Comparison of OCTA Factors in Patients With or Without Amyloid Pathology: A Prospective Study
Condition: Alzheimer Disease; Amyloid Angiopathy; Macular Ischemia; Dementia; Mild Cognitive Impairment
MeSH terms: Alzheimer Disease; Dementia; Amyloidosis; Ischemia; Cognitive Dysfunction
Study type: Observational

Summary: 
      To compare alternation of retinal microcirculation within the macula and optic disc in
      patients with dementia, mild cognitive impairment (MCI), and cognitively healthy subjects who
      had positive amyloid biomarkers (Aβ +) or not, using optical coherence tomography angiography
      (OCTA).
    

Detailed description: 
      Alzheimer disease dementia (ADD) is the most common neurodegenerative disease dementia in
      elderly population associated with the accumulation of beta-amyloid (Aβ) plaques and tau
      neurofibrillary tangles (NFTs). Diagnostic biomarkers reflecting underlying amyloid or tau
      pathology of ADD have actively been developed. Of these, amyloid or tau positron emission
      tomography (PET) imaging and cerebrospinal fluid (CSF) Aβ1-42 or phosphorylated tau are
      representative biomarkers for ADD. However, these tend to be expensive, invasive, or
      available only in a tertiary hospital or a specialized laboratory. Alternative biomarkers
      which are inexpensive, less invasive, and highly available could be needed.

      Patients with ADD commonly show visuospatial dysfunction which is mainly attributed to damage
      of parieto-occipital or temporo-occipital visual pathway. In addition, previous studies using
      optical coherence tomography (OCT) which is a useful tool measuring retinal nerve fiber layer
      thickness (RNFLT), macula ganglion cell/inner plexiform layer thickness (GC/IPLT) reported
      impaired pregeniculate afferent visual pathway, for example, reduction of RNFLT and loss of
      retinal ganglionic cells (RGCs) in patients with ADD.

      The retina and brain have the same embryological origin. These were branched off from the
      forebrain, so the brain and retina have similar anatomic and physiologic traits of the
      vasculature. In line with this, several studies using laser doppler ultrasonography, or
      retinal function imager (RFI) revealed narrowed central retinal vein and decreased its blood
      velocity, or low blood flow rate of retinal arterioles and venules in patients with mild
      cognitive impairment (MCI) and ADD. The authors suggested that in patients with ADD,
      accumulation of Aβ in the vessel walls could cause disruption of basement membrane and
      endothelium, leading to the decreased vascular lumen and density of retinal vessel. Indeed,
      postmortem study revealed accumulated Aβ inside or around RGCs in AD.

      OCTA can clearly visualize not only the specific layers of retinal vasculatures, including
      superficial, middle, and deep capillary plexuses, but also choroidal vessels with a high
      resolution and in a reproducible manner, without contrast agent. A few prior studies using
      OCTA reported enlarged foveal avascular zone (FAZ) and decrease of retinal vascular density
      and choroidal thickness in ADD or MCI compared to controls. On the other hand, the others
      showed no differences in FAZ area and vessel density between them.

      In this study, the investigators first evaluated structural and microvascular changes of
      retina and the microvascular change of macula and optic disc in patients with clinically
      diagnosed ADD, MCI and cognitively normal controls using OCT and OCTA. Then, to investigate
      whether impaired pregeniculate visual pathway is truly associated with underlying amyloid
      pathology, the investigators further investigated those OCT and OCTA parameters in each
      subgroup with positive or negative amyloid biomarker.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Neurologic Clinic of Pusan National University Hospital
      
Keywords: Alzheimer disease dementia; Mild cognitive impairment; Amyloid pathology; Optical coherence tomographic angiography