Regression-based formulas for predicting change in memory test scores in healthy older adults: Comparing use of raw versus standardized scores

Introduction: Standardized regression based (SRB) methods can be used to determine whether meaningful changes in performance on cognitive assessments occur over time. Both raw and standardized scores have been used in SRB models but it is unclear which score metric is most appropriate for predicting follow-up performance. The aim of the present study was to examine differences in SRB prediction formulas using raw versus standard scores on two memory tests commonly used in assessment of older adults.

Method: The sample consisted of 135 healthy older adults who underwent baseline and 1-year follow-up neuropsychological assessment including the Hopkins Verbal Learning Test–Revised and Brief Visuospatial Memory Test–Revised. Regression models were fit to predict Time 2 scores from Time 1 scores and demographic variables. Separate models were fit using raw scores and standardized scores. Akaike’s information criterion (AIC) was used to determine whether models using raw or standardized scores resulted in best fit. Pearson correlation and intraclass correlation coefficients were calculated between observed and predicted scores. Mean differences between observed and predicted scores were examined using pairwise t tests. To investigate whether a similar pattern of results would be evident using prediction formulas for nonmemory tests, all analyses were also conducted for nonmemory tests.

Results: All regression models were significant, and R² values for memory test raw score models were larger than those generated by standardized score models. Memory test raw score models were also a better fit based on smaller AIC values. For nonmemory tests, raw score models did not consistently outperform standardized score models. All correlations between observed and predicted Time 2 scores were significant, and none of the predicted scores significantly differed from their respective observed score.

Conclusion: For each memory measure, raw score models outperformed standardized score models. For nonmemory tests, neither score metric model consistently outperformed the other.     

Measurement of activated rCBF by the 133Xe inhalation technique: a comparison of total versus partial curve analysis

An initial assessment of the differential sensitivity of total versus partial curve analysis in estimating task related focal changes in cortical blood flow measured by the 133Xe inhalation technique was accomplished by comparing the patterns during the performance of two sensorimotor tasks by normal subjects. The validity of these patterns was evaluated by comparing them to the activation patterns expected from activation studies with the intra-arterial technique and the patterns expected from neuropsychological research literature. Subjects were 10 young adult nonsmoking healthy male volunteers. They were administered two tasks having identical sensory and cognitive components but different response requirements (oral versus manual). The regional activation patterns produced by the tasks varied with the method of curve analysis. The activation produced by the two tasks was very similar to that predicted from the research literature only for total curve analysis. To the extent that the predictions are correct, these data suggest that the 133Xe inhalation technique is more sensitive to regional flow changes when flow parameters are estimated from the total head curve. The utility of the total head curve analysis will be strengthened if similar sensitivity is demonstrated in future studies assessing normal subjects and patients with neurological and psychiatric disorders.     

The relationship between the fish consumption and blood total/methyl-mercury concentration of costal area in Korea

The purpose of this study was to evaluate the relationship between fish consumption and blood THg/MeHg concentration in Korean adults by measuring MeHg concentration in blood directly. The study subjects consisted of 400 adults aged 20 or older from 30 subareas in Busan, Ulsan and Gyeongsangnam-do province in Korea from August to October, 2010. We tried to recruit the same number of male and female participants in different age groups (20s, 30s, 40s, 50s and 60s) and allocated 13-16 subjects by district to represent Hg concentration in the research areas. The geometric means of THg and MeHg concentration in blood were 5.27 μg/L (5.00-5.57) and 4.05 μg/L (3.81-4.32), respectively. The proportion of MeHg/THg concentration was 78.53% (77.09-79.97). MeHg concentration was higher in coastal areas (4.26 μg/L) than in inland areas (3.52 μg/L) and was higher in men (4.68 μg/L) than in women (3.52 μg/L). In male participants, blood MeHg concentration increased with increasing annual fish consumption, and the proportion of MeHg/THg concentration showed an upward trend as THg concentration increased. However, none of the measures of the proportion of MeHg/THg showed significant differences. This is the first report in Korea about the relationship between blood MeHg concentration and related factors. Our findings suggest that MeHg concentration is affected by fish consumption as well as by gender difference and drinking status. Since the pathological mechanism has not been clarified, additional studies are needed for explaining the biological and lifestyle differences in the risk of adverse health effects by Hg exposure.     

