Mild Cognitive Deficits Research Articles

Abstract 064: Toll-like Receptor 2 Signaling Contributes To Cerebrovascular Dysfunction And Decreased Cerebral Blood Flow In Type-1 And Type-2 Diabetes.

We have shown that type 2 diabetic Goto-Kakizaki (GK) rats develop cerebrovascular endothelial dysfunction, impaired cerebral blood flow (CBF) and mild cognitive deficits. It is increasingly recognized that vascular cognitive impairment may be a new complication of the disease in both type 1 and type 2 diabetes. Toll-like receptor-2 (TLR2) plays a role in cardiovascular complications of diabetes but its involvement in diabetic cerebrovascular disease is unknown. Since brain function heavily depends on constant perfusion, and decreased CBF precedes development of inflammation and cognitive deficits, we hypothesized that enhanced TLR2 signaling in both type 1 and 2 diabetes would contribute to cerebrovascular dysfunction and decreased CBF. Endothelium-dependent relaxation was assessed by measuring acetylcholine (ACh, 10-9 -10-4 M) induced dilatory response in basilar arteries from GK rats in the presence and absence of an anti-TLR2 (1μg) antibody. Vascular contractility to serotonin (10-9 -10-5 M) stimulation was also assessed. Area under the curve (AUC) and maximal effective concentration (Emax as % of max KCl response) were calculated as indices of total relaxation and total contraction, respectively. Basilar artery relaxation was significantly improved in the vessels preincubated (30’) with antiTLR2 (184.8± 24.0 vs. 87.7± 4, p =0.007). The EMax in response to serotonin stimulation in the anti-TLR2 treated vessels was not significantly different than the vessels from the untreated diabetic GK rats (110.6± 4.9% vs 99.4.±4.5%). To further assess the in vivo functional effects of TLR2 signaling, CBF (relative intensity) was measured using laser speckle imaging in wild type and TLR2-knockout (KO) mice using an STZ induced diabetes model. Six weeks after induction of diabetes, wild-type diabetic mice exhibited a significant decrease in CBF vs. control (210±22.5 vs. 300.3±18.4, p<0.05). This decrease in cerebral perfusion was attenuated in the TLR2-KO diabetic mice compared to TLR2 KO control (322.6±10.1 vs. 344. 5±11. 04). These findings suggest that TLR2 signaling leads to vascular dysfunction through decreased endothelium dependent relaxation, and could contribute to decreased CBF in diabetes predisposing to vascular cognitive impairment.

Palmitoylethanolamide controls reactive gliosis and exerts neuroprotective functions in a rat model of Alzheimer's disease.

Given the complex heterogeneity of pathological changes occurring in Alzheimer's disease (AD), any therapeutic effort absolutely requires a multi-targeted approach, because attempts addressing only a single event may result ineffective. Palmitoylethanolamide (PEA), a naturally occurring lipid amide between palmitic acid and ethanolamine, seems to be a compound able to fulfill the criteria of a multi-factorial therapeutic approach. Here, we describe the anti-inflammatory and neuroprotective activities of systemic administration of PEA in adult male rats given intrahippocampal injection of beta amyloid 1–42 (Aβ 1–42). Moreover, to investigate the molecular mechanisms responsible for the effects induced by PEA, we co-administered PEA with the GW6471, an antagonist of peroxisome proliferator-activated receptor-α (PPAR-α). We found that Aβ 1–42 infusion results in severe changes of biochemical markers related to reactive gliosis, amyloidogenesis, and tau protein hyperphosphorylation. Interestingly, PEA was able to restore the Aβ 1–42-induced alterations through PPAR-α involvement. In addition, results from the Morris water maze task highlighted a mild cognitive deficit during the reversal learning phase of the behavioral study. Similarly to the biochemical data, also mnestic deficits were reduced by PEA treatment. These data disclose novel findings about the therapeutic potential of PEA, and suggest novel strategies that hopefully could have the potential not just to alleviate the symptoms but also to modify disease progression.

