the control group.Conclusions: The implementation of ILAT was efficient in improving clinical language deficits in people with fluent aphasia and contributes to improvement in mood after therapy.Trial registration: EUDRACT (2008-008481-12).

Dementia onset, incidence and risk in type 2 diabetes: a matched cohort study with the Fremantle Diabetes Study Phase I.

AIMS/HYPOTHESIS: The study aimed to assess the incidence, age of onset, survival and relative hazard of dementia in well-categorised community-based patients with type 2 diabetes compared with a matched cohort of individuals without diabetes. METHODS: A longitudinal observational study was undertaken involving 1291 participants with type 2 diabetes from the Fremantle Diabetes Study and 5159 matched residents without documented diabetes. Linkage with health-related databases was used to detect incident dementia. Relative hazards were assessed using both cause-specific and subdistribution proportional hazards models. RESULTS: During 13.8 ± 5.8 years of follow-up, incident dementia occurred in 13.9% and 12.4% of the groups of participants with and without diabetes, respectively (p = 0.15). With type 2 diabetes, the incidence of dementia was higher (incidence rate ratio [IRR] 1.28, 95% CI 1.08, 1.51), as was the competing risk of death (IRR 1.50, 95% CI 1.38, 1.64). The ages when dementia was first recorded and when death with dementia occurred were both earlier with diabetes, by 1.7 (95% CI 0.6, 2.9) and 2.3 (95% CI 1.1, 3.6) years, respectively (both p ≤ 0.004). Type 2 diabetes was associated with an adjusted subdistribution HR of 1.18 (95% CI 1.00, 1.39), and a cause-specific HR of 1.51 (95% CI 1.27, 1.78) for all-cause dementia. CONCLUSIONS/INTERPRETATION: Type 2 diabetes is associated with an increased incidence of dementia, and dementia onset occurs at a younger age. The relative hazards of both dementia and premature mortality are increased and, as a consequence, the increased risk of dementia in type 2 diabetes is not as marked as suggested by cause-specific HRs.

Modeling anxiety in Parkinson's disease.

BACKGROUND: The aim of this work was to construct a model for anxiety in PD and compare the relative contributions of PD-specific and -nonspecific general population risk factors for anxiety in this model. METHODS: Structural equation modeling of associations of risk factors with the anxiety outcome using a cross-sectional data set of 342 patients with PD were used. RESULTS: A model with acceptable to good fit was generated that explained 65% of the variance in anxiety scores. A previous history of depression and the severity of the depressive symptoms scored on the Hamilton Depression Rating Scale were the only nonspecific variables with a direct effect on anxiety. The presence of motor fluctuations and disease-related decline in activities of daily living were PD-specific markers of anxiety. Nonspecific risk factors had a greater influence in the model than PD-specific risk factors. Standardized regression coefficients suggested that the Hamilton Depression Rating Scale score was the most important contributor to the variation in anxiety. A post-hoc analysis showed that the effects of the following variables on anxiety levels were fully mediated by depression: sex; family history of depression; previous history of anxiety; cognitive status; difficulties in non-disease-specific activities of daily living; and severity of motor signs. CONCLUSION: In this cross-sectional study, we showed that nonspecific general population risk factors are more important markers for anxiety than PD-specific risk factors. Depression was the most prominent marker. PD-specific markers for anxiety appear to be more situational and related to off periods and disease-specific disturbances of activities of daily living.

Comorbid Anxiety and Depression and Their Impact on Cardiovascular Disease in Type 2 Diabetes: The Fremantle Diabetes Study Phase II.

