Dissociable mechanisms for memory impairment in bipolar disorder and schizophrenia

BACKGROUND: Although memory deficits are consistently reported in schizophrenia and bipolar disorder, the mechanisms underlying these impairments are poorly understood. Clarifying the nature and degree of overlap in memory deficits between the two illnesses could help to distinguish brain systems disrupted in these illnesses, and indicate cognitive remediation strategies to improve patient outcomes. METHOD: We examined performance on a non-verbal memory task in clinically stable out-patients with bipolar disorder (n=40), schizophrenia (n=40), and healthy comparison subjects (n=40). This task includes conditions in which distinct mnemonic strategies -- namely, using context to organize familiar stimuli or using holistic representation of novel stimuli -- facilitate performance. RESULT: When compared to a reference condition, bipolar patients had deficits consistent with organizational dysfunction and poor detection of novel information. Although patients with schizophrenia performed worse than the other groups, they were only differentially impaired when organizational demands were significant. Task performance was not correlated with severity of clinical symptomatology. CONCLUSIONS: This pattern of distinct memory impairments implies disturbances in partially overlapping neural systems in bipolar disorder and schizophrenia. Evidence of impairment in detection of novel stimuli that is unique to bipolar disorder suggests that, while the absolute level of cognitive dysfunction is less severe in bipolar disorder as compared to schizophrenia, subtle disruptions in memory are present. These findings can be used to plan targeted cognitive remediation programs by helping patients to capitalize on intact functions and to learn new strategies that they do not employ without training.     

The effects of traumatic brain injuries on information processing.

Many individuals experience memory impairment subsequent to traumatic brain injuries (TBI). These memory deficits may result from general impairment of information processing rather than damage to memory critical neurological systems. The investigators examined learning time and recall errors for easy and hard word pairs in a distraction and no-distraction condition to examine learning patterns. Although results indicated that individuals with and without TBI generally showed the same learning and retrieval patterns, individuals with TBI did so in an accentuated manner. This suggests that attentional deficits associated with TBI are not responsible for subsequent memory deficits.     

The role of the frontal lobes in memory: evidence from unilateral frontal resections for relief of intractable epilepsy.

The current investigation explored processes associated with memory deficits in patients with frontal lobe dysfunction. Specifically, we examined deficits associated with the encoding, consolidation, and retrieval of information in memory in 53 patients who underwent either a unilateral frontal (N=13) or temporal (N=40) lobe resection for relief of intractable epilepsy. Post-surgical memory scores indicated that the frontal group and the temporal group did not differ in consolidation of information, as defined by the information forgotten between immediate and delayed recall. Instead, the temporal group evidenced significantly poorer recall of verbal information at both immediate and delayed recall. This effect was especially strong in the left temporal group for the recall of verbal information. Although no group differences were observed in the degree to which patients semantically organized information or made recency discriminations, the frontal group exhibited significantly weaker release from proactive interference than the temporal group, suggesting some impairment in encoding and retrieval processes associated with frontal lobe dysfunction.     

Cognitive profiles of mild cognitive impairment with and without vascular disease

This study examined whether the cognitive profile of subjects with mild cognitive impairment (MCI) with vascular disease differs from that of MCI subjects with no vascular disease. Consecutive MCI subjects with vascular disease (n=60) and matched MCI subjects with no vascular disease (n=60) were included in the study and were compared with healthy control subjects (n=60). The neuropsychological assessment comprised tests of speed and attention, episodic memory, visuospatial function, language, and executive function. Control subjects performed significantly better than did both MCI groups on the neuropsychological battery. MCI subjects with no vascular disease performed better overall than did MCI subjects with vascular disease, most clearly on tests of speed and attention, visuospatial function, and executive function. MCI subjects with and without vascular disease exhibited differences, both in terms of overall performance and of cognitive profiles. These differences can be largely explained by deficits in speed and attention and in executive function of the MCI subjects with vascular disease.     

