Neuropsychological deficits among patients with late-onset minor and major depression.

Cognitive ability of minor depressed patients (N=28), major depressed patients (N=26) and healthy elderly (N=38) was examined cross-sectionally to determine if cognitive abilities of patients with late-onset depression decrease with increasing severity of disease and if cognitive scores for minor depressed patients fall between those of healthy elderly and major depressed patients. A pooled within-group principal component analysis of cognitive test scores identified five components, three of which showed significant group differences. Verbal Recall and Maintenance of Set separated controls from major depressed patients and minor from major depressed patients. Executive Functioning separated controls from minor depressed patients, and Working Memory was borderline for separating controls from major depressed patients. The component representing Nonverbal Recognition was not statistically significant. Partial correlations controlling for age and education indicate that cognitive performance does decrease as severity of depression increases, and the magnitude of the change varies from a trend to a significant deficit depending on the cognitive domain. This decline in cognitive performance parallels a similar trend observed in neuroanatomical studies in which the volume of the frontal and temporal lobes decrease with increasing severity of depression.     

Structural brain CT changes and cognitive deficits in elderly depressives with and without reversible dementia ('pseudodementia')

Twenty-six elderly (greater than 60 yrs) patients with DSM-III major depression were compared to 13 patients with NINCDS/ADRDA probable Alzheimer's disease (AD), and to 31 screened normal controls. Subjects were matched on age and sex. Fifteen of the 26 depressed patients were cognitively impaired on the Mini-Mental State Examination (MMSE) upon admission, but after treatment returned to the normal range. These 15 patients were defined as having the dementia syndrome of depression (DOD). The remaining 11 depressed patients were termed depressed, cognitively normal (DCN). All subjects received standardized cranial CT scans for assessment of ventricular brain ratio (VBR) and CT attenuation numbers. Subjects also received neuropsychological evaluation. CT values for the 26 depressed patients lay between those of AD patients and normal controls. CT values for the DOD subgroup clustered near those of AD patients. Patterns of cognitive deficits and correlations of CT attenuation values with cognitive measures were also similar in AD and DOD. Most patients were reassessed at a mean of two years after initial testing; of the 11 of the 15 DOD re-examined, only one had undergone cognitive decline. By contrast, all AD patients retested had declined significantly. Episodes of DOD and DCN tended to 'breed true'. This study suggests that while patients with DOD may have underlying structural brain abnormalities, obvious short-term progression to AD does not commonly occur.     

Emotional bias and inhibitory control processes in mania and depression

BACKGROUND: Despite markedly different clinical presentations, few studies have reported differences in neuropsychological functioning between mania and depression. The disinhibited behaviour characteristic of mania and evidence that subgenual prefrontal cortex is differentially activated in mania and depression both suggest that dissociable deficits will emerge on tasks that require inhibitory control and are subserved by ventromedial prefrontal cortex. METHODS: Manic patients and controls undertook computerized neuropsychological tests of memory and planning ability. In addition, manic and depressed patients were directly compared with controls on a novel affective shifting task that requires inhibitory control over different components of cognitive and emotional processing. RESULTS: Manic patients were impaired on tests of memory and planning. Importantly, affective shifting performance of manic patients differed from that of depressed patients. Manic patients were impaired in their ability to inhibit behavioural responses and focus attention, but depressed patients were impaired in their ability to shift the focus of attention. Depressed patients exhibited an affective bias for negative stimuli, and we believe this to be the first demonstration of an affective bias for positive stimuli in manic patients. CONCLUSIONS: Observed impairments on tests of memory and planning suggest a global pathology for mania consistent with previous profiles for this disorder and similar to established profiles for depression. The results on the affective shifting task demonstrate the presence of mood-congruent bias and dissociable components of inhibitory control in mania and depression. Against a background of memory and planning impairments in the two groups, these findings are consistent with a role for the ventromedial prefrontal cortex in mediating mood-cognition relationships.     

