The relationship between cognitive functioning and disease severity with depression in dementia of the Alzheimer's type

This study was conducted to determine the relationship between cognitive and functional impairment in depressed and non-depressed patients with Alzheimer's disease (AD). Subjects (N = 1,486) met NINCDS-ADRDA criteria for possible or probable AD; 183 where diagnosed with a DSM-III-R depressive disorder. All subjects resided in the community. The Mini-Mental States Examination (MMSE) assessed cognitive functioning and the Blessed-Roth Dementia Rating Scale (BRDRS) assessed functional abilities. A depression score was calculated based on the number of endorsed DSM-III-R major depression symptoms. Regression analyses determined the contribution of cognitive (MMSE) and functional severity (BRDRS) in explaining the depression score, while controlling for the effects of: demographic/psychosocial variables, history of depression, and current diagnosis of depression. Cognitive and functional impairment were found to be significantly related to depression. Also, as cognitive impairment and functional abilities worsened, the number of reported depressive symptoms increased. The results of this study underscore the importance of being aware of emotional factors which may compromise cognitive/functional skills in individuals with AD. In addition, depression can be present in all stages of the illness.     

A comparison of cognitive functioning in medicated and unmedicated subjects with bipolar depression

Objective: Neuropsychological studies of bipolar disorder reveal deficits in a variety of domains, including affective processing, memory, and sustained attention. These findings are difficult to interpret due to the potential confounding effects of mood-stabilizing medications. The present study aims to compare the cognitive performance of medicated and unmedicated subjects with bipolar depression to healthy control subjects. Method: Unmedicated subjects with bipolar depression (UBD, n = 32), subjects with bipolar depression on therapeutic doses of lithium or valproic acid (MBD, n = 33), and healthy control subjects (HC, n = 52) performed neuropsychological tasks measuring affective processing, visual memory, and sustained attention. Performance measures were covaried with age and mood ratings, where applicable. Results: With regard to affective processing, the MBD group exhibited greater response latency than the UBD and HC groups. For the same task, the MBD group made more omission errors during the happy condition than in the sad condition. On a task of sustained attention, the MBD group made more errors than the HC group. There were no significant group differences on measures of visual memory. Conclusions: Deficits in affective processing were found in the medicated group, while unmedicated subjects appear to be unaffected. In particular, the MBD group made more errors during happy conditions, indicating a potential attentional bias in subjects with bipolar depression on mood-stabilizing medications. The present study also implicates impairment in sustained attention for medicated subjects with bipolar disorder, particularly those with the type II variety.     

Contactins in the central nervous system: role in health and disease

Contactins are a group of cell adhesion molecules that are mainly expressed in the brain and play pivotal roles in the organization of axonal domains, axonal guidance, neuritogenesis, neuronal development, synapse formation and plasticity, axo-glia interactions and neural regeneration. Contactins comprise a family of six members. Their absence leads to malformed axons and impaired nerve conduction. Contactin mediated protein complex formation is critical for the organization of the axon in early central nervous system development. Mutations and differential expression of contactins have been identified in neuro-developmental or neurological disorders. Taken together, contactins are extensively studied in the context of nervous system development. This review summarizes the physiological roles of all six members of the Contactin family in neurodevelopment as well as their involvement in neurological/neurodevelopmental disorders.     

Pumilio2在中枢神经系统的作用

Pumilio2（Pum2）是近年新发现的一种转录后调控因子,与微小RNA功能相似,通过其特定的结构域与m RNA结合以阻断翻译起始复合物的形成、抑制靶基因的表达。近年研究表明,Pum2与中枢神经系统的形态发生和功能执行密切相关,其表达变化参与中枢神经系统疾病的生物学进程。本文拟就Pum2在中枢神经系统作用的研究进展简要概述。     

The role of microbiome in central nervous system disorders

Mammals live in a co-evolutionary association with the plethora of microorganisms that reside at a variety of tissue microenvironments. The microbiome represents the collective genomes of these co-existing microorganisms, which is shaped by host factors such as genetics and nutrients but in turn is able to influence host biology in health and disease. Niche-specific microbiome, prominently the gut microbiome, has the capacity to effect both local and distal sites within the host. The gut microbiome has played a crucial role in the bidirectional gut–brain axis that integrates the gut and central nervous system (CNS) activities, and thus the concept of microbiome–gut–brain axis is emerging. Studies are revealing how diverse forms of neuro-immune and neuro-psychiatric disorders are correlated with or modulated by variations of microbiome, microbiota-derived products and exogenous antibiotics and probiotics. The microbiome poises the peripheral immune homeostasis and predisposes host susceptibility to CNS autoimmune diseases such as multiple sclerosis. Neural, endocrine and metabolic mechanisms are also critical mediators of the microbiome–CNS signaling, which are more involved in neuro-psychiatric disorders such as autism, depression, anxiety, stress. Research on the role of microbiome in CNS disorders deepens our academic knowledge about host-microbiome commensalism in central regulation and in practicality, holds conceivable promise for developing novel prognostic and therapeutic avenues for CNS disorders.     