Iodine deficiency and its consequences for cognitive and psychomotor development of children

Dietary iodine intake is required for the production of thyroid hormones. Thyroxine (T4) and triiodothyronine (T3) are essential for the development of the central nervous system, they regulate genes involved in myelination and neuronal/glial cell differentiation, and play an important role in axonal and dendrite growth in synaptogenesis and myelination. Deficiencies in thyroid hormones in pregnant women directly affect brain development of the fetus, resulting in neurological and neurocognitive disorders in infants with defects ranging from decrease in intelligence and lethargy to mental retardation. Thyroid deficiency at different stages of pregnancy affects different brain regions, for example, basal ganglia are affected by early thyroid hormone deficiency and cerebellar and hippocampal development is influenced by late thyroid dysfunction [1]. Therefore the consequences of the brain damage depend upon the timing and severity of the hypothyroxinaemia, when it appearing before or at 12 weeks of pregnancy it may affect cognitive development. The neurological cretinism, a disease characterized by severe neurological lesions without clinical hypothyroidism may be a consequence of severe hypothyroxinaemia in early pregnancy. Congenital hypothyroidism is one of the most common preventable causes of mental retardation in children and describes the deficiency in thyroid hormones as of prenatal onset of severe thyroid dysfunction. Newborn screening and thyroid therapy started within 2 weeks of age can normalize cognitive development. Mild reductions in maternal thyroid hormone levels in early pregnancy are associated with reduced IQ in offspring and prenatal exposure to maternal hypothyroxinaemia increased the risk of expressive language delay and nonverbal cognitive delay in preschool age children [2]. Mild iodine deficiency during pregnancy may lead to hypothyroxinaemia in the mother and/or elevated thyroid-stimulating hormone levels in the foetus, and these conditions have been found to be related to mild and subclinical cognitive and psychomotor deficits in neonates, infants and children [3]. Moderate cognitive impairments have been observed in children from the age of 3 weeks up to 5 years. Low maternal iodine status could be associated with an increased risk of suboptimal scores for verbal IQ at age 8 years and reading accuracy, comprehension and reading scores at age 9 years. Correction of mild-to-moderate iodine deficiency improves cognitive performance in school age children [4]. As iodine deficiency is still the most widespread cause of maternal hypothyroxinaemia, the birth of many children with learning disabilities may already be preventable by advising women to take iodine supplements as soon as pregnancy starts, or earlier if possible.

Inpatient Rehabilitation of Cerebellopontine Angle Epidermoid Cysts: Report of 3 Cases.

Demonstrate the inpatient rehabilitation potential of cerebellopontine angle epidermoid cyst patients. Due to their location, symptoms may present with a complex combination of headache, cerebellar dysfunction, and cranial nerve deficits affecting functional status. This report describes the cases of 3 patients with cerebellopontine angle epidermoid cysts who underwent neurosurgical resection followed by inpatient rehabilitation. All 3 patients experienced gait instability and cranial nerve deficits before surgery, and 2 of the patients had mild cognitive deficits. A customized rehabilitation program for these patients can address these deficits. Each patient showed demonstrable gains in function with inpatient rehabilitation and good outcomes at discharge. When rehabilitating epidermoid cyst patients, the clinician must be aware of a higher likelihood of cranial neuropathies, need for increased psychosocial support, and the need for more vigilant long term medical monitoring to detect recurrence.

Visual motion processing deficits in infants with the fragile X premutation.

