A Preliminary Study of Apolipoprotein E Genotype and Psychiatric Manifestations of Alzheimer's Disease

We evaluated the frequency of depression and psychosis in 46 patients with AD and 135 control subjects with the apolipoprotein (APO) E3/3 or E3/4 genotype. Patients with AD and the APOE3/4 genotype had a more than threefold increase in the signs of depression and psychosis when compared with either patients with the APOE3/3 genotype or to control subjects. Our preliminary study suggests that the phenotype of AD associated with the epsilon 4 allele is more likely to include psychiatric manifestations

Consistency of Clinical Diagnosis in a Community-Based Longitudinal Study of Dementia and Alzheimer's Disease

We evaluated the consistency of the diagnosis of dementia in a multicultural, longitudinal community-based study of cognitive impairment and dementia. We diagnosed dementia using a fixed neuropsychological paradigm; the diagnosis also required historical evidence of functional impairment. In a sample of 656 subjects with at least one annual follow-up examination, dementia was confirmed at 1 year in 89% of the 304 subjects initially demented, and in 90% of the 136 subjects with the initial diagnosis of probable Alzheimer's disease (AD). The 34 initially demented subjects who failed to meet criteria for dementia at follow-up included 13 with an initial diagnosis of probable AD. All 34 still had evidence of cognitive impairment; this group was more likely to have a history of pulmonary disease, multiple medication use, or chronic alcohol use than other demented patients. Consistency of dementia diagnosis did not vary according to educational attainment or ethnic background. The use of a neuropsychological paradigm such as ours in large longitudinal studies of dementia may minimize interobserver diagnostic variability or diagnostic drift over time while contributing the benefits of a comprehensive cognitive evaluation to the diagnostic process

Neurologic and Neuropsychological Manifestations of Human Immunodeficiency Virus Infection in Intravenous Drug Users without Acquired Immunodeficiency Syndrome. Relationship to Head Injury

We examined 99 human immunodeficiency virus (HIV)—negative and 122 HIV-positive intravenous drug users (IVDUs) without acquired immunodeficiency syndrome (AIDS) to determine whether HIV-positive IVDUs had more neurologic and neuropsychological impairment than their HIV-negative counterparts. Controlling for age, education, drug use, history of head injury, and interactions between head injury and HIV status and drug use, HIV-positive subjects had more extrapyramidal signs and frontal release signs. These findings persisted when asymptomatic HIV-positive subjects without systemic signs of infection and HIV-negative subjects were compared. Neurologic findings were more severe in those with more systemic illness. Among those reporting a history of head injury with loss of consciousness, neuropsychological performance was significantly worse in the HIV-positive subjects, and this increased with severity of illness. This was not true in the group without head injury, suggesting an interaction between history of head injury and the seropositive state. No relationship was noted between head injury and either drug use or HIV state. Therefore, subtle neurologic and neuropsychological abnormalities may precede clinical evidence of AIDS in IVDUs and may be more evident in those with head injury

Mental Health Problems among Children One-Year after Sichuan Earthquake in China: A Follow-up Study

Background: On May 12, 2008, a destructive earthquake registering 8.0 on the Richter scale struck Sichuan Province, southwest China. Beichuan County was the epicenter which was one of the areas nearly completely destroyed by the earthquake. In Beichuan, about 15000 people died and 3000 people were missing. Specially, the earthquake took 1587 students' and 214 teachers' lives from the elementary and middle schools there. The main purpose of the study was to provide a better understanding of mental health problems and associated risk factors among children after earthquake

Role of P-Glycoprotein and the Intestine in the Excretion of DPC 333 [(2R)-2-{(3R)-3-Amino-3-[4-(2-methylquinolin- 4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy- 4-methylpentanamide] in Rodents

ABSTRACT: The role of the intestine in the elimination of (2R)-2-{(3R)-3-amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}

Pharmacological inhibition of DKK1 promotes spine fusion in an ovariectomized rat model

Osteoporosis is common in patients undergoing spine surgery, and carries a considerable risk of adverse out-comes. New methods to positively influence bone regeneration and spine fusion under osteoporotic conditions would be impactful. Neutralizing anti-Dickkopf-1 (DKK1) antibodies has been used as a bone anabolic agent, and recently reported by our group to aid in stem cell-mediated appendicular bone regeneration. Here, a small molecule designed as a DKK1 inhibitor, WAY-262611, was used to induce posterolateral spine fusion in an ovariectomized rat model. In vitro, pharmacological inhibition of DKK1 enhanced osteogenesis and Wnt signaling activity among rat bone marrow-derived stem/stromal cells (BMSCs). In vivo, systemic treatment with WAY-262611 promoted both chondrogenesis and osteogenesis within the spinal fusion site, and ultimately led to significant improvements in lumbar fusion as assessed by XR, mu CT, histology and manual palpation assessments. No significant effect on osteoclast numbers or fusion site angiogenesis was detected, suggesting a primary direct effect on mesenchymal cells of the implantation site. Finally, evidence from human stem/stromal cells further demonstrated that pharmacologic inhibition of DKK1 promoted osteogenic differentiation in vitro. Taken together, our results suggest that targeting DKK1 promotes local bone formation and suggests potential clinical value for osteoporotic bone repair