E.F.P.M. Vuurman

Cognitive dysfunctions and white matter lesions in patients with bipolar disorder in remission.

Krabbendam L, Honig A, Wiersma J, Vuurman EFPM, Hofman PAM, Derix MMA, Nolen WA, Jolles J. Cognitive dysfunctions and white matter lesions in patients with bipolar disorder in remission. Acta Psychiatr Scand 2000: 101: 274–280.

Thalamic volume predicts performance on tests of cognitive speed and decreases in healthy aging. A magnetic resonance imaging-based volumetric analysis.

Recent studies have indicated a role for the thalamus in attention, arousal and the capacity to perform tasks of speeded information processing. The present study evaluated the role of the thalamus in age-related cognitive decline by investigating the correlations between thalamic volume, cognition and age. This was done in 57 healthy subjects ranging from 21 to 82 years of age. All subjects underwent neurocognitive testing with information processing tests and structural magnetic resonance imaging. A significant decrease in volume of the thalamus with increasing age was found, relatively stronger than and independent of the decrease of total brain volume. The decrease of thalamic volume was apparent before the onset of loss of volume of the total brain. Over the age-span studied, the thalamic decrease in volume correlated with the diminished performance on tests of cognitive speed. Additionally, in young and middle-aged, but not in old subjects, the size of the thalamus predicted performance on tasks that require cognitive speed.

Effects of Semprex-D and Diphenhydramine on Learning in Young Adults with Seasonal Allergic Rhinitis

OBJECTIVES The purpose of this study was to test the hypothesis that learning ability is impaired in patients with seasonal allergic rhinitis relative to untreated individuals and to evaluate a combination compound (acrivastine 8 mg + pseudoephedrine 60 mg) for attenuation of the learning impairment in these patients. BACKGROUND In a previous study employing the same method it was shown that young children (10 to 12 yrs) suffering from seasonal allergic rhinitis performed significantly worse on tests of learning and using knowledge after acute treatment with a sedating antihistamine (diphenhydramine 50 mg) or placebo as compared with nontreated healthy controls. This effect was partially reversed by treatment with loratadine. METHODS Sixty-seven young adults suffering from seasonal allergic rhinitis and 28 matched controls were trained on didactic simulation for three consecutive days. Atopic subjects were treated differentially during training according to a double-blind, randomized, parallel group design with either diphenhydramine hydrochloride 50 mg, a combination compound (acrivastine 8 mg + pseudoephedrine 60 mg, A + P), or placebo, administered qd. After training, all atopic subjects were maintained on A + P treatment for 14 days at which time all groups returned for examination. RESULTS Mean performance at the end of training was worse for all atopic subjects combined compared with normal subjects. Subjects treated with diphenhydramine performed significantly worse than either normals (P < .001) or those treated with A + P (P < .001). At the examination, the diphenhydramine groups performance differed significantly from those of the normal (P < .001) and A + P groups (P < .001). CONCLUSION The study supports our previous finding that allergy symptoms reduce learning ability which is further reduced learning ability which is further reduced by diphenhydramine. Atopic subjects with allergies treated with acrivastine + pseudoephedrine learned as well as normal subjects.

Differences in cognitive performance during pregnancy and early motherhood

BACKGROUND Pregnancy has often been associated with cognitive deficits, but results are equivocal and little is known about how these deficits progress with time. METHOD In the present study, the cognitive performance of 57 pregnant women was compared with that of 50 non-pregnant women matched for age and education, using a well-validated neurocognitive test battery at weeks 14, 17, 29, and 36 of pregnancy, and 32 weeks postpartum in the pregnant group and at comparable times in the non-pregnant group. RESULTS Memory encoding and retrieval, as assessed with a word learning task, were significantly lower in the pregnant group than in the control group. This difference was still present at 32 weeks after delivery. The two groups did not differ in complex speed of information processing at any of the test moments; however, general speed of information processing was significantly compromised during early motherhood (week 32 postpartum). CONCLUSION Thus, memory performance is poorer during pregnancy and early motherhood, and general speed of information processing is slower during early motherhood.