Missing indicator function of growth hormone and luteinizing hormone blood levels for dopamine and serotonin concentration in the human brain

Summary To evaluate if the peripheral concentration of human growth hormone (GH) and luteinizing hormone (LH) in the blood could serve as an indicator for the brain concentration of dopamine and serotonin, as it could be anticipated from animal experiments, the effect of intravenous administration of L-DOPA and DL-5-HTP upon GH and LH blood levels in normal male volunteers was investigated.Dosages L-DOPA ranging from 12. 5 to 75. 0 mg before and after pre-treatment with the decarboxylase inhibitor Ro 4-4602 had no statistical significant effect upon GH-or LH-secretion. The administration of 75, 100 and 150 mg DL-5-HTP in combination with Ro 4-4602 had also no effect upon GH-and LH-secretion.This demonstrates that the GH and LH blood levels do not reflect in any way the concentration of biogenic amines in the brain.This work was supported by Deutsche Forschungsgemeinschaft, SFB 51.     

Experimental estimates of the constants relating signal change to contrast concentration for cerebral blood volume by T2* MRI.

Estimates of cerebral blood volume (CBV) obtained from dynamic contrast T2(*)-weighted magnetic resonance imaging (MRI) tend to be significantly higher than values obtained by other methods. This may relate to the common assumption that the proportionality constants relating signal change to contrast concentration are equal in tissue and artery. To test this hypothesis and provide estimates for the ratio of those proportionality constants, the authors compared measurements of CBV by both MRI and computed tomography (CT) scans in nine healthy volunteers obtained using identical kinetic paradigms for the two imaging modalities. Both boluses and infusions of contrast were studied. Measurements were made in nine anatomic regions of interest of the cerebral hemispheres bilaterally. Cerebral blood volume values obtained by CT were generally lower than those obtained by MRI, especially in the cerebral cortex. As a result, the calculated values of the ratios of proportionality constants relating signal change to concentration in tissue and artery after bolus injections were significantly less than 1 in cortex (0.69) and white matter (0.76), although not in deep gray matter structures (0.87). Values of the ratios based on infusion measurements were closer to 1. In addition, CBV measurement errors with bolus MRI were significantly larger than those observed with infusion MRI or by CT. The reasons that the constants differ from 1 and for the larger variance of bolus MRI are discussed in terms of the T2* signal mechanisms. These studies help define the magnitude by which CBV is overestimated with typical T2*-weighted perfusion imaging. Infusion measurements of CBV can reduce the variance intrinsic to T2* MRI and lessen the likelihood of type II error.     

Awake craniotomy versus craniotomy under general anesthesia for the surgical treatment of insular glioma: choices and outcomes

Objective: To investigate differences in outcomes in patients who underwent surgery for insular glioma using an awake craniotomy (AC) vs. a craniotomy under general anesthesia (GA).

Methods: Data from patients treated at our hospital between 2005 and 2015 were analyzed retrospectively. The preoperative, intraoperative, postoperative, and longer term follow-up characteristics and outcomes of patients who underwent surgery for primary insular glioma using either an AC or GA were compared.

Results: Of the 52 identified patients, 24 had surgery using an AC and 28 had surgery under GA. The extent of resection was similar for the two anesthesia techniques: the median extent of resection was 61.4% (IQR: 37.8–74.3%) in the WHO grade <4 AC group vs. 50.5% (IQR: 35.0–71.2%) in the grade <4 GA group and 73.4% (IQR: 54.8–87.2%) in the grade 4 AC group vs. 88.6% (IQR: 61.2–93.0%) in the grade 4 GA group. Consistent with literature, there were more early neurological deficits after an AC, while the GA group showed more new late neurological deficits; however, these trends were not significant. Survival was similar between the two groups, with 100% 1- and 2-year survival in the grade <4 groups.

Conclusion: Our results showed that the extent of resection, neurological outcomes, and survival were similar using the two anesthesia techniques. Since AC is more challenging for the patient and for his or her caregiver after surgery, this finding has implications for clinical decision-making.     