The cognitive neuropsychology of depression in the elderly

BACKGROUND: The cognitive impairment of older depressed patients with late- as opposed to early-onset illness may show important differences, in that patients with early onset may suffer predominantly from impaired episodic memory, and those with late onset mainly from reductions of executive function and processing speed. METHOD: We searched Medline and EMBASE as well as individual papers' reference lists for relevant publications, recording comparisons in neuropsychological test results between early-onset depression (EOD), late-onset depression (LOD) and healthy volunteers. Effect sizes are presented for cognitive domains, such as executive function, processing speed, episodic memory, semantic memory and mental state examination. RESULTS: Patients with LOD showed greater reductions in processing speed and executive function than patients with EOD and controls. Both patient groups showed reduced function in all domains, except mental state, compared with controls.CONCLUSION: Pronounced executive deficits are typical of the late-onset patients described in published studies, while episodic memory impairment is not specific to early-onset illness. Possible reasons and confounders are discussed.     

Decreased working memory and processing speed mediate cognitive impairment in geriatric depression

BACKGROUND: While neuropsychological dysfunction is common in geriatric depression, not all aspects of cognition are equally affected. It has been suggested that depressed patients are impaired only in tasks that make heavy demands on processing resources and that a resource decrement therefore underlies the neuropsychological decrements seen in geriatric depression. The present study examined whether processing resources in the form of working memory and information processing speed are decreased in depression and whether a decrease in these resources actually mediates neuropsychological impairment. METHODS: Measures of processing resources were administered to elderly depressed patients prior to treatment and to age-matched controls. Patients whose depression remitted were retested as were the controls. Subjects also received neuropsychological tests of episodic memory and visuospatial performance. RESULTS: Depressed patients performed significantly worse on measures of both processing speed and working memory. While performance on these measures improved in patients whose depression remitted, the amount of improvement was no greater than that seen in the controls with repeat testing. Hierarchical regression analyses showed that depression explained a significant amount of variance on the neuropsychological tasks. However, if the variance associated with processing resources was removed first, depression no longer accounted for a significant amount of neuropsychological variance. CONCLUSIONS: Processing resources are decreased in elderly depressed patients and this decrease in resources appears to mediate impairments in several areas of neuropsychological functioning including episodic memory and visuospatial performance. The resource decrement persists after remission of the depression and thus may be a trait marker of geriatric depression.     

Neuropsychological performance and dementia in depressed patients after 25-year follow-up: a controlled study

BACKGROUND: Previous research has yielded conflicting evidence regarding the long-term cognitive outcome of depression. Some studies have found evidence for a higher incidence of subsequent cognitive impairment or dementia, while others have refuted this. METHOD: Depression, neuropsychological performance, functional ability and clinical variables were assessed in a sample of patients who had been hospitalized for depression 25 years previously. RESULTS: Data were available on 71 depressed patients (10 of whom were deceased) and 50 surgical controls. No significant differences were found between depressed subjects and controls on any neuropsychological measure. Ten depressed patients but no controls were found to have dementia at follow-up (continuity corrected chi2 = 5.93, P < 0.01). Presence of dementia was predicted by older age at baseline. Vascular dementia was the most common type. CONCLUSIONS: We conclude that this study did not find evidence that early onset depression is a risk factor for Alzheimer's disease, but that for a small subgroup there appears to be a link with vascular dementia. Several plausible explanations for this link, such as lifestyle factors, require further investigation.     

Cognitive functioning in a population-based sample of young adults with a history of non-psychotic unipolar depressive disorders without psychiatric comorbidity