BACKGROUND: The aims were to determine whether anxious depression, defined by latent class analysis (LCA), predicts cardiovascular outcomes in type 2 diabetes and to compare the predictive power of anxious depression with Diagnostic & Statistical Manual Versions IV and 5 (DSM-IV/5) categories of depression and generalized anxiety disorder (GAD). METHODS: Prospective observational study of 1,337 type 2 participants. Baseline assessment with the 9-item Patient Health Questionnaire and the GAD Scale; LCA-defined groups with minor or major anxious depression based on anxiety and depression symptoms. Cox modeling used to compare the independent impact of: (1) LCA anxious depression, (2) DSM-IV/5 depression, (3) GAD on incident cardiovascular events and deaths after 4 years. RESULTS: LCA minor and major anxious depression was present in 21.9 and 7.8% of participants, respectively, DSM-IV/5 minor and major depression in 6.2 and 6.1%, respectively, and GAD in 4.8%. There were 110 deaths, 31 cardiovascular deaths, and 199 participants had incident cardiovascular events. In adjusted models, minor anxious depression (Hazard ratio (95% confidence intervals): 1.70 (1.15-2.50)) and major anxious depression (1.90 (1.11-3.25)) predicted incident cardiovascular events and major anxious depression also predicted cardiovascular mortality (4.32 (1.35-13.86)). By comparison, incident cardiovascular events were predicted by DSM-IV/5 major depression (2.10 (1.22-3.62)) only and cardiovascular mortality was predicted by both DSM-IV/5 major depression (3.56 (1.03-12.35)) and GAD (5.92 (1.84-19.08)). CONCLUSIONS: LCA-defined anxious depression is more common than DSM-IV/5 categories and is a strong predictor of cardiovascular outcomes in type 2 diabetes. These data suggest that this diagnostic scheme has predictive validity and clinical relevance.

A Randomized, Placebo-Controlled, Double-Blind Efficacy Study of Nefiracetam to Treat Poststroke Apathy.

BACKGROUND: To evaluate the efficacy of treatment with nefiracetam compared to placebo in poststroke apathy. METHODS: A parallel group, randomized, placebo-controlled, double-blind two-center trial in patients with recent stroke and apathy was conducted in 2 tertiary teaching hospitals in Perth, Western Australia, between March 2010 and October 2014. Consenting patients hospitalized with stroke were screened for participation at the time of hospitalization and, if diagnosed with apathy 8-36 weeks later, they were randomized to 12 weeks of 900 mg/day nefiracetam or placebo. The primary efficacy parameter was change in apathy at 12 weeks defined by the 14-item Apathy Scale (AS). RESULTS: Of 2514 patients screened, only 377 (15%) were eligible for the study after the first screening, 233 declined further participation, and 144 were assessed for apathy at 8-36 weeks post stroke to confirm eligibility. Twenty patients out of 106 with a complete psychiatric assessment had apathy (19%). Of this sample, 13 patients were randomized. Overall, the AS score decreased by a mean of 7.0 points (95% CI = -14.6 to .6), but there was no significant between-group difference at week 12 (mean paired t-tests, P > .14). CONCLUSIONS: Treatment with nefiracetam did not prove to be more efficacious than placebo in ameliorating apathy in stroke. The main limitation was the very small sample randomized, highlighting the limitations of conducting drug trials for behavioral problems among stroke patients. Pharmacological studies of apathy in stroke will require a large multicenter study and a massive sample of patients.

Is the Parkinson Anxiety Scale comparable across raters?

The Parkinson Anxiety Scale is a new scale developed to measure anxiety severity in Parkinson's disease specifically. It consists of three dimensions: persistent anxiety, episodic anxiety, and avoidance behavior. This study aimed to assess the measurement properties of the scale while controlling for the rater (self- vs. clinician-rated) effect. The Parkinson Anxiety Scale was administered to a cross-sectional multicenter international sample of 362 Parkinson's disease patients. Both patients and clinicians rated the patient's anxiety independently. A many-facet Rasch model design was applied to estimate and remove the rater effect. The following measurement properties were assessed: fit to the Rasch model, unidimensionality, reliability, differential item functioning, item local independency, interrater reliability (self or clinician), and scale targeting. In addition, test-retest stability, construct validity, precision, and diagnostic properties of the Parkinson Anxiety Scale were also analyzed. A good fit to the Rasch model was obtained for Parkinson Anxiety Scale dimensions A and B, after the removal of one item and rescoring of the response scale for certain items, whereas dimension C showed marginal fit. Self versus clinician rating differences were of small magnitude, with patients reporting higher anxiety levels than clinicians. The linear measure for Parkinson Anxiety Scale dimensions A and B showed good convergent construct with other anxiety measures and good diagnostic properties. Parkinson Anxiety Scale modified dimensions A and B provide valid and reliable measures of anxiety in Parkinson's disease that are comparable across raters. Further studies are needed with dimension C.

Apathy in older patients with type 2 diabetes.

