The nature and determinants of neuropsychological functioning in late-life depression

CONTEXT: Cognitive impairment in late-life depression (LLD) is highly prevalent, disabling, poorly understood, and likely related to long-term outcome. OBJECTIVES: To determine the characteristics and determinants of neuropsychological functioning LLD. DESIGN: Cross-sectional study of groups of LLD patients and control subjects. SETTING: Outpatient, university-based depression research clinic. PARTICIPANTS: One hundred patients without dementia 60 years and older who met DSM-IV criteria for current episode of unipolar major depression (nonpsychotic) and 40 nondepressed, age- and education-equated control subjects. MAIN OUTCOME MEASURES: A comprehensive neuropsychological battery. RESULTS: Relative to control subjects, LLD patients performed poorer in all cognitive domains. More than half exhibited significant impairment (performance below the 10th percentile of the control group). Information processing speed and visuospatial and executive abilities were the most broadly and frequently impaired. The neuropsychological impairments were mediated almost entirely by slowed information processing (beta =.45-.80). Education (beta =.32) and ventricular atrophy (beta =.28) made additional modest contributions to variance in measures of language ability. Medical and vascular disease burden, apolipoprotein E genotype, and serum anticholinergicity did not contribute to variance in any cognitive domain. CONCLUSIONS: Late-life depression is characterized by slowed information processing, which affects all realms of cognition. This supports the concept that frontostriatal dysfunction plays a key role in LLD. The putative role of some risk factors was validated (eg, advanced age, low education, depression severity), whereas others were not (eg, medical burden, age at onset of first depressive episode). Further studies of neuropsychological functioning in remitted LLD patients are needed to parse episode-related and persistent factors and to relate them to underlying neural dysfunction.     

Neurocognition in depression: patients on and off medication versus healthy comparison subjects

Patients with depression have neuropsychological deficits in attention, memory, psychomotor speed, processing speed, and executive function. It is not clear, however, whether neurocognition in depression is impaired in a global or nonspecific way or if specific cognitive domains are selectively impaired. This naturalistic cross-sectional study employed a computerized neurocognitive screening battery to evaluate 38 depressed, drug-free patients, compared to 31 patients who responded to antidepressant monotherapy and to 69 healthy comparison subjects. There was evidence for global neuropsychological impairment in untreated depressed patients. In patients who had been successfully treated, performance was improved but not normalized. There was also evidence for specific depression-related deficits in executive function and processing speed but not in memory, psychomotor speed, or reaction time. Although depressed patients have global neurocognitive impairments, deficits in certain cognitive domains are more important than in others. In particular, impairments are noted in tests of executive control and in tests that demand effortful attention. Information processing speed is also impaired but not reaction time. Computerized testing in the clinic setting demonstrates a range of neurocognitive problems in patients with depression. These problems may have a bearing on treatment and outcome.     

Neuropsychological functioning in euthymic bipolar disorder: a meta-analysis

OBJECTIVE: Although cognitive deficits are prominent in symptomatic patients with bipolar disorder, the extent and pattern of cognitive impairment in euthymic patients remain uncertain. METHOD: Neuropsychological studies comparing euthymic bipolar patients and healthy controls were evaluated. Across studies, effect sizes reflecting patient-control differences in task performance were computed for the 15 most frequently studied cognitive measures in the literature. RESULTS: Across the broad cognitive domains of attention/processing speed, episodic memory, and executive functioning, medium-to-large performance effect size differences were consistently observed between patients and controls, favoring the latter. Deficits were not observed on measures of vocabulary and premorbid IQ. CONCLUSION: Meta-analytic findings provide evidence of a trait-related neuropsychological deficit in bipolar disorder involving attention/processing speed, memory, and executive function. Findings are discussed with regard to potential moderators, etiologic considerations, limitations, and future directions in neuropsychological research on bipolar disorder.     

