Delayed lymphocytic infundibuloneurohypophysitis following successful transsphenoidal treatment of Cushing's disease.

Lymphocytic infundibuloneurohypophysitis is a rare disorder in which neurohypophyseal function is impaired by an autoimmune process. Although several etiologies for this rare entity have been suggested, its occurrence following transsphenoidal adenomectomy has not been reported. A 20-year-old man presented with diabetes insipidus - seven years after successful transsphenoidal microadenomectomy for Cushing's disease, first diagnosed at the age of 13. Seven years later, he developed fairly rapid onset of polydipsia and polyuria. Magnetic resonance imaging demonstrated swelling of the posterior pituitary gland with thickening of the pituitary stalk. Endocrinological evaluation revealed neurohypophyseal dysfunction without the adenohypophysis being affected. On the basis of these findings, a diagnosis of lymphocytic infundibuloneurohypophysitis was made. The mass lesion of the posterior pituitary resolved after the administration of corticosteroids for two months and no operation was required. Lymphocytic infundibuloneurohypophysitis should be considered in the differential diagnosis of pituitary mass lesions following transsphenoidal surgery, especially when the mass is confined to the posterior pituitary gland with neurohypophyseal function being compromised.     

Persistent cognitive impairment following surgical treatment of Cushing's syndrome

Chronic exposure to elevated glucocorticoid (GC) levels in Cushing's syndrome (CS) is associated with deficits in cognitive function. It has already been shown that CS patients scored significantly lower than controls on several aspects of cognitive function (J. Int. Neuropsychol. Soc. 6 (2000) 20). In the present study, 13 subjects who presented with CS were investigated one year after surgical treatment to determine the extent to which the effects of hypercortisolism on cognitive function are reversible. Subjects were evaluated with a battery of tasks, similar to the original battery of a year earlier and including tests of attention, visuospatial processing, memory, reasoning and verbal fluency. Except for one task of visual organization, the results showed little change in performance, suggesting that prolonged exposure to high levels of GC can cause long-lasting deleterious effects on cognitive function. The data suggest that correction of hypercortisolism is not necessarily correlated with short-term improvement in cognitive function.     

Comparative responsiveness of Parkinson's disease scales to change over time

The objective of the study is to examine the comparative responsiveness of outcome measures to assess progression over time in Parkinson's disease (PD). One hundred twenty‐eight patients participating in a clinic‐based naturalistic study of PD were assessed with the Hoehn and Yahr, UPDRS, MMSE, PDQ‐39, PDQL, EQ‐5D, and BDI scales at baseline and at 1 year. In addition, 82 patients in a community‐based study of patients with PD who had completed self‐rated Schwab and England, PDQ‐39, EQ‐5D, and BDI scales at baseline, were sent the same questionnaires at 1 and 4 years. Responsiveness was assessed using t‐tests, standardised effect size, and standardised response mean. In both samples, the Hr‐QoL measures were less responsive to change over time than the impairment and disability scales (Hoehn and Yahr, UPDRS, Schwab and England scales). In addition, in the clinic‐based sample, Hoehn and Yahr and UPDRS ADL scale (“on”) were more responsive to progression over time than UPDRS motor part and ADL part (“off”). Hr‐QoL measures are less responsive to change over time than measures of impairment and disability. Although this suggests that these measures are less accurate in detecting subtle changes, it may also indicate that the multifactorial subjective assessment of Hr‐QoL adapts to changes over time. Global assessment of overall impairment and disability (which incorporates motor and nonmotor features of PD), however, appeared relatively responsive to change over time in patients in a naturalistic setting. © 2009 Movement Disorder Society     

Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing's disease.

BACKGROUND: Decreased hippocampal volume is observed in patients with Cushing's syndrome and other conditions associated with elevated cortisol levels, stress, or both. Reversibility of hippocampal neuronal atrophy resulting from stress occurs in animals. Our study investigated the potential for reversibility of human hippocampal atrophy. METHODS: The study included 22 patients with Cushing's disease. Magnetic resonance brain imaging was performed prior to transsphenoidal microadenomectomy and again after treatment. RESULTS: Following treatment, hippocampal formation volume (HFV) increased by up to 10%. The mean percent change (3.2 +/- 2.5) was significantly greater (p < .04) than that of the comparison structure, caudate head volume (1.5 +/- 3.4). Increase in HFV was significantly associated with magnitude of decrease in urinary free cortisol (r = -.61, p < .01). This relationship strengthened after adjustments for age, duration of disease, and months elapsed since surgery (r = -.70, p < .001). There was no significant correlation between caudate head volume change and magnitude of cortisol decrease. CONCLUSIONS: Changes in human HFV associated with sustained hypercortisolemia are reversible, at least in part, once cortisol levels decrease. While many brain regions are likely affected by hypercortisolemia, the human hippocampus exhibits increased sensitivity to cortisol, affecting both volume loss and recovery.     

