Douglas R. Denney

Cognitive impairment in relapsing and primary progressive multiple sclerosis: Mostly a matter of speed

Based on the assumption that cognitive impairment in MS is consistent with subcortical dementia, a battery of neuropsychological tests was assembled that included measures of executive function (Tower of London and Wisconsin Card Sorting Test), verbal learning and memory (a paired associates learning test), and speeded information processing (Stroop Color Word Interference Test). The battery was administered to patients with relapsing and primary progressive MS and to healthy controls. Differences between patients and controls occurred on several of the measures. However, when differences with respect to fatigue and depression were statistically controlled, the only differences that remained significant involved measures relating to the speed of information processing. Patients performed more slowly than controls, with the disparity being greater for relapsing patients than for those with primary progressive disease. The slowing was evident on measures of automatic as well as controlled processing and regardless of whether speed was an explicit feature of successful performance or recorded unobstrusively while the patient concentrated on planning a correct solution to a problem. Parallels were noted between cognitive slowing associated with MS and that of normal aging.

The cognitive performance of patients with multiple sclerosis during periods of high and low fatigue

The objective of this study was to examine whether multiple sclerosis (MS)-related fatigue affects patients’ cognitive performance. Thirty patients who had substantial fatigue in conjunction with MS and who reported marked diurnal variability in the severity of their fatigue were tested on two occasions: during a period of high fatigue and during a period of relatively low fatigue. The order of these sessions was counterbalanced across patients. During both sessions, patients completed a questionnaire concerning their present state of fatigue and a battery of neuropsychological tests of planning, selective attention, and paired associate learning. A lthough patients confirmed greater fatigue during the period of high fatigue and felt they had performed more poorly during this period, there were no differences in cognitive performance that could be attributed to fatigue. Instead, all subjects showed improvement from the first to the second session regardless of whether the latter entailed a period of high or low fatigue. In contrast to studies reporting fatigue-related declines in MS patients’ cognitive performance, no differences in performance were found when MS patients were tested during periods of high versus low fatigue. These contrasting results, stemming from differences in experimental design, are discussed in terms of their implications for assessing cognitive function in patients with MS.

The association between cognitive impairment and physical disability in multiple sclerosis.

Background: The association between cognitive impairment and physical disability was examined in a larger, more representative sample of patients with multiple sclerosis (MS) than in previous studies. Method: Two hundred and fifty-three patients attending an MS clinic were assessed with respect to physical disability using the Expanded Disability Status Scale and cognitive impairment using a battery of neuropsychological tests. Results: Physical disability correlated with duration of disease; cognitive impairment did not. Virtually all measures derived from the cognitive battery were significantly correlated with physical disability. Three measures of speeded information processing and one involving delayed recall of verbal material were unique predictors of disability status. The relationship between cognitive impairment and physical disability was equivalent for patients with shorter (<3 years) versus longer (>10 years) disease duration. Cognitive impairment correlated with the rate of disability progression as reflected by the progression index. Conclusion: Cognitive impairment is more closely associated with physical disability than most previous studies indicate. This relationship appears to be stable throughout the duration of MS, although this conclusion is qualified by the cross-sectional design of the study. Further attention should be paid to cognitive impairment as a possible predictor of the rate of patients’ physical decline.

Lymphocyte subsets and interleukin-2 receptors in autistic children.

Blood samples were obtained from 10 male autistic children ages 7–15 years and 10 age-matched, male, healthy controls. Lymphocyte subsets (helper-inducer, suppressor-cytotoxic, total T, and total B cells) were enumerated using monoclonal antibodies and flow cytometry. Bound and soluble interleukin-2 receptors were assayed in unstimulated blood samples and in cell cultures following 72-hour stimulation with phytohemagglutinin. The children with autism had a lower percentage of helper-inducer cells and a lower helpersuppressor ratio, with both measures inversely related to the severity of autistic symptoms (r=−.56 and −.68, respectively). A lower percentage of lymphocytes expressing bound interleukin-2 receptors following mitogenic stimulation was also noted, and this too was inversely related to the seventy of autistic symptoms.

The effects of exemplary and cognitive models and self-rehearsal on children's interrogative strategies ☆

Abstract Children aged 6, 8, and 10 years were exposed to three types of training procedures aimed at increasing their use of constraint-seeking questions and enhancing their problem-solving efficiency. One group observed an exemplary model who merely illustrated several constraint-seeking questions. Another group observed a cognitive model who, prior to asking each of her constraint-seeking questions, verbalized her strategy for formulating constraint-seeking questions and integrating the information gained from such questions. A third group received a combination of cognitive modeling and self-rehearsal training in which the children repeated statements representing key features of the constraint-seeking strategy before asking questions on a series of training items. Cognitive modeling alone was the most successful training procedure, effecting changes in both constraint-seeking questioning and problem-solving efficiency for children of all three age groups. Differences between cognitive and exemplary models were most notable among the youngest children, who appeared to require the additional guidance afforded through the verbalizations of the cognitive model.

