A defect in a single transcription factor that regulates the balanced differentiation of GABAergic and glutamatergic neurons in the developing anterior brainstem, leads to several endophenotypes of ADHD
Amphetamine-induced dopamine release and amphetamine-induced place preference were normal in Tal1cko mice. Increased dopamine signaling failed to stimulate the locomotor activity of the Tal1cko mice, but instead alleviated their hyperactivity
Carola Salvi, Emanuela Bricolo, Steven L. Franconeri, John Kounios, Mark Beeman
Published: Dec 2015
Shutting down the visual input can occur on the brain level (increased alpha-frequency activity over the visual cortex found in previous studies) if participants are unable to look away or close their eyes.
Prior to solving creative problems people tend to look away from the problem and blink more.
Shadi Yaghi, Ayesha Sherzai, Markeith Pilot, Dean Sherzai, Mitchell S. V. Elkind
Published: Oct 2015
BACKGROUND: The CHADS2 score predicts stroke risk in patients with atrial fibrillation. Although strokes caused by atrial fibrillation carry the highest mortality when compared with other etiologies, it is not known whether the CHADS2 score predicts stroke-related mortality in patients with atrial fibrillation. We hypothesized that higher CHADS2 scores would be associated with higher stroke-related in-hospital mortality.METHODS: Data were obtained from administrative claims data from all emergency department encounters and hospitalizations at California's nonfederal acute care hospitals between 2008 and 2011. Patients with atrial fibrillation and an admission for acute stroke were identified using appropriate International Classification of Diseases, Ninth Revision (ICD-9), Clinical Modification codes. Age and ICD-9 codes for hypertension, diabetes, congestive heart failure, and prior stroke were used to calculate the CHADS2 score of patients with atrial fibrillation. The primary outcome was in-hospital stroke mortality and the primary predictor was CHADS2 score. A multivariate logistic regression model adjusted for sex and race was used to determine the odds ratio (OR) and 95% confidence interval (CI) for the association between CHADS2 and mortality.RESULTS: Between January 1, 2008, and December 31, 2011, 25,599 patients with atrial fibrillation were hospitalized with a stroke. The odds of in-hospital mortality was significantly higher with a CHADS2 score of 2 more versus less than 2 (OR, 1.15; 95% CI, 1.08-1.23); however, there was no dose-response association between the CHADS2 score and in-hospital mortality. Among the individual CHADS2 score items, factors associated with increased in-hospital mortality were congestive heart failure (OR, 1.61; 95% CI, 1.53-1.70), age 75 years or older (OR, 1.27; 95% CI, 1.19-1.35), and diabetes (OR, 1.24; 95% CI, 1.14-1.35).CONCLUSIONS: Unlike prior studies, our studies show that the prestroke CHADS2 score is of limited use in predicting in-hospital mortality in ischemic stroke hospitalizations in patients with atrial fibrillation.
BACKGROUND: Dementia with Lewy bodies (DLB) is characterized neuropathologically by brainstem and cortical Lewy bodies and Lewy neurites, neuronal loss in brainstem nuclei, and Alzheimer disease (AD) pathology. Previous studies have suggested that spongiform change in the entorhinal cortex may also be a pathologic feature; however, this change has not been well characterized.DESIGN/METHOD: An autopsy series of 40 subjects with DLB and 40 subjects with AD were matched on age, sex, and last Mini Mental State Examination before death. Using semistereological methods on representative sections through the transentorhinal and perirhinal cortices, quantitative counts and semiquantitative grading of vacuolization were performed by 1 rater (A.S.) blinded to subjects' diagnoses. In addition, electron microscopy of representative sections was performed.RESULTS: Vacuolization was 4- to 5-fold more prominent in the perirhinal, as compared with transentorhinal, cortex. Moderate to severe vacuolization was found in 57.5% of DLB, but only 7.5% of AD subjects. There were statistically significant differences between mean numbers of vacuoles in the perirhinal (DLB mean=27.91; AD mean=2.35; P<0.001) and transentorhinal (DLB mean=5.92; AD mean=0.5; P<0.001) cortices in DLB as well as AD cases. Electron microscopy revealed both axonal and dendritic pathology, with dilatation, vacuole formation, and abnormal membranous profiles.CONCLUSIONS: Although the exact mechanism remains to be elucidated, vacuolization seems to be more specific for DLB than AD, with disproportionate involvement of the perirhinal cortex.