Neuropsychological profile in bipolar disorder: a preliminary study of monotherapy lithium-treated euthymic bipolar patients evaluated at a 2-year interval

Objective: To investigate the cognitive impairment of a sample of euthymic bipolar patients treated with lithium monotherapy at baseline in a 2‐year longitudinal study. Method: Fifteen DSM‐IV‐TR bipolar out‐patients and 15 healthy‐matched controls were cognitively assessed twice over a 2‐year follow‐up. All patients underwent lithium monotherapy on the first evaluation, and they were euthymic in both evaluations. Cognitive assessment was performed by means of a neuropsychological test battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory). Results: Repeated measures multivariate analysis of variance showed that the bipolar disorder group was cognitively impaired in the executive domain, attention and processing speed, and such deficits were maintained over time. Conclusion: Our results showed that executive dysfunction is the main long‐term neuropsychological deficit of bipolar disorder. Also, the persistence of these deficits did not seem to be influenced by any clinical or pharmacological variables.     

Cortisol level predicts executive and memory function in depression, symptom level predicts psychomotor speed

OBJECTIVE: On a group level depression is related to hypercortisolism and to psychomotor retardation, executive dysfunction and memory impairment. However, intra-group heterogeneity is substantial. Why some are impaired while others remain in the normal range, is not clear. The present study aims at discerning the relative contribution of present symptom severity and hypercortisolism to impairment in the three domains of cognition. METHOD: Morning saliva cortisol was measured in 26 subjects with recurrent major depression prior to a neuropsychological examination with tests known to be sensitive to cognitive impairment in depression. RESULTS: Cortisol level correlated with executive dysfunction and post-encoding memory deficits, but not with processing speed. Depression level correlated with processing speed. These patterns remained significant after controlling for confounders through partial correlations. CONCLUSION: The association between cortisol and cognition is not an artifact of psychiatric symptom load. High level of saliva cortisol is associated with aspects of cognition that can be dissociated from psychomotor retardation, which is dependent on symptom load.     

Social support, neuropsychological performance, and depression in HIV infection.

The present study was designed to examine the impact of neuropsychological performance on the relationships between stress, social support, and depression in 217 HIV-infected men. Using path analysis, the contributions of four domains of cognitive functioning (memory, attention, executive function, and psychomotor speed), IQ, and relevant psychosocial variables to depression were evaluated. In the model which best fit the data, cognitive domains did not contribute directly to depression, but contributed significantly to psychosocial variables which affected levels of depression. Attention and executive function contributed to reduced illness-related disability; while higher IQ was associated with fewer stressful life events. Number of stressful life events and level of illness-related disability were associated with depressive symptoms. Higher IQ led to greater numbers of social contacts, which was associated with fewer reported symptoms of depression. These findings suggest that better neuropsychological performance may lead to reduced stress and perceived disability, and more available social contacts. By these multiple paths, different domains of cognitive ability contribute indirectly to ameliorating depression in HIV-infected men.     

