Subjective and polysomnographic characteristics of patients diagnosed with narcolepsy

In order to better characterize the subjective and polysomnographic findings in patients with narcolepsy, a follow-up questionnaire was mailed to all patients diagnosed with the disorder at the Henry Ford Hospital Sleep Disorders and Research Center. The questionnaire inquired regarding the present, previous, and change in status for the constellation of narcolepsy symptoms. Memory problems, problems of daytime function, and nocturnal sleep disturbance were included among the questions related to the symptomatic constellation. By definition, all patients were symptomatic of daytime sleepiness and were diagnosed with narcolepsy only if there were two or more rapid eye movement (REM) onsets documented on the polysomnographic evaluation. A high percentage of patients reported nocturnal sleep disturbance, which was one of the symptoms with the latest reported onset. Retrospective comparison of questionnaire responses to the clinical polysomnography revealed significantly more sleep maintenance difficulties in the group of patients reporting this symptom on the questionnaire. Patients with disturbed nocturnal sleep reported taking more naps during the day, although the Multiple Sleep Latency Test (MSLT) failed to show differences in sleep latency. Interestingly, this group of patients was found to have a significantly higher number of sleep onset REM episodes on the MSLT. Finally, the findings are discussed as they compare to studies that required the presence of cataplexy as part of their inclusion criteria.     

Memory and attention deficits in drug naive patients with schizophrenia

The present study was designed to evaluate the integrity of cognitive fronto-temporal processes in drug naive patients with schizophrenia. The evaluation of drug naive patients discards the potential influence of medication, and may allow the specification of cognitive impairments that are truly illness-related. Subcomponents of long-term memory as well as several measures of attention were examined. A group of 16 patients who had never taken antipsychotics and a group of 20 normal controls underwent tests of alertness, information maintaining, and sustained and selective attention, as well as tests of explicit and implicit recall. The psychopathological manifestations of patients were also assessed with the BPRS, PANSS, ESRS clinical scales. Attention test performances revealed that drug naive patients presented a decrease in their ability to respond promptly to a stimulus, sustain their attention on a task, display normal selective attention strategies, and maintain information for on-line processing. The results also suggest that the drug naive patients are impaired when both strategic and associative processes must be triggered to explicitly recover information in long-term memory. In contrast, the results revealed that implicit access to perceptual mental representations is spared in schizophrenic patients. Finally, features of the patients' clinical symptomatology and some cognitive deficits were also shown to be correlated. Overall, results showed that, in relation to normals, drug naive patients were mildly impaired, with little intersubject variability, and that not all cognitive processes were equally disturbed in relation to the normal subjects' performances. Results support the idea that an important part of the impairments seen in schizophrenia is present before the introduction of neuroleptic medication and chronic illness.     

Gray matter deficits in young adults with narcolepsy

Objectives – The aim of this study was to investigate gray matter volume changes in narcolepsy. Materials and methods – An optimized voxel‐based morphometry was conducted for 17 young adults with a sole diagnosis of human leukocyte antigen DQB₁ 0602 positive narcolepsy with cataplexy (26.6 ± 5.2 years old) and 17 comparison subjects (24.6 ± 4.9 years old) using 3 Tesla scanner. Gray matter volumes in the bilateral hypothalamic voxel of interests (VOI) were also calculated. Results – Compared with the comparison subjects, narcoleptic patients had gray matter volume decrease in the right hypothalamus and other regions including subcortical, prefrontal, limbic and occipital areas. Narcoleptic patients also had lower gray matter volume on predefined VOI at the bilateral hypothalamus, which correlated with the Ullanlinna Narcolepsy Scale score. Conclusions – Current findings suggest that narcoleptic patients have structural abnormalities in hypothalamus, which might be related to the clinical manifestation of narcolepsy with cataplexy.     

Sustained attention deficits in manic and euthymic patients with bipolar disorder

Sustained attention deficits are proposed to be both state and trait indicators of bipolar disorder. The nature of these deficits and their association with medication and symptoms is not clear yet. The aim of this study was to investigate the impairments in various components of sustained attention task in euthymic and manic patients and was to investigate the relationship between the deficits in the manic state and medication effects. The performances of 37 manic patients, 34 euthymic patients with bipolar disorder and 34 control subjects on eight scores from Conners' CPT II, reflecting three different dimensions of sustained attention were compared. Similar to some recent findings, euthymic patients had decreased target sensitivity (omission errors) and response time inconsistency. The increased false responding (commission errors), perseveration and vigilance deficits were prominent in the manic patients. These state dependent impairments could not be explained by the impact of medication. In contrast, the exacerbation of seemingly trait-related impairments in the manic state can be at least partly explained by the impact of pharmacological therapy.     

