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Objectives To investigate the prognostic value of the neurocognitive status measured by screening instruments, the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), individually and in combination with the stroke severity scale, the National Institute of Health Stroke Scale (NIHSS), obtained at the subacute stroke phase or the baseline (≤2 weeks), for functional outcome 3–6 months later. Design Prospective observational study. Setting Tertiary stroke neurology service. Participants 400 patients with a recent ischaemic stroke or transient ischaemic attack (TIA) received NIHSS, MoCA and MMSE at baseline and were followed up 3–6 months later. Primary outcome measures At 3–6 months following the index event, functional outcome was measured by the modified Rankin Scale (mRS) scores. Results Most patients (79.8%) had a mild ischaemic stroke and less disability (median NIHSS=2, median mRS=2 and median premorbid mRS=0), while a minority of patients had TIA (20.3%). Baseline NIHSS, MMSE and MoCA scores individually predicted mRS scores at 3–6 months, with NIHSS being the strongest predictor (NIHSS: R2 change=0.043, p2), baseline MoCA and MMSE had a significant and moderately large incremental predictive value to the baseline NIHSS for mRS scores at 3–6 months (MMSE: R2 changes=0.021, p=0.010; MoCA: R2 changes=0.017, p=0.021). Conclusions Cognitive screening at the subacute stroke phase can predict functional outcome independently and improve the predictive value of stroke severity scores for functional outcome 3–6 months later, particularly in patients with more severe stroke.

Type 2 diabetes predicts accelerated cognitive decline and brain atrophy. We hypothesized that impaired fasting glucose (IFG) and incident glucose disorders have detrimental effects on global cognition and brain volume. We further hypothesized that metabolic and inflammatory derangements accompanying hyperglycaemia contribute to change in brain structure and function. This was a longitudinal study of a community-dwelling elderly cohort with neuropsychological testing (n = 880) and brain volumes by magnetic resonance imaging (n = 312) measured at baseline and 2 years. Primary outcomes were global cognition and total brain volume. Secondary outcomes were cognitive domains (processing speed, memory, language, visuospatial and executive function) and brain volumes (hippocampal, parahippocampal, precuneus and frontal lobe). Participants were categorised as normal, impaired fasting glucose at both assessments (stable IFG), baseline diabetes or incident glucose disorders (incident diabetes or IFG at 2 years). Measures included inflammatory cytokines and oxidative metabolites. Covariates were age, sex, education, non-English speaking background, smoking, blood pressure, lipid-lowering or antihypertensive medications, mood score, apolipoprotein E genotype and baseline cognition or brain volume. Participants with incident glucose disorders had greater decline in global cognition and visuospatial function compared to normal, similar to that observed in baseline diabetes. Homocysteine was independently associated with the observed effect of diabetes on executive function. Apolipoprotein E genotype did not influence the observed effects of diabetes on cognition. Incident glucose disorders and diabetes were also associated with greater 2-year decline in total brain volume, compared to normal (40.0 ± 4.2 vs. 46.7 ± 5.7 mm(3) vs. 18.1 ± 6.2, respectively, p 0.005). Stable IFG did not show greater decline in global cognition or brain volumes compared to normal. Incident glucose disorders, like diabetes, are associated with accelerated decline in global cognition and brain volumes in non-demented elderly, whereas stable IFG is not. Preventing deterioration in glucose metabolism in the elderly may help preserve brain structure and function.

Background:The study of exceptionally long-living individuals can inform us about the determinants of successful aging. There are few population-based studies of centenarians and near-centenarians internationally, but none in Australia.Methods:Individuals 95 years and older were recruited from seven electoral districts in Sydney using the electoral roll, Medicare lists, and multiple other strategies to obtain a representative sample. Physical and mental health and cognitive status were assessed using standard instruments in multiple sessions, with assessments individually adapted. An informant was interviewed, and participants were invited to donate a blood sample, undergo an MRI scan, and enrol into the brain donation program.Results:Preliminary data on the first 200 participants are reported. Mean age was 97.4 years (range 95–106), with 29.5% being men, and 58.5% living in a private dwelling. Rates of heart disease and diabetes were lower than in octogenarians, but hearing and visual deficits were common. The mean mini-mental state examination (MMSE) score was 21.1, with men performing better. Rates of psychological distress were low and satisfaction with life high (mean 5.91 out of a maximum of 7); 54% scored Conclusions:This is a preliminary report describing the methodology of the study. It provides further evidence that dementia is not inevitable at this age and independent living is common. The study provides an excellent resource to determine the genetic and environmental contributions to long and successful cognitive aging.

