The role of dark adaptation in understanding early AMD.

The main aim of the paper is to discuss current knowledge on how Age Related Macular Degeneration (AMD) affects Dark Adaptation (DA). The paper is divided into three parts. Firstly, we outline some of the molecular mechanisms that control DA.

The Light and the Dark of Early and Intermediate AMD: Cone- and Rod-Mediated Changes Are Linked to Fundus Photograph and FAF Abnormalities.

Purpose: The purpose of this paper is to describe the extent to which scotopic and photopic measures of visual function predict color fundus photograph (CFP) and fundus autofluorescence (FAF) changes in early and intermediate nonexudative AMD.

Methods: Sixty-nine observers were recruited: 56 AMD patients (mean age, 73 ± 12.98 years) and 13 controls (mean age, 67.

Slowed Dark Adaptation in Early AMD: Dual Stimulus Reveals Scotopic and Photopic Abnormalities.

Purpose: The recovery of visual sensitivity after a photobleach in early AMD is slowed in rods but cones also may be abnormal. The purpose of this article was to test different stimulus locations to investigate cone function and its relation to rod abnormalities.

Methods: Stimuli were presented at two locations, 3.

Chips in the sunshine: color constancy with real versus simulated Munsell chips under illuminants adjacent to the daylight locus.

Accurate color judgments rely on a powerful cognitive component. Here we compare the performance of color constancy under real and simulated conditions. Shifts in the uv color plane induced by illuminant A (2750 K) and illuminant S (>20,000  K) were measured using asymmetric color matching.

Slowed dark adaptation in older eyes; effect of location.

Purpose: The rate of rod sensitivity recovery following a photobleach is a basic measure of the integrity of the outer retina. Rods are selectively impaired in aging and many disorders of the retina, notably Age-Related Macular Degeneration (AMD). It is not known for certain whether the age-related deficit is a pan-retinal effect or if there are localised regions of impaired rod function.

Rapid method for assessing rod function using recovery of spatial contrast thresholds following a bleach.

Poor vision in low light is a common complaint of elderly people. This poorly understood phenomenon is likely to involve both receptoral and post receptoral mechanisms. We investigated the recovery of contrast thresholds for sine-wave gratings of low spatial frequencies and low mean luminance as a function of time in darkness after photo pigment bleaching.

Assessment of age changes and repeatability for computer-based rod dark adaptation.

Purpose: To characterize the rate of rod-mediated sensitivity decline with age using a PC-driven cathode ray tube (CRT) monitor. To provide data regarding the repeatability of the technique.

Methods: Dark adaptation was monitored for 30 min following a minimum 30 % pigment bleach, using a white 1° stimulus (modulated at 1 Hz), presented 11° below fixation on a CRT monitor.

A novel on-eye wettability analyzer for soft contact lenses.

Purpose: To develop novel methodology to assess two in vivo wettability parameters, contact angle and index of liquid spreading (ILS), for hydrogel contact lenses and to provide a comprehensive investigation of the measurement errors (repeatability) associated with these two parameters.

Methods: A Novel On-eye Wettability Analyzer (NOWA) was constructed which delivered a drop of 0.4% sodium hyaluronate mixed with sodium fluorescein directly on to a lens surface in vivo while a two-camera digital system recorded both the resultant contact angle and liquid spreading.

Association of anxiety and depression with microtubule-associated protein 2- and synaptopodin-immunolabeled dendrite and spine densities in hippocampal CA3 of older humans.

Context: Chronic psychological distress has deleterious effects on many of the body's physiological systems. In experimental animal models, chronic stress leads to neuroanatomic changes in the hippocampus, in particular a decrease in the length and branching of dendrites as well as a decrease in the number of dendritic spines.

Objectives: To examine whether analogous distress-related neuroanatomic changes occur in humans and whether such changes might also be related to cognitive dysfunction observed in older people who report greater psychological distress.

Dynamic contact angle analysis of silicone hydrogel contact lenses.