Executive functioning in unipolar depression: a review

While several neuropsychological studies have demonstrated that cognitive deficits are seen across a broad range of cognitive domains, executive deficits associated with frontal lobe dysfunction may be prominent in depression. Executive function refers to cognitive processes that control and integrate other cognitive activities such as episodic memory. These executive functions involve a set of cognitive behaviors which include: dealing with novelty, selecting strategies, inhibiting incorrect responses, monitoring performance and using feedback to adjust future responding. The measurement of executive function relies mainly on the use of neuropsychological tests known to be sensitive to frontal lobe damage such as the Wisconsin and California Card Sorting Tests, verbal fluency tests, Stroop-test, Tower of London Task and Trail Making Test. The present review focuses on studies investigating executive functions in primary unipolar depression with these neuropsychological tasks. Unipolar depressed patients mainly exhibit cognitive inhibition deficits, problem-solving impairments and planning deficits. Cognitive inhibition deficits in depressed patients have been related to a reduction of cognitive resources and psychomotor retardation. Inhibition disturbance could lead depressed patients to process irrelevant information and consequently reduce their capacity to control transient mood changes. Several studies have found evidence of problem solving impairments in depressed patients. Depressed subjects show with card sorting tests difficulties in hypothesis testing with a loss of spontaneous and reactive cognitive flexibility. The cognitive rigidity and hypothesis-testing associated with dorsolateral prefrontal dysfunction in depression may prevent patients to cope with life events and lead to a perpetuation of depressed mood by a continuation of stress exposure. Planning tasks, such as the Tower of London Test, also demonstrate that depressed patients fail to use negative feedback as a motivational boost to improve their performance. Both trait and state factors influence the executive level of depressed patients. Executive deficits have been reported in more severely depressed subjects with melancholic or psychotic features. Executive functioning also might predict a poorer outcome in depression. Thus initiation and perseveration scores - a measure of cognitive flexibility - is associated with relapse and recurrence of depression and residual depressive symptoms. Brain imaging studies show that reduced blood flow, particularly in medial prefrontal cortex and dorsal anterior cingulate cortex subserve executive impairments in depression. However neuroimaging studies underscore the importance of mood-cognitive interactions in depression. A recent working model of depression (Mayberg et al., 1999) implicates failure of the coordinated interactions of distributed cortical-limbic pathways in the neuropsychopathology of depression. According to this model, neocortical (prefrontal and parietal regions) and superior limbic elements (dorsal anterior cingulate) are postulated to mediate impaired attention and executive function, whereas ventral limbic regions (ventral anterior cingulate, subcortical structures) are postulated to mediate circadian and vegetative aspects of depression. Further studies are needed to validate this model at the neuropsychological level as well as the brain level and to elucidate the complex interactions between mood, cognitive resources and executive function in depression.     

Predictors for cognitive impairment one year after surgery for aneurysmal subarachnoid hemorrhage

OBJECTIVE: To assess predictors for cognitive impairment one year after spontaneous subarachnoid hemorrhage (SAH). Evaluated predictors were the total amount of cisternal blood seen on computed tomography (CT) in the acute phase as measured by the Fisher grade, neurological grade at admission classified according to the Hunt and Hess scale, aneurysm site and patient's age, gender and education level. METHOD: 44 patients were operated by surgical clipping within 72 hours after CT verified aneurysmal SAH. After twelve months the remaining 42 patients were assessed by neuropsychological test, Beck Depression Inventory (BDI), the Glasgow Outcome Scale (GOS) and CT. Multiple regression analysis was conducted where predictor variables were independent factors and a global impairment index calculated for each patient was the dependent factor. RESULTS: The Fisher grade was the only independent predictor for neuropsychological impairment. Most patients had good neurological outcome as measured by the GOS and at the same time suffered from some degree of cognitive impairment at follow-up. Individual analysis of cognitive test scores showed mild to moderate dysfunction across multiple cognitive domains. Most frequent impairments were found in domains of memory, executive function and speed of information processing. Age below 50 years was associated with relatively better outcome. CONCLUSION: The severity of cognitive impairment one year post SAH is predicted by the volume of blood in the subarachnoid space as measured by the Fisher score.     

Neuropsychological deficits and functional impairment in bipolar depression, hypomania and euthymia