Introduction An aging population brings increasing burdens and costs to individuals and society arising from late-life cognitive decline, the causes of which are unclear. We aimed to identify factors predicting late-life cognitive decline. Methods Participants were 889 community-dwelling 70–90-year-olds from the Sydney Memory and Ageing Study with comprehensive neuropsychological assessments at baseline and a 2-year follow-up and initially without dementia. Cognitive decline was considered as incident mild cognitive impairment (MCI) or dementia, as well as decreases in attention/processing speed, executive function, memory, and global cognition. Associations with baseline demographic, lifestyle, health and medical factors were determined. Results All cognitive measures showed decline and 14% of participants developed incident MCI or dementia. Across all participants, risk factors for decline included older age and poorer smelling ability most prominently, but also more education, history of depression, being male, higher homocysteine, coronary artery disease, arthritis, low health status, and stroke. Protective factors included marriage, kidney disease, and antidepressant use. For some of these factors the association varied with age or differed between men and women. Additional risk and protective factors that were strictly age- and/or sex-dependent were also identified. We found salient population attributable risks (8.7–49.5%) for older age, being male or unmarried, poor smelling ability, coronary artery disease, arthritis, stroke, and high homocysteine. Discussion Preventing or treating conditions typically associated with aging might reduce population-wide late-life cognitive decline. Interventions tailored to particular age and sex groups may offer further benefits.

Language has been extensively investigated by functional neuroimaging studies. However, only a limited number of structural neuroimaging studies have examined the relationship between language performance and brain structure in healthy adults, and the number is even less in older adults. The present study sought to investigate correlations between grey matter volumes and three standardized language tests in late life. The participants were 344 non-demented, community-dwelling adults aged 70-90 years, who were drawn from the population-based Sydney Memory and Ageing Study. The three language tests included the Controlled Oral Word Association Task (COWAT), Category Fluency (CF), and Boston Naming Test (BNT). Correlation analyses between voxel-wise GM volumes and language tests showed distinctive GM correlation patterns for each language test. The GM correlates were located in the right frontal and left temporal lobes for COWAT, in the left frontal and temporal lobes for CF, and in bilateral temporal lobes for BNT. Our findings largely corresponded to the neural substrates of language tasks revealed in fMRI studies, and we also observed a less hemispheric asymmetry in the GM correlates of the language tests. Furthermore, we divided the participants into two age groups (70-79 and 80-90 years old), and then examined the correlations between structural laterality indices and language performance for each group. A trend toward significant difference in the correlations was found between the two age groups, with stronger correlations in the group of 70-79 years old than those in the group of 80-90 years old. This difference might suggest a further decline of language lateralization in different stages of late life.

This paper examines psychometric properties of scores derived from calibration curves (overconfidence, calibration, resolution, and slope) and an analogue of overconfidence that is based on a posttest estimate of the proportion of correctly solved items. Four tests from the theory of fluid and crystallized intelligence were used, and two of these tests employed both sequential and simultaneous methods of item presentation. The results indicate that the overconfidence score not only has the highest reliability, but is the only score with a reliability normally considered adequate for use in individual differences research. There is some, albeit weak, difference in subjects' level of overconfidence between sequential and simultaneous methods of item presentation. Correlational evidence confirms our previous findings that overconfidence scores from perceptual and ‘knowledge’ tasks define the same factor. In agreement with the results of Gigerenzer, Hoffrage and Kleinbolting (1991), subjects' post-test estimates of their performance showed lower levels of overconfidence than did the traditional measures based on subjects' confidence judgment responses to individual items. Also, after controlling for the actual test performances, the post-test performance estimates and average confidence ratings were only slightly positively correlated, suggesting that different psychological processes may underlie these two measures. Finally, our results suggest that average confidence over all items in the test may be a more useful measure in individual differences research than scores derived from calibration curves.

This study investigates adult age differences in the accuracy, or realism, of subjects' confidence judgements on the correctness of their answers to test items. Tests of fluid intelligence, crystallized intelligence, short-term memory and perceptual discrimination were given to 97 subjects between the ages of 17 and 85 years. For each test item subjects gave their best answer, rated their confidence that the item was correct, and decided whether to submit the item for scoring. Previously used measures describing different aspects of subjects' confidence judgements (overconfidence, calibration, resolution and slope) were also calculated for each subject on each of the tests. As expected, older people performed less well on traditional measures of fluid intelligence and short-term memory, but better than younger subjects on measures of crystallized intelligence. Older subjects responded more slowly to test items for all types of tasks. Regarding the confidence judgement measures, older subject showed a consistent tendency towards greater overconfidence compared to younger subjects. Older people also showed consistently worse performance on the resolution and slope scores, which measure the ability of the subject's confidence judgements to discriminate between correct and incorrect answers.