BackgroundFragile X syndrome (FXS) results from a trinucleotide repeat expansion (full mutation >200 cytosine-guanine-guanine (CGG) repeats) in the FMR1 gene, leading to a reduction or absence of the gene’s protein product, fragile X mental retardation protein (FMRP), ultimately causing cognitive and behavioral impairments that are characteristic of the syndrome. In our previous work with infants and toddlers with FXS, we have been able to describe much about their cognitive and visual processing abilities. In light of recent work on the mild cognitive deficits and functional and structural brain differences that are present in adults with the fragile X (FX) premutation, in the present study we examined whether some of the low-level visual processing deficits we have observed in infants with FXS would also be present in infants with the FX premutation (55–200 CGG repeats).MethodsWe chose a contrast detection task using second-order motion stimuli on which infants with FXS previously showed significantly increased detection thresholds (Vision Res 48:1471–1478, 2008). Critically, we also included a developmental delay comparison group of infants with Down syndrome (DS), who were matched to infants with FXS on both chronological and mental age, to speak to the question of whether this second-order motion processing deficit is a FX-specific phenomenon.ResultsAs reported previously, infants with the FX full mutation showed motion contrast detection threshold levels that were significantly higher than age-matched typically developing control infants. Strikingly, the motion detection contrast levels of FX premutation infants were also significantly higher than typically developing (TD) infants and not significantly different from the group of infants with FXS or with DS.ConclusionsThese results, which are in keeping with a growing body of evidence on the mild cognitive and perceptual processing deficits and functional and structural brain differences that are present in adults and older children with the FX premutation, underscore the pressing need to study and describe the processing capabilities of infants and toddlers with the FX premutation.

Propositional speech in unselected stroke: The effect of genre and external support

Distinguished from nominal language, propositional language generation refers to the spontaneous and voluntary aspect of language that introduces novel concepts to a specific context. Propositional language can be impaired in a range of neurological disorders, including stroke, despite well-preserved nominal language. Although external support can increase speech rate in patients with reduced propositional speech, no specific investigation of propositional speech has been carried out in unselected stroke patients. The current study investigated propositional language in an unselected post-acute stroke group (N = 18) with mild cognitive impairment and prominent executive dysfunction, but without significant aphasia. Specifically, we investigated whether genre or external support affected the number of words, sentences, and novel ideas produced, compared to healthy controls (N = 27). Results showed that discourse genre was not associated with differential performances. By contrast, speech quantity increased without external support although, for stroke patients, speech novelty decreased. Overall, the novelty deficit in unselected stroke patients highlights the importance of assessing cognition and propositional speech. Our findings suggest that for stroke patients with mild cognitive deficits, including executive dysfunction, introducing external support improved speech quality but not quantity. Implications for both assessment and rehabilitation of social communication are discussed.

Mechanisms of hepatic encephalopathy and thiamine deficiency.