BACKGROUND: There is evidence for cognitive dysfunction in unipolar depression among middle-aged and elderly patients, but cognitive functioning among depressed young adults has scarcely been systematically investigated. The aims of the present study were to examine cognitive functioning among depressed young adults identified from the general population and to determine whether cognitive deficits vary as a function of different disorder characteristics, such as severity and age at onset. METHODS: Performance in verbal and visual short-term memory, verbal long-term memory and learning, attention, processing speed, and executive functioning was compared between a population-based sample of 21-35-year-olds with a lifetime history of non-psychotic unipolar depressive disorders without psychiatric comorbidity (n=68) and healthy controls derived from the same population (n=70). RESULTS: Depressed young adults were not found to be impaired in any of the assessed cognitive functions, except for some suggestion of mildly compromised verbal learning. Nevertheless, younger age at depression onset was associated with more impaired executive functioning. LIMITATIONS: The results may slightly underestimate of the true association between depression and cognitive impairments in the young adult population due to possible dropout of participants. Additionally, the problem of multiple testing was not entirely corrected. CONCLUSION: The findings from this study indicate that a lifetime history of non-psychotic unipolar depressive disorders among young adults without psychiatric comorbidity may be associated only with minimal cognitive deficits, even when some residual depressive symptoms are prevalent. However, early-onset depression may represent a more severe form of the disorder, associated with more cognitive dysfunction.     

Relative memory deficits in recurrent versus first-episode major depression on a word-list learning task.

Although memory deficits are associated with major depressive disorder, few studies have identified which patient characteristics predict impairment. Because recurrent depression appears related to more severe cerebral dysfunction, the present study tested whether recurrent depressed individuals have worse memory function than first-episode depressed individuals. Two groups of young-adult, nonpsychotic, depressed inpatients (20 single episode [SE] and 46 recurrent episode [RE]) were administered the California Verbal Learning Test within a broader battery of neuropsychological tests. The groups were equivalent in age, education, estimated IQ, severity of depression, and demographic composition. The RE group demonstrated memory deficits relative to both the SE group and published norms, but no other significant difference was found across the battery. Data indicate that abnormal memory performance is associated with recurrent depression, whereas memory deficits are not prominent in first-episode depressed individuals.     

Neuropsychological functioning in patients with borderline personality disorder

Although results have been variable, studies suggest that individuals with borderline personality disorder (BPD) exhibit cognitive deficits suggestive of frontal- and temporal-lobe dysfunction. Patients diagnosed with BPD (n = 18) using two structured interviews, and who were carefully screened for neurological and substance-use disorders, were compared to depressed patients (n = 18) and a nonpsychiatric control group (n = 18) on a series of neuropsychological tasks. The role of emotion on cognitive functioning was assessed by including emotional stimuli and interference on several of the tasks. Little support was found for the neurobehavioral hypothesis of BPD. The BPD group performance did not differ from the normal group on most tasks of executive functioning or memory, and the introduction of emotional stimuli did not impair performance. The depressed group performed less effectively than the other groups. Reasons for variable findings and factors affecting the cognitive functioning of patients with BPD are discussed. There may be considerable heterogeneity in the cognitive functioning of BPD patients, with those exhibiting significant cognitive deficits comprising only a subgroup.     

Pure progressive amnesia: An atypical amnestic syndrome?

We report on M.S., an 83-year-old patient with isolated pure progressive amnesia. This rare, recently identified, form of amnesia has been described in elderly patients. Neuropathological studies suggest that this syndrome is an atypical clinical presentation of Alzheimer's disease. The aim of our study was to characterize the neuropsychological pattern of pure progressive amnesia in comparison with other amnestic syndromes and memory dissociations reported in the literature. Our results indicate that pure progressive amnesia is characterized by a highly unusual dissociation in the realm of memory, with severe deficits on tests based on recognition and recall of verbal and visual single items, contrasting with relatively preserved anterograde autobiographical and spatial memory and normal recall of complex material such as stories. These findings suggest that memory for single items could depend on an independent system. One hypothesis is that M.S.'s unusual memory profile results from relative dysfunction of the ventral medial temporal lobe pathway. An alternative explanation implicates cognitive reserve. Further studies are required in order to progress on this matter. In any case, pure progressive amnesia is a clinical syndrome that may provide further insight into the organization of declarative memory.     

Cognitive performance and subjective complaints before and after remission of major depression

Introduction. Patients with major depression report on severe cognitive deficits but objective neuropsychological test results indicate rather mild problems. In the present study we aimed at investigating neuropsychological performance, subjective complaints, and observer ratings of cognitive abilities in everyday life.