Multiple Indicators of Age-related Differences in Cerebral White Matter and the Modifying Effects of Hypertension

We investigated differences associated with age and hypertension, a common risk factor for vascular disease, in three aspects of white matter integrity--gross regional volumes of the white matter, volume of the white matter hyperintensities (WMH) and diffusion properties. We acquired MRI scans on 93 adult volunteers (age 50-77 years; 36 with diagnosis of hypertension or elevated blood pressure), and obtained all measures in seven brain regions: frontal, temporal, parietal and occipital white matter, and the genu, body and splenium of the corpus callosum. The results demonstrated robust age-related differences in diffusion-based indices of cerebral white matter integrity and age-related increase in the WMH volume, but no age differences in the gross regional volumes of the white matter. Hypertension was associated with decline in fractional anisotropy, and exacerbated age differences in fractional anisotropy more than those in the volume of WMH. These findings indicate that of all examined measures, diffusion-based indices of white matter integrity may be the most sensitive indicators of global and regional declines and vascular damage in the aging brain.

Additional dopamine reuptake inhibition attenuates vigilance impairment induced by serotonin reuptake inhibition in man

There is evidence for a specific impairment of human vigilance following enhancement of serotonergic activity by antidepressant drugs. In the present study, we investigated the putative role of serotonergic–dopaminergic interactions in diminished vigilance by comparing the attentional effects of sertraline, a selective serotonin reuptake inhibitor (SSRI) with additional mild dopamine stimulating effects, with those of paroxetine, a SSRI without dopamine activity, using a placebo-controlled, double-blind, three-way cross-over design. Twenty-one (of 24) healthy middle-aged subjects completed the three treatment periods of 2 weeks in which sertraline (50 mg, days 1–7; 100 mg, days 8–14), paroxetine (20 mg, days 1–7; 40 mg, days 8–14) and placebo were administered. Vigilance (Mackworth Clock Test), selective (Stroop, Dichotic Listening) and divided attention (Dichotic Listening) were assessed at baseline and on days 7 and 14 of each treatment period. Selective and divided attention were unaffected by SSRI treatment. Subchronic administration of paroxetine impaired vigilance performance at each investigated dose. Sertraline did not produce a significant decline in vigilance performance, presumably due to its concomitant effects on dopamine activity, counteracting the negative effects of serotonin on dopamine neurotransmission. It is concluded that a serotonergically mediated reduction of dopamine activity plays an important role in the reduction of human vigilance following SSRI administration.

Response speed, contingent negative variation and P300 in Alzheimer’s disease and MCI

BACKGROUND Decreased speed of information processing is a hallmark of Alzheimers disease (AD) and mild cognitive impairment (MCI). Recent studies suggest that response speed (RS) measures are very sensitive indicators of changes in longitudinal follow-up studies. Insight into the psycho-physiological underpinnings of slowed RS can be provided by measuring the associated event-related potentials (ERP). AIMS The current study aims to investigate the relation between RS and its psycho-physiological correlates in AD and MCI. METHODS Fifteen psychoactive drug-naïve AD patients, 20 MCI patients and twenty age-matched, healthy control subjects participated. Response speed was measured during a simple (SRT) and choice reaction time task (CRT). An oddball and contingent negative variation (CNV) paradigm were used to elicit ERP. To evaluate test-retest reliability (TRR), subjects underwent a similar assessment one week after the first. RESULTS The SRT and CRT distinguished the patient groups significantly. The P300 amplitude and latency also distinguished the groups and showed a significant correlation with response speed. The CNV amplitude did not reveal a significant difference between groups and also showed a low TRR. The TRR of the SRT, CRT and P300 amplitude and latency in general was moderate to high. The current study suggests that response speed measures on a behavioural and psycho-physiological level deserve attention as a possible marker in the diagnosis and follow-up of AD.