OBJECTIVE: To examine whether patients with bipolar disorder (BD) have subtle neuropsychological deficits that manifest clinically as cognitive and functional compromise, and this study attempted to determine the pattern of such cognitive deficits and their functional impact across all three phases of BD. We hypothesised that euthymia does not equate with normal neuropsychological function and that each phase has a characteristic pattern of deficits, with disturbance in attention and memory being common across all phases of the illness: (i) bipolar depression - psychomotor slowing and impairment of memory; (ii) hypomania by frontal-executive deficits and (iii) euthymia - a mild disturbance of attention, memory and executive function. METHODS: Twenty-five patients with a diagnosis of bipolar I disorder underwent neuropsychological testing over a period of 30 months in the natural course of their illness while hypomanic and/or depressed and/or euthymic. The results from these assessments were compared with findings from neuropsychological tests conducted on 25 healthy controls matched for age, sex, education and handedness. RESULTS: Initial analyses revealed modest impairment in executive functioning, memory and attention in both hypomanic and depressed bipolar patients, with additional fine motor skills impairment in the latter. Memory deficits, also noted in euthymic patients, were non-significant after controlling for confounding variables, although bipolar depressed patients remained significantly impaired on tests of verbal recall. Bipolar depressed and hypomanic patients differed with respect to the nature of their memory impairment. Depressed patients were more impaired as compared with euthymic patients on tests of verbal recall and fine motor skills. Psychosocial functioning was impaired across all three patient groups, but only in depressed and hypomanic patients did this correlate significantly with neuropsychological performance. CONCLUSIONS: The mood-state-related cognitive deficits in both bipolar depression and hypomania compromise psychosocial function when patients are unwell. In euthymic patients, subtle impairments in attention and memory suggest that an absence of symptoms does not necessarily equate to 'recovery'. The possibility of persistent cognitive deficits in BD is an issue of profound clinical and research interest that warrants further investigation; however, future research needs to adopt more sophisticated neuropsychological probes that are able to better define state and trait deficits and determine their functional impact.     

Cognitive features in euthymic bipolar patients in old age

Objectives:  Studies of cognition in bipolar disorder (BD) have reported impairments in processing speed, working memory, episodic memory, and executive function, but they have primarily focused on young and middle-aged adults. In such studies, the severity of cognitive deficits increases with the duration of illness. Therefore, one would expect more pronounced deficits in patients with longstanding BD. The first aim of the present study was to determine the pattern and the magnitude of cognitive impairment in older euthymic BD patients. The second aim was to explore the interrelationship between these cognitive deficits and determine whether they reflect a single core impairment or the co-occurrence of independent cognitive deficits.
Methods:  Twenty-two euthymic elderly BD patients and 22 controls, matched for gender, age, and education, underwent a comprehensive neuropsychological assessment.
Results:  Compared to controls, BD patients had significantly reduced performance in processing speed, working memory, verbal fluency, and episodic memory, but not in executive function. Hierarchical regression analyses showed that verbal fluency and working memory impairments were fully mediated by changes in processing speed. This was not the case for the episodic memory dysfunction.
Conclusion:  The cognitive profile in older euthymic BD cases is similar to the one described in younger BD cohorts. Our results further suggest that impaired processing speed plays a major role in the cognitive changes observed in BD patients except for deficits in episodic memory, thus providing strong evidence that processing speed and episodic memory are two core deficits in elderly BD patients.     

Neuropsychological predictors of everyday functioning in adults with intellectual disabilities

Background Very little is known about the neuropsychological correlates of adaptive functioning in people with intellectual disabilities (ID). This study examined whether specific cognitive deficits and demographic variables predicted everyday functioning in adults with ID. Method People with ID (n = 101; ages 19–41 years; mean education = 11 years; 34% women; 54% competitively employed; 41% with mild ID) completed a comprehensive neuropsychological battery grouped into four cognitive domains: processing speed, verbal memory and comprehension, visual perception/constructive function, and executive function. In addition, parents completed an 89‐item rating scale developed to assess a wide range of independent living skills. Results Confirmatory factor analysis results confirmed a correlated four‐factor model of cognitive function and a unidimensional model of everyday functioning. Furthermore, structural equation modelling results supported the predictive relationship of verbal memory/comprehension and employment status (standardized regression coefficients 0.45, 0.22, P ≤ 0.01 for each) to measures of everyday functioning. The two variables together explained 35% of the variance in everyday functioning. Conclusions Both general cognitive dysfunction and specific verbal memory and comprehension deficit impair daily functions in people with ID. These findings have implications for predictive models of adaptive functioning, and for cognitive rehabilitation and deficit compensation strategies for this group.     

