The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Changes in Hemoglobin Levels in Patients with Hiatal Hernia and Anemia Demonstrates a Durable Resolution When Surgery Utilized

Objective: To describe the patterns of care of patients presenting with anemia and a hiatal hernia and to document hemoglobin levels at each stage of care. Background data: Anemia may be associated with hiatal hernia. Current medical guidelines recommend iron supplements and proton pump inhibitors (PPIs) as initial steps, but not surgical repair is not routinely recommended despite evidence of cure. Methods: Retrospective review of patients with anemia and hiatal hernia who underwent surgical repair. Hemoglobin, PPI use, and symptoms were assessed at diagnosis, preoperatively, and postoperatively. Results: We identified 116 predominantly female patients with type 3 hernias with 52.6% (n = 61) having Cameron ulcers. At baseline, 24.1% (n = 28) were transfused, 52% (n = 60) started on iron supplements, 72% (n = 84) on PPIs, and 10% (n = 12) on H2-blockers. Referral to surgery occurred 454 days (IQR: 129-1332) after anemia diagnosis. The mean Hgb at diagnosis was 9.79 (range: 4.8-12.7) in females and 10.9 (range: 7.7-12.9) in males, increasing to 11.1 (range: 5.4-15) and 11.4 (range: 5.8-15.9) with medical management. After laparoscopic repair, it increased to 12.3 (range: 8.1-14.8) and 13.4 (range: 8.9-16.8) at short term follow up. This was sustained at 12.8 (range: 8.8-17.7) and 14.2 (8.1-17) long term. Medical management normalized Hgb in 36% (n = 40/111); whereas surgery normalized Hgb in 62% (n = 64/104) short term and 74% (n = 69/93) long term. Cameron’s ulcers were associated with normalization in 85% (38/45) but only 62% (n = 21/34) when not present. Conclusion: Anemia associated with a hiatal hernia improves with medication, but the addition of surgery normalizes Hgb, appears durable, allows cessation of medication, and improves quality of life

Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson's disease

This study was undertaken to determine the prevalence and correlates of cognitive impairment (CI) and neuropsychiatric symptoms (NPS) in early, untreated patients with Parkinson's disease (PD). Background: Both CI and NPS are common in PD and impact disease course and quality of life. However, limited knowledge is available about cognitive abilities and NPS. Methods: Parkinson's Progression Markers Initiative (PPMI) is a multi-site study of early, untreated PD patients and healthy controls (HCs), the latter with normal cognition. At baseline, participants were assessed with a neuropsychological battery and for symptoms of depression, anxiety, impulse control disorders (ICDs), psychosis, and apathy. Results: Baseline data of 423 PD patients and 196 HCs yielded no between-group differences in demographic characteristics. Twenty-two percent of PD patients met the PD-recommended screening cutoff for CI on the Montral Cognitive Assessment (MoCA), but only 9% met detailed neuropsychological testing criteria for mild cognitive impairment (MCI)-level impairment. The PD patients were more depressed than HCs (P<0.001), with twice as many (14% vs. 7%) meeting criteria for clinically significant depressive symptoms. The PD patients also experienced more anxiety (P<0.001) and apathy (P<0.001) than HCs. Psychosis was uncommon in PD (3%), and no between-group difference was seen in ICD symptoms (P=0.51). Conclusions: Approximately 10% of PD patients in the early, untreated disease state met traditional criteria of CI, which is a lower frequency compared with previous studies. Multiple dopaminergic-dependent NPS are also more common in these patients compared with the general population, but others associated with dopamine replacement therapy are not or are rare. Future analyses of this cohort will examine biological predictors and the course of CI and NPS

Correlates of excessive daytime sleepiness in de novo Parkinson's disease: A case control study

Objective: This study was undertaken to determine the frequency and correlates of excessive daytime sleepiness in de novo, untreated Parkinson's disease (PD) patients compared with the matched healthy controls. Methods: Data were obtained from the Parkinson's Progression Markers Initiative, an international study of de novo, untreated PD patients and healthy controls. At baseline, participants were assessed with a wide range of motor and nonmotor scales, including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Excessive daytime sleepiness was assessed based on the Epworth Sleepiness scale (ESS), with a cutoff of 10. Results: Four hundred twenty-three PD subjects and 196 healthy controls were recruited into the study. Mean ESS (min, max) score was 5.8 (0, 20) for the PD subjects and 5.6 (0, 19) for healthy controls (P=0.54). Sixty-six (15.6%) PD subjects and 24 (12%) healthy controls had ESS of at least 10 (P=0.28). No difference was seen in demographic characteristics, age of onset, disease duration, PD subtype, cognitive status, or utilization of sedatives between the PD sleepiness-positive versus the negative group. The sleepiness-positive group had higher MDS-UPDRS Part I and II but not III scores, and higher depression and autonomic dysfunction scores. Sleepiness was associated with a marginal reduction of A-beta (P=0.05) but not alpha-synuclein spinal fluid levels in PD. Conclusions: This largest case control study demonstrates no difference in prevalence of excessive sleepiness in subjects with de novo untreated PD compared with healthy controls. The only clinical correlates of sleepiness were mood and autonomic dysfunction. Ongoing longitudinal analyses will be essential to further examine clinical and biological correlates of sleepiness in PD and specifically the role of dopaminergic therapy