26 research outputs found
Retinal thickness as a potential biomarker in patients with amyloid-proven early- and late-onset Alzheimer's disease
Introduction: Retinal thickness measured with optical coherence tomography has been proposed as
a noninvasive biomarker for Alzheimer’s disease (AD). We therefore measured retinal thickness in
well-characterized AD and control participants, considering ophthalmological confounders.
Methods: We included 57 amyloid-proven AD cases and 85 cognitively normal, amyloid-negative
controls. All subjects underwent retinal thickness measurements with spectral domain optical
coherence tomography and an ophthalmological assessment to exclude ocular disease.
Results: Retinal thickness did not discriminate cases from controls, including stratified analyses for
early- versus late-onset AD. We found significant associations between macular thickness and global
cortical atrophy [b 20.358; P 5 .01] and parietal cortical atrophy on magnetic resonance imaging
[b 20.371; P , .01] in AD cases.
Discussion: In this study, representing the largest optical coherence tomography cohort with
amyloid-proven AD cases, we show that retinal thickness does not discriminate AD from controls,
despite evident changes on clinical, neuroimaging, and CSF measures, querying the use of retinal
thickness measurements as an AD biomarke
Retinal and Cerebral Microvasculopathy: Relationships and Their Genetic Contributions
PURPOSE: Retinal microvasculopathy may reflect small vessel disease in the brain. Here we test
the relationships between retinal vascular parameters and small vessel disease, the influence
of cardiovascular risk factors on these relationships, and their common genetic background in
a monozygotic twin cohort.
METHODS: We selected 134 cognitively healthy individuals (67 monozygotic twin pairs) aged
‡60 years from the Netherlands Twin Register for the EMIF-AD PreclinAD study. We measured
seven retinal vascular parameters averaged over both eyes using fundus images analyzed with
Singapore I Vessel Assessment. Small vessel disease was assessed on MRI by a volumetric
measurement of periventricular and deep white matter hyperintensities. We calculated
associations between RVPs and WMH, estimated intratwin pair correlations, and performed
twin-specific analyses on relationships of interest.
RESULTS: Deep white matter hyperintensities volume was positively associated with retinal
tortuosity in veins (P ¼ 0.004) and fractal dimension in arteries (P ¼ 0.001) and veins (P ¼
0.032), periventricular white matter hyperintensities volume was positively associated with
retinal venous width (P ¼ 0.028). Intratwin pair correlations were moderate to high for all
small vessel disease/retinal vascular parameter variables (r ¼ 0.49–0.87, P < 0.001). Crosstwin
cross-trait analyses showed that retinal venous tortuosity of twin 1 could predict deep
white matter hyperintensities volume of the co-twin (r ¼ 0.23, P ¼ 0.030). Within twin-pair
differences for retinal venous tortuosity were associated with within twin-pair differences in
deep white matter hyperintensities volume (r ¼ 0.39, P ¼ 0.001).
CONCLUSIONS: Retinal arterial fractal dimension and venous tortuosity have associations with
deep white matter hyperintensities volume. Twin-specific analyses suggest that retinal venous
tortuosity and deep white matter hyperintensities volume have a common etiology driven by
both shared genetic factors and unique environmental factors, supporting the robustness of
this relationship
Detection of a Single Identical Cytomegalovirus (CMV) Strain in Recently Seroconverted Young Women
Infection with multiple CMV strains is common in immunocompromised hosts, but its occurrence in normal hosts has not been well-studied.We analyzed CMV strains longitudinally in women who acquired CMV while enrolled in a CMV glycoprotein B (gB) vaccine trial. Sequencing of four variable genes was performed in samples collected from seroconversion and up to 34 months thereafter.199 cultured isolates from 53 women and 65 original fluids from a subset of 19 women were sequenced. 51 women were infected with one strain each without evidence for genetic drift; only two women shed multiple strains. Genetic variability among strains increased with the number of sequenced genetic loci. Nevertheless, 13 of 53 women proved to be infected with an identical CMV strain based on sequencing at all four variable genes. CMV vaccine did not alter the degree of genetic diversity amongst strains.Primary CMV infection in healthy women nearly always involves shedding of one strain that remains stable over time. Immunization with CMVgB-1 vaccine strain is not selective against specific strains. Although 75% of women harbored their unique strain, or a strain shared with only one other woman, 25% shared a single common strain, suggesting that this predominant strain with a particular combination of genetic loci is advantageous in this large urban area
The EMIF-AD PreclinAD study: study design and baseline cohort overview
BACKGROUND: Amyloid pathology is the pathological hallmark in Alzheimer’s disease (AD) and can precede clinical
dementia by decades. So far it remains unclear how amyloid pathology leads to cognitive impairment and dementia.
To design AD prevention trials it is key to include cognitively normal subjects at high risk for amyloid pathology and to
find predictors of cognitive decline in these subjects. These goals can be accomplished by targeting twins, with
additional benefits to identify genetic and environmental pathways for amyloid pathology, other AD biomarkers,
and cognitive decline.
METHODS: From December 2014 to October 2017 we enrolled cognitively normal participants aged 60 years and
older from the ongoing Manchester and Newcastle Age and Cognitive Performance Research Cohort and the
Netherlands Twins Register. In Manchester we included single individuals, and in Amsterdam monozygotic twin
pairs. At baseline, participants completed neuropsychological tests and questionnaires, and underwent physical
examination, blood sampling, ultrasound of the carotid arteries, structural and resting state functional brain magnetic
resonance imaging, and dynamic amyloid positron emission tomography (PET) scanning with [18F]flutemetamol. In
addition, the twin cohort underwent lumbar puncture for cerebrospinal fluid collection, buccal cell collection,
magnetoencephalography, optical coherence tomography, and retinal imaging.
RESULTS: We included 285 participants, who were on average 74.8 ± 9.7 years old, 64% female. Fifty-eight participants
(22%) had an abnormal amyloid PET scan.
CONCLUSIONS: A rich baseline dataset of cognitively normal elderly individuals has been established to estimate risk
factors and biomarkers for amyloid pathology and future cognitive declin
Systematic review of the association between Alzheimer’s disease and chronic glaucoma
Sarah F Janssen,1 Nomdo M Jansonius,2 Femke Bouwman,3 Frank D Verbraak,1,4 Arthur A Bergen51Department of Ophthalmology, VU Medical Center, Amsterdam; 2Department of Ophthalmology, University of Groningen, University Medical Center Groningen, Groningen; 3Alzheimer Center, VU Medical Center, 4Department of Ophthalmology, 5Department of Clinical Genetics, Academic Medical Center, Amsterdam, the NetherlandsWe read with great interest the paper by Tsilis et al entitled "Systematic review of the association between Alzheimer’s disease and chronic glaucoma" published recently in this journal.1 The potential overlap in the pathobiological background of Alzheimer’s disease (AD) and primary open angle glaucoma (POAG) is currently a topic of intense discussion and could provide further insight into both of these complex diseases.View original paper by Tsilis et al