Tsolaki et al Studies epidemiological studies Chandra et al4 reported, based on a register study of US death certificates, an increased prevalence of glaucoma among patients who died bearing the official diagnosis of senile and presenile dementia. More recently, Bayer et al5 announced a higher prevalence of glaucoma among AD patients (25.9%) in comparison to the prevalence observed in a control group of non-AD individuals (5.2%). Tamura et al6 reached the same conclusion based on a larger prospective study sample, comprised of 172 AD and 176 control individuals. The reverse relationship, that of an augmented occurrence of AD among glaucomatous patients, has also been investigated. Recently, Yochim et al7 found that more than 40% of a 41-person sample of aged glaucomatous patients showed cognitive impairment, in the form of either memory impairment or executional dysfunction, but without an official diagnosis of AD. This fact has implications in the ability of these patients to comply with an adequate antiglaucoma regimen. However, the relationship between dementia and glaucoma could not be proven in a large study (sample size more than 11,000 subjects) performed by Kessing et al,8 which however had the major disadvantage of being a retrospective register- based study. Similarly, Bach-Holm et al,9 in a recently published register-based study with a 20-year follow-up that comprised 69 normal-tension glaucoma patients reported a lack of correlation of this disorder with AD, as none of the enlisted patients developed AD. experimental studies on animals As a disorder in the production and deposition of Amyloid- beta (Aβ) in the brain, amyloid plaques are characteristics of Alzheimer’s disease. Many researchers have focused their research on the role of Αβ in the development of glaucoma. Guo et al,10 using a rat model experimental study, induced augmented intraocular pressure in male rats and found augmented amyloid beta aggregation in the affected retinal ganglion cells, a finding missing in the related cells of the contralateral, non-affected eyes. In a similar, more recent study, Kipfer-Kauer et al11 managed to detect an amyloid regulating protein, called amyloid precursor protein (APP), as well as Aβ in augmented concentrations in the optic nerves and retinal ganglion cells of rat eyes in which ocular hyper- tension was surgically induced. McKinnon12 also worked with a rat glaucoma experimental model, elucidating the role of apoptotic cell death through activation of a family of proteases, called caspases. These proteolytic enzymes (especially caspase-3 and caspase-8) act on APP to cause 888 submit your manuscript | www.dovepress.com Dovepress Dovepress the production of neurotoxic fragments, which include Aβ, thus providing an extra pattern of common etiology between AD and glaucoma at the cellular level. Vickers13 has also emphasized the role of cellular damage and cellular reaction to stress in the development of AD and glaucoma; He focused his studies on the neurofilament triplet, a group of cytoskeletal proteins accumulated in cases of damage to the larger retinal ganglion cells. Clinical-laboratory studies on humans A very interesting study that added a lot to the elucidation of the putative association between Alzheimer’s disease and glaucoma was conducted by Gupta et al.14 The researchers used human ocular tissue specimens gained during glaucoma operations, and compared their immunohistochemical characteristics to those of living and postmortem control tissue specimens. They found that patients with unregulated intraocular pressure had decreased concentrations of normal tau-protein (BT2) and increased presence of abnormal hyper- phosphorylated tau-protein molecules (AT8), especially within the posterior retina; such molecules can also be detected in the cerebrospinal fluid (CSF) of AD patients. In another clinical-laboratory study, Yoneda et al15 measured the Aβ 42 and tau-protein levels of the vitreous fluid in patients with retinal pathologies undergoing vitrectomy (including glaucomatous patients) and compared them to those of con- trol patients. Patients with glaucoma had decreased levels of Aβ and increased levels of tau-proteins in their vitreous fluid. This finding is possibly linked to the decreased levels of Aβ and increased levels of tau-proteins in the CSF of AD patients. Another possible link between AD and glaucoma lies in the CSF pressure, which appears to be decreased in AD patients, a fact also observed among POAG patients.16 Ren et al, in two recent studies,17,18 which recruited patients with high-tension glaucoma, normal-tension glaucoma, patients with intraocular pressure without glaucoma and healthy subjects, highlighted the importance of the translamina- cribrosa pressure difference in the development of at least one of the characteristic optic nerve damages of glaucoma, loss of neuroretinal rim (the others being deepening of the optic cup and parapapillary atrophy), and of the subsequent visual deficits. The translamina-cribrosa pressure difference may be a combination of normal intracranial/intraocular pressure and decreased CSF pressure or of an elevated intracranial/ intraocular pressure and normal CSF pressure. Berdahl and Allingham19 also highlighted the importance of reduced CSF pressure in the pathogenesis of glaucoma, in addition Clinical Ophthalmology 2011:5