Direct Causal Link Proposed Between Neurodegenerative Disorders

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Several studies have identified similarities in the pathogenic processes underlying Alzheimer's disease and glaucoma^1-3 and reported a higher incidence of glaucoma among patients with Alzheimer's disease.^4,5 A new hypothesis posits a direct causal link between these progressive neurodegenerative disorders.⁶

A retrospective case-controlled study by Berdahl et al found that patients with primary open-angle glaucoma had mean cerebrospinal fluid pressures that were 33% lower than those of nonglaucomatous controls (9.2 vs 13.0 mm Hg, respectively).⁷

In a separate study, Silverberg et al found that 96.1% of patients with Alzheimer's disease had statistically significantly lower mean cerebrospinal fluid pressures (103 ± 44 mm H2O [approximately 7.5 mm Hg]) than Alzheimer's patients with elevated cerebrospinal fluid pressures and a control group of younger patients with Parkinson's disease (140 ±60 mm H2O [approximately 10.3 mm Hg]).⁸

Extrapolating from the data published by Berdahl et al and Silverberg et al, Wostyn et al have proposed that a reduction in cerebrospinal fluid pressure may create an abnormally high difference in pressure across the lamina cribrosa, cause the porous structure to bow posteriorly, and lead to glaucomatous damage of the optic nerve. Normal IOP and cerebrospinal fluid pressure normally range from10 to 21 mm Hg and from 5 to 15 mm Hg, respectively.

According to Wostyn et al, investigators can test this hypothesis by comparing the cerebrospinal fluid pressures among Alzheimer's patients with glaucoma, Alzheimer's patients without glaucoma, and appropriate controls.⁶

1. Selkoe DJ. Alzheimer's disease is a synaptic failure. Science. 2002;298(5594):789-791.
2. McKinnon SJ. Glaucoma: ocular Alzheimer's disease. Front Biosci. 2003;8:s1140-s1156.
3. Guo L, Salt TE, Luong V, et al. Targeting amyloid-beta in glaucoma treatment. Proc Natl Acad Sci USA. 2007;104(33):13444-13449.
4. Bayer AU, Ferrari F, Erb C. High occurrence rate of glaucoma among patients with Alzheimer's disease. Eur Neurol. 2002;47(3):165-168.
5. Tamura H, Kawakami H, Kanamotoa T, et al. High frequency of open-angle glaucoma in Japanese patients with Alzheimer's disease. J Neurol Sci. 2006;15;246(1-2):79-83.
6. Wostyn P, Audenaert K, De Deyn PP. Alzheimer's disease and glaucoma: is there a causal relationship? [published online ahead of print March 13, 2009]. Br J Ophthalmol. doi:10.1136/bjo.2008.148065.
7. Berdahl JP, Allingham R, Johnson DH. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology. 2008;115:763-768.
8. Silverberg G, Mayo M, Saul T, et al. Elevated cerebrospinal fluid pressure in patients with Alzheimer's disease. Cerebrospinal Fluid Res. 2006;3:7.

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