Methods. Fifteen patients with major depression were studied in the acute state of illness and after remission. Fifteen healthy control subjects were investigated, too. A comprehensive neuropsychological battery, questionnaires for self and observer rating of cognitive abilities, and clinical questionnaires were administered.

Results. As expected problems reported in self and observer ratings exceeded neuropsychological deficits in tests. Neuropsychological test results tended to be improved at the second test session, with patients showing a more pronounced improvement in flexibility.

Conclusions. The data support the hypothesis that cognitive problems in everyday life indeed exceed results in standardised tests. However, it seems also likely from our data that results are additionally influenced by patients negative self perception.     

Decision-making cognition in mania and depression

BACKGROUND: Despite markedly different clinical presentations, few studies have reported differences in neuropsychological functioning between mania and depression. Recent work has suggested that differences may emerge on cognitive tasks requiring affective processing, such as decision-making. The present study sought to compare decision-making cognition in mania and depression in order to clarify the current profiles of impairment for these disorders and to contribute to our more general understanding of the relationship between mood and cognition. METHODS: Medicated manic patients, depressed patients, and normal healthy controls completed a computerized decision-making task. All subjects were asked to win as many points as possible by choosing outcomes based on variably-weighted probabilities and by placing 'bets' on each decision. RESULTS: Both patient groups were impaired on this task, as evidenced by slower deliberation times, a failure to accumulate as many points as controls and suboptimal betting strategies. Manic, but not depressed, patients made suboptimal decisions--an impairment that correlated with the severity of their illness. CONCLUSIONS: These findings are consistent with a growing consensus that manic and depressed patients are characterized by significant impairments in cognitive and particularly executive, functioning. Furthermore, the distinct patterns of observed impairment in manic and depressed patients suggests that the nature and extent of cognitive impairment differ between these two groups. Viewed in the context of other recent studies, these findings are consistent with a role for the ventromedial prefrontal cortex in mediating mood-cognition relationships.     

Cognitive function in adults with type 2 diabetes and major depression

The aim of this study was to identify characteristics of neuropsychological functioning among type 2 diabetic adults with and without major depression. Twenty type 2 diabetics with major depression, 20 non-depressed type 2 diabetics and 34 controls without diabetes or depression were compared. A mixed effects repeated measures analysis of covariance indicated significant differences in overall cognitive functioning between diagnostic groups, specifically depressed diabetics demonstrated greater cognitive dysfunction than controls. Further comparisons indicated that depressed diabetics performed significantly worse than non-depressed diabetics in attention/information processing speed. Relative to controls, depressed diabetics performed significantly worse in attention/information processing speed and executive functioning, while there was a trend for non-depressed diabetics to perform worse in executive functioning. These findings suggest that depression negatively impacts cognitive performance among adults with type 2 diabetes, which may have implications for neural circuitry underlying cognitive and mood changes in diabetic patients.     

Executive dysfunction predicts nonresponse to fluoxetine in major depression

BACKGROUND: Functional brain imaging studies of major depression have consistently revealed hypometabolism or hypoperfusion in specific regions of the prefrontal cortex and basal ganglia. Studies of cognitive functioning in major depression have suggested that some but not all subjects exhibit cognitive deficits that are consistent with frontal-subcortical dysfunction, although the reasons for this heterogeneity are unclear. In this study, we explored this heterogeneity among depressed subjects by examining the relationship between cognitive functioning and treatment outcome. METHOD: Subjects with major depression were administered a complete neuropsychological test battery prior to treatment with fluoxetine. RESULTs: There were no significant differences between responders and nonresponders to fluoxetine in terms of age, educational achievement, number of past episodes of depression, and estimated premorbid IQ. However, nonresponders performed significantly worse than responders on several pretreatment measures of executive functioning, after controlling for baseline group differences in depression severity. LIMITATIONS: The results are based on a small sample of primarily female subjects, resulting in low statistical power and less generalizability to samples of male subjects with depression. CONCLUSIONS: The findings suggest that subtle prefrontal dysfunction in subjects with major depression may be predictive of poor response with particular medications. Assessment of the executive functions may play a particular role in pretreatment identification of subjects likely to respond to specific medications.     

