Serum neurofilament light chain in healthy elderly and in patients with age‐related macular degeneration

Abstract Background Age-related conditions such as glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DRP) and cataract have become the major cause of visual impairment and blindness in high-income countries and carry a major socio-economic burden. The aim of the current study is to investigate the prevalence of age-related eye diseases such as glaucoma, age-related macular degeneration, diabetic retinopathy and cataract in a cohort of self-proclaimed healthy elderly, and thus get a rough estimation of the prevalence of undiagnosed age-related eye conditions in the Belgian population.Methods Individuals aged 55 and older without ophthalmological complaints were asked to fill in a general medical questionnaire and underwent an ophthalmological examination, which included a biomicroscopic examination, intraocular pressure measurement, axial length measurement, and acquisition of fundus pictures and Optical Coherence Tomography scans. Information regarding follow-up was collected in the subset of participants who received the advice of referral to an ophthalmologist or the advice to have more frequent follow-up visits, based on the ophthalmological changes detected in their evaluation.Results The cohort included 102 people and comprised 46% men (median age 70 years, range 57-85 years). Referral for additional examinations based on clinical findings, was made in 26 participants (25%). The advice to have more regular follow-up ophthalmologist visits was given to nine additional participants (9%). No significant correlations between baseline characteristics, including eye care consumption, and the need for referral could be identified. Follow-up information was available for 25 out of 26 referred volunteers (96%). Out of these, four (16%) underwent a therapeutical intervention based on study referral, up until 18 months after study participation. All four interventions took place in the age group 65 - 74 years.Conclusions This study shows that even in an elderly population with self-proclaimed healthy eyes and good general health, a significant proportion of subjects showed ocular findings that need regular follow up and/or intervention. Moreover, the frequency of prior ophthalmological examinations does not seem to be relevant to this proportion, meaning that everyone above 55 years old needs a routine ophthalmological evaluation.

Download Full-text

Biological Age in Healthy Elderly Predicts Dementia in the Absence of a Brain Marker

10.21203/rs.3.rs-119310/v1 ◽

2020 ◽

Author(s):

Julia Wu ◽

Amber Yaqub ◽

Yuan Ma ◽

Wouter Koudstaal ◽

Albert Hofman ◽

...

Keyword(s):

Elevated Risk ◽

Biological Age ◽

Chronological Age ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Significance Level ◽

Healthy Elderly ◽

Age Related ◽

Major Shortcoming ◽

One Year

Abstract Application of biological age as a measure of an individual´s health status offers new perspectives into extension of both lifespan and healthspan. While algorithms predicting mortality and most aging-related morbidities have been reported, the major shortcoming has been an inability to predict dementia. We present a community-based cohort study of 1930 participants with a mean age of 72 years and a follow-up period of over 7 years, using two variants of a phenotypic blood-based algorithm that either excludes (BioAge1) or includes (BioAge2) neurofilament light chain (NfL) as a neurodegenerative marker. BioAge1 and BioAge2 predict dementia equally well, as well as lifespan and healthspan. Each one-year increase in BioAge1/2 was associated with 11% elevated risk (HR=1.11; 95%CI 1.08-1.14) of mortality and 7% elevated risk (HR=1.07; 95%CI 1.05-1.09) of first morbidities. We additionally tested the association of microRNAs with age and identified 263 microRNAs significantly associated with biological and chronological age alike. Top differentially expressed microRNAs based on biological age had a higher significance level than those based on chronological age, suggesting that biological age captures aspects of aging signals at the epigenetic level. We conclude that biological age is a predictor of major age-related diseases, including dementia, among healthy elderly.

Download Full-text

Effect of Visual Search Training on Saccades in Age-related Macular Degeneration Subjects

Current Aging Science ◽

10.2174/1874609812666190913125705 ◽

2020 ◽

Vol 13 (1) ◽

pp. 62-71 ◽

Cited By ~ 3

Author(s):

Hortense Chatard ◽

Laure Tepenier ◽

Talal Beydoun ◽

Olivier Offret ◽

Sawsen Salah ◽

...

Keyword(s):

Visual Search ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Eye Tracker ◽

Mean Velocity ◽

Healthy Elderly ◽

Age Related ◽

Before And After ◽

Search Training ◽

The Impact

Objective: To compare the impact of unilateral versus bilateral Age-related Macular Degeneration (AMD) on saccadic movements, and to show the effect of visual search training on these eye movement performances in AMD subjects. We hypothesized that unilateral and bilateral AMD subjects had abnormal saccadic performances, and that visual search training could improve their performances. Methods: Three groups participated in visual search training: 13 elderly unilateral AMD subjects (mean age: 74.6 ± 1.6 years), 15 elderly bilateral AMD subjects (mean age: 74.2 ± 1.2 years), and 15 healthy age-matched control subjects (mean age: 70.9 ± 1.3 years). Horizontal saccadic performances were recorded before and after visual search training (Metrisquare®) with the Mobile Eye Tracker (Mobile EBT®). We analyzed the saccadic movement performances: latency, mean velocity and gain. We measured the training performances for each exercise: the time, the number of omissions and the number of errors. We analyzed the performances with Kruskal-Wallis and posthoc tests. Results: The latency of saccades in AMD subjects is significantly longer compared to healthy elderly for 15° (p<0.03), 10° (p<0.003) and 5° (p<10-3). Unilateral and bilateral AMD subjects normalized their latency of saccades after training for small saccades (respectively p=0.30 and p=0.23 for 10°, and p=0.09 and p=0.52 for 5°). In elderly, performances depend on the saccade’s amplitude. Conclusion: AMD subjects’ saccadic movements are disrupted: the execution needs more time but is efficient. The visual search training improved the saccadic performances in AMD subjects. Further studies will aim to improve knowledge on such issues and to explore the benefit of training over time in unilateral AMD subjects.