OBJECTIVE: To determine the prevalence, incidence, persistence, likely causes, and consequences of apathy in patients with Type 2 diabetes and to compare the prevalence with a healthy control sample. DESIGN: Cross-sectional comparison of diabetic and nondiabetic samples; longitudinal follow-up of diabetic sample. SETTING: Academic research department. PARTICIPANTS: Non-demented, older patients with long-standing Type 2 diabetes (N = 122) recruited from a community-based cohort study and 69 healthy volunteers. MEASUREMENTS: Clinical assessments of apathy and potential causative conditions, repeated in the diabetic sample after 16.7 ± 2.5 months. Informant rated symptoms from the 14-item Apathy Scale were used to generate apathy diagnoses based on standardized criteria. Cognition was assessed by Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). RESULTS: The diabetic and comparison samples had the same age and MMSE scores, but the diabetic sample had a higher frequency of depression, cerebrovascular history, and cognitive deficits. Apathy was more prevalent in diabetes (diabetic 13.9% versus control sample 1.4%, p = 0.005) and was independently associated with CDR 0.5 status (OR [95% CI]: 3.66 [1.25-19.70]) and depression (8.48 [2.74-26.21]). In 108 diabetic patients who were followed up, incident apathy occurred in 7.4% of cases, and persisted in 50% of those with baseline apathy. Baseline apathy was independently associated with lnHbA1c levels (ß: 0.20, t = 2.29, df = 119, p = 0.024; model R(2) = 0.10) and incident/persistent apathy was associated with greater risk of cognitive decline (6.72 [1.19-37.87]). CONCLUSION: Apathy is a frequent neuropsychiatric syndrome in older patients with Type 2 diabetes, and is associated with poor glycaemic control and cognitive decline.

The Parkinson Anxiety Scale (PAS): development and validation of a new anxiety scale.

Existing anxiety rating scales have limited construct validity in patients with Parkinson's disease (PD). This study was undertaken to develop and validate a new anxiety rating scale, the Parkinson Anxiety Scale (PAS), that would overcome the limitations of existing scales. The general structure of the PAS was based on the outcome of a Delphi procedure. Item selection was based on a canonical correlation analysis and a Rasch analysis of items of the Hamilton Anxiety Rating Scale (HARS) and the Beck Anxiety Inventory (BAI) from a previously published study. Validation was done in a cross-sectional international multicenter study involving 362 patients with idiopathic PD. Patients underwent a single screening session in which the PAS was administered, along with the Hamilton Depression Rating Scale, the HARS, and the BAI. The Mini International Neuropsychiatric Interview was administered to establish Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses of anxiety and depressive disorders. The PAS is a 12-item observer or patient-rated scale with three subscales, for persistent, episodic anxiety and avoidance behavior. Properties for acceptability and reliability met predetermined criteria. The convergent and known groups validity was good. The scale has a satisfactory factorial structure. The area under the receiver operating characteristics curve and Youden index of the PAS are higher than that of existing anxiety rating scales. The PAS is a reliable and valid anxiety measure for use in PD patients. It is easy and brief to administer, and has better clinimetric properties than existing anxiety rating scales. The sensitivity to change of the PAS remains to be assessed.

Anxiety has specific syndromal profiles in Parkinson disease: a data-driven approach.

BACKGROUND: Anxiety symptoms are common in Parkinson disease (PD). Recent evidence suggests that anxiety syndromes as encountered in clinical practice may not correspond to the DSM-IV classification of anxiety disorders. OBJECTIVE: To examine the syndromal pattern of the anxiety spectrum in a large series of patients with PD, as determined with a data-driven approach using latent class analysis (LCA). METHODS: 342 patients with PD were recruited from referrals to movement disorders or psychiatry clinics at six tertiary centers. Participants were assessed with a structured psychiatric interview and specific scales rating the severity of anxiety, depression, cognition and parkinsonism. The main outcome measure was classes of patients with a specific syndromal profile of anxiety symptoms based on LCA. RESULTS: LCA identified four classes that were interpreted as "no anxiety or depression", "episodic anxiety without depression", "persistent anxiety with depression", and "both persistent and episodic anxiety with depression". Symptoms of persistent anxiety were almost invariably associated with symptoms of depression. There were significant differences between classes in terms of history of depression and anxiety, use of psychoactive medication, and on the Mentation and Complications sections of the Unified Parkinson Disease Rating Scale. CONCLUSIONS: Patients with PD show different syndromic profiles of anxiety that do not align with the symptom profiles represented by DSM-IV anxiety disorders and major depression. Accordingly, DSM-IV criteria for anxiety disorders may not be clinically useful in PD. The different classes identified here provide empirically validated phenotypes for future research.

The Clinical Relevance of Diabetes Distress versus Major Depression in Type 2 Diabetes: A Latent Class Analysis from the Fremantle Diabetes Study Phase II.