OBJECTIVE: Age differences in episodic memory (memory) have been attributed to a general reduction in processing speed (the "speed mediation hypothesis"), but also to declines in the efficiency of executive functions operations ("executive decline hypothesis"). To test predictions from these competing models, we examined the mediating effects of processing speed (speed) and executive functions (executive) on age and episodic memory in three older adult cohorts. METHOD: The first sample comprised 842 individuals from the Sydney Memory and Aging Study (MAS). The second and third samples included 476 individuals from the Older Australian Twins Study (OATS), with each twin from a pair randomly assigned to form two samples. A series of regression analyses was performed on each of the three samples independently, so as to obtain the sizes and statistical significances of the indirect effects of age on each of the memory variables, mediated by each of the Executive and Speed composites. Sex was a control variable for all analyses. Analyses were repeated with current depression as an additional control variable. RESULTS: Data from the MAS sample suggested that both Speed and Executive composites were significant mediators, with the former having a stronger mediation effect. A similar pattern was found in the two OATS samples. CONCLUSIONS: These findings are consistent with those of previous studies in which speed had a stronger mediating effect than executive on age-related variation in memory. They provide further support for the speed mediation hypothesis, although not negating the executive decline hypothesis.

Objectives To examine age- and sex-related differences in risk and protective factors for mild cognitive impairment (MCI) in community-based elderly individuals. Design Cross-sectional study. Setting The population-based Sydney Memory and Ageing Study. Participants A total of 757 nondemented, community-dwelling elderly individuals from an English-speaking background categorized as younger (70–79 years) or older (80–90 years). Measurements Risk of MCI was determined for sociodemographic, lifestyle, and cardiac, physical, mental, and general health factors using age- (and sex-) adjusted multiple regressions comprising initially significant univariate factors. Results The point prevalence of MCI within our sample was 39.1% overall: it was lowest in younger women (32.3%) and similar across men and older women (41.9%–43.6%). The risk of MCI across all participants was increased by the APOE ɛ4 allele, high homocysteine, and heart disease; and decreased by better odor identification, visual acuity, and mental activity. Risk factors in all younger participants were slow 6-m walk, poor odor identification, and high homocysteine. Risk of MCI was associated in younger women with history of depression, less mental activity, slower 6-m walk, poorer visual acuity, and higher homocysteine; and in younger men with poorer odor identification and higher homocysteine. Older participants showed no significant risk factors for MCI, except for poorer visual acuity in men. Supporting these findings were statistically significant interactions that reflected the differences in risk factor profiles between age and/or sex groups. Conclusions Risk factors for MCI differ in men and women and vary with age. This has implications for preventing MCI and possibly dementia.

Introduction: Trials of acupuncture for the treatment of depression have produced mixed results. We examined the effectiveness of laser acupuncture compared with placebo acupuncture for the treatment of major depression. Methods: A randomised, double blinded, placebo controlled trial was conducted in Sydney, Australia. Participants aged 18‐50 years with DSM-IV major depressive disorder were eligible to join the study. Forty-seven participants were randomised to receive laser acupuncture or placebo laser at acupoints LR14, CV14, LR8, HT7 and KI3. The intervention was administered twice a week for 4 weeks and once a week for another four weeks, for a total of 12 sessions. The primary outcome assessed the change in severity of depression using the Hamilton-Depression Rating Scale (HAM-D), and secondary outcomes assessed the change in severity of depression using the Quick Inventory for Depression-Self Reporting (QID-SR), the Quick Inventory for Depression-Clinician (QIDS-CL), with outcomes assessed at eight weeks. The treatment response (greater than 50% improvement in HAM-D) and remission (HAM-Do8) were analysed. Results: At eight weeks participants showed greater improvement in the active laser group on the primary and clinician-rated secondary outcome measures (HAM-D (mean 9.28 (SD 6.55) vs. mean 14.14 (SD 4.78 po0.001); QIDS-CL (mean 8.12 (SD 6.61 versus 12.68 (mean SD 3.77)) po0.001). The selfreport QIDS-SR scores improved in both groups but did not differ significantly between the groups. In the active laser group, QIDS-SR scores remained significantly lower than baseline at 3 months followup. Response rates (active laser, placebo laser) on ITT (intention to treat) analyses were 72.0% and 18.2% (po0.001), respectively. Remission rates on ITT analyses (active laser, placebo laser) were 56.0% and 4.5% (po0.001). Transient fatigue was the only adverse effect reported. Limitations: There was no follow-up for the placebo group at one and 3 months. Conclusion: Laser acupuncture showed a clinically and statistically significant benefit with reducing symptoms of depression on objective measures.

While some have argued that top management is interested mainly in short-term monetary benefits from training and staff development (TSD), in this study the majority of Australian top managers were seen to adopt longer-term perspectives. These longer-term views were found to be associated with higher levels of top management interest in TSD, more adequate resources for TSD, greater influence on the part of senior TSD and human resource management staff, and a more positive, performance-orientated organizational climate. Very few relationships were found, however, between the apparent purpose of TSD in the organization and the processes by which TSD is actually imple mented, other human resource management activities or other aspects of the organization such as strategy, structure and environment. Thus, while top managers who adopt a long-term perspective tend to support TSD, the function itself appears to remain inward looking and isolated from most other aspects of the organization.

Objectives Apolipoproteins have recently been implicated in the etiology of Alzheimer’s disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort. Methods 664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique. Results At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E e4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years. Conclusions Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals.

