Cognitive impairment in late-life generalized anxiety disorder.

OBJECTIVE: This study sought to characterize cognitive functioning in elderly patients with generalized anxiety disorder (GAD), as compared with normal comparison subjects and patients with major depression. METHODS: The cognitive functioning in GAD (N=19) was assessed with the Mattis Dementia Rating Scale and across specific domains of naming, executive ability, and memory, in comparison with late-life major depressive disorder (MDD; N=68) and versus no psychiatric illness (N=40). RESULTS: In comparison to healthy normal comparison subjects, anxious subjects were impaired on measures of short-term and delayed memory. Depressed subjects also performed worse than normal comparison subjects on delayed memory, as well as in naming. Anxious subjects did not differ significantly from depressed subjects in any measure of cognitive function. CONCLUSION: In this preliminary study, anxious subjects displayed cognitive impairments in short-term memory; while depressed patients compared to normal comparison subjects showed executive dysfunction and more general cognitive impairments not evident in anxious subjects. Studies of neuropsychological function in elderly anxious subjects may be informative in developing treatment interventions that mitigate cognitive dysfunction and illuminate the course of illness and underlying neural pathways.     

Cognitive function across manic or hypomanic, depressed, and euthymic states in bipolar disorder

OBJECTIVE: The study aims were to address neuropsychological functioning across different states of bipolar illness and to determine relationships among clinical features, neuropsychological performance, and psychosocial functioning. METHOD: Several domains of cognitive function were examined in 30 depressed bipolar patients (DSM-IV criteria for major depression, Hamilton Depression Rating Scale score > or = 17), 34 manic or hypomanic bipolar patients (DSM-IV criteria for manic or hypomanic episode, Young Mania Rating Scale score > or = 12), and 44 euthymic bipolar patients (6 months of remission, Hamilton depression scale score < or = 8, and Young Mania Rating Scale score < or = 6). The comparison group consisted of 30 healthy subjects without history of neurological or psychiatric disorders. A neuropsychological battery assessed executive function, attention, and verbal and visual memory. RESULTS: The three groups showed cognitive dysfunction in verbal memory and frontal executive tasks in relation to the comparison group. Low neuropsychological performance was associated with poor functional outcome. Impairment of verbal memory was related to the duration of illness and the numbers of previous manic episodes, hospitalizations, and suicide attempts. CONCLUSIONS: A poorer performance was observed in all bipolar groups regarding executive function and verbal memory in relation to the healthy comparison subjects. These cognitive difficulties, especially related to verbal memory, may help explain the impairment regarding daily functioning, even during remission. Further studies should focus on testing, whether optimizing prophylactic pharmacological treatment and psychoeducation might reduce cognitive impairment, and whether bipolar patients would benefit from neuropsychological rehabilitation in order to reduce the impact of cognitive impairment in their overall functioning.     

Executive dysfunction in geriatric depression

OBJECTIVE: The purpose of this study was to characterize the neuropsychological presentation of geriatric depression and to determine whether depression-related executive dysfunction is more pronounced during advanced age. METHOD: The attention and executive functioning of 40 adults with major depression were compared with those of 40 healthy comparison subjects; 20 subjects were 20-60 years old, and 20 were > or =61 years. It was hypothesized that depressed subjects, regardless of age, would perform more poorly than comparison subjects on both attention and executive tasks but that the older depressed adults would evidence significantly greater impairment on executive measures. RESULTS: A significant interaction between age and depressive status was noted for tasks of executive functioning, while no age-depression interaction was found for tasks of selective or sustained attention. Older depressed adults demonstrated the slowest psychomotor speed and the poorest performance on tasks requiring set shifting, problem solving, and initiation of novel responses. CONCLUSIONS: Patients with late-life depression have significant impairment in executive functioning. These findings can guide the development of stimulated functional neuroimaging paradigms that may clarify the pathophysiology of geriatric depression. Timely identification of attentional and executive processes fundamental to the daily functioning of depressed older adults may lead to compensatory strategies that will improve the outcomes of late-life depression.     

Cognitive performance in suicidal depressed elderly: preliminary report.