Executive deficits in elderly patients with major unipolar depression

Several studies have evaluated executive function in depressed patients, and the results vary from significant impairment relative to controls to virtually intact performances. To better comprehend executive impairment in elderly patients with major unipolar depression, the performance of 21 elderly depressed patients was compared with that of 19 elderly normal controls on executive tasks. The relationships between memory deficits and depression severity and between memory deficits and executive dysfunction were also examined. Depressed patients' performance was significantly worse than that of controls on almost all executive tasks. Their score for logical memory was significantly correlated with that for several executive tasks. Executive performance was also correlated with depression severity. Unipolar depressed patients present executive deficits. Memory failure in these patients may reflect impairment in retrieval processes, which in turn depends on executive function. Executive deficits are associated with depression severity. These results may be useful in the differential diagnosis between depression and early Alzheimer's disease.     

Relative risk of attention deficits in siblings of patients with schizophrenia

OBJECTIVE: Impaired attention has frequently been observed in studies of unaffected siblings of patients with schizophrenia. To assess the suitability of impaired attention for use as an intermediate phenotype in genetic studies, the authors estimated the relative risk of impaired attention in a large group of siblings. METHOD: The authors used the Continuous Performance Test, 1-9 version, with and without a distraction condition, to study 147 patients with schizophrenia, 193 of their siblings, and 47 normal comparison subjects. Relative risk (l) was estimated by using cutoff scores that were one, two, and three standard deviations below the mean sensitivity index value (d cent) of the normal comparison group in both Continuous Performance Test conditions. RESULTS: Patients but not their siblings performed worse than the normal comparison subjects in both conditions. Fifty percent of the patients, 24% of their siblings, and 18% of the normal comparison subjects scored one standard deviation below the mean score of the comparison group for the more difficult distraction version of the Continuous Performance Test. The patients with Continuous Performance Test scores one standard deviation below the mean score of the comparison group had a total of 97 siblings. Compared with the comparison group, this subgroup of siblings had significantly lower Continuous Performance Test scores. Relative risk was also significantly higher for the siblings of patients whose scores were one standard deviation (l=2. 1) and two standard deviations (l=3.3) below the mean of comparison subjects. Attempts to assess ascertainment bias suggest that this may be an underestimate. CONCLUSIONS: Poor performance on the Continuous Performance Test appears to be familial and, possibly, genetic. Relative risk estimates were in the moderate range. Given the ease of administering the Continuous Performance Test, the use of impaired attention as an intermediate phenotype could increase the power of genetic studies of schizophrenia.     

Reversal of atypical depression,sleepiness, and REM-sleep propensity in narcolepsy with bupropion

We successfully treated a 46-year-old narcoleptic woman suffering from atypical depression with bupropion hydrochloride. Diagnostic evaluation revealed a Beck Depression Inventory (BDI) score of 24, a short nocturnal REM-sleep latency, subjective and objective sleepiness (mean sleep latency (MSL) = 1.8 minutes), and three sleep onset REM-sleep periods during the five nap multiple sleep latency test. Bupropion (100 mg t.i.d.) Normalized her mood (BDI = 6), sleepiness (MSL = 9.1 minutes), and REM-sleep propensity. Upon discontinuation of bupropion, these parameters reverted to pretreatment levels. This “activating” antidepressant's reversal of the sleepiness and REM-sleep propensity in narcolepsy may be due to blockade of dopamine or norepinephrine reuptake. Clinicians need to be alert to the fact that depression can mask the diagnosis of narcolepsy. Bupropion warrants further investigation as a treatment for narcolepsy in an open-label, double-blind, placebo-controlled paradigm. Depression and Anxiety 7:92–95, 1998. © 1998 Wiley-Liss, Inc.     

Hippocampal and anterior cingulate activation deficits in patients with geriatric depression

OBJECTIVE: The authors assessed frontotemporal function in patients with geriatric depression, a debilitating and increasingly prevalent disorder that has not been examined with brain activation paradigms. METHOD: Six depressed elderly patients and five healthy comparison subjects underwent high-sensitivity [(15)O]H(2)O positron emission tomography scans during a paced word generation task and a resting condition. RESULTS: Bilateral activation deficits were noted in the dorsal anterior cingulate gyrus and hippocampus of the depressed geriatric patients relative to the comparison subjects. Patients had memory deficits that correlated with lower hippocampal activity during both rest and activation. CONCLUSIONS: These initial findings suggest that hippocampal and dorsal anterior cingulate hypoactivation may constitute contributing neural substrates of geriatric depression. They also suggest that hippocampal dysfunction is related to the memory dysfunction characteristic of this disorder.     