Effects of depression and Parkinson's disease on cognitive functioning

This study compared the performance of Parkinson's disease (PD) patients with and without depression, patients with depression alone, and normal control subjects on a cognitive screening instrument, the Mattis Dementia Rating Scale (DRS) to evaluate the influences of depression and Parkinson's disease on cognition. PD affects overall level of cognitive functioning and, to a lesser extent, DRS Initiation/Perseveration, Construction, and Attention. Diminished memory was primarily related to depression. Treatment of depression may ameliorate aspects of cognitive dysfunction in the PD patient with depression.     

Brain-derived neurotrophic factor (BDNF) and its role in the functioning of the central nervous system

Brain-derived neurotrophic factor (BDNF) is an important signaling molecule that participates in the regulation of neurogenesis, as well as neuronal growth and survival in the central nervous system. In this review we discuss its molecular structure, the regulation of gene and protein expression, the main types of BDNF receptors, and signaling mechanisms that become activated after their interaction. We consider the influence of BDNF on synaptic transmission in the neuronal network, which is mediated by slow metabolic pathways that are associated with gene expression and by rapid mechanisms that depend on the opening of ionic channels and respective shifts in membrane potential. We summarized the data on the role of BDNF in learning and memory processes, during ischemic lesions and neurodegenerative disorders, and its contribution to the correction of these processes in vitro and in vivo.     

The central nervous system in motor neurone disease

Forty-five necropsied cases with primary degeneration of lower motor neurones are described and discussed. Of these, 36 are considered to be `typical' cases of motor neurone disease, eight of which showed no upper motor neurone lesions. The relation of the nine `atypical' cases to the remainder is discussed. It is concluded that motor neurone disease constitutes an ill-defined band in a broad spectrum of multiple system atrophies. The authors have found no evidence suggesting a causal relation between motor neurone disease and either vascular or malignant diseases. They point out suggestive analogies with various subacute encephalomyelopathies in man and other animals.     

Autonomic nervous system arousal and cognitive functioning in bipolar disorder

Levy B. Autonomic nervous system arousal and cognitive functioning in bipolar disorder. Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objective: Previous theories about the etiology of cognitive dysfunction in bipolar disorder (BD) emphasized trait factors such as neurological impairment. State factors, other than mood symptoms, that may exacerbate functional deficits have not yet been considered. The purpose of this study was to examine autonomic nervous system (ANS) arousal following cognitive challenge. The study compared patients with BD and healthy controls (HC) in physiological measures and neuropsychological test scores. Methods: Thirty euthymic patients with BD and 22 HC completed the study. Participants completed mood [Beck Depression Inventory‐II (BDI‐II) and Young Mania Rating Scale (YMRS)], anxiety (State–Trait Anxiety Inventory), and substance abuse (Drug Abuse Screening Test–20 item and Alcohol Use Disorders Identification Test) measures. They were connected to an electrogram, a sensitive thermometer for measuring finger temperature, and electrodes that measure galvanic skin response. After a five‐min baseline measurement in a restful state, participants completed a computerized neuropsychological battery (CNS Vital Signs). Results: The group with BD reported significantly more mood symptoms (BDI‐II, t = 3.71, p < 0.001; YMRS, t = 6.73, p < 0.001) and scored higher on a measure of trait‐anxiety (State–Trait Anxiety Inventory, t = 2.91, p < 0.001) than HC. A multivariate analysis of variance revealed higher arousal on all physiological measures in the BD group relative to HC at baseline [F(3,48) = 13.1, p < 0.001] and during cognitive testing [F(3,48) = 11.3, p < 0.001]. The increase in physiological arousal from a restful state to the time of testing was higher for the BD group [F(3,37) = 8.06, p < 0.001]. With respect to cognitive data, HC scored higher than patients with BD across the measures of memory (F = 8.5, p < 0.001), sustained (F = 9.5, p < 0.001) and complex (F = 2.7, p < 0.04) attention, processing speed (F = 10.0, p < 0.001), reaction time (F = 7.8, p < 0.001), cognitive flexibility (F = 19.7, p < 0.001), working memory (F = 10.8, p < 0.001), and social acuity (F = 5.7, p < 0.01), with partial eta‐squared from 0.18 to 0.62. Correlational analysis revealed significant associations between various cognitive test scores and changes in physiological arousal from baseline to testing (?0.59 ≤ r ≤ 0.22). Conclusions: Relative to HC, patients with BD experience larger changes in ANS arousal between a restful baseline and cognitive testing, and achieve lower cognitive test scores. Further research is needed to determine whether acute physiological symptoms of anxiety directly compromise cognitive functioning in BD.     