OBJECTIVE: Deficits in executive functions may play an important role in late-life suicide; however the association is understudied. This study examined cognitive function in general and executive functioning specifically in depressed elderly with and without suicidal ideation and attempts. DESIGN: Case-control study. Setting: University-affiliated psychiatric hospital. PARTICIPANTS: We compared 32 suicidal depressed participants aged 60 and older with 32 non-suicidal depressed participants equated for age, education, and gender. MEASUREMENTS: We assessed global cognitive function and executive function with the Dementia Rating Scale (DRS) and the Executive Interview (EXIT25), respectively. RESULTS: Suicidal and non-suicidal depressed groups were comparable in terms of severity of depression and burden of physical illness. Suicidal participants performed worse on the EXIT25, and on the DRS total scale, as well as on Memory and Attention subscales. The differences were not explained by the presence of dementia, substance use, medication exposure, or brain injury from suicide attempts. CONCLUSIONS: Poor performance on tests of executive function, attention, and memory is associated with suicidal behavior in late-life depression.     

Apathy and cognitive performance in older adults with depression

OBJECTIVES: Recent studies have linked apathy to frontal lobe dysfunction in persons with dementia, but few studies have explored this relationship in older, depressed persons without dementia. We examined the association between apathy and cognitive function in a group of older persons with major depression using standardized neuropsychological tests. We hypothesized that presence of apathy in depression is associated with poorer frontal executive performance. METHODS: We analyzed data from 89 older adults with major depression. We defined apathy using four items from the Hamilton Psychiatric Rating Scale for Depression which reflect the clinical state of apathy, including 'diminished work/interest,' 'psychomotor retardation,' 'anergy' and 'lack of insight.' RESULTS: Apathy most strongly correlated with two verbal executive measures (Stroop C and FAS), a nonverbal executive measure (Wisconsin Card Sorting Test-Other Responses), and a measure of information processing speed (Stroop B). Apathy was not associated with age, sex, education, medical illness burden, Mini-Mental State Examination score and Full Scale IQ score. Stepwise regression analyses of significant cognitive tests showed that apathy alone or apathy plus depression severity, age, or education accounted for a significant amount of the variance. CONCLUSIONS: The results of this study provide support for an apathy syndrome associated with poorer executive function in older adults with major depression.     

Differential cognitive impairment in subjects with geriatric depression who will develop Alzheimer's disease and other dementias: a retrospective study

OBJECTIVE: The aim of this study was to retrospectively differentiate the cognitive profile of subjects with geriatric depression who will later be diagnosed with Alzheimer's disease (AD) from those who will be diagnosed with other dementias, and subjects who will remain with no dementia. METHODS: Forty-four depressed patients admitted to a day hospital program for depression who participated in a historical cohort study were assessed after 7.5 years of follow-up. Fourteen of these subjects subsequently developed dementia: seven met the criteria for probable AD and seven met the criteria for dementias other than AD (Dementia-No-AD; D-NAD, such as dementia with Lewy bodies (DLB), vascular and mixed dementia). Thirty subjects remained without dementia (No Dementia, ND) at follow-up. The three groups were thus compared on their baseline cognitive performances on the six sections of the Mini-mental State Examination (MMSE) and on the five subscales of the Dementia Rating Scale (DRS). RESULTS: An analysis of variance (ANOVA) and post-hoc Student-Newman-Keuls analyses with an alpha of p < 0.05 revealed that the subjects who received a diagnosis of dementia at follow-up had previously had more impairment on tasks measuring attention and memory (DRS-MMSE) than those who did not develop dementia (AD = D-NAD < ND). Moreover, the future AD subjects could be differentiated on the basis of their difficulties on the MMSE-orientation subtest (AD < ND = D-NAD), whereas the future D-NAD subjects initially had more problems with executive functions (DRS) and MMSE-visuospatial abilities (D-NAD < AD = ND). CONCLUSION: The identification of early neuropsychological markers in elderly depressed patients highlights the need to evaluate this population broadly as soon as possible in the depression/dementia process in order to improve the prognosis.     