Cognitive effects of methylphenidate in healthy volunteers: a review of single dose studies

Methylphenidate (MPH), a stimulant drug with dopamine and noradrenaline reuptake inhibition properties, is mainly prescribed in attention deficit hyperactivity disorder, is increasingly used by the general population, intending to enhance their cognitive function. In this literature review, we aim to answer whether this is effective. We present a novel way to determine the extent to which MPH enhances cognitive performance in a certain domain. Namely, we quantify this by a percentage that reflects the number of studies showing performance enhancing effects of MPH. To evaluate whether the dose-response relationship follows an inverted-U-shaped curve, MPH effects on cognition are also quantified for low, medium and high doses, respectively. The studies reviewed here show that single doses of MPH improve cognitive performance in the healthy population in the domains of working memory (65% of included studies) and speed of processing (48%), and to a lesser extent may also improve verbal learning and memory (31%), attention and vigilance (29%) and reasoning and problem solving (18%), but does not have an effect on visual learning and memory. MPH effects are dose-dependent and the dose-response relationship differs between cognitive domains. MPH use is associated with side effects and other adverse consequences, such as potential abuse. Future studies should focus on MPH specifically to adequately asses its benefits in relation to the risks specific to this drug.

A controlled study of temporal lobe structure volumes and P300 responses in schizophrenic patients with persistent auditory hallucinations

Recent studies of cerebral pathology in patients with schizophrenia have focused on symptomatological and electrophysiological correlates of reduced temporal lobe structure volumes. Volume deficits of the left superior temporal gyrus have been correlated with auditory hallucinations as well as to left-sided P300 amplitude reduction. However, caution is needed to interpret correlational data as evidence of a specific relationship. Therefore, a controlled study was undertaken on schizophrenic patients with and without auditory hallucinations. MRI-defined volumes of the left superior temporal gyrus and other temporal lobe structures were quantified from 3-mm coronal slices in 15 schizophrenic patients with chronic auditory hallucinations (hallucinators), 15 schizophrenic patients without auditory hallucinations (nonhallucinators) and 17 healthy controls. In all subjects a simple oddball paradigm was used to elicit P300 responses at temporal and centro-parietal electrode sites. No evidence was found for volume reductions of temporal lobe structures in the combined patient group compared with controls, or in the hallucinators compared with the nonhallucinators. The patients did show left P300 amplitude reduction compared with controls, particularly in the hallucinator group. Correlations between volumes of left temporal lobe structures and left P300 amplitudes were low and not significant. The results of the present study do not indicate that auditory hallucinations and associated abnormal electrophysiological activity are the consequence of atrophy of localized temporal lobe structures. However, replication in a larger sample of subjects is needed before firm conclusions can be drawn.

Effects of mizolastine and clemastine on actual driving and psychomotor performance in healthy volunteers

The acute effect of doses of mizolastine 5, 10, 20 and 40 mg, an active control (clemastine 2 mg) and placebo on actual car driving and psychomotor performance have been compared. Twenty four healthy volunteers were treated according to a double-blind, 6-way cross-over design. In the driving test, lasting about 1 h, lateral position control and speed were continuously measured; the psychomotor test battery, lasting 50 min, comprised critical flicker-fusion frequency, critical instability tracking, divided attention, memory search and choice reaction time, and vigilance studies; and mood changes and possible adverse-effects were rated on visual analogue scales.The results showed a dose-response relationship: mizolastine 40 and 20 mg impaired driving and psychomotor performance. The effect of mizolastine 40 mg on driving was strongly correlated with that of clemastine (r=0.78) and was comparable to the effect of a blood ethanol level of 0.8 mg·ml−1. Mizolastine 5 mg and 10 mg did not have a significant effect on driving performance and psychomotor tests.It was concluded that at a 10 mg dose of mizolastine, the therapeutic dose, it could be considered a safe antihistamine, although individual adverse reactions cannot be completely ruled out.