No association of dynamin binding protein (DNMBP) gene SNPs and Alzheimer's disease.

A recent scan of single nucleotide polymorphisms (SNPs) on chromosome 10q found significant association of six correlated SNPs with late-onset Alzheimer's disease (AD) among Japanese. We examined the SNP with the highest statistical significance (rs3740058) in a large Caucasian American case-control cohort and the remaining five SNPs in a smaller subset of cases and controls. We observed no association of statistical significance in either the total sample or the APOE*4 non-carriers for any of the SNPs.

Association of increased cortical soluble abeta42 levels with diffuse plaques after severe brain injury in humans.

Background: Traumatic brain injury (TBI) is an environmental risk factor for developing Alzheimer disease. This may be due, in part, to changes associated with beta-amyloid (Abeta) plaque formation, which can occur within hours after injury, regardless of the patient's age. In addition to being precursors of toxic fibrils that deposit into plaques, soluble (nonfibrillar) Abeta peptides are posited to disrupt synaptic function and are associated with cognitive decline in Alzheimer disease.

Molecular imaging with Pittsburgh Compound B confirmed at autopsy: a case report.

Objective: To determine the correspondence between uptake of Pittsburgh Compound B (PiB) in life and measures of beta-amyloid (Abeta) in postmortem tissue analysis. Patient A 76-year-old man with a clinical diagnosis of dementia with Lewy bodies underwent fluorodeoxyglucose (18)F and PiB positron emission tomographic brain scans. Imaging revealed marked region specific binding of PiB and abnormal fluorodeoxyglucose uptake.

Incidence of dementia in mild cognitive impairment in the cardiovascular health study cognition study.

Objectives: To examine the incidence of dementia in subjects with mild cognitive impairment (MCI) in the Cardiovascular Health Study Cognition Study.

Design: Prospective epidemiological study.

Setting: The Cardiovascular Health Study Cognition Study of Pittsburgh, Pa, was conducted from 2002 through 2003 to determine the incidence of dementia in participants classified as having MCI in 1998 and 1999.

Making sense of mild cognitive impairment: a qualitative exploration of the patient's experience.

Purpose: The proposed dementia precursor state of mild cognitive impairment is emerging as a primary target of aging research. Yet, little is known about the subjective experience of living with a diagnosis of mild cognitive impairment. This study examines, from the patient's perspective, the experience of living with and making sense of the diagnosis.

Chronic traumatic encephalopathy in a national football league player: part II.

Objective: We present the second reported case of autopsy-confirmed chronic traumatic encephalopathy in a retired professional football player, with neuropathological features that differ from those of the first reported case. These differing pathological features underscore the need for further empirical elucidation of the pathoetiology and pathological cascades of long-term neurodegenerative sequelae of professional football.

Methods: A psychological autopsy was performed with the next-of-kin and wife.

Primary prevention trials in Alzheimer disease.

Many new treatments under development for Alzheimer disease (AD) will be disease-modifying rather than symptomatic. Clinical evaluation of these treatments will require primary and secondary prevention trials. We describe some of the methodologic challenges in designing primary prevention trials for AD and illustrate these with examples from the ADAPT (Alzheimer Disease Anti-Inflammatory Prevention Trial) Study and GEM (Ginkgo in Evaluation of Memory) Study.

Maintaining adherence and retention in dementia prevention trials.

Incidence and prevalence of Alzheimer Disease (AD) will rise in a accelerating fashion through the middle of the 21st century. Increased understanding of the pathological cascades in AD, and the knowledge that the initial brain changes begin years prior to clinical manifestations, have led to initiation of trials to prevent AD. With many of the designs being used or contemplated, prevention trials will involve repeated cognitive and functional assessments over years, require cooperation and collaboration of both the subject and a partner or proxy, and represent a substantial time and resource investment by the research team.

Use of herbal medicine and other dietary supplements in community-dwelling older people: Baseline data from the ginkgo evaluation of memory study.

Objectives: To analyze baseline data from the Ginkgo Evaluation of Memory (GEM) study, in which information was collected on the use of all dietary supplements.

Design: Cross-sectional regression analysis.

Setting: GEM study sites in California, Maryland, North Carolina, and Pennsylvania.

X-34 labeling of abnormal protein aggregates during the progression of Alzheimer's disease.

Postmortem pathological diagnosis and basic research investigations of neurodegenerative disorders rely on histochemical staining procedures developed specifically to visualize abnormal protein conformation. In Alzheimer's disease (AD), two major pathological hallmarks are required to confirm the clinical diagnosis. Both consist of abnormally aggregated proteins that share the structural and histological properties common to all amyloid deposits.

Lack of association of two chromosome 10q24 SNPs with Alzheimer's disease.

Several groups have reported evidence of linkage on chromosome 10 to late-onset Alzheimer's disease (LOAD). In a recent scan of single nucleotide polymorphisms (SNPs) on chromosome 10, significant associations between the rs498055 and rs4417206 SNPs and risk of LOAD were observed. We examined the association of these two SNPs with LOAD risk in a large Caucasian American cohort comprising about 2000 cases and controls.

Association of tagSNPs in the urokinase-plasminogen activator (PLAU) gene with Alzheimer's disease and associated quantitative traits.

The gene coding for urokinase-plasminogen activator (PLAU) is a strong biological and positional candidate gene for Alzheimer's disease (AD). Previously some studies have examined the role of common variation in the PLAU gene with AD risk but the results have been inconsistent and this inconsistency could have been due to the use of relatively small sample sizes. In this study we evaluated the distribution of four tagSNPs (rs2227562 in intron 5, rs2227564 in exon 6, rs2227571 in intron 9, and rs4065 in 3'UTR) in the PLAU gene in a large case-control study consisting of up to 1,000 AD patients and 697 white control subjects.