Neuropsychological testing in the diagnosis of dementia

Neuropsychological testing can play a major role in the diagnosis of dementia by documenting cognitive deficits, the key criteria for the diagnosis. Because the most common dementia diagnosis, Alzheimer's disease, focuses on memory impairment, tests to assess this domain and to detect and characterize memory deficit are well established with recognized predictive value. Other neuropsychological domains are less well characterized and there are fewer tools to assess them. One domain that has been characterized as important in a number of other dementias is executive function. Improved neuropsychological assessment and characterization of other domains, such as executive function and attention, may assist in better identifying the pathophysiology of deficits in these areas, perhaps in combination with new technologies such as functional imaging. Finally, improved assessment tools for specific cognitive domains should assist in identifying a broad range of cognitive deficits at earlier stages and ultimately lead to more effective interventions for a wider range of cognitive deficits.     

Distinct profiles of neurocognitive function in unmedicated unipolar depression and bipolar II depression.

BACKGROUND: Studies have demonstrated neuropsychological deficits across a variety of cognitive domains in depression. Few studies have directly compared depressed subjects with major depressive disorder (MDD) and bipolar disorder (BD), and many are confounded by medication status across subjects. In this study, we compared the performance of unmedicated currently depressed MDD and BD groups on a battery of neuropsychological tests that included measures of risk taking and reflection impulsivity. METHODS: Twenty-two MDD, seventeen BDII, and 25 healthy control subjects (HC), matched for age and IQ, were assessed on a battery of neuropsychological tests. RESULTS: The depressed groups showed comparable ratings of depression severity and age of illness onset. The MDD group was impaired on tests of spatial working memory and attentional shifting, sampled less information on a test of reflection impulsivity, and was oversensitive to loss trials on a decision-making test. The BDII subjects were generally intact and did not differ significantly from control subjects on any test. CONCLUSIONS: These data indicate differing profiles of cognitive impairment in unmedicated depressed MDD versus BDII subjects. Moderately depressed BDII subjects displayed relatively intact cognitive function, whereas MDD subjects demonstrated a broader range of executive impairments. These cognitive deficits in depression were not attributable to current medication status.     

Neuropsychological profiles in MCI and in depression: Differential cognitive dysfunction patterns or similar final common pathway disorder?

The concept of “mild cognitive impairment” (MCI) refers to alterations in cognition in the transition between normal aging and dementia. However, from a neuropsychological point of view the conventional diagnostic criteria appear not sufficiently valid. In particular, it is still difficult to differentiate between subjects with MCI and subjects with depression plus cognitive deficits on the basis of their neuropsychological profiles. The aim of this study is to compare cognitive deficit patterns of subjects with MCI and with depression. 24 subjects with MCI, 50 subjects with depression (DEP) and 20 healthy control subjects were included (age: 55-74 years). The neuropsychological assessment consisted of standardized tests to assess attention, memory, and executive functions. Compared to healthy controls both subject groups showed significantly lower performance in all cognitive domains. However, we did not find significant differences in cognitive performance between MCI and DEP subjects, neither at baseline nor at follow-up. In addition, preliminary results of follow-up assessments after 2 (DEP) and 6 months (MCI), respectively, revealed no significant changes in cognition in subjects with depression, regardless of whether depressive symptoms had improved. Subjects with MCI also showed no changes in cognition at follow-up. The comparable neuropsychological patterns identified in the two subject groups may be understood as a consequence of similar alterations in cognitive systems, supporting the idea of a final common pathway disorder. Thus, the cognitive deficits present in a subgroup of subjects with depression may possibly better be understood in the context of MCI.     

Effects of information processing speed on learning,memory, and executive functioning in people living with HIV/AIDS