Inflammation may contribute to cognitive decline and dementia. This study examined the cross-sectional relationships between markers of systemic inflammation (C-reactive protein, interleukins-1β, -6, -8, -10, -12, plasminogen activator inhibitor, serum amyloid A, tumour necrosis factor-α and vascular adhesion molecule-1) and cognitive function in 873 non-demented community-dwelling elderly participants aged 70–90 years. Regression analyses were performed to determine the relationships between cognitive domains and inflammatory markers, controlling for age, sex, education, cardiovascular risk factors, obesity and other metabolic factors, smoking, alcohol consumption, depression and presence of the apolipoprotein e4 genotype. Regression analyses were repeated using four factors derived from a factor analysis of the cognitive tests. After Bonferroni correction for multiple testing, associations remained between raised levels of interleukin-12 and reduced performance in processing speed. Marked sex differences were noted in the abovementioned findings, with only females being significantly affected. Using the four factors derived from the factor analyses of cognitive test as dependent variables, interleukins-12 and -6 were both associated with the processing speed/executive function factor, even after controlling for relevant confounding factors. Thus, markers of systemic inflammation are related to cognitive deficits in a non-clinical community-dwelling elderly population, independent of depression, cardiovascular or metabolic risk factors, or presence of apolipoprotein e4 genotype. Additional research is required to elucidate the pathophysiology and longitudinal development of these relationships.

Mild cognitive impairment (MCI) is a heterogeneous neurocognitive disorder that can be classified into various subtypes. The present study aims to examine the gray matter (GM) atrophy patterns of MCI subtypes in comparison with a cognitively healthy group. Participants, including 135 MCI subjects and 120 cognitively healthy controls, were drawn from the Sydney Memory and Ageing Study. The MCI subjects were first categorized into amnestic (aMCI) and non-amnestic (naMCI) subtypes, which were then divided into single-domain (aMCI-SD and naMCI-SD) and multiple-domain subtypes (aMCI-MD and naMCI-MD). Furthermore, naMCI-SD was divided into three subgroups (language, processing speed, and executive function) according to individual cognitive impairment. Voxel-wise GM volumes were then compared between MCI subtypes and controls. The aMCI group had significantly lower GM volumes in the bilateral hippocampi and temporal cortices than the controls. This was mainly due to GM reduction of aMCI-MD but not aMCI-SD, as the latter did not show any significant GM reduction. GM reduction of naMCI and its two subdivisions was shown in widespread brain regions compared to controls. GM volumes of the multiple-domain subtypes (aMCI-MD and naMCI-MD) were lower than their single-domain counterparts (aMCI-SD and naMCI-SD) in the frontal and temporal lobes, respectively. Moreover, the language subgroup of naMCI-SD showed GM reduction in the frontal and temporal lobes compared to controls. MCI subtypes displayed specific patterns of GM atrophy that appear to be related to their various clinical presentations, which implies that underlying mechanisms of MCI subtypes are different.

Objectives To document the prevalence of self- and informant report of cognitive problems, usually referred to as "subjective cognitive complaints" (SCCs), in a community-dwelling sample of older adults and to examine the relationship between SCCs and objective impairment, mood, and personality measures. Participants Eight hundred twenty-seven nondemented community-dwelling adults aged 70–90 years. Measurements Participants were asked 24 SCC questions, including the Memory Complaint Questionnaire (MAC-Q), and completed neuropsychological testing in the domains of memory, language, executive function, visuospatial skills, and psychomotor speed. The Geriatric Depression Scale, Goldberg Anxiety Scale, and Neuroticism, Openness, and Conscientiousness from the NEO-Five Factor Inventory were used as measures of participants' psychological status. Informants completed 19 SCC questions, including a modified short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Results Overall, 95.5% of participants or their informants endorsed at least one SCC. Although participants were more likely to endorse a memory complaint, informants seemed more accurate in endorsing a complaint when cognitive impairment was objectively present. SCC correlated with participants' scores on measures of depression, anxiety, neuroticism, and inversely with measures of openness and conscientiousness. Age, education, and sex had little impact on these effects. Regression analysis showed that psychological factors explained the number of complaints more than cognitive performance. Conclusions The usefulness of SCCs as a criterion for mild cognitive impairment is questioned because of their high prevalence and their relationship to psychological factors. This may be helpful for clinicians to bear in mind when presented with patients with cognitive complaints.