Specific Neuropsychological Deficits in Schizophrenic Patients with Preserved Intellectual Function

Although a wide range of cognitive deficits have been demonstrated in schizophrenia, it is not clear whether specific deficits stand out from general intellectual decline. Separate cases have been made for selective impairments in mnemonic and in executive function but these remain unconfirmed. A common problem in studies of schizophrenia is heterogeneity of deficits and Shallice, Burgess, and Frith (1991) have addressed this by using a single case study approach. The present study used the CANTAB battery of neuropsychological tests to examine cognitive performance in a small group of schizophrenic patients with preserved intellectual function. This test battery allows a componential analysis of performance, and its neurological validation may enable specific neurobiological hypotheses to be addressed. Twelve schizophrenic patients with current IQ greater than 90 and within 10 points of premorbid IQ were assessed on tests of visuospatial memory, spatial working memory, planning, and attentional set-shifting. Their performance was compared to that of 12 matched controls. The patient group, as a whole, was impaired on all tasks but the pattern of impairment varied across individuals. Consistently, severe deficits were seen on tests of delayed matching to sample and attentional set-shifting. These deficits are compared to those seen in patients with unipolar depression, who showed similar deficits in delayed matching to sample but not set-shifting, and are considered in terms of common cognitive mechanisms and possible neural substrates.     

Neurocognitive function in users of MDMA: the importance of clinically significant patterns of use

BACKGROUND: Use of MDMA (ecstasy), a serotonin neurotoxin, has been associated with memory impairment and psychological dysfunction. This study examined cognitive functioning in abstinent MDMA users and MDMA-naive controls. METHOD: Participants completed measures of intelligence, motor function, attention, memory span, verbal fluency, immediate and delayed verbal memory, and working memory. They were also assessed for the presence of psychopathology. In addition to comparing cognitive function in MDMA users relative to controls, the possibility that clinically dysfunctional MDMA use increases the risk of cognitive impairment was examined. RESULTS: MDMA users exhibited relative deficits in mnemonic and executive functions. Additionally, users that met DSM-IV substance use disorder criteria for lifetime MDMA abuse or dependence exhibited a number of additional deficits relative to those who did not meet these criteria. CONCLUSION: These findings suggest that clinically dysfunctional, rather than purely recreational, MDMA use is associated with cognitive impairment. Future research studies of diverse samples of users may shed light on the mechanisms that underlie these differences.     

Encoding and retrieval processes in velo-cardio-facial syndrome (VCFS)

Velo-cardio-facial syndrome (VCFS) is a neurogenetic disorder associated with very high risk for developing schizophrenia. More than half of affected individuals experience transient psychotic symptoms during childhood and a third may develop schizophrenia. Memory regulation deficits disturbing both the encoding and retrieval stages of memory represent core deficits in the cognitive profile associated with schizophrenia. In this study, the authors investigate memory regulation processes in 33 individuals with VCFS along with 33 age- and sex-matched control participants. By using a directed forgetting paradigm and a continuous recognition paradigm, the authors examined selective encoding and suppression of irrelevant contents during retrieval in VCFS. Group comparison analyses revealed comparable performances on selective encoding and recognition accuracy between the VCFS group and control group. However, individuals with VCFS were more likely to make false recognitions and showed deficits in the suppression of irrelevant contents. Results suggest that trait-like deficits of memory regulation in VCFS can be observed during the retrieval stage, while selective encoding remains efficient. Memory regulation processes during retrieval may constitute a trait deficit in the memory profile of individuals with VCFS and may contribute to the cognitive deficits underlying an increased risk for developing schizophrenia in this population.     

Cognitive profile of fragile X premutation carriers with and without fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS) develops in a subset of fragile X premutation carriers and involves gait ataxia, action tremor, Parkinsonism, peripheral neuropathy, autonomic disorders, and cognitive impairment. The study was designed to define the nature of cognitive deficits affecting male premutation carriers with and without FXTAS. A sample of 109 men underwent motor, cognitive, genetic, and neurologic testing, as well as brain magnetic resonance imaging. Subjects were classified into 3 groups: (a) asymptomatic premutation carriers, (b) premutation carriers with FXTAS, and (c) normal controls. Men with FXTAS performed worse than controls on mental status, intelligence, executive cognitive functioning (ECF), working memory, remote recall of information, declarative learning and memory, information processing speed, and temporal sequencing, as well as 1 measure of visuospatial functioning. Language and verbal comprehension were spared. Asymptomatic carriers performed worse than controls on ECF and declarative learning and memory. This comprehensive examination of cognitive impairment in male premutation carriers suggests that FXTAS involves substantial executive impairment and diffuse deficits in other cognitive functions. Longitudinal research currently underway will provide insight into the progression of the disorder.     