Contact angle measurements are used to infer the clinical wetting characteristics of contact lenses. Such characterization has become more commonplace since the introduction of silicone hydrogel contact lens materials, which have been associated with reduced in vivo wetting due to the inclusion of siloxane-containing components. Using consistent methodology and a single investigator, advancing and receding contact angles were measured for 11 commercially available silicone hydrogel contact lens types with a dynamic captive bubble technique employing customized, fully automated image analysis.

No longer "if," but "when": the coming abbreviated approval pathway for follow-on biologics.

Abbreviated approval of follow-on biologics involves answering complex scientific, legal, and policy questions. The Food and Drug Administration (FDA or the Agency) asserts that it lacks the statutory authority to approve follow-on versions of biologics licensed under Section 351 of the Public Health Service Act (PHSA). Despite persuasive arguments to the contrary the one hundred and tenth Congress entertained four legislative proposals to give FDA this authority, each markedly different.

Self-reported experiences of everyday discrimination are associated with elevated C-reactive protein levels in older African-American adults.

Self-reported experiences of "everyday" discrimination have been linked to indices of cardiovascular disease and overall mortality and findings have been particularly pronounced for African-American populations. However, the biological mechanisms underlying these associations remain unclear. C-reactive protein (CRP), a marker of inflammation, is a known correlate of cardiovascular and other health outcomes and has also been linked to several psychosocial processes.

The APOE epsilon4 allele is associated with incident mild cognitive impairment among community-dwelling older persons.

Background: The apolipoprotein E (APOE) epsilon4 allele is a well-known risk factor for the development of Alzheimer's disease, but little is known about the association of the epsilon4 allele with incident mild cognitive impairment (MCI).

Objective: Test the hypothesis that the epsilon4 allele is associated with an increased risk of developing MCI.

Methods: More than 600 older Catholic clergy members from the Religious Orders Study without any cognitive impairment at baseline underwent APOE genotyping and detailed annual clinical evaluations for up to 16 years of follow-up (mean: 10.

Apolipoprotein E e4 allele is associated with more rapid motor decline in older persons.

We tested the hypothesis that apolipoprotein E allele status predicts the rate of motor decline in the elderly. Eight hundred seventy-six older participants without dementia underwent baseline and annual motor testing for up to 10 years. In a generalized estimating equation controlling for age, sex, and education, motor function declined by about 0.

Fine-mapping the genetic basis of CRP regulation in African Americans: a Bayesian approach.

Basal levels of C-reactive protein (CRP) have been associated with disease, particularly future cardiovascular events. Twin studies estimate 50% CRP heritability, so the identification of genetic variants influencing CRP expression is important. Existing studies in populations of European ancestry have identified numerous cis-acting variants but leave significant ambiguity over the identity of the key functional polymorphisms.

Levels of estrogen receptors alpha and beta in frontal cortex of patients with Alzheimer's disease: relationship to Mini-Mental State Examination scores.

Estrogen exerts beneficial effects on the brain throughout life. Studies demonstrate that estrogen is neuroprotective and that reduced brain estrogen activity may influence the clinical course of Alzheimer's disease (AD). Changes in levels of estrogen receptors have been detected in postmortem brain tissue of AD patients.

Sex-dependent association of a common low-density lipoprotein receptor polymorphism with RNA splicing efficiency in the brain and Alzheimer's disease.

Since apoE allele status is the predominant Alzheimer's disease (AD) genetic risk factor, functional single nucleotide polymorphisms (SNPs) in brain apoE receptors represent excellent candidates for association with AD. Recently, we identified a SNP, rs688, as modulating the splicing efficiency of low-density lipoprotein receptor (LDLR) exon 12 in female human liver and in minigene-transfected HepG2 cells. Moreover, the rs688T minor allele was associated with significantly higher LDL and total cholesterol in women within the Framingham Offspring Study cohort.

Loneliness and risk of Alzheimer disease.