Verbal cognition and attention deficits do not explain the verbal memory decline associated with pharmacoresistant partial epilepsy

The aim of this study was to explore whether change in verbal memory with time in patients with epilepsy is influenced by performance on tasks assessing verbal cognition or attention/processing speed. Thirty-six patients and twenty-five healthy controls were tested twice with median retest intervals of 4.8 and 3.1 years, respectively. Aspects of verbal memory, verbal cognition, and attention/processing speed were assessed. Decline in one verbal memory variable (Cronholm-Molander Memory Test Paired Associates -- Delayed Recall) was the strongest correlate of epilepsy. The second strongest correlate was a decrease in one attention/processing speed variable (Digit Symbol). The relationship between decline in verbal memory and epilepsy was not influenced by the decline in attention/processing speed, and the results did not support the notion that limited mental reserves as reflected in impaired verbal cognition or attention/processing speed can explain the relationship between verbal memory and epilepsy.     

Subjective memory complaints, white-matter lesions, depressive symptoms, and cognition in elderly patients.

OBJECTIVES: Subjective memory complaints (SMC) and cerebral white-matter lesions (WML) are very prevalent among elderly subjects, but their clinical significance is controversial. The authors sought to determine whether SMCs are related to WML, independently of the presence of depressive symptoms, which are known to be associated with both. The relationship between SMC and cognition was also examined. METHODS: This is a cross-sectional study on 60 elderly subjects without dementia. All subjects underwent FLAIR and T2-weighted axial MRI scans, a memory-complaint questionnaire, a geriatric depression scale, and a comprehensive cognitive assessment. RESULTS: Multiple linear regression showed that although the best correlate of SMC was the severity of depressive symptoms, SMC and WML were strongly correlated. Objective cognitive performance was not significantly associated with SMC after adjusting for WML and mood. The presence of a history of late-onset depression was a strong correlate of WML severity, even after adjusting for age, gender, and education. CONCLUSIONS: Complaints of cognitive decline are significantly associated with the severity of WML, independently of level of cognition and depression.     

Behaviour, attention and cognition in severe dyslexia

Information about coexisting problems in dyslexia may be vital for diagnostic and remedial procedures. There are few studies in this area, and to our knowledge none for the students in focus in this study. They all have phonological deficits and severely impaired reading abilities, in spite of prolonged educational remediation. The aim was to assess if these students have more behavioural/emotional problems than normal reading students. A clinical sample of 70 students, 59 males and 11 females, were compared to a normal reading control group. The groups were pair-wise matched on age, gender, cognitive level, and whether they lived in rural or urban areas. Mean age for the two groups was 150 months, and mean IQ scores approximately 100. Information on behaviour/emotions was obtained from parents, teachers and participants by means of the Child Behavior Checklist, Teacher's Report Form and Youth Self Report. The dyslexia group showed significantly more problems in all areas than the controls. This was reported from all three groups of informants. Parents reported most problems, internalizing behaviour for more than 50% of the participants and total problem behaviour for nearly 45%. Significantly more attention problems were also reported for the dyslexia group from all informants. Parents reported that nearly half the group demonstrated attention problems. Both groups of participants had more problems reported for those with IQ scores of 100 or lower. Further research is needed in this area, but the results clearly indicate that identifying additional behavioural/emotional problems may be imperative for students with severe reading problems.     

Selective deficits in cognition and memory in high-functioning parkinsonian patients.

To evaluate the profile and extent of cognitive deficits in Parkinson's disease, afflicted patients of exceptional professional distinction, who continue to function successfully in leadership positions, were compared neuropsychologically to neurologically normal individuals, matched for sex, age, education and professional standing. While patients showed relative preservation of verbal skills and higher executive function, they exhibited a significant reduction in episodic memory and visuospatial function. The observation of circumscribed impairment in this select group of Parkinsonian patients further implicates cognitive and memory deficits as consistent features of Parkinson's disease.     

Relationship between memory, attention, and depression in chronic cerebro-vascular patients

Vascular dementia patients show a component of their impairment as emotional. In the two studies that we present it was possible to illustrate the characteristics of such emotional component. a. The discrepancy between immediate recall and delayed recall appears to be very sensitive to anxiety interference when immediate recall is lower than delayed. b. The presence of emotional problems contributing to memory complaints in VaD patients is not equally distributed along the severity of deterioration dimension but can be identified as a specific component different from the cognitive one especially in that subgroup of patients who present an intermediate level of deterioration.     