Tissue aluminum concentrations stability over time, relationship to age, and dietary intake

Aluminum concentration was measured in serum, whole blood, hair, and urine by neutron activation analysis. Seventy-six nondemented subjects were investigated. Not all assays were done on all subjects (e.g., serum aluminum on 76 subjects, whole blood aluminum on 42 subjects), but tissue aluminum concentrations were estimated on more than one occasion on 32 subjects. The mean +/- SD aluminum concentration in serum was 0.219 +/- 0.063 micrograms/ml (N = 76), in whole blood 0.368 +/- 0.091 micrograms/ml (N = 42), in urine 0.092 +/- 0.076 micrograms/ml (N = 42), and in hair 6.42 +/- 2.22 micrograms/g (N = 42). Using product moment correlation coefficient there was no significant correlation between age and tissue aluminum concentrations, nor between dietary intake of aluminum and tissue aluminum. The tissue aluminum concentrations were not stable over time even when dietary intake was constant. Tissue aluminum concentrations were measured in 14 patients after 7 days of dietary control and repeated approximately 6 weeks later, again after 7 days of dietary control. There was no significant correlation between the two estimations in any tissue measured. These results suggest that raised tissue aluminum concentrations reported in Alzheimer's disease are not an exaggeration of a normal ageing process, are not likely to be simply secondary to increased dietary aluminum intake, and that Alzheimer's disease does not represent the chronic toxic effect of moderately raised aluminum levels at the upper end of the normal distribution.     

Changes on brief cognitive instruments over time in Parkinson's disease

Two hundred and twenty-one subjects with Parkinson's disease (PD) were examined using the Mini-Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA), with a subset of these (n = 98) examined on repeat testing up to 3 years. The MoCA was more sensitive in identifying cognitive deficit, specifically in the domains of visuospatial abilities, language, and memory. In longitudinal study, the MMSE changed significantly over time, particularly in patients with disease duration of >10 years. The MoCA, however, did not change significantly, even when subjects were stratified by age, MMSE score, and disease duration. This suggests that the MoCA may be more sensitive for detecting early cognitive change in PD, but that the MMSE, and not the MoCA, may be better for tracking cognitive decline. ? 2012 Movement Disorder Society.     

Sustained cognitive improvement following treatment of Alzheimer's disease with donepezil

OBJECTIVES: To audit response to the anticholinesterase inhibitor donepezil in patients referred to a specialist memory clinic, to identify possible means of targeting the drug more accurately. DESIGN: All referrals to the clinic who were assessed and treated against a protocol, with structured follow-up. SUBJECTS: All referrals of any age with the diagnosis of probable Alzheimer's disease, mild to moderately severe. Main outcome measures Cognitive improvement as measured by serial ADAS-cog and MMSE examinations. RESULTS: Two hundred and eight-two patients commenced on treatment, improved cognitive functioning in over 65% of patients reaching 3 months (N=184), 51% on intention to treat analysis (N=231), with significantly greater improvement (p=0.03) in those aged 65 and under. Carer reports of behavioural improvement not always linked to cognitive improvement. Trend to increased response in those on concomitant antidepressants. CONCLUSION: Three-month assessment for response prior to agreeing continuation of treatment selects a group who maintain their response. Younger patients should be targeted for early assessment and treatment.     

Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment

OBJECTIVE: Novel antipsychotic medications have been reported to have beneficial effects on cognitive functioning in patients with schizophrenia. However, these effects have been assessed in studies with considerable variation in methodology. A large number of investigator-initiated and industry-sponsored clinical trials are currently underway to determine the effect of various novel antipsychotics on cognitive deficits in patients with schizophrenia. The ability to discriminate between high- and low-quality studies will be required to understand the true implications of these studies and their relevance to clinical practice. METHOD: This article addresses several aspects of research on cognitive enhancement in schizophrenia, emphasizing how the assessment of cognitive function in clinical trials requires certain standards of study design to lead to interpretable results. RESULTS: Novel antipsychotic medications appear to have preliminary promise for the enhancement of cognitive functioning. However, the methodology for assessing the treatment of cognitive deficits is still being developed. CONCLUSIONS: Researchers and clinicians alike need to approach publications in this area with a watchful eye toward methodological weaknesses that limit the interpretability of findings.     

