The effects of poor sleep quality on cognitive function of patients with cirrhosis.

OBJECTIVES: This study was conducted to assess the ill-defined relationship between sleep quality and multiple, specific domains of cognitive function in patients with cirrhosis. METHODS: A comprehensive battery of neuropsychological tests (divided into six neurocognitive domains) and a standardized, validated measure of sleep quality (Pittsburgh Sleep Quality Index [PSQI]) were administered to patients with cirrhosis and without evidence of overt hepatic encephalopathy, recruited from liver transplant and advanced liver disease clinics (n = 34). An inflammatory bowel disease (IBD) control group (n = 23) was similarly recruited and evaluated to control for the secondary effect of a chronic illness on cognition. PSQI global and component scores were used to predict cognitive function in each neurocognitive domain, using linear regression. RESULTS: Global PSQI scores were significantly higher (indicating poorer sleep quality) in the cirrhosis group (median [range] = 10 [1-19]) than in IBD controls = 5 (1-14); p = 0.002). After controlling for age and education, short duration of sleep was associated with impaired memory for patients with cirrhosis; the use of soporific agents was associated with poor visual-perceptual function in patients with IBD. CONCLUSIONS: Poor sleep was associated with worsening of the already impaired cognitive function of patients with cirrhosis.

The cognitive profile of depressed patients with cirrhosis.

OBJECTIVE: To determine whether patients with cirrhosis and depressive symptoms have a different neuropsychological cognitive profile from patients with cirrhosis without depressive symptoms in order to show that cirrhosis may not be the only cause for cognitive decline in patients with cirrhosis. METHOD: Adult outpatients with a diagnosis of cirrhosis based on histologic findings and clinical characteristics, who did not have clinically overt hepatic encephalopathy and who were being treated in the advanced liver disease and liver transplant clinics, were recruited for the study from May 2003 to May 2006. Patients underwent neuropsychological testing and evaluation for depression using the Beck Depression Inventory-II (BDI-II). Age-adjusted standard neuropsychological domain scores were compared between depressed (BDI-II score ≥ 14) and nondepressed (BDI-II score < 14) patients. RESULTS: Seventy-five subjects were included in the study. The 23 patients with depression were similar to the 52 nondepressed patients in level of education, age, and race; the laboratory parameters of international normalized ratio, bilirubin, creatinine, and albumin concentration; and Model for End-Stage Liver Disease scores. There was a higher percentage of women in the depressed group than in the nondepressed group, with a trend toward significance (52% vs 29%; P = .07). No etiology of liver disease was associated with depression. In linear regression analyses, decreases in cognitive function were associated with higher BDI-II scores for the domains of working memory (P = .026), with a trend toward significance for visual-perception (P = .056). Approximately 7% of the variability in working memory score was predicted using the BDI score. CONCLUSIONS: Depressive symptoms are associated with worsened cognitive function in cirrhosis.

Development of a three-factor neuropsychological approach for detecting minimal hepatic encephalopathy.

BACKGROUND: Minimal hepatic encephalopathy (HE) has profoundly negative effects on daily functioning ad quality of life. However, standard psychometric procedures have not been widely incorporated into efforts to develop a neuropsychological battery for this condition. AIMS: To establish the construct and diagnostic validity of a neuropsychological approach for the recognition of minimal HE in patients with cirrhosis. METHODS: A comprehensive battery of neuropsychological tests was administered to cirrhotic patients with at most grade 1 HE, recruited from the liver transplant and advanced liver disease clinics. An inflammatory bowel disease comparison group was similarly evaluated, thus controlling for the secondary effects of chronic illness on cognition. Testing results for the cirrhosis group were subjected to principal component analysis to establish the relevant cognitive constructs and associated measures. Factor analysis was applied to the neuropsychological battery of 20 tests to determine the cognitive factors to be used. Age-adjusted standardized neuropsychological factor scores were then compared for the two groups. RESULTS: Factor analysis revealed that our battery of 20 tests was measuring three cognitive factors. Based on the pattern of factor loadings, we labeled these important cognitive factors: global cognitive function; psychomotor speed; and learning and memory. Logistic regression revealed that only impaired psychomotor speed distinguished cirrhotics with no more than grade 1 HE from medically ill controls. CONCLUSIONS: The cirrhosis group was characterized by a pattern of preserved global cognitive functioning, mild memory impairment, and moderate psychomotor speed impairment. DISCUSSION: This distinctive pattern of focal psychomotor speed deficits is suggestive of subcortical pathway involvement in minimal HE.