Hepatic encephalopathy (HE) and thiamine deficiency (TD) represent two disorders in which metabolic derangements play a major role in their pathophysiology. They also define the areas of primary focus of Dr. Roger F. Butterworth, Ph.D., D.Sc. who retired from the University of Montreal in the summer of 2013. This special issue of Metabolic Brain Disease commemorates his valuable contribution to the study of these maladies. Although HE is considered a metabolic disorder, new evidence is emerging to show that it has a molecular basis as well. Vemuganti et al reports altered cerebral profiles of microRNAs after acute liver failure (ALF) that likely contribute in a significant way to gene expression changes associated with the ensuing HE. Disrupted ammonia detoxification is considered a major precipitator of neurological dysfunction in HE, and current understanding of the contribution of ammonia in liver diseases is discussed in an article by Ott and Vilstrup, while the effects of hyperammonemia on cerebral metabolic function are focussed on in an article by Schousboe and colleagues. In addition, impaired brain energy metabolism is a serious complicating feature of liver failure, with lactate production being a major consequence of this problem. In relation to this, the role of increased lactate accumulation and its pathogenetic basis in HE is discussed by Bosoi and Rose. Also, a major and often lethal complication of ALF is brain edema, and the significance of this edema and its underlying basis in ALF-induced HE is examined by Rama Rao et al, while the usefulness of magnetic resonance imaging as a tool in both acute and chronic liver failure is considered by Chavarria and Cordoba. Minimal hepatic encephalopathy (MHE) represents the mildest of the spectrum of HE forms in which patients do not display clinical symptoms but have mild cognitive and psychomotor deficits. It is also associated with poor survival rates. Two papers examine aspects of MHE, in which cognitive impairment and the issue of cognitive variability as a contributing factor in these patients is a focus of attention in Bisiacchi et al, and in an experimental model of chronic liver failure in which focal increases in the binding of translocator (18kD) protein in brain is reported by Agusti et al. Increasingly, the phenomenon of acute-on-chronic liver failure, in which acute deterioration of liver function in patients with cirrhosis is a consequence, is being considered a distinct clinical entity. The subject is discussed in Wright et al. In addition, considerable evidence has shown that astrocyte dysfunction plays a major role in HE. Karabara and colleagues explore the potential role of GlcNAcylation in these cells, while the protective effect of inhibition of glutamine synthesis is examined in neurological diseases, including HE, by Jeitner and Cooper. Development of well-defined biomarkers and improved therapeutic targets represents an important subject regarding HE. In this regard, the paper by Cooper and Kuhara shows that α-ketoglutaramate is a good marker of HE, and the paper by Mondal and Trigun demonstrates that pannexin-1 can be a marker as well as a target for HE. Although the mechanism(s) underlying the beneficial effects of rifaximin in HE remain largely unknown, the topic is tackled using multi-modal MRI in Ahluwalia et al. In addition, the subject of microglial proliferation and its significance in alcoholics with HE is explored experimentally in Dennis et al. Dienel and Cruz address the subject of decreased proteolysis as a result of hyperammonemia due to liver failure, and the effects of thioacetamide-induced ALF on citrulline uptake is examined in a study by Zielinska et al. Finally, Roger’s interest in the pathophysiology of TD has been long and enduring. A number of papers in this special issue deal with different aspects of TD. Afadlal et al shows that astrocytes play a significant role in TD-induced encephalopathy, while Bettendorff explores the role of thiamine triphosphate in cells. In addition, since mitochondrial dysfunction is an important aspect of both TD and Alzheimer’s disease in which thiamine-dependent enzyme activity is reduced, Huang et al explores how cellular calcium stores are affected in a fibroblast cell line, an important first step towards the eventual determination of how this process comes about in the AD patient and development of protective/treatment strategies targeting this mechanism, which may also have relevance for the future treatment of TD.

Cognitive Deficit Reversal as Shown by Changes in the Veterans Affairs Saint Louis University Mental Status (SLUMS) Examination Scores 7.5 Years Later

ObjectiveThe Veterans Affairs Saint Louis University Mental Status (SLUMS) examination is a screening tool that has the sensitivity to detect mild neurocognitive impairment and dementia. This study explores patients' cognitive impairment trajectories based on the SLUMS examination score changes after 7.5 years. DesignRetrospective chart review. SettingThe Geriatric Research, Education, and Clinical Center at the Department of Veterans Affairs Medical Center (VAMC), St Louis, MO. ParticipantsA review of 533 charts indicated that 357 patients who had participated in the SLUMS examination validation study in 2003 were still alive. MeasurementCharts were screened for indicators of cognitive status in both 2003 and 2010 and interventions after baseline evaluation. ResultsThe mean age of the 357 individuals in 2003 was 74, all were men, and 73% had a high school education or more. A total of 223 (62%) of the 357 completed the SLUMS examination at baseline and at the 7.5-year follow-up visit; of those, 33 (15%) progressed to mild cognitive deficit, 20 (9%) progressed to severe cognitive deficit, and 53 (24%) improved or reverted back to normal. Further exploration revealed that at least one reversible cause was identified for most (n = 36/53, 68%) of the reversions. The primary interventions that differentiated reversers from nonreversers were correction of visual loss (P = .005) and discontinuation of anticholinergic medications (P = .002). ConclusionCognitive improvement (reversion) as indicated by the SLUMS examination after 7.5 years was associated with the correction of some reversible causes. This stresses the importance of early detection and exclusion of reversible causes for persons screened for cognitive dysfunction using the SLUMS examination.

MP2RAGE provides new clinically-compatible correlates of mild cognitive deficits in relapsing-remitting multiple sclerosis.