Cognitive impairment in remission in bipolar affective disorder

BACKGROUND: Although the traditional view of bipolar affective disorder is that the majority of patients have full remission between episodes, recent evidence suggests that residual cognitive deficits are present. The aim of this study was to determine whether memory and executive deficits were present in a well-defined clinically remitted group of patients. METHODS: This was a case-control study of bipolar patients in remission (N = 18). Subjects had to fulfil stringent clinical criteria for inclusion into the study and had to have been in remission for at least 4 months. Subjects also had no history of substance dependence. The cognitive battery examined memory and executive function. RESULTS: Patients in excellent clinical remission and who reported good social adaptation showed imipairment on tests of visuospatial recognition memory. Accuracy on four tests of executive function was not impaired in patients in remission compared with controls, although response latency on these executive tests was still impaired. CONCLUSIONS: As our group and others have shown, patients with mania and unipolar depression show generalized impairment on tests of memory and executive function. In comparison, this study has demonstrated that patients in remission show a relatively specific impairment in memory with recovery of accuracy measures on executive function task. The increased response latency on the executive tasks suggests a possible small residual impairment. These findings suggest that in netIroanatomical terms, more posterior cortical function (temporal lobe) has not improved but there is at least some recovery of frontal lobe function in remission.     

Heterogeneity of semantic and visuospatial deficits in early Alzheimer's disease

Staging of visuospatial and semantic deficits in patients with dementia of the Alzheimer type (DAT) was examined. The authors hypothesized that semantic ability would be more impaired in these patients, reflecting predominant temporal pathology early in the disease. However, in the 1st study (n = 26), 3 patients (11.5%) had marked visual but no semantic impairment. This finding was extended in a 2nd study with a 2nd patient sample (n = 21) and more specific tasks. Two patients (9.5%) again had visual but no semantic impairment. These studies confirm that, in patients with DAT presenting with relatively focal deficits, visual deficits sometimes occur before semantic problems. The findings are discussed with regard to the cognitive demands and neuroanatomical underpinning of the tests used and point to the necessity of using cognitively specific tests to enable accurate analysis of deficits in the context of the neuroanatomical basis of impairment.     

Cognitive impairment in preclinical Alzheimer's disease: a meta-analysis

To determine the size of the impairment across different cognitive domains in preclinical Alzheimer's disease (AD), a meta-analysis based on 47 studies involving 9,097 controls and 1,207 preclinical AD cases was conducted. There were marked preclinical deficits in global cognitive ability, episodic memory, perceptual speed, and executive functioning; somewhat smaller deficits in verbal ability, visuospatial skill, and attention; and no preclinical impairment in primary memory. Younger age (< 75 years) and shorter follow-up intervals (< 3 years) were associated with larger effect sizes for both global cognitive ability and episodic memory. For global cognitive ability, studies that used population-based sampling yielded larger effect sizes; for episodic memory, larger differences were seen in studies that preidentified groups in terms of baseline cognitive impairment. Within episodic memory, delayed testing and recall-based assessment resulted in the largest effect sizes. The authors conclude that deficits in multiple cognitive domains are characteristic of AD several years before clinical diagnosis. The generalized nature of the deficit is consistent with recent observations that multiple brain structures and functions are affected long before the AD diagnosis.     

Bipolar I and bipolar II disorder: cognition and emotion processing

BACKGROUND: Cognitive impairment may be part of the endophenotype of bipolar disorder (BP), but little is known about patterns and severity of impairment in BP subgroups and their relation to depression. The same applies to deficits in emotion processing known to be present in BP. METHOD: To explore the relationship between depression and impairment in cognition and emotion processing and the differences between BP subgroups, we assessed 36 (25 BP I and 11 BP II) patients using a cognitive battery and a facial emotion recognition task. RESULTS: BP patients were impaired compared to published norms on memory, naming and executive measures (Binomial Single Proportion tests, p<0.05). Cognitive performance was largely unrelated to depression ratings. Surprise recognition was the only emotion processing impairment in BP patients compared to controls (patients' recognition score 75% v. controls' 89%, p=0.024). Patients with higher depression ratings were more impaired in recognizing expressions of anger (t23=2.21, p=0.037). BP II patients were more impaired than BP I patients in IQ, memory and executive measures (Mann-Whitney tests, p<0.05). Depression severity or exposure to medication or electroconvulsive therapy (ECT) did not explain these differences. CONCLUSIONS: We confirm cognitive impairment and an isolated facial emotion processing deficit in BP patients and suggest that these deficits are largely unrelated to depressive symptoms. Our study also provides evidence that cognitive deficits are more severe and pervasive in BP II patients, suggesting that recurrent depressive episodes, rather than mania, may have a more detrimental and lasting effect on cognition.     