Depressive symptoms are common in the elderly and they have been associated with cognitive and functional impairment. However, relatively less is known about the relationship of a lifetime history of depression to cognitive impairment and functional status. The aim of this cross-sectional study was to assess whether current depressive symptoms and past depression are associated with cognitive or functional impairment in a community-based sample representative of east Sydney, Australia. We also examined whether there was an interaction between current and past depression in their effects on cognitive performance. Eight hundred non-demented aged participants received a neuropsychological assessment, a past psychiatric history interview and the 15-item Geriatric Depression Scale. The Bayer-Activities of Daily Living scale was completed by an informant to determine functional ability. Clinically relevant depressive symptoms were present in 6.1% of the sample and 16.6% reported a history of depression. Participants with current depression had significantly higher levels of psychological distress and anxiety, and lower life satisfaction and performed worse on memory and executive function compared to participants without current depression. After controlling for anxiety the effect on executive function was no longer significant while the effect on memory remained significant. A history of depression was associated with worse executive function, higher levels of psychological distress and anxiety, and lower life satisfaction. After controlling for psychological distress the effect of past depression on executive function was no longer significant. There were no significant interactions between current and past depression in their effects on cognitive performance. There were no differences between participants with or without current depression and with or without past depression on functional abilities. These results support the view that current and past depressive episodes are associated with poorer cognitive performance but not with functional abilities.

There have been many attempts at explaining age-related cognitive decline on the basis of regional brain changes, with the usual but inconsistent findings being that smaller gray matter volumes in certain brain regions predict worse cognitive performance in specific domains. Additionally, compromised white matter integrity, as suggested by white matter hyperintensities or decreased regional white matter fractional anisotropy, has an adverse impact on cognitive functions. The human brain is, however, a network and it may be more appropriate to relate cognitive functions to properties of the network rather than specific brain regions. We report on graph theory-based analyses of diffusion tensor imaging tract-derived connectivity in a sample of 342 healthy individuals aged 72–92 years. The cognitive domains included processing speed, memory, language, visuospatial, and executive functions. We examined the association of these cognitive assessments with both the connectivity of the whole brain network and individual cortical regions. We found that the efficiency of the whole brain network of cortical fiber connections had an influence on processing speed and visuospatial and executive functions. Correlations between connectivity of specific regions and cognitive assessments were also observed, e.g., stronger connectivity in regions such as superior frontal gyrus and posterior cingulate cortex were associated with better executive function. Similar to the relationship between regional connectivity efficiency and age, greater processing speed was significantly correlated with better connectivity of nearly all the cortical regions. For the first time, regional anatomical connectivity maps related to processing speed and visuospatial and executive functions in the elderly are identified.

Hereditary nephrogenic diabetes insipidus is a rare, X-linked disorder manifested by an inability to concentrate the urine despite high plasma concentrations of arginine vasopressin or the administration of large doses of vasopressin or its analogues1,2. Affected males have profound hyposmotic polyuria soon after birth, often leading to recurrent episodes of severe dehydration. Unless recognized and treated early, these episodes may lead to failure to thrive, growth retardation, repeated bouts of cerebral edema with resultant mental retardation, or death. Females who are carriers of the gene for the disease have symptoms that range from a defective urinary-concentrating ability demonstrable . . .

Two studies were carried out to investigate the relationship between performances on two experimental tasks—Triplet Numbers and Swaps—and measures of fluid intelligence (Gf) and short-term memory (SAR). For each of these tasks four different versions of increasing complexity were constructed by varying the number of rules or mental steps required for their solution. Both tasks in the first study, and Swaps in the second study, were given twice with the instruction to work as quickly and as accurately as possible. Changes in speed/accuracy emphasis produced reliable differences in performance on the Triplet Numbers test in the first study only. As expected, increasing task complexity resulted in lower accuracy and slower responding. Regarding the relationship between the experimental tasks and intelligence factors, Gf and SAR, the most consistent and strongest association was between the accuracy measures of these tasks and Gf, although in all cases the relationship between both factors and speed scores were statistically significant. Importantly, the most consistent and strongest interaction between task complexity and Gf was obtained using accuracy measures from the experimental tasks. Other interactions with task complexity were weak. In general, as the task becomes more complex, its correlation with measures of intelligence tends to increase.

Objective While activities of daily living are by definition preserved in mild cognitive impairment (MCI), there is evidence of poorer instrumental activities of daily living (IADL) functioning in MCI compared to normal ageing. The aims of the present study were to examine differences in IADL between individuals with MCI and cognitively normal elderly, and to examine the relationships of IADL with cognitive functions. Methods The sample of 762 community-living participants aged 70–90 were assessed with a comprehensive neuropsychological test battery and with the informant-completed Bayer-Activities of Daily Living Scale (B-ADL). Results Compared to cognitively normal individuals, the MCI group was rated as having more difficulties on the B-ADL and performed worse on cognitive tests. Factor analysis of the B-ADL items yielded two factors, which were labelled ‘high cognitive demand’ (HCD) and ‘low cognitive demand’ (LCD). Individuals with MCI scored worse than cognitively normal participants on the HCD factor but similarly on the LCD factor. Men were rated as having more difficulties on the HCD, but not the LCD, factor compared to women. The HCD factor score correlated significantly with all five cognitive domains measured, but the LCD factor correlated significantly only with attention/processing speed and to a lesser extent with executive function. Conclusions Having more difficulties in IADL, especially those with higher demand on cognitive capacities, was found to be associated with MCI and overall cognitive functioning. This has implications for the definition of MCI, as lack of functional impairment is generally used as a criterion for diagnosis. Copyright © 2010 John Wiley & Sons, Ltd.

