Postoperative Cognitive Dysfunction in Patients with Preoperative Cognitive Impairment: Which Domains Are Most Vulnerable?

Background: The authors explored the database of the first International Study of Postoperative Cognitive Dysfunction study to specify the domains of cognitive function that were most vulnerable and to determine the pattern of deterioration in patients with preoperative cognitive impairment.

Methods: One thousand two hundred eighteen patients were included in the first International Study of Postoperative Cognitive Dysfunction, where neuropsychological testing was performed at entry to the study, at 1 week, and at 3 months after surgery. The authors' analyses determined the extent to which seven neuropsychological measures changed after surgery with focus on the relation with preoperative cognitive impairment, defined as a preoperative score 1.5 SD below healthy controls in the memory test.

Results: Preoperative cognitive impairment was found in 74 patients at baseline. At 1 week, cognitive deterioration was seen in all tests, but in particular in the Letter Digit Coding and the time of the Stroop interference test, with 14% and 16% of the total sample (n = 1,016) exceeding 2 SD, respectively. At 3 months, deterioration was more uniform. Significantly fewer in the preoperative cognitive impairment group had deterioration in the memory test, both at 1 week and at 3 months, with no patient displaying a deterioration exceeding 2 SD.     

WAVE1 and regulation of actin nucleation in myelination.

The myelin sheath can be compared to the neuronal growth cone in that the unfurled sheath looks like a giant lamellum. The authors recently tested this hypothesis by examining the importance of WAVE1, a regulator of lamellipodia formation in neurons and other cells, in myelinogenesis. They found that WAVE1 is critical for formation of oligodendrocyte lamellae and myelin sheaths. They review the regulation of WAVE1 and how WAVE1 is transported and localized to lamellipodia. Because they found that some but not all myelination was impaired by knockout of WAVE1 function, they hypothesize that other regulators of actin nucleation help oligodendrocytes produce myelin in parallel with WAVE1 function. Interestingly, they found that oligodendrocyte maturation also is disturbed with WAVE1 knockout and propose that proper localization and transport of signaling molecules relevant to the integrin signaling cascade are disrupted by loss of WAVE1 function.     

Fine mapping by genetic association implicates the chromosome 1q23.3 gene UHMK1, encoding a serine/threonine protein kinase, as a novel schizophrenia susceptibility gene.

BACKGROUND: Linkage studies by us and others have confirmed that chromosome 1q23.3 is a susceptibility locus for schizophrenia. Based on this information, several research groups have published evidence that markers within both the RGS4 and CAPON genes, which are 700 kb apart, independently showed allelic association with schizophrenia. Tests of allelic association with both of these genes in our case control sample were negative. Therefore, we carried out further fine mapping between the RGS4 and CAPON genes. METHODS: Twenty-nine SNP and microsatellite markers in the 1q23.3 region were genotyped in the United Kingdom based sample of 450 cases and 450 supernormal control subjects. RESULTS: We detected positive allelic association after the eighth marker was genotyped and found that three microsatellite markers (p = .011, p = .014, p = .049) and two SNPs (p = .004, p = .043) localized in the 700 kb region between the RGS4 and CAPON genes, within the UHMK1 gene, were associated with schizophrenia. Tests of significance for marker rs10494370 remained significant following Bonferroni correction (alpha = .006) for multiple tests. Tests of haplotypic association were also significant for UHMK1 (p = .009) using empirical permutation tests, which make it unnecessary to further correct for both multiple alleles and multiple markers. CONCLUSIONS: These results provide preliminary evidence that the UHMK1 gene increases susceptibility to schizophrenia. Further confirmation in adequately powered samples is needed. UHMK1 is a serine threonine kinase nuclear protein and is highly expressed in regions of the brain implicated in schizophrenia.     

Gonadal steroid preservation of central synaptic input to hamster facial motoneurons following peripheral axotomy

In recent work, we have demonstrated that testosterone propionate accelerates recovery from facial nerve injury in the adult male hamster. Central synaptic stripping following peripheral motor neuron damage is a well-established component of the injury response. Gonadal steroids regulate synaptogenesis in the normal nervous system. In this study, we tested the hypothesis that testosterone propionate administration at the time of facial nerve transection alters the synaptic connectivity of injured facial motoneurons. Adult hamsters were subjected to right facial nerve transection at the level of the stylomastoid foramen. Half the animals received subcutaneous implants of testosterone propionate; the other half were sham implanted. At 5 days postoperative, the animals were killed by intracardiac perfusion-fixation, and the control and axotomized facial nuclear groups from the brainstems of nonhormone- and testosterone propionate-treated animals processed for routine transmission electron microscopy. Quantiative analysis of the synaptic ratio (percent somal membrane covered by synaptic profiles) and the average length of axosomatic synapses was accomplished. The results indicate that axotomy alone resulted in an 81% reduction in the synaptic ratio and a 26% decrease in the average synaptic length of axosomatic synapses. Exposure to testosterone propionate from the time of facial nerve transection resulted in only a 48% reduction in the synaptic ratio and a 16% decrease in the average synaptic length of axosomatic synapses following injury. Thus, testosterone propionate significantly attenuated the amount of synaptic stripping that occurred at 5 days postoperative and the decrease in average length of the remaining synapses as well. It is concluded that gonadal steroids modulate central synaptic plasticity following peripheral nerve injury. The results are discussed in light of our recent findings of steroidal effects on the central astrocyctic response to facial nerve injury as well.     

Cotinine in the serum, saliva, and urine of nonsmokers, passive smokers, and active smokers.

Cotinine was measured in the serum, saliva, and urine of nonsmokers, passive smokers, and active smokers. Serum and saliva could not discriminate between nonsmokers and passive smokers. Mean urine cotinine was higher in passive smokers than nonsmokers but there was a great deal of intersubject overlap. Cotinine in all body fluids could separate active smokers from the other two groups. Among smokers, light smokers had lower levels than heavier smokers.     

Ascorbic acid, HDL, and total plasma cholesterol in the elderly

The relationships between ascorbic acid (plasma and dietary) and plasma HDL cholesterol (HDL-C), total plasma cholesterol (T-C) and T-C:HDL-C ratio were examined in a population of 235 males and 445 females, age 60-98 years. Many known or suspected determinants of HDL-C and T-C, including age, sex, triceps skinfold thickness, fasting blood glucose, alcohol intake, and others, were considered as covariates due to their potential confounding or modifying effects on the relationships under study. The results show that plasma ascorbic acid is significantly (p less than 0.05) correlated with HDL-C (r = 0.09), T-C:HDL-C (r = 0.10), but not with T-C (r = 0.03). There is a strong age interaction with the largest effect of ascorbic acid in the youngest age group studied (60-69 years). The effects of dietary ascorbic acid are similar but slightly reduced in magnitude.