抑郁对帕金森病患者执行功能的影响

目的 探讨抑郁对帕金森病(PD)患者执行功能的影响。方法 对41例PD患者及20例对照组进行整体认知功能、执行功能及抑郁状况的评定。整体认知功能评定使用简易智力状态量表(MMSE); 执行功能评定包括言语流畅性测验(VFT),连线测验(TMT),Stroop字色干扰测验(SCWT),画钟测验(CDT),数字符号替换测试(DSST)及数字广度测试(DST)等; 使用贝克抑郁自评量表(BDI)评估抑郁状态。结果 抑郁组SFT, PFT, DST, DSST, CDT, TMA,TMB, Stroop-B, Stroop-C,SIE评分均差于对照组(P<0.05); 非抑郁组PFT, DST, DSST,TMA,TMB, Stroop-C,SIE评分差于对照组(P<0.05); 与非抑郁组比较,抑郁组SFT, PFT, DST, DSST, TMA, TMB, Stroop-B, Stroop-C, SIE评分较差(P<0.05)。结论 PD患者存在明显的执行功能障碍,抑郁可以明显加重PD患者的执行功能障碍。     

Slowed Processing Speed Disrupts Patient Expectancy in Late Life Depression

ObjectiveSlowed processing speed and executive dysfunction are associated with poor outcomes in Late Life Depression (LLD), though it is unclear why. We investigated whether these variables interfere with the development of positive treatment expectancies in an antidepressant trial.MethodsDepressed older subjects were randomized to Open (intended to increase patient expectancy) or Placebo-controlled (termed ‘Hidden,’ intended to decrease expectancy) administration of antidepressant medication for 8 weeks. Analysis of covariance analyzed the between-group difference on expectancy (Credibility and Expectancy Scale [CES]) and depression (Hamilton Rating Scale for Depression [HRSD], Clinical Global Impressions [CGI] Severity). Moderator analyses examined whether these Open versus Hidden differences varied based on higher versus lower processing speed and executive function.ResultsAmong the 108 participants, a significant between-group difference was observed on expectancy (effect size [ES, Cohen's d] = 0.51 on CES Item 2; ES = 0.64 on Item 4), indicating the manipulation was effective. Processing speed as measured by the Stroop Color-Word Test (number color-words named in congruent condition) was a significant moderator of the Open versus Hidden effect on expectancy. Depressive symptom improvement was greater on average for Open versus Hidden participants who received active drug (CGI-severity ES = 1.25, HRSD ES = 0.41), but no neurocognitive moderators of the between-group difference reached statistical significance.ConclusionsSlowed processing speed impairs the development of expectancies in antidepressant trials for LLD, which may help explain lower antidepressant response among older adults. Future studies may address whether interventions to optimize treatment expectancies are capable of improving treatment outcomes.     

Late-life depression as a risk factor for mild cognitive impairment or Alzheimer's disease in 30 US Alzheimer's disease centers

Identification of potentially modifiable risk factors for cognitive deterioration is important. We conducted a prospective study of 5,607 subjects with normal cognition and 2,500 subjects with mild cognitive impairment (MCI) at 30 Alzheimer's Disease Centers in the Unites States between 2005 and 2011. Cox regression was used to determine whether depression predicted transition from normal to MCI, or MCI to Alzheimer's disease (AD). Over an average of 3.3 visits, 15% of normal subjects transitioned to MCI (62/1000 per year), while 38% of MCI subjects transitioned to AD (146/1000 per year). At baseline, 22% of participants had recent (within the last two years) depression defined by clinician judgment; 9% and 17% were depressed using the Geriatric Depression Scale (GDS score ≥5) and the Neuropsychiatric Inventory Questionnaire (NPI-Q), respectively. At baseline, depressed subjects performed significantly worse on cognitive tests. Those always depressed throughout follow-up had an increased risk for progression from normal to MCI (RR = 2.35; 95% CI 1.93-3.08) versus never depressed. Normal subjects, identified as depressed at first visit but subsequently improved, were found to have lower risk of progression (RR 1.40 (1.01-1.95)). The 'always depressed' had only a modest increased risk of progression from MCI to AD (RR = 1.21 (1.00-1.46). Results were similar using time-dependent variables for depression or when defining depression via the GDS or NPI-Q. We found no effect of earlier depression (>2 years past). The effect of recent depression did not differ by antidepressant treatment, APOE4 allele status, or type of MCI. In conclusion, late-life depression is a strong risk factor for normal subjects progressing to MCI.     