Despite that cognitive impairment is a known early feature present in multiple sclerosis (MS) patients, the biological substrate of cognitive deficits in MS remains elusive. In this study, we assessed whether T1 relaxometry, as obtained in clinically acceptable scan times by the recent Magnetization Prepared 2 Rapid Acquisition Gradient Echoes (MP2RAGE) sequence, may help identifying the structural correlate of cognitive deficits in relapsing-remitting MS patients (RRMS). Twenty-nine healthy controls (HC) and forty-nine RRMS patients underwent high-resolution 3T magnetic resonance imaging to obtain optimal cortical lesion (CL) and white matter lesion (WML) count/volume and T1 relaxation times. T1 z scores were then obtained between T1 relaxation times in lesion and the corresponding HC tissue. Patient cognitive performance was tested using the Brief Repeatable Battery of Neuro-psychological Tests. Multivariate analysis was applied to assess the contribution of MRI variables (T1 z scores, lesion count/volume) to cognition in patients and Bonferroni correction was applied for multiple comparison. T1 z scores were higher in WML (p < 0.001) and CL-I (p < 0.01) than in the corresponding normal-appearing tissue in patients, indicating relative microstructural loss. (1) T1 z scores in CL-I (p = 0.01) and the number of CL-II (p = 0.04) were predictors of long-term memory; (2) T1 z scores in CL-I (β = 0.3; p = 0.03) were independent determinants of long-term memory storage, and (3) lesion volume did not significantly influenced cognitive performances in patients. Our study supports evidence that T1 relaxometry from MP2RAGE provides information about microstructural properties in CL and WML and improves correlation with cognition in RRMS patients, compared to conventional measures of disease burden.

THU0017 Cognitive Dysfunction in Active and Remitted Egyptian Non-Neuropsychiatric Systemic Lupus Erythematosus Patients

BackgroundFew studies reported mild cognitive deficits in patients with Non-Neuropsychiatric Systemic Lupus Erythematosus (Non-NPSLE) with no consistent pattern of cognitive deficits with suggest of the presence of a subtle CNS...

Imaging changes associated with cognitive abnormalities in Parkinson's disease.

The current study investigates both gray and white matter changes in non-demented Parkinson's disease (PD) patients with varying degrees of mild cognitive deficits and elucidates the relationships between the structural changes and clinical sequelae of PD. Twenty-six PD patients and 15 healthy controls (HCs) were enrolled in the study. Participants underwent T1-weighted and diffusion tensor imaging (DTI) scans. Their cognition was assessed using a neuropsychological battery. Compared with HCs, PD patients showed significant cortical thinning in sensorimotor (left pre- and postcentral gyri) and cognitive (left dorsolateral superior frontal gyrus [DLSFG]) regions. The DLSFG cortical thinning correlated with executive and global cognitive impairment in PD patients. PD patients showed white matter abnormalities as well, primarily in bilateral frontal and temporal regions, which also correlated with executive and global cognitive impairment. These results seem to suggest that both gray and white matter changes in the frontal regions may constitute an early pathological substrate of cognitive impairment of PD providing a sensitive biomarker for brain changes in PD.

Socioeconomic disparities in work performance following mild stroke

Purpose: The purpose of this study was to investigate the relationships among the factors that influence return to work for young individuals with mild stroke from different socioeconomic backgrounds. Methods: Prospective cohort study of working adults with mild stroke (N = 21). Participants completed an assessment battery of cognitive, work environment and work performance measures at approximately 3 weeks and 7 months post mild stroke. Individuals were placed in “skilled” and “unskilled” worker categories based on the Hollingshead Index. Results: Unskilled workers had significantly poorer scores on the majority of the cognitive assessments. Unskilled workers also perceived less social support (p = 0.017) and autonomy (p = 0.049) in work responsibilities than individuals in the skilled worker group and also reported significantly poorer work productivity due to stroke than those in the skilled group (p = 0.015). Conclusions: Individuals from low socioeconomic backgrounds have more difficulty returning to work following mild stroke than individuals from higher socioeconomic backgrounds. Future work is needed to identify factors that can increase long-term work success and quality of work performance following a mild stroke that specifically targets the needs of individuals who have a lower socioeconomic status.Implications for RehabilitationMany persons, especially those of low socioeconomic status (SES), have decreased work productivity following mild stroke despite having no physical impairments and receiving little to no post-acute rehabilitation services.Acute care rehabilitation measures are not detecting mild cognitive deficits and work environment factors that could impact successful reintegration into work and the community.Follow-up services for individuals with mild stroke could improve readiness for work, work productivity and work sustainability, especially among individuals of low SES.

