Visual and Ocular Manifestations of Alzheimer’s Disease and Their Use as Biomarkers for Diagnosis and Progression

Abstract

Alzheimer’s disease (AD) is the most common form of dementia affecting the growing aging population today, with prevalence expected to rise over the next 35 years. Clinically, patients exhibit a progressive decline in cognition, memory, and social functioning due to deposition of amyloid β (Aβ) protein and intracellular hyperphosphorylated tau protein. These pathological hallmarks of AD are measured either through neuroimaging, cerebrospinal fluid analysis, or diagnosed post-mortem. Importantly, neuropathological progression occurs in the eye as well as the brain, and multiple visual changes have been noted in both human and animal models of AD. The eye offers itself as a transparent medium to cerebral pathology and has thus potentiated the development of ocular biomarkers for AD. The use of non-invasive screening, such as retinal imaging and visual testing, may enable earlier diagnosis in the clinical setting, minimizing invasive and expensive investigations. It also potentially improves disease management and quality of life for AD patients, as an earlier diagnosis allows initiation of medication and treatment. In this review, we explore the evidence surrounding ocular changes in AD and consider the biomarkers currently in development for early diagnosis.

Ocular indicators of Alzheimer’s: exploring disease in the retina

“…Among the earliest symptoms documented in some AD patients are visual impairments, especially loss of contrast and color sensitivity, limited visual field, compromised visual attention, reduced stereopsis, deficits in the perception of shape from motion, and impaired object and face recognition [9, 31, 90, 97, 138, 140, 161, 162, 174]. However, unlike well-established retinal structural deficits, various changes in visual function appear to manifest inconsistently across AD patients, and further study should expand upon the currently limited findings.…”

“…While many aspects of visual acuity, such as recognition, localization, and target detection, were not found to be significantly different in AD patients when compared with controls [31, 90], loss of contrast sensitivity was markedly different [64, 90, 157]. Since the latter parameter may be detected clinically in a routine eye examination, it may serve as a biomarker for AD-related neurodegeneration [31].…”

“…However, loss of color sensitivity and the possibility of using this parameter to determine AD status remain highly controversial [9, 31]. Abnormal visual field has also been correlated with disease severity, with AD patients showing sensitivity loss greater than controls [31, 90, 175]. Deficits in motion perception have been associated with severity of dementia, and evidence suggests that AD patients may have impaired motion sensitivity due to selective damage to the magnocellular pathway [31, 65, 83, 99].…”

“…With various reports of retinal structural deficits, other ocular abnormalities, and even visual dysfunctions experienced by AD patients [19–22, 31, 35, 59, 60, 69, 81, 90, 97, 98, 107, 108, 113, 130, 163, 180], it is no surprise that the field has begun shifting its attention to the eye as a site of AD manifestation. The retina is a CNS tissue originating in the developing diencephalon, and it contains high-density neuronal cells and fibers that form a sensory extension of the brain [25].…”

Modelo neurocomputacional dos estágios iniciais da doença de Alzheimer

“…Segundo Javaid et al (2016), os exames dos olhos permitem um diagnóstico precoce da doença de Alzheimer porque suas manifestações, como a deposição das placas Aβ e a hiperfosforilação da proteína tau, aparecem primeiro na retina. Estes mesmos autores afirmam que "outro fator importante para se observar em pacientes com AD é o aumento da prevalência de catarata que afeta a acuidade visual".…”