An open-label trial of riluzole in patients with treatment-resistant major depression

OBJECTIVE: This study was conducted to determine the efficacy and safety of riluzole, a glutamate-modulating agent, in patients with recurrent major depression. METHOD: After a 1-week drug-free period, subjects 18 years or older with a diagnosis of recurrent major depression and a Montgomery-Asberg Depression Rating Scale score > or = 20 received riluzole monotherapy (100-200 mg/day) openly for 6 weeks. RESULTS: Nineteen treatment-resistant depressed patients, 53% of whom were classified as having stage 2 treatment resistance or greater, received riluzole at a mean dose of 169 mg/day. Significant improvement occurred during weeks 3 through 6 for all patients and weeks 2 through 6 for completers. CONCLUSIONS: Although preliminary, these results indicate that riluzole may have antidepressant properties in some patients.     

Prefrontal dysfunction and treatment response in geriatric depression.

BACKGROUND: This study investigated the relationship of clinical, neuropsychological, and electrophysiological measures of prefrontal dysfunction with treatment response in elderly patients with major depression. METHODS: Forty-nine depressed elderly subjects were studied before and after 6 weeks of adequate antidepressant treatment and compared with 22 psychiatrically normal controls. The psychomotor retardation item of the Hamilton Depression Rating Scale, the initiation/perseveration subscore of the Mattis Dementia Rating Scale, and the latency of the P300 auditory evoked potential were used as indices of prefrontal dysfunction. The intensity of antidepressant drug treatment was classified and monitored for a 6-week period. RESULTS: Abnormal initiation/perseveration score, psychomotor retardation, and long P300 latency predicted 58% of the variance in change of depression scores from baseline to 6 weeks (F3= 20.1, P<.001). Depressed patients who remained symptomatic (n = 25) had more abnormal initiation/perseveration scores and longer P300 latency compared with depressed patients who achieved remission (n = 24) and control subjects. There were no differences between the last 2 groups. The association between psychomotor retardation, initiation/perseveration scores, P300 latency, and response to antidepressant treatment could not be explained by differences in demographic and clinical characteristics or treatment intensity between remitted and nonremitted depressed patients. CONCLUSIONS: Prefrontal dysfunction was associated with poor or delayed antidepressant response in depressed elderly patients. This observation, if confirmed, may aid clinicians in identifying candidates for aggressive somatic therapies and for interventions offering structure of daily activities.     

Beta-adrenoceptor density of intact mononuclear leukocytes in subgroups of depressive disorders.

Binding parameters of (-)-iodopindolol to beta 2-adrenoceptors were determined on intact mononuclear cells in 41 untreated patients with different DSM-III subtypes of depression. Both maximal beta-receptor density (Bmax) and dissociation constant (Kd) were not significantly different between control and all depressed subjects. However, Bmax was significantly decreased in unipolar patients as compared to controls (p less than 0.001) whereas no significant difference was found in bipolar or dysthymic patients. In unipolar patients, a very strong association was found between Bmax values and the severity of the depression as assessed by the Hamilton Depression Rating Scale score (r = -0.75; p less than 0.005). This correlation was also highly significant in the entire depressed population (r = -0.58; p less than 0.0009). These results suggest that the lower number of beta-adrenoceptors in intact leukocyte cells of depressed patients is related to the depression severity.     

Cardiac beta-adrenergic sensitivity in depression: relation with endogenous subtype and desipramine response

The authors studied the responsiveness of cardiac beta-receptors to isoproterenol, a noradrenergic agonist, in 29 depressed patients and 13 control subjects. They showed a significantly lower sensitivity in depressed patients as compared with the control subjects. Focussing on the group of depressed patients without antidepressant treatment in the month preceding the study (n = 15) in order to avoid a bias, the following significant results were obtained: cardiac beta-adrenergic receptor sensitivity was lower in patients suffering from endogenous depression than in those suffering from reactive depression (as classified by Newcastle Scale). There was a negative linear relation between cardiac beta-adrenergic sensitivity and the posttreatment clinical state (as expressed by the MADRS score) for the 9 patients who ended a 3-week desipramine treatment period.     