Download Full-text

Biological age in healthy elderly predicts aging-related diseases including dementia

Scientific Reports ◽

10.1038/s41598-021-95425-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Julia W. Wu ◽

Amber Yaqub ◽

Yuan Ma ◽

Wouter Koudstaal ◽

Albert Hofman ◽

...

Keyword(s):

Elevated Risk ◽

Biological Age ◽

Chronological Age ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Significance Level ◽

Healthy Elderly ◽

Age Related ◽

Major Shortcoming ◽

One Year

AbstractApplication of biological age as a measure of an individual´s health status offers new perspectives into extension of both lifespan and healthspan. While algorithms predicting mortality and most aging-related morbidities have been reported, the major shortcoming has been an inability to predict dementia. We present a community-based cohort study of 1930 participants with a mean age of 72 years and a follow-up period of over 7 years, using two variants of a phenotypic blood-based algorithm that either excludes (BioAge1) or includes (BioAge2) neurofilament light chain (NfL) as a neurodegenerative marker. BioAge1 and BioAge2 predict dementia equally well, as well as lifespan and healthspan. Each one-year increase in BioAge1/2 was associated with 11% elevated risk (HR 1.11; 95%CI 1.08–1.14) of mortality and 7% elevated risk (HR 1.07; 95%CI 1.05–1.09) of first morbidities. We additionally tested the association of microRNAs with age and identified 263 microRNAs significantly associated with biological and chronological age alike. Top differentially expressed microRNAs based on biological age had a higher significance level than those based on chronological age, suggesting that biological age captures aspects of aging signals at the epigenetic level. We conclude that accelerated biological age for a given age is a predictor of major age-related morbidity, including dementia, among healthy elderly.

Download Full-text

Cathepsin B pH-Dependent Activity Is Involved in Lysosomal Dysregulation in Atrophic Age-Related Macular Degeneration

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/5637075 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 1

Author(s):

Audrey Voisin ◽

Christelle Monville ◽

Alexandra Plancheron ◽

Emile Béré ◽

Afsaneh Gaillard ◽

...

Keyword(s):

Macular Degeneration ◽

Cell Lines ◽

Cathepsin B ◽

Retinal Pigment ◽

Induced Pluripotent Stem Cell ◽

Age Related Macular Degeneration ◽

Rpe Cells ◽

Healthy Elderly ◽

Age Related

Age-related macular degeneration (AMD) is characterized by retinal pigment epithelial (RPE) cell dysfunction beginning at early stages of the disease. The lack of an appropriate in vitro model is a major limitation in understanding the mechanisms leading to the occurrence of AMD. This study compared human-induced pluripotent stem cell- (hiPSC-) RPE cells derived from atrophic AMD patients (77 y/o±7) to hiPSC-RPE cells derived from healthy elderly individuals with no drusen or pigmentary alteration (62.5 y/o±17.5). Control and AMD hiPSC-RPE cell lines were characterized by immunofluorescence, flow cytometry, and electronic microscopy. The toxicity level of iron after Fe-NTA treatment was evaluated by an MTT test and by the detection of dichloro-dihydro-fluorescein diacetate. Twelve hiPSC-RPE cell lines (6 AMD and 6 controls) were used for the experiment. Under basal conditions, all hiPSC-RPE cells expressed a phenotypic profile of senescent cells with rounded mitochondria at passage 2. However, the treatment with Fe-NTA induced higher reactive oxygen species production and cell death in hiPSC-RPE AMD cells than in hiPSC-RPE Control cells. Interestingly, functional analysis showed differences in lysosomal activity between the two populations. Indeed, Cathepsin B activity was higher in hiPSC-RPE AMD cells compared to hiPSC-RPE Control cells in basal condition and link to a pH more acidic in this cell population. Moreover, oxidative stress exposure leads to an increase of Cathepsin D immature form levels in both populations, but in a higher proportion in hiPSC-RPE AMD cells. These findings could demonstrate that hiPSC-RPE AMD cells have a typical disease phenotype compared to hiPSC-RPE Control cells.

Download Full-text

Age related macular degeneration (ARMD) – pathophysiological and clinical features and therapeutic concepts

Therapeutische Umschau ◽

10.1024/0040-5930.58.1.28 ◽

2001 ◽

Vol 58 (1) ◽

pp. 28-35 ◽

Cited By ~ 1

Author(s):

Ursula Körner-Stiefbold

Keyword(s):

Macular Degeneration ◽

Clinical Features ◽

Altersbedingte Makuladegeneration ◽

Age Related Macular Degeneration ◽

Genetische Faktoren ◽

Age Related ◽

Therapeutic Concepts

Die altersbedingte Makuladegeneration (AMD) ist eine der häufigsten Ursachen für einen irreversiblen Visusverlust bei Patienten über 65 Jahre. Nahezu 30% der über 75-Jährigen sind von einer AMD betroffen. Trotz neuer Erkenntnisse in der Grundlagenforschung ist die Ätiologie, zu der auch genetische Faktoren gehören, noch nicht völlig geklärt. Aus diesem Grund sind die Behandlungsmöglichkeiten zum jetzigen Zeitpunkt noch limitiert, so dass man lediglich von Therapieansätzen sprechen kann. Die derzeit zur Verfügung stehenden Möglichkeiten wie medikamentöse, chirurgische und laser- und strahlentherapeutische Maßnahmen werden beschrieben.

Download Full-text