KALLMANN'S SYNDROME is an inherited disorder characterized by hypogonadism and anosmia.1 The hypogonadism is due to deficiency of gonadotropin-releasing hormone (GnRH),2 and the anosmia is due to hypoplasia or aplasia of the olfactory bulbs and tracts.3 , 4 In addition to hypogonadotropic hypogonadism and anosmia, other abnormalities may be present in patients with Kallmann's syndrome. They include neurologic deficits such as synkinesia,1 , 5 spatial attentional abnormalities,6 spastic paraplegia,7 cerebellar dysfunction, gaze-evoked horizontal nystagmus, pes cavus,5 , 8 mental retardation,9 color-vision disturbance and hearing loss,10 and other somatic defects, such as unilateral renal agenesis,9 horseshoe kidney,11 cryptorchidism,12 and cleft lip and palate.10 Several of these abnormalities . . .

Background and Methods. The effect of delayed puberty on peak bone mineral density in men is unknown. To determine whether such a delay reduces normal peak bone density and leads to osteopenia during adulthood, we measured radial bone mineral density by single-photon absorptiometry and spinal bone mineral density by dual-energy x-ray absorptiometry in 23 men who had a history of constitutionally delayed puberty and 21 men who underwent normal puberty. Their mean ages were 26 and 24 years, respectively. The groups were matched for other factors known to affect bone mass. Results. The mean (±SD) radial bone mineral density was significantly lower in the men with a history of delayed puberty than in the normal men (0.73±0.07 vs. 0.80±0.05 g per square centimeter; P

This paper evaluates the role of electric cues in the sex recognition behavior of an African electric fish, Pollimyrus isidori, during courtship behavior observed in the laboratory.

Wittenborn (1943; Psychometrica, 8, 19–35) devised a number of tests of ‘attention’ which were intended to measure the ability to maintain high levels of concentration or mental effort. Because of their apparent elementary and algorithmic nature, performances on the tasks were assumed not to be significantly related to subjects' ‘intellectual level’ or to the extent of their background knowledge. A correlational study was carried out to investigate the relationship between such tests of attention and common measures of intelligence. The framework for the selection of tests was provided by the Horn-Cattell theory of fluid and crystallised intelligence. The battery of tests contained markers of fluid and crystallised intelligence, short-term memory, spatial ability and perceptual/clerical speed, as well as ‘attention’ tasks derived from Wittenborn (1943). A serial short-term memory (SSTM) task was also included in the battery. On factor analysis, it was found that the attention tests, and the SSTM task, did not form a separate factor but had their major factor loadings on the same factor as was defined by the traditional measures of fluid intelligence. It was concluded that these results give support to accounts of intelligence based on such concepts as mental energy (Spearman, 1927; The abilities of man. New York: Macmillan) or non-automatic mental processing (e.g. Jensen, 1979; Creative Science and Technology, 2, 16–29).

To assess sleep-associated changes in gonadotropin-releasing hormone secretion during sexual maturation, we studied nighttime and daytime patterns of LH and FSH secretion in two groups with qualitatively similar sex steroid levels: girls with central precocious puberty and young adult women in the early follicular phase of an ovulatory menstrual cycle. In the girls with central precocious puberty, all indices of LH secretion were significantly higher at night than during the day (mean LH levels, 12 +/- 2 versus 5 +/- 1 IU/L, p less than or equal to 0.01; LH pulse amplitude 16 +/- 2 versus 7 +/- 1 IU/L, p less than or equal to 0.01; and LH pulse frequency 0.70 +/- 0.05 versus 0.35 +/- 0.08 pulse/patient-h, p less than or equal to 0.01). Girls with a history of menses, who were presumably the most mature, lacked this diurnal variability. Mean nocturnal FSH levels were only slightly higher than daytime levels (7.6 +/- 0.5 versus 7.2 +/- 0.5 IU/L, p less than or equal to 0.05) resulting in alternating periods of LH (nighttime) and FSH (daytime) predominance in this pubertal population.(ABSTRACT TRUNCATED AT 250 WORDS)

It has been more than seven decades since Drs. Fuller Albright and Donovan McCune published the first reports on individuals with McCune-Albright syndrome (MAS). Since then, the classic triad of precocious puberty, café-aulait spots, and polyostotic bone dysplasia continues to define the syndrome. However, having gathered a better picture of the pathophysiology of MAS, the way this condition is understood has changed. Isolated activating mutations of the alpha subunit of the G protein (GNAS1) have been found in different tissues, including pituitary adenomas, thyroid adenomas, ovarian cysts, monostotic bone dysplasia, and the adrenal glands, to name a few. For this reason, we have added 'and disorders due to activating mutations of GNAS1' to the title of this review. We discuss here the clinical consequences of GNAS1 activating mutations in different body systems and organs, the diagnostic approach to MAS, and the current therapeutic recommendations.