BACKGROUND: The nosological position and clinical relevance of the concept of diabetes distress (DD) are uncertain. The aim of this study was to use latent class analysis (LCA) to categorise classes of people with type 2 diabetes and to compare their characteristics. METHODS: Data from 662 participants in the longitudinal observational Fremantle Diabetes Study Phase II were analysed. LCA identified latent subgroups based on individual responses to the Patient Health Questionnaire-9, the Generalised Anxiety Disorder Scale, and the 5-item Problem Areas in Diabetes Scale. RESULTS: Four classes were identified: Class 1 (65.7%, no symptoms), Class 2 (14.0%, DD), Class 3 (12.6%, subsyndromal depression (SSD)), and Class 4 (7.6%, major depression (MD)). Multinomial regression analysis with Class 1 as reference showed significant associations between the DD class and Southern European and Asian ethnic background, HbA1c, and BMI. The SSD class was significantly associated with HbA1c, cerebrovascular disease, and coronary heart disease (CHD). The MD class had significant associations with age (inversely), Southern European ethnic background, HbA1c, BMI, and CHD. In conclusion, LCA identified a pure DD group comprising 14.0% of participants. The only variable uniquely associated with the DD class was Asian ethnic background. CONCLUSION: Although identification of DD may have some utility in assessing the psychological wellbeing of individuals with type 2 diabetes, it adds little to the assessment of depressive disorder and its significant clinical sequalae.

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.

Apathy in Parkinson's disease: diagnostic and etiological dilemmas.

About one-third of patients with Parkinson's disease (PD) are diagnosed with apathy in cross-sectional studies. However, once patients with concomitant depression and dementia are excluded, the frequency of apathy drops to 5% to 10%. Several scales have been recommended to rate apathy in PD, but specific psychiatric interviews have not been developed, and recently proposed standardized diagnostic criteria are still in the validation process. Most studies assessing the association between subthalamic deep brain stimulation (STN-DBS) and apathy have reported a relative increase in the frequency and severity of apathy, although discrepant findings have also been reported. Several mechanisms to explain apathy in PD have been proposed, from dopaminergic imbalances in frontal-basal ganglia circuits to dysfunction of nondopaminergic circuits and the cingulate gyrus. Future studies should provide reliable and valid instruments to diagnose apathy in PD, and should examine the mechanism of apathy accounting for relevant confounders, such as depression and cognitive deficits, and important contextual factors. Finally, treatment for apathy in PD should not be restricted to psychoactive drugs, but should also include nonpharmacological techniques such as psychotherapy and occupational therapy.

Temporal Trends in Mortality Associated with Comorbid Type 2 Diabetes and Schizophrenia: The Fremantle Diabetes Study.

BACKGROUND: In Phase I of the community-based Fremantle Diabetes Study (FDS1), there was evidence of a deleterious interactive effect of schizophrenia and type 2 diabetes on mortality. Our aim was to investigate whether the mortality gap had improved in FDS Phase II (FDS2) conducted 15 years later. METHODS: Participants with type 2 diabetes from FDS1 (n = 1291 recruited 1993-1996) and FDS2 (n = 1509 recruited 2008-2011) were age-, sex- and postcode-matched 1:4 to people without diabetes. Schizophrenia at entry and incident deaths were ascertained from validated administrative data. RESULTS: Schizophrenia affected 50/11,195 (0.45%) of participants without diabetes and 17/2800 (0.61%) of those with type 2 diabetes (p = 0.284). During 142,304 person-years of follow-up, the mortality rate (95% CI) was lowest for the FDS2 subgroup without diabetes/schizophrenia (18.2 (16.9, 19.6)/1000 person-years) and highest in FDS2 and FDS1 subgroups with type 2 diabetes/schizophrenia (53.3 (14.5, 136.6) and 98.0 (31.8, 228.8)/1000 person-years, respectively). Compared to the respective FDS subgroup without diabetes/schizophrenia, the mortality rate ratio was approximately 50% higher in the type 2 diabetes subgroup, and three times higher in those with type 2 diabetes/schizophrenia. In Cox regression, unadjusted hazard ratios were highest in those with type 2 diabetes/schizophrenia in FDS1 (HR (95% CI): 3.71 (1.54, 8.93) and FDS2 (2.96 (1.11, 7.91)), increasing to 5.61 (2.33, 13.5) and 26.9 (9.94, 72.6), respectively, after adjustment for age. CONCLUSIONS: Although limited by small numbers of schizophrenia cases, these data suggest that comorbid type 2 diabetes and schizophrenia remains associated with a substantial and possibly increasing mortality gap.

