Verbal memory is linked to average oxygen saturation during sleep, not the apnea-hypopnea index nor novel hypoxic load variables.

INTRODUCTION: The apnea-hypopnea index (AHI) is the current diagnostic parameter for diagnosing and estimating the severity of obstructive sleep apnea (OSA). It is, however, poorly associated with the main clinical symptom of OSA, excessive daytime sleepiness, and with the often-seen cognitive decline among OSA patients. To better evaluate OSA severity, novel hypoxic load parameters have been introduced that consider the duration and depth of oxygen saturation drops associated with apneas or hypopneas. The aim of this paper was to compare novel hypoxic load parameters and traditional OSA parameters to verbal memory and executive function in OSA patients. METHOD: A total of 207 adults completed a one-night polysomnography at sleep laboratory and two neuropsychological assessments, the Rey Auditory Verbal Learning Test and Stroop test. RESULTS: Simple linear regression analyses were used to evaluate independent associations between each OSA parameter and cognitive performance. Associations were found between immediate recall and arousal index, hypoxia <90 %, average SpO2 during sleep, and DesSev100+RevSev100. Total recall was associated with all OSA parameters, and no associations were found with the Stroop test. Subsequently, sex, age, and education were included as covariates in multiple linear regression analyses for each OSA parameter and cognitive performance. The main findings of the study were that average SpO2 during sleep was a significant predictor of total recall (p < .007, ß = -.188) with the regression model explaining 21.2 % of performance variation. Average SpO2 during sleep was also a significant predictor of immediate recall (p < .022, ß = -.171) with the regression model explaining 11.4 % of performance variation. Neither traditional OSA parameters nor novel hypoxic load parameters predicted cognitive performance after adjustment for sex, age, and education. CONCLUSION: The findings validate that the AHI is not an effective indicator of cognitive performance in OSA and suggest that average oxygen saturation during sleep may be the strongest PSG predictor of cognitive decline seen in OSA. The results also underline the importance of considering age when choosing neurocognitive tests, the importance of including more than one test for each cognitive domain as most tests are not pure measures of a single cognitive factor, and the importance of including tests that cover all cognitive domains as OSA is likely to have diffuse cognitive effects.

CDKN2A mutations and melanoma risk in the Icelandic population.

BACKGROUND: Germline CDKN2A mutations have been observed in 20-40% of high risk, melanoma prone families; however, little is known about their prevalence in population based series of melanoma cases and controls. METHODS: We resequenced the CDKN2A gene, including the p14ARF variant and promoter regions, in approximately 703 registry ascertained melanoma cases and 691 population based controls from Iceland, a country in which the incidence of melanoma has increased rapidly. RESULTS: We identified a novel germline variant, G89D, that was strongly associated with increased melanoma risk and appeared to be an Icelandic founder mutation. The G89D variant was present in about 2% of Icelandic invasive cutaneous malignant melanoma cases. Relatives of affected G89D carriers were at significantly increased risk of melanoma, head and neck cancers, and pancreatic carcinoma compared to relatives of other melanoma patients. Nineteen other germline variants were identified, but none conferred an unequivocal risk of melanoma. CONCLUSIONS: This population based study of Icelandic melanoma cases and controls showed a frequency of disease related CDKN2A mutant alleles ranging from 0.7% to 1.0%, thus expanding our knowledge about the frequency of CDKN2A mutations in different populations. In contrast to North America and Australia where a broad spectrum of mutations was observed at a similar frequency, in Iceland, functional CDKN2A mutations consist of only one or two different variants. Additional genetic and/or environmental factors are likely critical for explaining the high incidence rates for melanoma in Iceland. This study adds to the geographic regions for which population based estimates of CDKN2A mutation frequencies are available.

Necrolytic migratory erythema: a report of three cases.

Necrolytic migratory erythema (NME) is a cutaneous reaction pattern with specific histopathologic features that is typically associated with a functioning pancreatic islet cell neoplasm such as a glucagonoma. Three examples of NME, each associated with a different cause, are presented: glucagonoma, pancreatic insufficiency, and gluten-sensitive enteropathy. All three patients were successfully treated by surgical resection of the pancreatic tumor, total parenteral nutrition and pancreatic enzyme replacement, or a strict gluten-free diet, respectively. All remain free of skin disease more than 2 years later. Any patient with NME should be evaluated for glucagonoma and small bowel disease that may be associated with malabsorption and malnutrition.