A deficit in attentional set-shifting of violent offenders

BACKGROUND: Recent brain imaging studies suggest that proneness to violence and antisocial behaviour may be associated with dysfunction of the prefrontal cortex. The present study. therefore, examined aspects of prefrontally guided executive functions in a group of criminal violent men. METHODS: Violent offenders undergoing forensic psychiatric examination by court order undertook computerized tasks for planning, visual working memory and attentional set-shifting from the Cambridge Neuropsychological Test Automated Battery. Their performance was compared to that of subjects with marginal mental retardation and normal controls. RESULTS: Violent offenders performed well on tasks for spatial and figurative working memory, as well as on a test for planning. A marked impairment was observed in the attentional set-shifting task: offenders made significantly more errors than the other groups when required to shift attention from one perceptual dimension to another. Reversal learning was also deficient. Correlational analyses within the offender group revealed that poor performance on the perceptual shift problem was associated with fewer errors in tasks for working memory and planning. CONCLUSIONS: The present results suggest that violent offenders show dual impairments in inhibitory cognitive control. First, they are deficient in shifting attention from one category to another. Secondly, the ability to alter behaviour in response to fluctuations in the emotional significance of stimuli is compromised. These deficits might constitute cognitive reflections of the biological prefrontal alterations observed in this group of people.     

Memory encoding and retrieval in frontotemporal dementia and Alzheimer's disease

Memory encoding and retrieval strategies were assessed in patients with behavior-executive variant frontotemporal dementia (FTD), language variant FTD, and Alzheimer's disease (AD) using verbal and visuospatial supraspan learning tests. FTD patients obtained higher free recall, cued recall, and recognition scores than AD patients. Comparison of free recall scores with cued recall and recognition scores was similar in the 3 dementia groups. Groups did not differ in semantic clustering strategies during learning, but serial-order recall was more common in FTD patients. These data do not support the idea that FTD patients' poor memory is due to a selective retrieval disorder, though FTD patients may fail to implement sophisticated organizational strategies during learning. FTD patients' retained capacity for encoding new information into long-term declarative memory is likely due to relatively spared medial temporal lobe involvement.     

The relationship between semantic organization and memory in obsessive-compulsive disorder

BACKGROUND: A variety of evidence suggests that frontostriatal dysfunction is involved in obsessive-compulsive disorder (OCD). This evidence includes both neuroimaging findings and results from studies using neuropsychological assessments. Previous studies have documented nonverbal memory deficits in individuals with OCD, whereas verbal learning and memory were less affected. METHODS: The present study examined both verbal and nonverbal memory in a sample of 17 untreated outpatients with OCD. We also evaluated the effects of encoding strategies which are believed to be mediated by frontostriatal system functioning. RESULTS: OCD patients were significantly impaired in both verbal and nonverbal memory performance. This deficit was correlated with impairments in organizational and semantic clustering strategies at the time of encoding. CONCLUSIONS: Deficits in organizational strategies are consistent with frontostriatal dysfunction models in OCD.     

The association between neuropsychological impairment, self-perceived cognitive deficits, fatigue and health related quality of life in breast cancer survivors following standard adjuvant versus high-dose chemotherapy

OBJECTIVE: The possible association between neuropsychological impairment, self-perceived cognitive deficits, fatigue and health related quality of life has been studied in high-risk breast cancer survivors 5 years following standard adjuvant (n=23) versus high-dose chemotherapy (n=24) and in early-stage breast cancer patients (n=29) (comparison group) following radiation therapy. METHODS: A neuropsychological assessment covering attention, memory and executive functions was used together with the questionnaire for self-perceived deficits in attention (FEDA), the multidimensional fatigue inventory (MFI-20) and the EORTC-QLQ-C30. RESULTS: Findings have shown that neuropsychological impairment is not directly associated with self-perceived cognitive deficits, fatigue and HRQOL. However, 46% of patients reported self-perceived cognitive deficits and 82% of the patients complained about cancer related fatigue. Except for reduced activity we did not find significant group differences, even though patients who received standard-dose chemotherapy had consistently higher levels of self-perceived cognitive deficits and fatigue, and the lowest HRQOL. CONCLUSION: Results emphasize the need for psychosocial counseling and support during treatment phase and follow up care as well. Sensitive cancer-specific measures for the assessment of self-perceived cognitive deficits in different cognitive domains according to neuropsychological measurements are required. PRACTICE IMPLICATIONS: The role of self-perceived cognitive deficits and fatigue should be considered in educational interventions and counseling. Specific rehabilitation measures should be developed, implemented and evaluated in order to meet the needs of these patients and to decrease the frequency of cognitive deficits following cancer treatment.     

