There has been a surge of interest in the functional consequences of neurocognitive deficits in schizophrenia. The published literature in this area has doubled in the last few years. In this paper, we will attempt to confirm the conclusions from a previous review that certain neurocognitive domains (secondary verbal memory, immediate memory, executive functioning as measured by card sorting, and vigilance) are associated with functional outcome. In addition to surveying the number of replicated findings and tallying box scores of results, we will approach the review of the studies in a more thorough and empirical manner by applying a meta-analysis. Lastly, we will discuss what we see as a key limitation of this literature, specifically, the relatively narrow selection of predictor measures. This limitation has constrained identification of mediating variables that may explain the mechanisms for these relationships.

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Neurocognitive Deficits and Functional Outcome in Schizophrenia: Are We Measuring the “Right Stuff”?

'Oops!': performance correlates of everyday attentional failures in traumatic brain injured and normal subjects

Summary Multiple sclerosis (MS) is a progressive disease of the CNS that is characterised by widespread lesions in the brain and spinal cord. MS results in motor, cognitive, and neuropsychiatric symptoms, all of which can occur independently of one another. The common cognitive symptoms include deficits in complex attention, efficiency of information processing, executive functioning, processing speed, and long-term memory. These deficits detrimentally affect many aspects of daily life, such as the ability to run a household, participate fully in society, and maintain employment—factors that can all affect the overall quality of life of the patient. The increased use of neuroimaging techniques in patients with MS has advanced our understanding of structural and functional changes in the brain that are characteristic of this disease, although much remains to be learned. Moreover, examination of efforts to treat the cognitive deficits in MS is still in the early stages.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(08)70259-X.pdf

Cognitive impairment in multiple sclerosis

Multiple sclerosis (MS) is an inflammatory-mediated demyelinating disease of the human central nervous system. The clinical disease course is variable, usually starts with reversible episodes of neurological disability in the third or fourth decade of life, and transforms into a disease of continuous and irreversible neurological decline by the sixth or seventh decade. We review data that support neurodegeneration as the major cause of irreversible neurological disability in MS patients. We question whether inflammatory demyelination is primary or secondary in the disease process and discuss the challenges of elucidating the cause of MS and developing therapies that will delay or prevent the irreversible and progressive neurological decline that most MS patients endure.

Multiple Sclerosis: An Immune or Neurodegenerative Disorder?

Accurate diagnosis of vascular dementia is important for the recognition of underlying pathophysiology and the institution of appropriate therapy. It is also important for the determination of the incidence and prevalence of not only vascular dementia but also Alzheimer's disease (AD), since differentiating between these two entities is often problematic. The State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) herein propose criteria for the diagnosis of ischemic vascular dementia (IVD). These criteria broaden the conceptualization of vascular dementia, include the results of neuroimaging studies, emphasize the importance of neuropathologic confirmation, refine nosology, and identify areas that require further research. Parallel use of the proposed definitions of "possible" and "mixed" categories in the diagnosis of both AD and IVD would ensure compatibility between the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) criteria for AD and the ADDTC criteria for IVD. Uniform classification of subtypes of IVD will improve the generalizability of individual studies and aid in multicenter collaborations.

Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer's Disease Diagnostic and Treatment Centers

Previous frequency estimates of cognitive dysfunction in multiple sclerosis have ranged from 54 to 65 percent. These studies may overestimate the frequency in the general MS population, since the patients in these studies were recruited from clinic populations. In the present study, we administered a comprehensive neuropsychological test battery to 100 community‐based MS patients and 100 demographically matched healthy controls. Of 31 cognitive test indices examined, 48 MS patients and five controls were impaired on four or more test indices, yielding an overall frequency rate of 43% for the MS group. The pattern of cognitive decline was not uniform: MS patients were more frequently impaired on measures of recent memory, sustained attention, verbal fluency, conceptual reasoning, and visuospatial perception, and less frequently impaired on measures of language and immediate and remote memory. We developed a brief (20‐minute) screening battery empirically by selecting the four most sensitive test indices from the comprehensive battery. The brief battery yielded a sensitivity value of 71% and a specificity value of 94% in discriminating cognitively intact from impaired MS patients, as defined by the comprehensive battery. Cognitive impairment was not significantly associated with illness duration, depression, disease course, or medication usage, but was significantly (albeit weakly) correlated with physical disability. NEUROLOGY 1991;41:685‐691

Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction

We designed a study to assess the specific contribution of cognitive dysfunction to multiple sclerosis patients9 problems in daily living. Based on the results of a comprehensive neuropsychological test battery, we classified 100 MS patients as either cognitively intact (N = 52) or cognitively impaired (N = 48). In addition to a neurologic examination, MS patients completed questionnaires on mood and social functioning, underwent a comprehensive in‐home occupational therapy evaluation, and were rated by a close relative or friend regarding specific personality characteristics. While there were no significant differences between the two groups on measures of physical disability and illness duration, patients in the cognitively impaired group were less likely to be working, engaged in fewer social and avocational activities, reported more sexual dysfunction, experienced greater difficulty in performing routine household tasks, and exhibited more psychopathology than cognitively intact patients. These findings suggest that cognitive dysfunction is a major factor in determining the quality of life of patients with MS. NEUROLOGY 1991;41:692‐696

Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning

Previous research has suggested that cerebral lesions observed on magnetic resonance imaging (MRI) of MS patients are clinically “silent.” We examined the validity of this assertion by correlating neuropsychological test performance with MRI findings in 53 MS patients. We used a semiautomated quantitation system to measure three MRI variables: total lesion area (TLA), ventricular-brain ratio (VBR), and size of the corpus callosum (SCC). Stepwise multiple regression analyses indicated that TLA was a robust predictor of cognitive dysfunction, particularly for measures of recent memory, abstract/conceptual reasoning, language, and visuospatial problem solving. SCC predicted test performance on measures of mental processing speed and rapid problem solving, while VBR did not independently predict cognitive test findings. These findings suggest that cerebral lesions in MS produce cognitive dysfunction and that MRI may be a useful predictor of cognitive dysfunction.

https://n.neurology.org/content/neurology/39/2/161.full.pdf

Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis

We have recently proposed that the cognitive deficits of patients with multiple sclerosis (MS) share numerous characteristics associated with the syndrome of subcortical dementia. One such characteristic, slowness of mental processing, was evaluated in the present study. Thirty-six MS patients were compared to 26 normal controls of equivalent age, education, and verbal intelligence on the Sternberg memory scanning test. As anticipated, the motor-involved MS patients had an overall slower reaction time than did controls. Their scanning rate, a measure of pure cognitive speed, was also significantly slower than controls. These results suggest that MS patients exhibit a slowing of mental processing independent of motor involvement.

Gary J. Leo

Papers

Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction

Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning

Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis

Information processing speed in patients with multiple sclerosis

Memory Dysfunction in Multiple Sclerosis: Its Relation to Working Memory, Semantic Encoding, and Implicit Learning.