Studies on the three types of process improvement programmes (Continuous Improvement, Reengineering and Benchmarking) have appeared many times in the literature. These studies suggest that certain organizational variables act as enablers and their presence or absence can significantly influence success rates. Such studies have tended to examine companies where a single programme has been implemented. In contrast, this paper examines a sample of companies who have experienced all three programmes. Our aim is to compare and contrast each programme's impact on firm performance and identify which organizational variables are common and which are programme-specific enablers of success. We build and test an integrative framework to support our analysis. Our study found that: (1) Reengineering delivered the greatest impact on performance; (2) executive commitment was needed to make this happen; (3) strategic alignment was the major influence on the success rate of Reengineering and Continuous Improvement programmes; and (4) employee empowerment was necessary for each programme to work effectively.

Patients with pseudohypoparathyroidism type Ib (PHP-Ib) have hypocalcemia and hyperphosphatemia due to renal parathyroid hormone (PTH) resistance, but lack physical features of Albright hereditary osteodystrophy. PHP-Ib is thus distinct from PHP-Ia, which is caused by mutations in the GNAS exons encoding the G protein alpha subunit. However, an imprinted autosomal dominant form of PHP-Ib (AD-PHP-Ib) has been mapped to a region of chromosome 20q13.3 containing GNAS. Furthermore, loss of methylation at a differentially methylated region (DMR) of this locus, exon A/B, has been observed thus far in all investigated sporadic PHP-Ib cases and the affected members of multiple AD-PHP-Ib kindreds. We now report that affected members and obligate gene carriers of 12 unrelated AD-PHP-Ib kindreds and four apparently sporadic PHP-Ib patients, but not healthy controls, have a heterozygous approximately 3-kb microdeletion located approximately 220 kb centromeric of GNAS exon A/B. The deleted region, which is flanked by two direct repeats, includes three exons of STX16, the gene encoding syntaxin-16, for which no evidence of imprinting could be found. Affected individuals carrying the microdeletion show loss of exon A/B methylation but no epigenetic abnormalities at other GNAS DMRs. We therefore postulate that this microdeletion disrupts a putative cis-acting element required for methylation at exon A/B, and that this genetic defect underlies the renal PTH resistance in AD-PHP-Ib.

Mormyrid electric fish use sounds for communication and have unusual ears. Each ear has a small gas-filled tympanic bladder coupled to the sacculus. Although it has long been thought that this gas-filled structure confers acoustic pressure sensitivity, this has never been evaluated experimentally. We examined tone detection thresholds by measuring behavioral responses to sounds in normal fish and in fish with manipulations to one or to both of the tympanic bladders. We found that the tympanic bladders increase auditory sensitivity by approximately 30 dB in the middle of the animal's hearing range (200–1200 Hz). Normal fish had their best tone detection thresholds in the range 400–500 Hz, with thresholds of approximately 60 dB (re 1 microPa). When the gas was displaced from the bladders with physiological saline, the animals showed a dramatic loss of auditory sensitivity. In contrast, control animals in which only one bladder was manipulated or in which a sham operation had been performed on both sides had normal hearing.

Objective. To assess whether treatment of virilizing congenital adrenal hyperplasia (CAH) with long-acting glucocorticoids is associated with favorable growth outcomes. Method. We examined the long-term growth of 17 boys and 9 girls with CAH treated with dexamethasone (.27 ± .01 mg/m2/day). Results. For individuals with comparable bone age (BA) and chronological age (CA) at the onset of dexamethasone therapy, males were 2.8 ± .8 years (mean ± standard error of the mean;n = 13) and females were 2.4 ± 1.0 years (n = 6). Males were treated for 7.3 ± 1.1 years (ΔCA) over which time the change in BA (ΔBA) was 7.0 ± 1.3 years, and the change in height age (ΔHA) was 6.9 ± 1.1 years. Females were treated for 6.8 ± 1.3 years, over which time the ΔBA was 6.5 ± 1.0 years, and the ΔHA was 6.3 ± .8 years. During treatment 17 ketosteroid excretion rates were normal for age and 17-hydroxyprogesterone values were 69.6 ± 18 ng/dL. Testicular enlargement was first detected at 10.7 ± .8 years and breast tissue at 9.9 ± 1.2 years. Three boys and 1 girl had final heights of 171.8 ± 6 cm and 161 cm, respectively, compared with midparental heights of 176.1 ± 4.1 cm and 160 cm. Predicted adult heights for 6 other boys and 5 girls were 176.8 ± 2.0 cm and 161.4 ± 2.8 cm, respectively, compared with midparental heights of 174.6 ± 1.4 cm and 158.2 ± 2.0 cm. Statural outcomes were less favorable for 7 children started on dexamethasone when BAs were considerably advanced, although height predictions increased during therapy. Conclusions. These observations show that children treated with dexamethasone for CAH can achieve normal growth with the convenience of once-a-day dosing in most cases. congenital adrenal hyperplasia, dexamethasone, growth.