Experimental evidence for a motivational origin of cognitive impairment in major depression

BACKGROUND: Diagnostic criteria and empirical evidence support the existence of cognitive deficits in depression. However, depressed mood, loss of interest and low self-efficacy might influence cognitive performance. METHOD: Goal-setting instructions were used to promote motivation in depressed patients and control subjects during neuropsychological assessment. The resulting performance was compared with performance using standard instructions. Sixty in-patients with non-psychotic unipolar depression and 60 age- and education-matched healthy control subjects were assessed with standard neuropsychological tests [the Auditory Verbal Learning Test (AVLT), the Digit Symbol Test (DST), the Regensburg Word Fluency Test (RWT), and the Number Combination Test (Zahlen-Verbindungs-Test, ZVT)] using either goal-setting or standard test instructions. RESULTS: Depressed patients showed lower baseline performance and lower generalized self-efficacy (p<0.0005) than controls. However, goal-setting instructions significantly improved patients' memory performance by 10% [AVLT: F(5, 54)=3.611, p=0.007] and psychomotor performance by 13% [ZVT: F(3, 56)=3.667, p=0.017]. Consequently, patients and control subjects demonstrated similar results when goal-setting instructions were applied. Goal-setting instructions showed a statistical trend, increasing patients' performance in the DST by 12% [F(1, 58)=2.990, p=0.089], although their verbal fluency measured by the RWT did not increase. No significant correlations of increased performance with generalized self-efficacy were found. CONCLUSIONS: Cognitive deficits in depressed patients are influenced by motivational shortcomings. Because generalized self-efficacy failed to correlate to increased test performance, future research needs to disentangle the effective components of goal-setting instructions. Task-specific self-efficacy as well as enhancement of task-focused attention might underlie the significant goal-setting effect in depressed patients.     

Deficient inhibition of emotional information in depression

BACKGROUND: There are numerous indications that impaired inhibition of negative affective material could be an important cognitive component of depression. To study whether impaired inhibition of negative affect is a cognitive vulnerability factor explaining (recurrent) depression, inhibition of positive and negative affective stimuli was examined in hospitalized depressed patients, formerly depressed individuals and never-depressed controls. METHODS: To investigate inhibitory dysfunctions in the processing of emotional material, we used an affective modification of the negative priming task with pictures of sad and happy facial expressions. RESULTS: Compared to never-depressed controls, depressed patients showed a specific failure to inhibit negative information, whereas inhibition function for positive material was unaffected. Surprisingly, formerly depressed individuals demonstrated impaired inhibition of negative and positive information. LIMITATIONS: Because of the significant correlations between depression and anxiety self-report scores, the observed reduced inhibitory effect toward negative material in the depression group cannot strictly be attributed as depression-specific. CONCLUSIONS: In accordance with our hypothesis, strongly impaired inhibition of negative affect was found in depressed patients. Based on the present findings, we argue that impaired inhibition of negative affect could be an important construct in cognitive theories on depression linking cognitive biases to neuropsychological impairments in depression. The data in the formerly depressed individuals are less conclusive and several hypotheses are detailed that could explain how the absence of inhibition of affective information could relate to recurrent depression.     