Religiosity, depression and pain in patients with breast cancer

There is a growing body of evidence that religiosity can buffer depression and support the healing process. Our objective was to assess the relationship between religiosity, depression and pain in patients with breast cancer. Participants in our study were 115 breast cancer female patients recruited from a radiotherapy unit of a cancer teaching hospital, surveyed during the course of 6 months. The assessment used the Santa Clara Strength of Religious Faith Questionnaire as the measure of religiosity, and the subjects were categorized into low-, moderate- and high-religiosity groups according to its score. Depression was measured with the Center for Epidemiologic Studies Depression Scale, a 20-item self-report scale. The score of >or=16 indicated clinically relevant depression. A visual analogue scale was used for the assessment of pain. High religiosity was associated with a significantly lower prevalence of depression (chi(2)=6.635; df=2; P=.036), but religiosity was not related to the intensity of pain perception. Higher religiosity was associated with older age, lower education, unemployment and more children. Depression was associated with a higher pain level (U=1027.5; P=.004). The type of operation and tumor stage were not associated with categories of depression or religiosity, but mastectomized patients who belonged to the high-religiosity group were significantly less depressed (chi(2)=9.552; df=2; P=.008).     

An open-label trial of the glutamate-modulating agent riluzole in combination with lithium for the treatment of bipolar depression.

BACKGROUND: Preclinical and clinical evidence indicate that the glutamatergic system might play a role in the pathophysiology of mood disorders. This study was conducted to determine the efficacy and safety of riluzole, a glutamate-modulating agent, in bipolar depression. METHODS: This was an 8-week add-on study of riluzole in combination with lithium in acutely depressed bipolar patients aged 18 years and older. After open treatment with lithium for a minimum period of 4 weeks, subjects who continued to have a Montgomery-Asberg Depression Rating Scale (MADRS) score of >/=20 received riluzole (50-200 mg/day) for 8 weeks. RESULTS: Fourteen bipolar depressed patients entered the study. The linear mixed models for total MADRS score showed a significant treatment effect. No switch into hypomania or mania was observed. Overall, riluzole was well tolerated. CONCLUSIONS: Although preliminary, these results suggest that riluzole might indeed have antidepressant efficacy in subjects with bipolar depression.     

Dysfunctional attitudes in depressed patients before and after clinical treatment and in normal control subjects

To evaluate the role of maladaptive thinking patterns in depression, the authors administered the Dysfunctional Attitude Scale to 112 depressed patients before and after 3-6 weeks of treatment with antidepressants or placebo. Twenty-two normal subjects were also assessed twice. Depressed patients had a significantly higher initial mean score than control subjects, but during treatment their score significantly decreased, and the posttreatment score of those with complete recoveries was nearly as low as the control subjects' final score. The higher the initial dysfunctional attitude score the poorer the response to treatment. Patients with endogenous depression had significantly lower scores than nonendogenously depressed patients.     

Psychiatric and psychosocial outcome of cardiac surgery with cardiopulmonary bypass: a prospective 12-month follow-up study

Little is known concerning the natural history of psychiatric morbidity, postoperative delirium, cognitive decline and health-related quality of life (HRQOL) in cardiac surgery patients and the impact of neurocognitive dysfunction on HRQOL after cardiac surgery with cardiopulmonary bypass (CPB). In a prospective study, we followed up for 1 year 30 of the original 34 patients who had undergone cardiac surgery with CPB. Patients were assessed preoperatively, before discharge, and at 1 year after surgery with the Structural Clinical Interview for DSM-IV and a series of neuropsychological tests. Psychometric scales were administered to evaluate cognitive functioning (Syndrom Kurztest), depressive symptomatology (Montgomery-Asberg Depression Rating Scale), posttraumatic stress symptoms (Posttraumatic Stress Syndrome 10-Questions Inventory) and HRQOL (SF-36 Health Status Questionnaire). Delirium Rating Scale (DRS) was used daily over the course of intensive care unit treatment. Postoperative delirium developed in 11 of the 34 patients (mean DRS rating scale score+/-S.D.: 20.36+/-6.22, range: 14-31). Short-term consequences of cardiac surgery included adjustment disorder with depressed features (n=11), posttraumatic stress disorder (n=6), major depression (n=6) and clinically relevant cognitive deficits (n=13). At 12 months, the severity of depression and anxiety disorders improved and returned to the preoperative level, and 6 out of the 30 followed-up patients displayed cognitive deficits. Our patients' HRQOL SF-36 self-reports significantly improved compared with baseline quality of life data. However, 1-year overall lower cognitive function scores were associated with lower HRQOL. Cardiac surgery with CPB is associated with improvements in HRQOL relative to the preoperative period, but the presence of cardiac surgery-related cognitive decline impairing HRQOL is a complication for a subgroup of cardiac surgical patients in the long-term outcome.     