Spatial attention deficits in patients with acquired or developmental cerebellar abnormality.

Recent imaging and clinical studies have challenged the concept that the functional role of the cerebellum is exclusively in the motor domain. We present evidence of slowed covert orienting of visuospatial attention in patients with developmental cerebellar abnormality (patients with autism, a disorder in which at least 90% of all postmortem cases reported to date have Purkinje neuron loss), and in patients with cerebellar damage acquired from tumor or stroke. In spatial cuing tasks, normal control subjects across a wide age range were able to orient attention within 100 msec of an attention-directing cue. Patients with cerebellar damage showed little evidence of having oriented attention after 100 msec but did show the effects of attention orienting after 800-1200 msec. These effects were demonstrated in a task in which results were independent of the motor response. In this task, smaller cerebellar vermal lobules VI-VII (from magnetic resonance imaging) were associated with greater attention-orienting deficits. Although eye movements may also be disrupted in patients with cerebellar damage, abnormal gaze shifting cannot explain the timing and nature of the attention-orienting deficits reported here. These data may be consistent with evidence from animal models that suggest damage to the cerebellum disrupts both the spatial encoding of a location for an attentional shift and the subsequent gaze shift. These data are also consistent with a model of cerebellar function in which the cerebellum supports a broad spectrum of brain systems involved in both nonmotor and motor function.     

Neural correlates of attention and working memory deficits in HIV patients

OBJECTIVES: To evaluate the neural correlates of attention and working memory deficits in patients with HIV-1. METHOD: fMRI was used to evaluate brain activity in 11 patients with HIV and 11 age-, sex-, education-, and handedness-matched seronegative subjects, while performing a battery of tasks that required different levels of attention for working memory. RESULTS: Patients with HIV showed greater brain activation (blood oxygenation level dependent signal changes) in some regions compared with control subjects while performing the same tasks. For the simpler tasks, patients with HIV showed greater activation in the parietal regions. However, with more difficult tasks, patients with HIV showed greater activation additionally in the frontal lobes. Reaction times during these tasks were slower but accuracy was similar in the patients with HIV compared with control subjects. CONCLUSION: Injury to the neural substrate caused by HIV infection may necessitate greater attentional modulation of the neural circuits, hence a greater use of the brain reserve; additional activation of the frontal lobes is required to perform the more complex tasks. The task-dependent increased frontal activation in patients with HIV suggests that the neural correlate of attentional deficits may be excessive attentional modulation as a result of frontostriatal brain injury.     

Subjective memory complaints, mood, and memory deficits among HIV/AIDS patients in Hong Kong

Diagnosis of HIV-associated neurobehavioral disorders often heavily relies upon patient complaints of cognitive difficulties. Yet, research in North America suggests that such complaints may be heavily influenced by affective factors. However, no work in this area has been done in China. The present study examined the relationships among depressed mood, anxiety, memory performance and subjective memory complaints among HIV/AIDS patients in Hong Kong. A total of 90 individuals with HIV were administered the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory, Patient's Assessment of Own Functioning Inventory (PAOF), and Hong Kong List Learning Test. Forward regression analysis indicated that the BDI Cognitive-Affective score was the most significant predictor of subjective memory complaints on the PAOF. Furthermore, present results also supported previous findings that some individuals with HIV infection are more "accurate" than others in the self-appraisal of their memory ability. Given inaccuracies that exist in subjective memory complaints, these findings highlight the importance of comprehensive cognitive assessment when evaluating the neuropsychological status of individuals of HIV.     

Social cognition and neurocognitive deficits in schizophrenia

While research equivocally supports a relationship between social cognition and neurocognition, it is less clear whether social cognition is related to general cognitive functioning or whether specific aspects of social cognition are linked with specific forms of neurocognition. Thus, this study sought to investigate the relationships between various domains of neurocognition and two forms of social cognition, social cue recognition and social problem solving, for 40 people with schizophrenia spectrum disorders. Step-wise multiple regressions found that performance on neurocognitive tests was able to predict 47% and 38% of the variance on measures of the ability to recognize actual and suggested social cues, respectively, and 13% of participants' ability to problem solve in ambiguous social situations. Once estimated intelligence and hospitalization history were controlled, however, neurocognition no longer significantly predicted social problem solving. Executive functioning was uniquely related to each type of social cue recognition, while memory predicted only the recognition of concrete social cues.