The fish auditory system provides important insights into the evolution and mechanisms of vertebrate hearing. Fish have relatively simple auditory systems, without a cochlea for mechanical frequency analysis. However, as in all vertebrates, the primary auditory afferents of fish represent sounds as stimulus-entrained spike trains. Thus, fish provide important models for studying how temporal spiking patterns are used in higher level neural computations. In this paper we demonstrate that one of the fundamental transformations of information in the auditory system of a sound-producing fish,Pollimyrus,takes place in the auditory medulla. We discovered a class of neurons in which evoked spiking patterns were relatively independent of the stimulus fine structure and appeared to reflect intrinsic properties of the neurons. These neurons generated sustained responses but were poorly phase-locked to tones compared with the primary afferents. The interval histograms showed that spike timing was regular. However, in contrast to primary afferents, the mode of the interspike interval distribution was independent of the period of tonal stimuli. The tuning of the neurons was broad, with best sensitivity in the same spectral region where these animals concentrate energy in their communication sounds. The physiology of these neurons was similar to that of the chopper neurons known in the auditory brainstem of mammals. Our findings suggest that this medullary transformation, from phase-locked afferent input to chopper-like physiology, is basic to vertebrate auditory processing, even within lineages that have not evolved a cochlea.

The African weakly electric fishes Pollimyrus isidori and Pollimyrus adspersus (Mormyridae) produce elaborate acoustic displays during social communication in addition to their electric organ discharges (EODs). In this paper, we provide new data on the EODs of these sound-producing mormyrids and on the mechanisms they use to generate species-typical sounds. Although it is known that the EODs are usually species-specific and sexually dimorphic, the EODs of closely related sound-producing mormyrids have not previously been compared. The data presented demonstrate that there is a clear sexual dimorphism in the EOD waveform of P. isidori. Females have a multi-phasic EOD that is more complex than the male’s biphasic EOD. In this respect, P. isidori is similar to its more thoroughly studied congener P. adspersus, which has a sexually dimorphic EOD. The new data also reveal that the EODs of these two species are distinct, thus showing for the first time that species-specificity in EODs is characteristic of these fishes, which also generate species-specific courtship sounds. The sound-generating mechanism is based on a drumming muscle coupled to the swimbladder. Transverse sections through decalcified male and female P. adspersus revealed a muscle that envelops the caudal pole of the swimbladder and that is composed of dorso-ventrally oriented fibers. The muscle is five times larger in males (14.5±4.4 μl, mean ± S.D.) than in females (3.2±1.8 μl). The fibers are also of significantly larger diameter in males than in females. Males generate courtship sounds and females do not. The function of the swimbladder muscle was tested using behavioral experiments. Male P. adspersus normally produce acoustic courtship displays when presented with female-like electrical stimuli. However, local anesthesia of the swimbladder muscle muted males. In control trials, males continued to produce sounds after injection of either lidocaine in the trunk muscles or saline in the swimbladder muscles.

Review of the records of 678 children with acute injuries referred during an eight year period to this burn unit indicated that flame burns from a single ignition source (50%) outranked scalds (27%) or house fires (12%) as causes of injury. There was no temporal trend in the rank pattern. The majority of these single-source flame injuries were severe and involved ignition of the child's clothing. From 1969 through 1973, sleepwear was the clothing involved in 32% of the instances. Since that time and coincident with promulgation of strict federal and state standards for flammability of children's night clothing, a dramatic decline in the number of children referred with injuries of this type has taken place. It is probable that the single factor most important to the decline, in our experience with these injuries, is lower fabric flammability but, because our data may not be representative, corroboration is needed before one can exclude factors such as altered garment design, fire safety related practices at home, or changing patterns of hospital referral.

An analysis of the natural bioacoustic signals made by two closely related African fishes (P. adspersus and P. isidori) revealed that these species separated along several acoustic dimensions that are likely to be important for species isolation. Both species produced grunts that were composed of a trains of pulses, but the pulse repetition rates were distinctly different (56 +/- 3 s.d. vs 44 +/- 4 s.d. pps). Complex tone bursts (moans) were also used, but the species differed substantially in the location of the fundamental peak (240 Hz +/- 12 s.d. vs 332 Hz +/- 34 s.d.). Some P. adspersus males sustained these tones for over a second (812 ms +/- 495 s.d.), whereas P. isidori produced shorter tones (121 ms +/- 35 s.d.). During interactions with females, the two species produced the grunts and moans in distinct species-typical patterns: P. adspersus males alternated grunts with moans and P. isidori produced a single grunt followed by a succession of moans. A detailed analysis of identified individual P. adspersus showed that acoustic features constituted individual signatures which could be used by conspecifics to identify individuals. Grunt spectral peak frequency was shown to be a good predictor of male mass, with peak frequency decreasing at 72 Hz per gram. Simulated standardized courtship encounters with females revealed that males differ markedly in their apparent ability to produce sustained moans and it is suggested that this may be particularly important to females in mate selection.