Skip to main content

Table 3 Overview and timing of study assessments

From: Tear biomarkers for Alzheimer’s disease screening and diagnosis (the TearAD study): design and rationale of an observational longitudinal multicenter study

Assessment

Baseline

12 months

24 months

In-/exclusion criteria

X

  

Informed consent

X

  

Medical history and medication

X

X

X

Routine neuropsychological testsa

X

X

X

CT or MRI scanb

X

  

PET scan or CSF samplingc

X

  

Blood samplingd

X

 

X

Routine ophthalmic examinatione

X

X

X

Tear samplingf

X

X

X

Fundus imagingg

X

X

X

OCT imagingh

X

X

X

  1. a Neuropsychological assessment will be performed according to local routine protocol of memory clinic, as described elsewhere [19]. Covering the cognitive domains of global cognition, memory, attention, executive functioning and language
  2. b Images will be acquired with a 3 Tesla MRI-scan and 7 Tesla MRI for a small sub-cohort. The Scheltens MTA visual rating scale will be used to score each hemisphere (range 0–4) [22]. A summed score of both hemispheres will be defined abnormal with a cutoff of ≥ 2 [24]
  3. c CSF fluid will be available from a subset of participants and will be analyzed for Aβ 42, t-tau and p-tau-181 using an immunoassay, local cut-off values for each clinic will be used [20, 25]. A PET scan will also be available from a subset of participants, from which standard uptake value ratio (SUVr) images will be generated and visually read by an experienced nuclear physician. Images will be classified as positive or negative rating for Aβ according to criteria defined by the manufacturer (GE Healthcare) [26]
  4. d Participants will undergo venipuncture for blood sampling and subsequent analysis of Aβ42/40, t-tau and p-tau AD biomarker levels using immunoassays
  5. e The presence of potential ocular pathologies or unexpected findings will be assessed during the standard ophthalmic examination during which we will analyze visual acuity (using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart (27)), (auto-) refraction, intraocular pressure (using non-contact tonometry), axial length (IOLMaster™, Carl Zeiss Meditec AG, Jena, Germany) and general eye health (using slit lamp biomicroscopy and funduscopy)
  6. f Tear sampling will be performed by absorption of tear fluid in a paper Schirmer’s strip (TEAR strips, Contacare Ophthalmics and diagnostics, Gujarat, India). The Schirmer’s strip will be placed in de lower eyelid of both eyes. After 5 min, the Schirmer’s strip will be gently removed using tweezers and stored at -80 °C. Tear fluid will be extracted from Schirmer’s strips [27], and analyzed with targeted immuno-assays for Aβ 42/40, t-tau and p-tau
  7. g Fundus imaging captures images of the retina, optic nerve head, macula, retinal blood vessels, choroid, and the vitreous. We will use a the Clarus 700 fundus camera (Carl Zeiss Meditec AG, Jena, Germany) to capture images of the central retina. Color and autofluorescence ultra-wide field images of 200 degrees of the peripheral retina will be acquired using the Californiarg fundus camera (Optos, Dunfermline, United Kingdom). Additionally, hyperspectral retinal imaging will be performed using the hyperspectral camera Optina-4 C (Optina Diagnostics, Quebec, Canada). Optina-4 C is a non-CE marked mydriatic camera combined with a tunable filter, thereby only permitting selected wavelengths (energy spectrum between 450 and 900 nm) [28]. In a subset of participants the macular pigment optical density will be determined in the right eye with the macular pigment reflectometer [29]
  8. h Optical coherence tomography (OCT) imaging will generate cross sectional retinal images from the (papillary) retinal nerve fiber layer thickness (RNFL) along with other parameters will be extracted. For each eye the following scans will be made, (i) fast enhanced depth imaging retina macula scan, (ii) dense macular scans, (iii) axonal ring scan around the optic nerve head (ONH), and (iv) an ONH scan using spectral domain OCT. Additionally, an OCT angiography (OCTA) will be done in a subset of the study population (Heidelberg Engineering, Heidelberg, Germany)
Back to article page

BMC Neurology

ISSN: 1471-2377

Contact us