Context: Social isolation in old age has been associated with risk of developing dementia, but the risk associated with perceived isolation, or loneliness, is not well understood.

Objective: To test the hypothesis that loneliness is associated with increased risk of Alzheimer disease (AD).

Design: Longitudinal clinicopathologic cohort study with up to 4 years of annual in-home follow-up.

Decision rules guiding the clinical diagnosis of Alzheimer's disease in two community-based cohort studies compared to standard practice in a clinic-based cohort study.

We developed prediction rules to guide the clinical diagnosis of Alzheimer's disease (AD) in two community-based cohort studies (the Religious Orders Study and the Rush Memory and Aging Project). The rules were implemented without informant interviews, neuroimaging, blood work or routine case conferencing. Autopsies were performed at death and the pathologic diagnosis of AD made with a modified version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria.

Chronic psychological distress and risk of Alzheimer's disease in old age.

Clinical and pathological data from the Rush Memory and Aging Project were used to test the hypothesis that distress proneness is associated with increased risk of Alzheimer's disease (AD). More than 600 older persons without dementia completed a 6-item measure of neuroticism, a stable indicator of proneness to psychological distress. At annual intervals thereafter, they underwent uniform evaluations that included clinical classification of AD and administration of 18 cognitive tests.

Glial heme oxygenase-1 expression in Alzheimer disease and mild cognitive impairment.

We determined whether oxidative stress is an early event in the pathogenesis of sporadic Alzheimer disease (AD), and correlated oxidative stress with neuropsychological functions and neurofibrillary pathology in AD and mild cognitive impairment (MCI). Oxidative stress was measured as the percentage of astrocytes expressing heme oxygenase-1 (HO-1) in post mortem temporal cortex and hippocampus after dual HO-1/glial fibrillary acidic protein (GFAP) immunohistochemistry. Glial HO-1 expression in the MCI temporal cortex and hippocampus was significantly greater than in the non-demented group and did not differ from AD values.

High-resolution serum proteomic profiling of Alzheimer disease samples reveals disease-specific, carrier-protein-bound mass signatures.

Background: Researchers typically search for disease markers using a "targeted" approach in which a hypothesis about the disease mechanism is tested and experimental results either confirm or disprove the involvement of a particular gene or protein in the disease. Recently, there has been interest in developing disease diagnostics based on unbiased quantification of differences in global patterns of protein and peptide masses, typically in blood from individuals with and without disease. We combined a suite of methods and technologies, including novel sample preparation based on carrier-protein capture and biomarker enrichment, high-resolution mass spectrometry, a unique cohort of well-characterized persons with and without Alzheimer disease (AD), and powerful bioinformatic analysis, that add statistical and procedural robustness to biomarker discovery from blood.

Lack of genetic association of cholesteryl ester transfer protein polymorphisms with late onset Alzheimers disease.

Dysregulation of cholesterol homeostasis may be associated with the pathogenesis of coronary artery disease (CAD) and Alzheimers disease (AD). Recently, several single nucleotide polymorphisms (SNPs) in cholesteryl ester transfer protein (CETP) were associated with altered plasma CETP concentrations, cholesterol concentrations and CAD. Hence, these CETP SNPs represent excellent candidates for evaluating association with AD.

Genetic association of low density lipoprotein receptor and Alzheimer's disease.

The low density lipoprotein receptor (LDLR) is an attractive candidate gene for genetic association with Alzheimer's disease (AD) because: (i) the LDLR is an apolipoprotein E (apoE) receptor, alleles of which have been associated with AD, (ii) LDLR resides at chromosome 19p13.3 within a region linked to AD, and (iii) LDLR modulates the homeostasis of cholesterol, which itself appears associated with AD. Therefore, we evaluated whether LDLR haplotypes alter the odds of AD by performing an association study examining three LDLR single nucleotide polymorphisms (SNPs) in 118 AD patients and 133 non-AD subjects.