Spectrum of neuropsychiatric symptoms in chronic post-stroke aphasia.

BACKGROUND: Neuropsychiatric symptoms (NPS) have been insufficiently examined in persons with aphasia (PWA) because most previous studies exclude participants with language and communication disorders. AIM: To report a two-part study consisting of a literature review and an observational study on NPS in post-stroke aphasia. METHODS: Study 1 reviewed articles obtained from PubMed, PsycINFO, Google Scholar and Cochrane databases after cross-referencing key words of post-stroke aphasia to NPS and disorders. Study 2 examined language deficits and activities of daily living in 20 PWA (median age: 58, range: 28-65 years; 13 men) with the Western Aphasia Battery-Revised and the Barthel Index, respectively. Informants of these 20 PWA were proxy-evaluated with the Neuropsychiatric Inventory and domain-specific scales, including the Stroke Aphasia Depression Questionnaire-10 item version and the Starkstein Apathy Scale. In addition, an adapted version of the Hospital Anxiety and Depression Scale was directly administered to the PWA themselves. This observational study is based on the baseline assessment of an intervention clinical trial (EudraCT: 2017-002858-36; ClinicalTrials.gov identifier: NCT04134416). RESULTS: The literature review revealed a broad spectrum of NPS in PWA, including depression, anxiety, apathy, agitation/aggression, eating and sleep disorders, psychosis, and hypomania/mania. These findings alert to the need for improving assessment and treatment approaches of NPS taking into consideration their frequent occurrence in PWA. Study 2 showed that the 20 participants had mild- to-moderate aphasia severity and were functionally independent. A wide range of comorbid NPS was found in the post-stroke aphasic population (median number of NPS: 5, range: 1-8). The majority of PWA (75%) had depressive symptoms, followed by agitation/aggression (70%), irritability (70%), anxiety (65%) and appetite/eating symptoms (65%). Half of them also presented symptoms of apathy, whereas euphoria and psychotic symptoms were rare (5%). Domain-specific scales revealed that 45% of participants had apathy and 30% were diagnosed with depression and anxiety. CONCLUSION: Concurrent NPS are frequent in the chronic period of post-stroke aphasia. Therefore, further research on reliable and valid assessment tools and treatment for this aphasic population is strongly warranted.

Clinicopathological correlates of behavioral and psychological symptoms of dementia.

Behavioral and psychological symptoms are commonly observed in a majority of demented patients at some time during the course of their illness. Many of these psychiatric manifestations, especially those related to mood, may be early expressions of dementia and/or mild cognitive impairment. The literature suggests that behavioral and psychological symptoms of dementia (BPSD) are an integral part of the disease process. The dissociation, in many cases, between BPSD and the rather linear decline in cognitive functions suggests that independent pathophysiological mechanisms give rise to these symptoms. A review of the neuroimaging and neuropathology literature indicates that BPSD are the expression of regional rather than diffuse brain pathology. Psychotic symptoms in demented patients usually demonstrate preferential involvement of the frontal lobe and/or limbic regions. Visual hallucinations differentiate themselves from other psychotic symptoms by their tendency to involve the occipital lobes. There is a significant association between apathy and structural changes of the anterior cingulate gyrus. White matter hyperintensities occur in a significant number of depressed patients; otherwise, there is lack of association between depression and either specific brain changes or affected regions. Strictly neuropathological explanations are likely to be insufficient to explain BPSD. Environmental changes, neurochemical abnormalities, past psychiatric history (including premorbid personality), social history (e.g., intellectual achievement and life-long learning), family history, and genetic susceptibility are factors, among others, that influence BPSD.

Symptomatology and markers of anxiety disorders in Parkinson's disease: a cross-sectional study.