首次确诊帕金森病患者情绪和认知功能障碍的关系

目的观察研究首次确诊帕金森痛患者情绪和认知功能障碍之间的关系。方法60例首次确诊帕金森病（PD）患者,采用简易智能状态检查量表（MMSE）和词ir-流畅性测验评定患者的认知功能;采用汉密尔顿抑郁量表（HAMD）和汉密尔顿焦虑量表（HAMA）评定患者的情绪障碍。采用统一帕金森病评分量表（UPDRS）和改良Hoehn—Yahr分级评定患者的帕金森病严重程度。结果（1）60例首次确诊PD患者改良H0ehn～Yahr分级显示：I级11例,Ⅱ级32例,Ⅲ级16例,Ⅳ级1例。其中具有抑郁障碍患者28例,占46．7％;具有焦虑障碍患者20例,占33．3％,20例焦虑障碍PD患者都具有抑郁障碍。（2）60例首次确诊PD患者中,具有认知功能障碍患者23例,占38．3％;MMSE评分和词汇流畅性测验评分均与病程呈负相关,差异具有统计学意义（r分别为-0．42,-0．46;P〈0．05）。（3）60例首次确诊PD患者HAMD评分和MMSE评分及词汇流畅性测验评分呈负相关,差异具有统计学意义（r分别为-0．69,-0．76;P〈0．01）。PD患者HAMA评分和MMSE评分及词汇流畅性测验评分亦呈负相关,差异具有统计学意义（r分别为～0．60,-0．68;P〈0．01）。结论首次确诊PD患者多为轻、中度患者,早期即表现情绪障碍和认知功能障碍,且两者具有高度相关性。     

Normal rates of cognitive change in successful aging: the freedom house study.

We determined the rates of cognitive change associated with twenty individual measures. Participants included 547 noninstitutionalized septuagenarians and octogenarian residents of a comprehensive care retirement community who were studied over three years. Latent growth curves (LGC) of multiple cognitive measures were compared to a LGC model of the rates of change in Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL). All curves were standardized relative to each variable's baseline distribution. Baseline scores were within their expected normal age-specific ranges. Most measures showed significant rates of change over time. There was also significant variability about those rates, suggesting clinical heterogeneity. Many deteriorated over time, as did ADLs and IADLs. However, performance on some measures improved, consistent with learning effects. The rates of change in two measures, the Executive Interview and the Trail Making Test, were closely related to decline in IADLs. These results suggest that age-related cognitive decline is a dynamic longitudinal process affecting multiple cognitive domains. Heterogeneity in the rates of cognitive change may reflect the summed effects of age and comorbid conditions affecting cognition. Some measures may be ill-suited for measuring age-related changes in cognition, either because they are insensitive to change, or hindered by learning effects. Nonverbal measures appear to be particularly well suited for the prediction of age-related functional decline. These observations are relevant to the definition and diagnosis of "dementing" conditions.     

The sensitivity to change over time of the Bristol Activities of Daily Living Scale in Alzheimer's disease

Activities of daily living scales can be a useful tool in assessing change in people with dementia, either as the disease progresses or in response to treatment. However, little data exist as to the sensitivity to change of instruments used. The Bristol Activities of Daily Living Scale was developed with assistance from the carers of community dwelling people with dementia to be completed by such people and has been shown to have internal consistency as well as face and construct validity. This study aimed to analyse the sensitivity to change of the Bristol Activities of Daily Living Scale in people with Alzheimer's disease receiving anticholinesterase medication. Using the Clinician's Global Rating of Change as a gold standard for change, differences between Bristol Activities of Daily Living Scale scores before and after medication were compared with change in Mini-Mental State Examination, Alzheimer's Disease Assessment Scale - Cognitive and the Nurses Observation Scale for Geriatric Patients, in 61 older adults receiving anticholinesterase medication for Alzheimer's disease. Both the Bristol Activities of Daily Living Scale and the Nurses Observation Scale for Geriatric Patients are sensitive and specific in predicting improvement or stability as measured by the clinician's global rating of change. However, unlike the Nurses Observation Scale for Geriatric Patients, change over time in the Bristol Activities of Daily Living Scale significantly correlates with change in the Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale - Cognitive. The Bristol Activities of Daily Living Scale is sensitive to change in activities of daily living and shows the expected and desirable relationship with measures of cognition.     