Selective colocalization of immunoreactivity for intracellular gonadal hormone receptors and tyrosine hydroxylase in the ventral tegmental area,substantia nigra,and retrorubral fields in the rat

Gonadal hormones influence brain functions, including motor and motivational behaviors, transmitter release, and receptor binding in midbrain dopamine systems. Much of this influence suggests genomic hormone action. To identify which midbrain cells may be targets of genomic influence, double label immunocytochemistry was used to map intracellular estrogen and androgen receptors and tyrosine hydroxylase (TH) in the ventral tegmental area (VTA), substantia nigra (SN), and retrorubral fields (RRF) in intact, adult rats. The distribution of estrogen and androgen receptor immunoreactivity was highly selective, similar in males and females, and largely nonoverlapping. Estrogen receptors were present within subpopulations of cells in the ventrolateral paranigral VTA and rostrolateral RRF; of these, only a few cells in the RRF were immunoreactive for TH. Cells immunoreactive for androgen receptors were numerous in the paranigral and parabrachial VTA, SN pars lateralis and dorsomedial pars compacta, and lateral RRF. Nearly every androgen receptor-bearing cell in the VTA and SN pars compacta, roughly half in the SN pars lateralis, and about one-third in the RRF were TH immunopositive. The localization of estrogen receptors approximates the distribution of subsets of cells labeled following neostriatal injections, whereas androgen receptors tend to occupy regions labeled by injections in cortical or limbic targets. These receptor-specific alignments with origins of nigrostriatal, mesolimbic, and mesocortical projections are consistent with identified estrogen influence over motor behaviors and androgen involvement in motivational functions and may hold clues for understanding hormone action in these and other functions and dysfunctions of midbrain dopamine systems. J. Comp. Neurol. 379:247–260, 1997. © 1997 Wiley-Liss, Inc.     

Estrogen positive feedback to gonadotropin-releasing hormone (GnRH) neurons in the rodent: the case for the rostral periventricular area of the third ventricle (RP3V)

Increasing levels of circulating estradiol during the follicular phase of the ovarian cycle act on the brain to trigger a sudden and massive release of gonadotropin-releasing hormone (GnRH) that evokes the pituitary luteinizing hormone surge responsible for ovulation in mammals. The mechanisms through which estrogen is able to exert this potent “positive feedback” influence upon the GnRH neurons are beginning to be unravelled. Recent studies utilizing mouse models with global and cell-specific deletions of the different estrogen receptors (ERs) have shown that estrogen positive feedback is likely to use an indirect pathway involving the modulation of ER-expressing neurons that project to GnRH neurons. Conventional tract tracing studies in rats, and experiments involving conditional pseudorabies virus tract tracing from GnRH neurons in the transgenic mouse, indicate that the dominant populations of ER-expressing neuronal afferents to GnRH neurons reside in the anteroventral periventricular, median preoptic and periventricular preoptic nuclei. Together these estrogen-sensitive afferents to GnRH neurons form a periventricular continuum that can be referred to as rostral periventricular area of the third ventricle (RP3V) neurons. The neurochemical identity of some RP3V neurons has been determined and there is mounting evidence for important roles of glutamate, GABA, kisspeptin and neurotensin-expressing RP3V neurons in estrogen positive feedback. The definition of the key cluster of estrogen-sensitive neurons responsible for activating the GnRH neurons to evoke the GnRH surge (and ovulation) should be of substantial value to on-going efforts to understand the molecular and cellular basis of the estrogen positive feedback mechanism.     

Two cases of medically-refractory spontaneous orthostatic headaches with normal cerebrospinal fluid pressures responding to epidural blood patching: Intracranial hypotension versus hypovolemia and the need for clinical awareness

The diagnosis of spontaneous intracranial hypotension or cerebrospinal fluid (CSF) hypovolemia syndrome requires a high index of suspicion and meticulous history taking, demonstration of low CSF pressure and/or neuroimaging features. A 31-year-old male, presented with subacute onset moderate occipital and sub-occipital headaches precipitated by upright posture and relieved on recumbency and neck pain for 2 years. There was no trauma, cranial/spinal surgery. Clinical examination was normal and CSF opening pressure and laboratory study were normal. Magnetic resonance imaging (MRI) brain showed thin subdural hygroma. Another patient, 41-year-old male presented with 1 month of subacute onset severe bifrontal throbbing orthostatic headaches (OHs). CSF opening pressure was normal. Contrast MRI brain showed the presence of bilateral subdural hygromas, diffuse meningeal enhancement, venous distension, sagging of the brain, and tonsillar herniation. We report two cases of “spontaneous OHs” with normal CSF pressures who were successfully treated with epidural blood patching after poor response to conservative management.Key Words: Cerebrospinal fluid hypovolemia, epidural blood patch, pachymeningeal enhancement, spontaneous intracranial hypotension, spontaneous orthostatic headache