Ayesha Z. Sherzai, Magda Shaheen, Jeffrey J. Yu, Konrad Talbot, Dean Sherzai
Published: Jan 2018
OBJECTIVES: To examine the relationship between homeostatic model of insulin resistance (HOMA-IR) and cognitive test performance among population≥60years in a national database.HYPOTHESIS: Higher insulin resistance is associated with lower cognitive test performance score in the population≥60years.PARTICIPANTS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 and 2001-2002.MEASUREMENTS: Cognitive test performance was measured by the Digit Symbol Substitution (DSS) exercise score. The main independent variable was the homeostasis model assessment of insulin resistance (HOMA-IR). We used bivariate analysis and generalized linear model adjusting for age, gender, race, education, body mass index, and systolic and diastolic blood pressures; total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride levels; and physical activity, diabetes mellitus, stroke, and congestive heart failure. STATA 14 was used to analyze the data taking into consideration the design, strata and weight.RESULTS: Of the 1028 participants, 44% were male and 85% were white. The mean age was 70.0±0.28 (SE) years. Their average HOMA-IR was 3.6±0.14 and they had a mean of 49.2±0.8 correct DSS score in the cognitive test. Adjusting for the confounding variables, HOMA-IR was associated with decline in DSS score (B=-0.30, 95% confidence interval=-0.54 and -0.05, p=0.01). The model explained 44% of the variability of the DSS score (R2=0.44). Significant predictors of decline in DSS score were age, gender, race, and education (p=0.01).CONCLUSION: Insulin resistance as measured by HOMA-IR was independently associated with lower cognitive test performance score among elderly participants aged ≥60years. Longitudinal studies are needed to test the mechanism and the causal relationship.
Introduction: Despite advances in imaging retinal amyloidosis, a quantitative and topographical investigation of retinal amyloid beta burden in patients with cognitive decline has never been reported.Methods: We used the specific amyloid-binding fluorophore curcumin and laser ophthalmoscopy to assess retinal amyloid imaging (RAI) in 34 patients with cognitive decline. We automatically quantified retinal amyloid count (RAC) and area in the superotemporal retinal sub-regions and performed correlation analyses with cognitive and brain volumetric parameters.Results: RAC significantly and inversely correlated with hippocampal volume (HV; r = -0.39, P = .04). The proximal mid-periphery (PMP) RAC and RA areas were significantly greater in patients with Montreal Cognitive Assessment (MOCA) score < 26 (P = .01; Cohen d = 0.83 and 0.81, respectively). PMP showed significantly more RAC and area in subjects with amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared to cognitively normal (P = .04; Cohen d = 0.83).Conclusion: Quantitative RAI is a feasible technique and PMP RAC may predict HV. Future larger studies should determine RAI's potential as a biomarker of early AD.
OBJECTIVE: To evaluate the safety, tolerability, and amyloid beta (Abeta) response to the gamma-secretase inhibitor LY450139 in Alzheimer disease.DESIGN: Multicenter, randomized, double-blind, dose-escalation, placebo-controlled trial.SETTING: Community-based clinical research centers. Patients Fifty-one individuals with mild to moderate Alzheimer disease were randomized to receive placebo (n=15) or LY450139 (100 mg [n=22] or 140 mg [n=14]), with 43 completing the treatment phase. Intervention The LY450139 groups received 60 mg/d for 2 weeks, then 100 mg/d for 6 weeks, and then either 100 or 140 mg/d for 6 additional weeks.MAIN OUTCOME MEASURES: Primary outcome measures were adverse events, plasma and cerebrospinal fluid Abeta levels, vital signs, electrocardiographic data, and laboratory safety test results. Secondary outcome measures included the Alzheimer's Disease Assessment Scale cognitive subscale and the Alzheimer's Disease Cooperative Study Activities of Daily Living Scale.RESULTS: Group differences were seen in skin and subcutaneous tissue concerns (P=.05), including 3 possible drug rashes and 3 reports of hair color change in the treatment groups. There were 3 adverse event-related discontinuations, including 1 transient bowel obstruction. The plasma Abeta(40) concentration was reduced by 58.2% for the 100-mg group and 64.6% for the 140-mg group (P<.001). No significant reduction was seen in cerebrospinal fluid Abeta levels. No group differences were seen in cognitive or functional measures.CONCLUSIONS: LY450139 was generally well tolerated at doses of up to 140 mg/d for 14 weeks, with several findings indicating the need for close clinical monitoring in future studies. Decreases in plasma Abeta concentrations were consistent with inhibition of gamma-secretase. Trial Registration clinicaltrials.gov Identifier: NCT00244322.