Introduction: the importance of cognition in movement disorders.

In the past decade, there has been an explosion in clinical attention and research on the cognitive aspects of all movement disorders. This is, in part, driven by the aging of the world’s population in developed countries, which has increased attention on neurodegenerative diseases that differentially affect the elderly, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and atypical parkinsonism (corticobasal syndrome [CBS], MSA, PSP, and SCA). Additionally, the increasing recognition of dementia with Lewy bodies (DLB) has highlighted the overlap between movement disorders and dementia. Another contributing factor is emerging data from prospective, long-term epidemiological studies that have led to a dramatic increase in estimates of cumulative dementia prevalence in PD. Finally, with the focus increasingly on those patients in the predementia stage, the scope of cognition-related clinical care and research has broadened significantly. Besides the aforementioned disorders, other movement disorders have either long been associated with frank cognitive impairment (i.e., Huntington’ disease; HD) or are increasingly recognized to be associated with mild cognitive deficits (i.e., essential tremor).

Differentiating Alzheimer Disease, Lewy Body, and Parkinson Dementia Using DSM-5

Dementia is a growing problem with global, social, and financial repercussions. Early screening, diagnosis, education, planning, and treatment of dementia in primary care may reduce this burden. Presently, dementia is often diagnosed relatively late in the disease process, resulting in greater financial and caregiver burden. Primary care providers are often most likely to encounter patients with cognitive impairment early. The new guidelines outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition are presented to promote annual screening and early diagnosis of mild cognitive deficits by primary care providers.

Micronutrients supplementation and nutritional status in cognitively impaired elderly persons: a two-month open label pilot study

BackgroundMalnutrition is a widespread problem in elderly people and is associated with cognitive decline. However, interventional studies have produced ambiguous results. For this reason, we wanted to determine the effect of micronutrient supplementation on blood and tissue levels and on general nutritional status in persons with mild or moderate cognitive impairment.MethodsWe performed a 2-month, open-label trial, administering a daily micronutrient supplement to 42 memory clinic patients with mild cognitive deficits. Blood levels of antioxidants, zinc, and B vitamins were determined before and after supplementation. In addition, we assessed metabolic markers for B vitamins and intracellular (buccal mucosa cell [BMC]) antioxidant levels. Nutritional status was assessed by using the Mini Nutritional Assessment (MNA).ResultsBlood levels of B vitamins, folic acid, lutein, β-carotene, α-carotene, and α-tocopherol increased significantly. Decreases in homocysteine levels and the thiamine pyrophosphate effect and an increase in holotranscobalamin were observed. We found no increase in intracellular antioxidant levels of BMC. The MNA score in subjects at risk for malnutrition increased significantly, mainly owing to better perception of nutritional and overall health status.ConclusionsMicronutrient supplementation improved serum micronutrient status, with improved metabolic markers for B vitamins but not for intracellular antioxidant status, and was associated with improved self-perception of general health status. Our data underline the necessity of determining micronutrient status and support the use of additional assessments for general health and quality of life in nutritional supplementation trials.