Influence of age and executive functioning on verbal memory of inpatients with depression

BACKGROUND: Despite many studies demonstrating memory and executive impairments in young and old depressed patients, the relationships between age, executive functioning and memory have not been evaluated in depression. The aim of this study was to investigate if older patients were more vulnerable than younger patients to the impact of depression on memory and if the differences between young and old depressed could be related to executive functioning. METHODS: Forty-nine inpatients, with unipolar and bipolar depression, ranging in age from 19 to 72 years were compared with 70 controls on a verbal memory task. Age cut-off of 45 years was used as a categorical variable to divide subjects into subgroups. A subset of patients (n=41) was also evaluated with the modified version of the Wisconsin Card Sorting Test and separated into a non-dysexecutive group and a group of patients with mild-executive impairment. RESULTS: Depressed patients exhibited memory deficits with a pattern of memory failure -- impaired free recall and normal cued recall and recognition -- interpreted as a retrieval problem. Both age and executive function influenced memory performance in depression, however neither group x age interaction nor age x executive status interaction were significant. Multiple regression analysis showed that free recall scores were related to age and psychomotor retardation in depressed patients. CONCLUSION: Age and executive functioning have different influences on the memory performance of depressed patients. Our findings support an 'executive memory decline hypothesis' in young as well as old depressed patients. The memory deficits in depression may be associated with both trait and state factors and raise questions about the long-term cognitive functioning of patients with recurrent affective disorders.     

Pure progressive amnesia: An atypical amnestic syndrome?

We report on M.S., an 83-year-old patient with isolated pure progressive amnesia. This rare, recently identified, form of amnesia has been described in elderly patients. Neuropathological studies suggest that this syndrome is an atypical clinical presentation of Alzheimer's disease. The aim of our study was to characterize the neuropsychological pattern of pure progressive amnesia in comparison with other amnestic syndromes and memory dissociations reported in the literature. Our results indicate that pure progressive amnesia is characterized by a highly unusual dissociation in the realm of memory, with severe deficits on tests based on recognition and recall of verbal and visual single items, contrasting with relatively preserved anterograde autobiographical and spatial memory and normal recall of complex material such as stories. These findings suggest that memory for single items could depend on an independent system. One hypothesis is that M.S.'s unusual memory profile results from relative dysfunction of the ventral medial temporal lobe pathway. An alternative explanation implicates cognitive reserve. Further studies are required in order to progress on this matter. In any case, pure progressive amnesia is a clinical syndrome that may provide further insight into the organization of declarative memory.     

Neuropsychological Correlates of Major Depression: A Short-term Follow-up

The present study investigated neuropsychological correlates of major depression and their course following treatment. We investigated 41 patients with major depression according to DSM-III-R criteria, who do not fulfil criteria of Alzheimer's disease, with a standardised clinical interview, different self- and observer-rating depression scales, and a comprehensive neuropsychological examination, and 27 subjects were reinvestigated 4.5 weeks after the first assessment. We found deficits in all cognitive domains with a predominant decline in tasks of cognitive flexibility and fluency. Patients who respond to antidepressive treatment showed a significant improvement in executive functions at the followup examination. Our data support the hypothesis that cognitive disorders in major depression may be associated with a frontostriatal dysfunction.     

Abnormal response to negative feedback in depression

BACKGROUND: Recent studies have suggested that subjects with depression suffer a diagnosis-specific motivational deficit, characterized by an abnormal response to negative feedback that endures beyond clinical recovery. Furthermore, it has been suggested that negative feedback may motivate non-depressed controls, but not depressed patients, to improve their performance in neuropsychological tests. METHODS: We describe two studies. The first compared performance on the simultaneous and delayed match to sample (SDMS) task from the CANTAB neuropsychological test battery, in 20 patients with severe depression with 20 with acute schizophrenia, 40 with chronic schizophrenia and 40 healthy controls. The second examined the performance of depressed patients with diurnal variation in symptoms and cognitive function. RESULTS: All patients groups showed impairments on the simultaneous and delayed match to sample task compared to controls. Depressed patients did not show an abnormal response to negative feedback. Controls did not show a motivational effect of negative feedback. Depressed patients with diurnal variation showed no variation in their response to perceived failure. There was no evidence of abnormal response to negative feedback in any patient group using the 'runs test' or of a motivational effect in controls. Conditional probability analysis was not independent of the total number of errors made in the SDMS task. CONCLUSIONS: Further studies are suggested to examine whether an abnormal response to negative feedback characterizes particular subgroups of patients suffering from depression.