Introduction: It is unclear whether or to what degree literacy, aging, and other neurologic abnormalities relate to cognitive deficits among people living with HIV/AIDS in the combined antiretroviral therapy (CART) era. The primary aim of this study was to simultaneously examine the association of age, HIV-associated motor abnormalities, major depressive disorder, and reading level with information processing speed, learning, memory, and executive functions, and to determine whether processing speed mediated any of the relationships between cognitive and noncognitive variables. Method: Participants were 186 racially and ethnically diverse men and women living with HIV/AIDS who underwent comprehensive neurological, neuropsychological, and medical evaluations. Structural equation modeling was utilized to assess the extent to which information processing speed mediated the relationship between age, motor abnormalities, major depressive disorder, and reading level with other cognitive abilities. Results: Age, motor dysfunction, reading level, and current major depressive disorder were all significantly associated with information processing speed. Information processing speed fully mediated the effects of age on learning, memory, and executive functioning and partially mediated the effect of major depressive disorder on learning and memory. The effect of motor dysfunction on learning and memory was fully mediated by processing speed. Conclusions: These findings provide support for information processing speed as a primary deficit, which may account, at least in part, for many of the other cognitive abnormalities recognized in complex HIV/AIDS populations. The association of age and information processing speed may account for HIV/aging synergies in the generation of CART-era cognitive abnormalities.     

Impaired verbal memory in young adults with unipolar and bipolar depression

Aim: Early stages of severe mood disorders may be accompanied by neurocognitive changes. Specifically, deficits in verbal memory have been linked to depression in young people. This study examined whether young adults with unipolar compared with bipolar depression showed similar neurocognitive deficits. Methods: A total of 57 young adults (16–32 years) were assessed in this study. Twenty with unipolar and 20 with bipolar depression, all currently depressed, were compared with 17 healthy controls. Neuropsychological assessment included psychomotor speed, attention for routine mental operations, attentional switching, executive control and verbal learning and memory. Results: Both unipolar and bipolar subjects showed significant impairments in verbal memory and attentional switching compared with controls. Both mood disorder groups showed no impairments in psychomotor speed, attention for routine mental operations and executive control. Effects size calculations show that the unipolar and bipolar groups do not differ from each other across a range of neurocognitive measures. Conclusion: Neurocognitive deficits in young adults with current depressive syndromes appear to differ from those typically seen in older patients. In early adulthood, both unipolar and bipolar depression may be distinguished by poor verbal memory, despite intact speed of processing, attention and executive functions. This study suggests that there is utility in neuropsychological testing for young adults in the early stages of severe mood disorders. In order to prevent neurobiological changes inherent to the disease, pharmacological and non-pharmacological interventions that target verbal memory deficits may be optimally delivered early in the disease course.     

The assessment of neuropsychological functioning in schizophrenia

Overwhelming evidence suggests that compromised neuropsychological function is frequently observed in schizophrenia. The neuropsychological profile is typically characterized by prominent specific deficits in memory and learning, working memory, executive functions, attention, and processing speed, which are evident on a background of a generalized cognitive deficit. This paper provides a review of studies of neuropsychological functioning in schizophrenia. The main cognitive ability areas affected in schizophrenia are described, and the degree of impairment in each ability area as found in studies of schizophrenia patients is summarized, based on meta-analytic findings. Recent studies that have compared neuropsychological functioning across psychotic disorders are presented, and finally, neuropsychological assessment batteries specifically developed for schizophrenia are introduced.     

Neuropsychological Profiles in Different At-Risk States of Psychosis: Executive Control Impairment in the Early—and Additional Memory Dysfunction in the Late—Prodromal State

Impairments in neuropsychological functioning have been described in subjects clinically at high risk for psychosis, but the specific cognitive deficits in different clinical high-risk groups remain to be elucidated. The German Research Network on Schizophrenia employs a heuristic 2-stage model: a putatively late prodromal state (LPS), characterized by the onset of attenuated positive or brief psychotic symptoms, and an early prodromal state (EPS), mainly characterized by the presence of basic symptoms, which are predictive for psychosis within the next 10 years.A total of 205 subjects met the criteria for either an EPS or an LPS of psychosis and were assessed with a comprehensive neuropsychological test battery. Neurocognitive profiles of high-risk groups were compared with data of 87 healthy controls comparable with regard to gender, age, and premorbid verbal IQ.Patients in the LPS were impaired in all neurocognitive domains (memory/learning, executive control/processing speed, and working memory) examined, with memory being the worst. Deficits were less pronounced in patients in the EPS, with a specific deficit in the executive control/processing speed domain. Consistent with a progressive neurodevelopmental disorder, some cognitive abilities were already impaired in patients in the EPS, followed by further deterioration in the LPS. Specifically, deficits in executive control functioning were related to the presence of basic symptoms, indicating a vulnerability for psychosis. Memory deficits were associated with the onset of psychotic symptoms indicating further disease progression in the trajectory to psychosis and, thus, may be useful in predicting psychosis and targeting early intervention.     