Amyloid in central nervous system disease

A review is presented of diseases of the central nervous system associated with amyloid deposition. The name amyloid is given to substances with particular physical characteristics which are independent of the chemical constitution of the proteins in the substance. Ideally, a classification of amyloid diseases should be based on the chemical composition of the amyloid deposits; this has only been partially realized. The best documented group of diseases with amyloid deposition in the central nervous system is the group of ‘cerebral β amyloid diseases’, characterized by the deposition of β-protein. This group includes: Alzheimer's disease, sporadic cerebral amyloid angiopathy, Down's syndrome, Parkinson-dementia of Guam, hereditary cerebral hemorrhage with amyloidosis-Dutch type and age-related asymptomatic amyloid angiopathy.     

Whipple's disease of the central nervous system

Summary Whipple's disease presenting as a neurological disease without gastrointestinal symptoms is an unusual occurrence. A 40 year old man suffered hypersomnia, memory loss and progressive ophthalmoplegia for 6 months prior to death. The nature of his disease was not established during life. Extensive granulomatous inflammation affecting the hypothalamus, hippocampus and periaqueductal gray matter of the brain was found to represent Whipple's disease by electron microscopy. Characteristic lesions were also present in spleen, mesenteric lymph nodes, small intestine and myocardium. Bacillary bodies and membranous inclusions similar to those seen in visceral lesions of Whipple's disease were present in macrophages. The findings supported the theory of direct involvement of the central nervous system by bacilli rather than a metabolic origin for the lesions.     

Greater depression severity associated with less improvement in depression-associated cognitive deficits in older subjects.

OBJECTIVES: Elderly depressed patients often exhibit cognitive deficits, which may improve with drug therapy. The authors investigated the relationship of baseline depression severity and cognitive improvement with antidepressant treatment in depressed patients with mild cognitive impairment. METHODS: Mini-Mental State Exam (MMSE) and Montgomery-Asberg Depression Rating Scale (MADRS) scores were measured in 52 depressed geriatric patients without dementia at baseline, 6, and 12 months, during an intent-to-treat period. A repeated-measures regression model tested the effect of MADRS score on MMSE. RESULTS: MMSE changes were significant and linear over time, with an average increase of 0.72 in the MMSE per 6-month interval. The final model showed that for every point increase in baseline MADRS, the average 6-month increase in MMSE decreased by 0.12. Repeated MADRS measurements did not significantly alter its predictive value. CONCLUSION: Greater baseline depression severity in older subjects with mild cognitive deficits is associated with less improvement in those deficits even with successful antidepressant therapy.     

The role of IL-15 in central nervous system disorders

IL-15 is a proinflammatory cytokine. It is produced by activated blood monocytes, macrophages, dendritic cells, and activated glial cells. It promotes T-cell proliferation, induction of cytolytic effector cells including natural killer and cytotoxic cells and stimulates B-cell to proliferate and secrete immunoglobulins. Little information is available on the exact role of IL-15 in the neurological diseases. Microglial cells are the main regulators of both innate and adaptive immune responses in the central nervous system (CNS). IL-15 may be involved in the inflammatory reactions and microglial activation of some common CNS disorders such as multiple sclerosis, Alzheimer's and Parkinson's disease, but its exact role in their pathogenesis is not clear.     

The role of interleukin-6 in central nervous system demyelination

正Demyelination of the central nervous system(CNS)is a hallmark of multiple sclerosis(MS),chronic inflammatory and neurodegenerative disease.Chronic demyelination favors neurodegeneration of denuded axons,which is a major cause of irreversible neuronal deficits and disability in MS patients(Lucchinetti et al.,2000).MS remains an incurable disease,despite formida-     

The role of intedeukin-6 in central nervous system demyelination

Demyelination of the central nervous system (CNS) is a hallmark of multiple sclerosis (MS),chronic inflammatory and neurodegenerative disease.Chronic demyelination favors neurodegeneration of denuded axons,which is a major cause of irreversible neuronal deficits and disability in MS patients (Lucchinetti et al.,2000).MS remains an incurable disease,despite formidable global research efforts.     

Kawasaki disease with predominant central nervous system involvement

A 4-year-old female was hospitalized with clinical and electroencephalographic evidence of acute encephalopathy. Five days later the classic signs of Kawasaki disease appeared. The neurologic outcome in this female was poor despite early treatment with immunoglobulin. Like many other vasculitidies, Kawasaki disease can have predominant neurologic symptoms as the initial presentation and during the subsequent evolution of the condition.     

Gender hormones: role in the pathogenesis of central nervous system disease and demyelination

Gender hormones are associated with the evolution of Multiple Sclerosis (MS) like changes in experimental models of MS. Several clinical studies have attempted to elucidate the role of gender hormones in the evolution of the clinical spectrum of the disease. We attempt to describe the currently known data regarding such associations emphasizing the potential clinical applications in different MS scenarios i.e. pregnancy, menstruation, use of oral contraceptives and hormonal replacement therapy. Moreover we discuss relevant effects of gender hormones on immunological parameters relating to MS pathogenesis. Beneficial neuroprotective effects were noted for elevated levels of estrogens, progesterone and elevated dosages of androgens. Some of these changes may be explained by a favorable immunological shift from a Th1 to Th2 response. Further elucidation of the clinical implications of such associations is necessary.