Evolution of the cognitive profile in school-aged patients with severe TBI during the first 2 years of neurorehabilitation

Objective: Persistent post-injury cognitive, academic and behavioural deficits have been documented in children who sustained severe TBI during the school-age years. The major aim of this study was to examine and follow-up for 2 years the cognitive profile of a sample of post-injured patients (aged 6–16.11), in order to verify to what extent they recovered their intellectual functions after rehabilitation.Method: Twenty-six patients who received a specific neuropsychological treatment and three cognitive evaluations with WISC-III were selected from a pool of 77.Results: This group of patients showed a mild cognitive deficit at baseline, which improved over the 2 years to a borderline level. Despite the improvement in intellectual quotients and single sub-test scores achieved through rehabilitation, different recovery times were seen according to the function under study. The most common deficits are in processing speed, inferential and lexical-semantic skills.Conclusions: Detailed analysis of the WISC-III sub-tests allows for an accurate description of single cognitive functions after TBI. This allows one to make differential diagnoses between functional profiles and plan individualized rehabilitation treatments. Post-injured school-aged patients should receive rehabilitation for a period of at least 2 years, which is the time necessary for an at-least partial reorganization of basic cognitive functions.

Relação entre qualidade do sono e funções cognitivas em pacientes com doença de Parkinson

Here, we describe the clinical characteristics of patients with Parkinson's disease, as well as study the relationship between sleep quality and cognitive functions. This is a descriptive-analytical cross-sectional study in which we evaluate episodes of depression and anxiety, as well as the state of general health, disease progression, sleepiness, sleep quality and cognitive functions of 24 patients with Parkinson's disease without dementia. We found a moderate inverse correlation between memory and sleep disturbances, and a moderate inverse correlation of memory and visuospatial function. We also observed other associations between subjective sleep quality and visuospatial function, sleep latency and the overall result of the SCOPA-COG, and between sleep duration and attention; all of these correlations were inverse and weak. This study suggests that mild cognitive deficits in the absence of dementia are associated with poor sleep quality.

Relação entre qualidade do sono e funções cognitivas em pacientes com doença de Parkinson

Here, we describe the clinical characteristics of patients with Parkinson's disease, as well as study the relationship between sleep quality and cognitive functions. This is a descriptive-analytical cross-sectional study in which we evaluate episodes of depression and anxiety, as well as the state of general health, disease progression, sleepiness, sleep quality and cognitive functions of 24 patients with Parkinson's disease without dementia. We found a moderate inverse correlation between memory and sleep disturbances, and a moderate inverse correlation of memory and visuospatial function. We also observed other associations between subjective sleep quality and visuospatial function, sleep latency and the overall result of the SCOPA-COG, and between sleep duration and attention; all of these correlations were inverse and weak.This study suggests that mild cognitive deficits in the absence of dementia are associated with poor sleep quality.

A systematic review and quantitative analysis of neurocognitive outcomes in children with four chronic illnesses

Concern has been expressed that infants and children exposed to uneventful surgery and anesthesia may incur neurological injury that becomes manifest in poor scholastic performance or future learning difficulties. A recent meta-analysis of seven clinical studies examined the relationship between learning or behavior difficulties and pediatric exposure to anesthesia/surgery and reported an odds ratio of 1.4; however, the level of association and causal factors remain unclear. The purpose of our study is to provide context to the pediatric anesthesia neurotoxicity question by reviewing the evidence linking four childhood illnesses with neurocognitive development. In the present review, we have sought to quantify the magnitude of the impact of chronic illness on neurocognitive development through a systematic review of publications that report the developmental trajectory of patients with four childhood diseases: cystic fibrosis (CF), hemophilia A, end-stage renal disease (ESRD) and end-stage liver disease (ESLD). Studies were identified by searching the electronic databases OVID MEDLINE and Pubmed and scanning reference lists of articles by two authors. Limits were applied to the English language and to humans. We used the following search terms: CF, hemophilia A, ESRD, ESLD in combination with academic performance, educational status, educational measurement, learning, achievement, developmental delay, learning disabilities, intellectual disabilities, behavioral disorders, intelligence quotient (IQ), cognition, school problems, absenteeism, school attendance, anxiety, learning regression, or developmental regression. The search strategy was reviewed independently by all four authors. Eligibility assessment was performed independently in an unblinded standardized manner by two authors who chose relevant articles from the overall search results by scanning the titles and abstracts of articles and from the references within citations. The full-text publications were reviewed by all four authors. All pertinent data related to the objectives were collected and independently reviewed by two authors. The data were summarized in the form reported in the studies. When possible, reported data were submitted to analysis with the Mantel-Haenszel method using a random effects model. Analyses were performed using the Review Manager computer program. In the studies retrieved, the main outcomes were measures of intellectual or cognitive characteristics, as exemplified by the Wechsler battery of tests. Reporting of measures of achievement (for example, GPA) was rare. Children with CF and hemophilia A did not appear disadvantaged by their disease as general intelligence levels were comparable with the general population norms. In children with ESRD, mean IQ reported during dialysis improved after transplantation. Although they improved relative to their pretransplantation cognitive functioning, children with ESLD who received transplants are approximately eight IQ points below the population norm. Overall, the results suggest that the burden of chronic childhood illness, by itself, does not impair cognitive development in children with hemophilia A and CF. Children with ESRD and ESLD, despite optimal management, show a mild cognitive deficit compared with the population norm. Given the impact of these four specific chronic illnesses on neurocognitive outcome in children and the improvement in IQ post-transplant in both ESRD and ESLD, the results suggest that the effect of an uncontrolled confounding illness on neurocognitive development is small.