认知能力发展与年龄的关系

目的:采用新编的华文认知能力量表探讨中国普通人群的认知能力发展与年龄的关系。方法:采用华文认知能力量表对791名来自无锡和芜湖的普通人群进行个别测试,分析认知能力的年龄发展趋势。结果:言语智商、操作智商、总智商、各因子商数、以及认知能力量表的分量表与年龄的趋势图均呈类似倒U字形;言语智商、操作智商、总智商、各因子商数、以及认知能力量表的分量表的高分基本在15.5~20岁年龄组或20~30岁年龄组,在15.5~20岁年龄组之前随年龄的增长逐渐升高,在20~30岁年龄组之后随年龄升高逐渐降低。结论:认知能力的成长曲线呈类倒U字形,在20~30岁年龄组之后逐渐呈非线性衰退。     

库欣病神经内镜下经蝶入路手术治疗

库欣综合征（Cushing＇s syndrome,CS）又称皮质醇增多症,即高皮质醇血症及由其产生的一系列病理生理改变,是三种独立的病理综合征（垂体病变、肾上腺肿瘤、异位性癌肿）的统称。CS中约70％～90％是由库欣病（Cushing＇s disease,CD）即垂体肾上腺皮质激素（adrenoeortieotropic hormone,ACTH）腺瘤或垂体ACTH细胞增生引起。内镜配套设备的完善、内镜操作技术的成熟,以及内镜自身的优越性,使得纯内镜下经蝶手术迅速在临床推广应用。     

Positive and negative symptoms of schizophrenia. Their course and relationship over time.

Recent approaches to subtyping schizophrenia have made use of the concepts of positive and negative symptoms. It is sometimes assumed that positive and negative symptoms are distributed discontinuously or inversely. Many of the studies that have examined this concept are cross-sectional. This research examines the relationships among positive and negative symptoms in a sample of 41 DSM III diagnosed schizophrenics. Using the SANS and the SAPS, symptoms are assessed, first, in the acute phase of the illness and then, 6 months later, in a period of relative remission. Results showed that positive and negative symptoms were not inversely related at either phase of the illness. Secondly, in comparison to positive symptoms, negative symptoms were highly intercorrelated at both times. Thirdly, the presence of negative symptoms in the acute phase was highly predictive of the presence of negative symptoms at follow-up. Implications for the longitudinal course of symptoms in schizophrenia are discussed.     

The relationship between age and cognitive function in HIV-infected men

Several studies have identified increased age as a risk factor for the development of cognitive impairment in human immunodeficiency virus (HIV)-infected subjects, but few have examined the potential synergistic effect of age and HIV serostatus on cognitive decline. The authors examined the possible combined effect of age and HIV serostatus on cognitive decline in 254 subjects stratified by age group and HIV status. After controlling for the effect of education, there were significant effects for serostatus and age group on overall cognitive impairment and a number of neuropsychological measures but no interaction effects. These data suggest that older seropositive individuals are not at an increased risk for HIV-related cognitive impairment when normal age-related cognitive changes are considered.     

Timing of cognitive deficits following neonatal seizures: relationship to histological changes in the hippocampus.

Neonatal seizures are frequently associated with cognitive impairment and reduced seizure threshold. Previous studies in our laboratory have demonstrated that rats with recurrent neonatal seizures have impaired learning, lower seizure thresholds, and sprouting of mossy fibers in CA3 and the supragranular region of the dentate gyrus in the hippocampus when studied as adults. The goal of this study was to determine the age of onset of cognitive dysfunction and alterations in seizure susceptibility in rats subjected to recurrent neonatal seizures and the relation of this cognitive impairment to mossy fiber sprouting and expression of glutamate receptors. Starting at postnatal day (P) 0, rats were exposed to 45 flurothyl-induced seizures over a 9-day period of time. Visual-spatial learning in the water maze and seizure susceptibility were assessed in subsets of the rats at P20 or P35. Brains were evaluated for cell loss, mossy fiber distribution, and AMPA (GluR1) and NMDA (NMDAR1) subreceptor expression at these same time points. Rats with neonatal seizures showed significant impairment in the performance of the water maze and increased seizure susceptibility at both P20 and P35. Sprouting of mossy fibers into the CA3 and supragranular region of the dentate gyrus was seen at both P20 and P35. GluR1 expression was increased in CA3 at P20 and NMDAR1 was increased in expression in CA3 and the supragranular region of the dentate gyrus at P35. Our findings indicate that altered seizure susceptibility and cognitive impairment occurs prior to weaning following a series of neonatal seizures. Furthermore, these alterations in cognition and seizure susceptibility are paralleled by sprouting of mossy fibers and increased expression of glutamate receptors. To be effective, our results suggest that strategies to alter the adverse outcome following neonatal seizures will have to be initiated during, or shortly following, the seizures.