The effects of memory, attention, and executive dysfunction on outcomes of depression in a primary care intervention trial: the PROSPECT study

OBJECTIVE: To describe the influence of domains of cognition on remission and response of depression in an intervention trial among older primary care patients. METHODS: Twenty primary care practices were randomly assigned to Usual Care or to an Intervention consisting of a depression care manager offering algorithm-based care for depression. In all, 599 adults 60 years and older with a depression diagnosis were included in these analyses. Depression severity and remission of depression were assessed by the 24-item Hamilton Depression Rating Scale. The Mini-Mental State Examination (MMSE) was our global measure of cognitive function. Verbal memory was assessed with the memory subscale of the Dementia Rating Scale. Attention was measured with the digit span from the Weschler Adult Intelligence Test. Response inhibition, one of the executive functions, was assessed with the Stroop Color-Word test. RESULTS: The intervention was associated with improved remission and response rates regardless of cognitive impairment. Response inhibition as measured by the Stroop Color-Word test appeared to significantly modify the intervention versus usual care difference in remission and response at 4 months. Patients in the poorest performance quartile at baseline on the Stroop Color-Word test in the Intervention Condition were more likely to achieve remission of depression at 4 months than comparable patients in Usual Care [odds ratio (OR) = 17.76, 95% Confidence Interval (CI), 3.06, 103.1]. CONCLUSIONS: Depressed older adults in primary care with executive dysfunction have low remission and response rates when receiving usual care but benefit from depression care management.     

Ascending digits task as a measure of executive function in geriatric depression

The authors hypothesized that older depressed patients would perform more poorly on the Ascending Digits Task (ADT) when matched against a nondepressed elderly comparison group. In a novel measure, the ADT, 129 older depressives scored more poorly than 129 comparison subjects in bivariate analyses and models controlling for demographic variables. The ADT may be a good measure of executive function in older adults.     

Neuropsychological and functional correlates of clock‐drawing test in elderly institutionalized patients with schizophrenia

Background: There has been a growing need for a cognitive assessment tool that can be used for older adults with schizophrenia in clinical settings. The clock‐drawing test (CDT) is a brief cognitive test that covers a wide range of cognitive function. Although it is widely used to assess patients with dementia, limited data are available on its usefulness in older patients with schizophrenia. Thus, we investigated the psychometric properties of the CDT and their relationship with life functions to examine the test's usefulness for assessing cognitive function in older adults with schizophrenia. Methods: Seventy‐three older adults with chronic schizophrenia who had been hospitalized for over 1 year participated in the study. We adopted the executive clock‐drawing task for administration and scoring of the CDT, which consists of free‐drawn and copy conditions. The Mini‐Mental State Examination and the Brief Assessment of Cognition in Schizophrenia were administered. Symptom severity and life functions were assessed with the Positive and Negative Syndrome Scale and the Life Skills Profile, respectively. Results: Both free‐drawn and copy scores significantly correlated with the Mini‐Mental State Examination score and the Brief Assessment of Cognition in Schizophrenia composite score. These scores also significantly correlated with symptom severity and length of current hospitalization. Stepwise regression analysis showed that only the copy score, together with symptom severity, predicted the Life Skills Profile score. Conclusions: The CDT can assess cognitive function in older adults with schizophrenia. Moreover, CDT performance is associated with life functions independent from other clinical variables. These results suggest that the CDT is a useful cognitive assessment tool for this population.