O.21 Congenital Myasthenic Syndrome (CMS), autophagic myopathy, and cognitive dysfunction caused by mutations in DPAGT1

We recently identified two CMS patients with CNS involvement. Patient 1 is a16-year-old mentally retarded girl with severe generalized CMS since infancy. One of her siblings is also affected and has autistic features. Patient 2 is a 14-year-old girl with mild cognitive deficits and progressive limb-girdle CMS since infancy. Both respond poorly to anti-AChE therapy. Intercostal muscle specimens in both show small tubular aggregates in type 2 fibers, type1 fiber atrophy, and a vacuolar myopathy with autophagic features. Endplate studies reveal that quantal release, postsynaptic response to acetylcholine, and endplate AChR content are reduced to ∼50% of normal. Quantitative EM of 65 endplate regions shows hypoplastic endplates, very small nerve terminals, and poorly differentiated postsynaptic regions. Neither patient harbors mutations in currently recognized CMS disease genes but exome sequencing in each identified two heteroallelic mutations in DPAGT1 coding for dolichyl-phosphate N-acetylglucosamine phosphotransferase, an enzyme subserving protein N-glycosylation. Immunoblots of muscle extracts probed by two different antibodies demonstrates reduced to absent glycosylation of ∼70 kDa proteins in Patient 1 but not in Patient 2. We conclude that DPAGT1 mutations result in both pre- and postsynaptic structural and electrophysiologic abnormalities. We hypothesize that hypoglycosylation of synapse-specific proteins causes defects in motor as well as central synapses. We recently identified two CMS patients with CNS involvement. Patient 1 is a16-year-old mentally retarded girl with severe generalized CMS since infancy. One of her siblings is also affected and has autistic features. Patient 2 is a 14-year-old girl with mild cognitive deficits and progressive limb-girdle CMS since infancy. Both respond poorly to anti-AChE therapy. Intercostal muscle specimens in both show small tubular aggregates in type 2 fibers, type1 fiber atrophy, and a vacuolar myopathy with autophagic features. Endplate studies reveal that quantal release, postsynaptic response to acetylcholine, and endplate AChR content are reduced to ∼50% of normal. Quantitative EM of 65 endplate regions shows hypoplastic endplates, very small nerve terminals, and poorly differentiated postsynaptic regions. Neither patient harbors mutations in currently recognized CMS disease genes but exome sequencing in each identified two heteroallelic mutations in DPAGT1 coding for dolichyl-phosphate N-acetylglucosamine phosphotransferase, an enzyme subserving protein N-glycosylation. Immunoblots of muscle extracts probed by two different antibodies demonstrates reduced to absent glycosylation of ∼70 kDa proteins in Patient 1 but not in Patient 2. We conclude that DPAGT1 mutations result in both pre- and postsynaptic structural and electrophysiologic abnormalities. We hypothesize that hypoglycosylation of synapse-specific proteins causes defects in motor as well as central synapses.