Comprehension,encoding, and monitoring in the production of confabulation in memory: A study with schizophrenic patients

Introduction. The aim of the present study was to test the hypotheses proposed by Nathaniel‐James and collaborators (; ) to account for the cognitive deficits involved in the production of confabulations in schizophrenic patients: impairments in comprehension, memory encoding, and memory monitoring.

Method. Five patients were investigated in this multiple single‐case study. Comprehension abilities were investigated in several tests in which a memory bias was avoided. The encoding deficit hypothesis was tested by manipulating cues at encoding and/or retrieval. “Memory monitoring” abilities were examined in two tasks: the Hayling test for all patients and an AB‐AC word pairs learning task for two patients.

Results. Four of the patients produced an abnormal level of confabulations in story and fable learning tests. All patients exhibited encoding deficits and specific comprehension difficulties. However, some demonstrated preserved memory monitoring abilities. Across different tests, it was observed that the more the confabulations occurred, the more severe were the comprehension difficulties.

Conclusion. The results are in favour of the hypothesis that verbal comprehension difficulties lead to the production of confabulation. They are inconsistent with the idea that memory monitoring impairment is necessarily involved.     

A profile of neuropsychological deficits in alcoholic women

Neuropsychological deficits, most notable in executive, visuospatial, and functions of gait and balance, are detectable in alcoholic men even after a month of sobriety. Less well established are the severity and profile of persisting deficits in alcoholic women. The authors used an extensive test battery to examine cognitive and motor functions in 43 alcoholic women who were sober, on average, for 3.6 months. Functions most severely affected in alcoholic women involved visuospatial and verbal and nonverbal working memory processes as well as gait and balance. Areas of relative sparing were executive functions, declarative memory, and upper-limb strength and speed. The authors found that lifetime alcohol consumption was related to impairment severity on Block Design (Wechsler Adult Intelligence Scale-Revised, D. Wechsler, 1981) and verbal and nonverbal working memory, suggesting a dose effect of alcohol abuse. The alcohol-related deficits in working memory, visuospatial, and balance implicate disruption of prefrontal, superior parietal, and cerebellar brain systems.     

Short-term memory and cognitive variability in adult fragile X females

We investigated the possibility that adult fragile X [fra(X)] heterozygotes have a distinct or specific cognitive profile, with a particular focus on visuospatial and/or memory deficits. With a sample of 13 adult fra(X) female carriers (2 fra(X) positive) and age-matched control women, we performed 2 tests: Wechsler Adult Intelligence Scale-Revised (WAIS-R) and the Revised Visual Retention Test (RVRT). An identifiable cognitive profile was not evident in the study group, but significant differences were evident in RVRT performance in number correct and number of errors when compared to controls and normative data. The combination of the WAIS-R and RVRT data suggests that the short-term memory component of the tasks may be of more significance than visuospatial performance in the deficits observed.     

Effects of continuous positive airway pressure on cognitition and neuroimaging data in sleep apnea

Obstructive sleep apnea (OSA) has been associated with a broad range of neurocognitive difficulties. The current view is that the neurocognitive impairment in OSA is due to the adverse effects of sleep fragmentation and/or intermittent hypoxia. The overall picture of cognitive deficits in OSA is complex. On balance, there appears to be negative effects of OSA on cognition, most likely in the domains of attention/vigilance, verbal and visual delayed long-term memory, visuospatial/constructional abilities, and executive dysfunction. Continuous positive airway pressure (CPAP) is the most effective and widely used treatment of OSA. In the majority of studies of OSA patients treated with CPAP, attention/vigilance improved, but changes in global functioning, executive functioning, and memory improved in about half of the studies. This may be due, in part, to variability in study design and sampling methodology across studies.