Lower levels of glutathione in the brains of secondary progressive multiple sclerosis patients measured by 1H magnetic resonance chemical shift imaging at 3 T

Background: Disability levels for patients with secondary progressive multiple sclerosis (SPMS) often worsen despite a stable MRI T2 lesion burden. The presence of oxidative stress in the absence of measurable inflammation could help explain this phenomenon. In this study, the assessment of an in vivo marker of oxidative stress, cerebral glutathione (GSH), using magnetic resonance chemical shift imaging (CSI) is described, and GSH levels were compared in patients with SPMS and healthy controls. Objective: To assess whether GSH, a key antioxidant in the brain, is lower in the SPMS patients compared to matched controls. Methods: Seventeen patients with SPMS (Expanded Disability Status Scale = 4.0–7.0; length of MS diagnosis = 19.4 ± 7 years) and 17 age- and gender-matched healthy controls were studied. GSH levels were measured in the fronto-parietal regions of the brain using a specially designed magnetic resonance spectroscopy technique, CSI of GSH, at 3T. Results: The levels of GSH were lower for SPMS patients than for controls, the largest reduction (18.5%) being in the frontal region (p = 0.001). Conclusion: The lower GSH levels in these patients indicate the presence of oxidative stress in SPMS. This process could be at least partially responsible for ongoing functional decline in SPMS.

The role of neuroticism in relation to life stress and illness

Abstract If Eysencks construct of neuroticism corresponds to an inherent reactivity to stress, then neuroticism scores should function as a moderator variable influencing the relationship between life stress and illness. Two studies are reported in which this diathesis-stress model of illness is evaluated. In both studies, neuroticism and life stress emerged as significant independent predictors of self-reported health problems, but the tests of neuroticism as a moderator variable were not significant. In the latter study, locus of control did emerge as a near significant moderator variable. A reinterpretation of the neuroticism construct in the context of the present studies is offered, and two methods for evaluating possible moderator variables are illustrated.

The behavioral treatment of insomnia: An alternative to drug therapy

Abstract The use of hypnotic drugs to treat insomnia is criticized because of (a) tolerance effects, (b) carry-over effects, (c) alterations in sleep patterns, (d) rebound effects, and (e) attributional effects. Behavioral treatments represent a more viable alternative and are reviewed under four headings: (a) systematic desensitization: (b) applied relaxation; (c) attribution-based therapies; and (d) classical conditioning therapies. The behavioral therapies are predicated upon three views of insomnia: first, that insomnia results from excessively high levels of arousal prior to and during sleep; second, that insomnia occurs when the sleep environment lacks sufficient stimulus control over sleeping; and finally, that insomnia is often enhanced and maintained by exacerbation cycles in which worries about not falling asleep interfere even further with ones sleep.

Anxiety management and applied relaxation in reducing general anxiety

Abstract Sixty-three generally anxious subjects were assigned to anxiety management training, applied relaxation training, relaxation-only, placebo and untreated control conditions. After 6 weeks of treatment, anxiety management training led to reductions on a variety of self-report measures of state and trait anxiety and decreases in maladaptive cognitions during a laboratory stress procedure. On several measures, subjects in anxiety management training differed from relaxation-only and placebo subjects as well as untreated controls. However, treatment effects did not extend to performance and physiological measures of anxiety. Applied relaxation training, which in contrast to anxiety management training lacks structured rehearsal involving the recognition and reduction of tension cues during the treatment sessions, resulted in less consistent decreases in measures of general anxiety.

Factor structure of the menstrual symptom questionnaire: Relationship to oral contraceptives, neuroticism and life stress

Abstract The Menstrual Symptom Questionnaire was administered to initial and cross-validation samples of college-age women. Factor analyses performed on the data from each sample failed to support Daltons distinction between spasmodic and congestive forms of primary dysmenorrhea. Instead, a more complicated factor structure evolved, closely resembling Websters findings, with factors representing menstrual pain, pre-menstrual negative affect, pre-menstrual water retention, pre-menstrual pain, menstrual backache and menstrual gastrointestinal symptoms. Oral contraceptive use was negatively related to menstrual pain and backache. Neuroticism scores were positively related to all six factors, and negative life changes to four of these factors, suggesting a role for psychogenic factors in both pre-menstrual and menstrual symptomatology.