The relationship between caffeine and blood pressure in preadolescent African American girls.

BACKGROUND: While high caffeine consumption has been shown to be associated with increased blood pressure in controlled experiments, the relationship between caffeine consumption and blood pressure in preadolescent (ages 6-11 years) and adolescent (ages 12-19 years) children has not been well studied. The primary objective of this study was to assess the cross-sectional relationship between caffeine intake and blood pressure in 8- to 10-year-old African American girls who eat an unrestricted diet. METHODS: Demographic, 24-hour dietary recall, and blood pressure data collected at baseline from 303 African American girls aged 8-10 years in the Girls health Enrichment Multisite Studies (GEMS) cohort were analyzed by using linear and multiple regression models. RESULTS: Dietary caffeine intake was not associated with either systolic or diastolic blood pressure (P=.33 and P=.36, respectively). However, consistent with the literature, height and body mass index were each positively and independently associated with systolic blood pressure (both P<.0001). Height and amount of sodium intake were positively associated with diastolic blood pressure (P=.01 and P=.02, respectively). CONCLUSIONS: Dietary caffeine intake in low amounts is not associated with elevated blood pressure in 8- to 10-year-old African American girls who eat an unrestricted diet.

Diagnostic ionizing radiation exposure in a population-based cohort of patients with inflammatory bowel disease.

OBJECTIVE: For diagnosis, assessing disease activity, complications and extraintestinal manifestations, and monitoring response to therapy, patients with inflammatory bowel disease undergo many radiological studies employing ionizing radiation. However, the extent of radiation exposure in these patients is unknown. METHODS: A population-based inception cohort of 215 patients with inflammatory bowel disease from Olmsted County, Minnesota, diagnosed between 1990 and 2001, was identified. The total effective dose of diagnostic ionizing radiation was estimated for each patient. Linear regression was used to assess the median total effective dose since symptom onset. RESULTS: The number of patients with Crohn's disease and ulcerative colitis was 103 and 112, with a mean age at diagnosis of 38.6 and 39.4 yr, respectively. Mean follow-up was 8.9 yr for Crohn's disease and 9.0 yr for ulcerative colitis. Median total effective dose for Crohn's disease was 26.6 millisieverts (mSv) (range, 0-279) versus 10.5 mSv (range, 0-251) for ulcerative colitis (P < 0.001). Computed tomography accounted for 51% and 40% of total effective dose, respectively. Patients with Crohn's disease had 2.46 times higher total effective dose than ulcerative colitis patients (P= 0.001), adjusting for duration of disease. CONCLUSIONS: Annualizing our data, the radiation exposure in the inflammatory bowel disease population was equivalent to the average annual background radiation dose from naturally occurring sources in the U.S. (3.0 mSv). However, a subset of patients had substantially higher doses. The development of imaging management guidelines to minimize radiation dose, dose-reduction techniques in computed tomography, and faster, more robust magnetic resonance techniques are warranted.

MYH Y165C and G382D mutations in hepatocellular carcinoma and cholangiocarcinoma patients.

PURPOSE: Production of reactive oxygen species (ROS) during chronic inflammation has been implicated in the progression of liver diseases and carcinogenesis. Subjects with inflammatory liver disease and one non-functional allele of the base excision repair gene, MYH, may be more susceptible to progression to cancer due to MYH haploinsufficiency in repairing oxidative damage caused by ROS. Here, we investigated the association of two common germline MYH mutations in patients with hepatocellular carcinoma (HCC) and cholangiocarcinoma. METHODS: DNA from patients with HCC (n=48) or cholangiocarcinoma (n=84) compared to non-cancerous controls (n=308) were genotyped for the Y165C and G382D mutations in MYH. RESULTS: There was no significant difference in MYH mutation carrier status between patients with HCC (1/48), cholangiocarcinoma (3/84), and non-cancerous controls (4/308). CONCLUSIONS: Patients with HCC or cholangiocarcinoma do not have an increased incidence of monoallelic MYH mutations pre-disposing them to disease.