Cognition in the early stage of multiple sclerosis

Objective Cognitive dysfunctions may contribute to limitation of everyday activities of patients with multiple sclerosis (MS). Recent studies have demonstrated that 45 to 65% of MS-patients are cognitively impaired. The profile of MS-related cognitive dysfunctions varies greatly. It includes memory and learning deficits, attention deficits, executive dysfunctions and visuo-spatial deficits. Most studies of cognition in MS examined patients in later stages, often including MS-patients with marked physical disabilities. Studies of cognitive dysfunctions in the early stage of the disease are rare. This study specifically aimed at evaluating and characterizing cognitive impairments in the early stage of MS, and determining specific patterns of cognitive dysfunction. Methods 21 MS patients, experiencing their first neurological symptoms not more than two years previously, and 22 healthy controls were compared. A comprehensive neuropsychological test-battery was used to evaluate MS-related cognition. The battery consisted of memory and learning tests, executive functioning tests and a visuo spatial functioning test. A computerized attention test-battery was also included, which assess accuracy and speed of test responses. In addition depression and intellectual capabilities were assessed. Results Compared with healthy controls, MS-patients in the early stage of the disease performed significantly lower on each neuropsychological assessment, except for verbal short-term memory. In particular, MS-patients showed a lengthened reaction time for simple and focused attention (19–38%), impaired non-verbal memory function (RVDLT recognition: 33%) and a planning deficit (24%). Associations between information processing speed and disease course and the employment situation were additionally found. However, patients did not have clinically relevant depression rates on the ADS-L and visuo spatial abilities remain preserved. Conclusion Our findings revealed discrete cognitive dysfunction in MS-patients within the early stage of the disease. Received in revised form: 18 January 2006     

Regional white matter hyperintensity burden in automated segmentation distinguishes late-life depressed subjects from comparison subjects matched for vascular risk factors

OBJECTIVE: Segmented brain white matter hyperintensities were compared between subjects with late-life depression and age-matched subjects with similar vascular risk factor scores. Correlations between neuropsychological performance and whole brain-segmented white matter hyperintensities and white and gray matter volumes were also examined. METHOD: Eighty-three subjects with late-life depression and 32 comparison subjects underwent physical examination, psychiatric evaluation, neuropsychological testing, vascular risk factor assessment, and brain magnetic resonance imaging (MRI). Automated segmentation methods were used to compare the total brain and regional white matter hyperintensity burden between depressed patients and comparison subjects. RESULTS: Depressed patients and comparison subjects did not differ in demographic variables, including vascular risk factor, or whole brain-segmented volumes. However, depressed subjects had seven regions of greater white matter hyperintensities located in the following white matter tracts: the superior longitudinal fasciculus, fronto-occipital fasciculus, uncinate fasciculus, extreme capsule, and inferior longitudinal fasciculus. These white matter tracts underlie brain regions associated with cognitive and emotional function. In depressed patients but not comparison subjects, volumes of three of these regions correlated with executive function; whole brain white matter hyperintensities correlated with executive function; whole brain white matter correlated with episodic memory, processing speed, and executive function; and whole brain gray matter correlated with processing speed. CONCLUSIONS: These findings support the hypothesis that the strategic location of white matter hyperintensities may be critical in late-life depression. Further, the correlation of neuropsychological deficits with the volumes of whole brain white matter hyperintensities and gray and white matter in depressed subjects but not comparison subjects supports the hypothesis of an interaction between these structural brain components and depressed status.