Anxiety is understudied in Parkinson's disease (PD), which is not justified by the prevalence and impact of anxiety disorders on quality of life in PD patients. In this cross-sectional study, 342 patients suffering from idiopathic PD underwent a research-based assessment including DSM IV criteria for anxiety disorders, the Hamilton anxiety rating scale (HARS) and the beck anxiety inventory (BAI). Thirty-four percent (34%) of subjects met the DSM IV criteria for at least one anxiety disorder; 11.8% met criteria for multiple anxiety disorders; and 11.4% had clinically relevant anxiety symptoms without meeting the criteria for any specific anxiety disorder. Score profiles on the HARS and BAI differed significantly between the disorders, but these differences were associated with different scores on a limited number of items, and the respective symptom profiles were not readily interpretable. Female sex, the presence of motor fluctuations, as well as a previous history of an anxiety disorder were markers for anxiety disorders. The use of a mono-amino oxidase (MAO)-B inhibitor was associated with a reduced prevalence of anxiety disorders. Research into anxiety in PD is hampered by the questionable validity of DSM IV defined anxiety disorders in this population. A first focus for research should therefore be the identification of clinically useful anxiety presentations and their validation in PD.

Anxiety rating scales in Parkinson's disease: a validation study of the Hamilton anxiety rating scale, the Beck anxiety inventory, and the hospital anxiety and depression scale.

BACKGROUND: Anxiety is a prevalent and disabling condition in Parkinson's disease (PD). The lack of anxiety rating scales validated for this population hampers research into anxiety in PD. The aim of this study is to assess the clinimetric properties of the Hamilton anxiety rating scale (HARS), the Beck anxiety inventory (BAI), and the hospital anxiety and depression scale (HADS) in PD patients. DESIGN: Three hundred forty-two PD patients underwent a standardized assessment including a structured interview for diagnostic and statistical manual diagnoses of anxiety disorders and completion of the HARS, BAI, and HADS. Inter-rater reliability of the HARS was assessed in 60 patients; test-retest reliability of the BAI and HADS in 213 and 217 patients, respectively. RESULTS: Thirty-four percent of patients suffered from an anxiety disorder, whereas an additional 11.4% had clinically significant anxiety symptoms in the absence of a diagnosis of anxiety disorder. Acceptability, score distribution, and known groups validity over different levels of anxiety were adequate. Inter-rater reliability for the HARS and test-retest reliability for the BAI and HADS were good. The HARS, but not the BAI and HADS, had a satisfactory inter-item correlation, convergent validity and factorial structure. For all scales, the positive predictive value was poor, and the negative predictive value was moderate. CONCLUSIONS: Given the adequate known groups validity of all three rating scales, each of these scales is likely to be useful in clinical practice or research for evaluation of symptom severity. Limitations in the construct validity of the anxiety scales in this study raise questions regarding suitability for their use in PD.

Diagnostic criteria for depression in Alzheimer disease: a study of symptom patterns using latent class analysis.

CONTEXT: Although depression in Alzheimer disease (AD) has a negative emotional and functional impact on patients and caregivers, specific criteria to diagnose depression in AD are still to be validated. OBJECTIVE: To validate a set of diagnostic criteria for major depression in AD. DESIGN: Cross-sectional design using latent cluster analysis (LCA). SETTING: Participants were recruited from consecutive referrals to a Memory Clinic of a tertiary hospital. PARTICIPANTS: A consecutive series of 971 outpatients with probable AD. MAIN OUTCOME MEASURE: Clusters of patients with or without major depression as determined with LCA. RESULTS: A LCA demonstrated three clusters that were considered to represent major depression, minor depression, and no depression. All nine Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depression were significantly associated with the major depression cluster. Although a diagnosis of generalized anxiety disorder (GAD) and apathy were also associated with the major depression cluster, irritability was not. CONCLUSIONS: The DSM-IV criteria for major depression should be used unmodified to diagnose depression in AD. Future studies should determine whether GAD should be included as an additional diagnostic criterion.

Apathy and Parkinson's disease.

OPINION STATEMENT: Apathy, a frequent finding in Parkinson's disease (PD), is significantly associated with depression and dementia. Few studies have examined the efficacy of psychotropic or psychological treatments of apathy in PD, and adequate randomized controlled trials are still lacking. There is anecdotal evidence that dopaminergic agonists may be a useful treatment modality. Levodopa may improve the loss of motivation in the "off" motor state, and dopaminergic agonists could be useful to treat apathy after the withdrawal of dopaminergic treatment in patients undergoing deep brain stimulation of the subthalamic nucleus. On the other hand, the selective norepinephrine reuptake inhibitor atomoxetine did not demonstrate efficacy in improving apathy in a randomized controlled trial with apathy as a secondary efficacy measure. Given the significant association between apathy and both depression and cognitive decline, future studies should examine whether improving mood and cognition may also have a positive impact upon apathy in PD. For those PD patients with "pure" apathy, specific psychotherapeutic techniques should be developed.