Recruitment of the elderly into a pharmacologic prevention trial: the Ginkgo Evaluation of Memory Study experience.

The difficulty involved in recruiting healthy older adults into clinical trials, especially those involving pharmacologic agents, is an important issue in research. The Ginkgo Evaluation of Memory (GEM) Study, a double-blind, placebo-controlled randomized clinical trial evaluating Ginkgo biloba to prevent dementia, successfully recruited 3072 participants age 75 years and older at four U.S.

Lack of association of 5 SNPs in the vicinity of the insulin-degrading enzyme (IDE) gene with late-onset Alzheimer's disease.

Insulin-degrading enzyme (IDE) is a strong biological and positional candidate gene for Alzheimer's disease (AD). Previously some studies have examined the role of common variation in the IDE gene with AD risk but the results have been inconsistent. In this study we examined the role of 5 SNPs that define a linkage disequilibrium (LD) block spanning 276kb around IDE.

Evaluation of voxel-based methods for the statistical analysis of PIB PET amyloid imaging studies in Alzheimer's disease.

Deposition of amyloid plaques is believed to be a central event in the development of Alzheimer's disease (AD). The present study was undertaken to evaluate statistical methods for the assessment of group differences in retention of an amyloid imaging agent, PIB, throughout the brain and to compare these results to FDG studies of glucose metabolism performed in the same subjects on the same day. PET studies were performed in 10 mild to moderate AD and 11 control subjects.

The relation of white matter hyperintensities to cognitive performance in the normal old: education matters.

This study examined whether the severity of cerebral white matter abnormalities (evident on MR images as white matter hyperintensities (WMH)) was related to the cognitive performance of 141 high-functioning older adults. The elderly showed the typical age decrement on measures of processing speed, working memory, and inhibition; however WMH severity was significantly related only to processing speed. The strength of this relationship was, however, influenced by the educational level of the participants, such that processing speed was more associated with WMH severity in less-educated than in well-educated participants.

Perspectives on assessing benefits and risks in clinical trials for Alzheimer's disease.

Balancing benefits and risks in the development of treatments for Alzheimer's disease is challenging given the nature of the disease but critically important to ensure effective treatments are available. Drawing on a diverse panel of scientists, regulators, caregivers, patients and advocates convened by the Alzheimer's Association, insights are offered into benefit/risk assessment, decision-making, regulatory and societal factors affecting clinical trials on AD. Several policy solutions are offered to improve the drug testing, review and approval process.

Gender-specific association of ATP-binding cassette transporter 1 (ABCA1) polymorphisms with the risk of late-onset Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder caused by a complex interaction of genetic and environmental factors. Increasing evidence highlights a potential role for cholesterol in the pathophysiology of AD. The ABCA1 gene, located in close vicinity to the 9q linkage peaks identified by genome-wide AD linkage studies, plays an important role in cellular cholesterol efflux, and is likely a good candidate gene.

The Ginkgo Evaluation of Memory (GEM) study: design and baseline data of a randomized trial of Ginkgo biloba extract in prevention of dementia.

The epidemic of late life dementia, prominence of use of alternative medications and supplements, and initiation of efforts to determine how to prevent dementia have led to efforts to conduct studies aimed at prevention of dementia. The GEM (Ginkgo Evaluation of Memory) study was initially designed as a 5-year, randomized double-blind, placebo-controlled trial of Ginkgo biloba, administered in a dose of 120 mg twice per day as EGb761, in the prevention of dementia (and especially Alzheimer's disease) in normal elderly or those with mild cognitive impairment. The study anticipates 8.

Prediction of psychosis onset in Alzheimer disease: The role of cognitive impairment, depressive symptoms, and further evidence for psychosis subtypes.

Background: Psychotic symptoms in Alzheimer disease (AD+P) identify a heritable phenotype associated with more rapid cognitive decline. The authors have proposed that AD+P is itself a composite of a misidentification and a paranoid subtype with increased cognitive impairment restricted to the misidentification type. Most prior studies of the clinical correlates of AD+P have been limited, however, by the inclusion of prevalent cases.

Galanin fiber hypertrophy within the cholinergic nucleus basalis during the progression of Alzheimer's disease.

Galanin (GAL)-containing fibers enlarge and hyperinnervate remaining cholinergic basal forebrain (CBF) neurons within the anterior nucleus basalis (NB) in late-stage Alzheimer's disease (AD). Whether GAL hypertrophy occurs in the CBF in the prodromal or early stages of AD remains unknown. The present study used GAL immunohistochemistry and an unbiased semiquantitative scoring method to evaluate GAL innervation in the anterior NB of subjects clinically diagnosed as having no cognitive impairment, mild cognitive impairment or early-stage (mild/moderate) AD.

A randomized, double-blind, placebo-controlled trial of two doses of Ginkgo biloba extract in dementia of the Alzheimer's type.

Context: Previous studies of Ginkgo biloba extract (GbE) in patients with various forms of cognitive impairment or dementia have shown promising results.

Objective: To determine the clinical efficacy of GbE in mild to moderate dementia of the Alzheimer type.

Design: Randomized, placebo-controlled, double-blind, parallel-group, multicenter trial.

Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans.

Objectives: Amyloid-beta(42) (Abeta(42)) appears central to Alzheimer's disease (AD) pathogenesis and is a major component of amyloid plaques. Mean cerebrospinal fluid (CSF) Abeta(42) is decreased in dementia of the Alzheimer's type. This decrease may reflect plaques acting as an Abeta(42) "sink," hindering transport of soluble Abeta(42) between brain and CSF.