More advanced Alzheimer's disease may be associated with a decrease in cerebrospinal fluid pressure
© Wostyn et al; licensee BioMed Central Ltd. 2009
Received: 3 September 2009
Accepted: 16 November 2009
Published: 16 November 2009
In a recent article, elevated cerebrospinal fluid pressure (CSFP) consistent with very early normal pressure hydrocephalus (NPH), was found in a small subset of Alzheimer's disease (AD) patients (possible AD-NPH hybrids) enrolled in a clinical trial for chronic low-flow cerebrospinal fluid drainage. Also in the same study, was another interesting finding that merits further discussion: a substantial proportion of AD patients had very low CSFP. Based on the characteristics of these subjects, we hypothesize that more advanced AD may be associated with a decrease in CSFP. Reduced CSFP among a group of AD patients could provide a clue towards a better understanding of the high rate of comorbidity reported between AD and glaucoma since it has been shown that mean CSFP is lower in subjects with primary open-angle glaucoma. This could result in an abnormally high trans-lamina cribrosa pressure difference and lead to glaucomatous damage.
In a recent article published in Cerebrospinal Fluid Research, Silverberg et al. reported elevated cerebrospinal fluid pressure (CSFP), consistent with very early normal pressure hydrocephalus (NPH), in a small subset of Alzheimer's disease (AD) patients enrolled in a clinical trial of chronic low-flow cerebrospinal fluid (CSF) drainage . This AD-elevated CSFP group provided further support for the existence of an AD-NPH hybrid and CSF circulatory failure. However, the same study reported another interesting finding that we believe merits further discussion, in that a substantial proportion of AD patients had very low CSFP. In the present article, we briefly summarize supportive evidence from these observations that suggest that more advanced AD may be associated with a decrease in CSFP. Interestingly, the finding of a high occurrence of reduced CSFP among patients with AD could shed new light on the link between AD and glaucoma [2, 3].
The finding of a high occurrence of reduced CSFP among AD patients is of major importance because it may provide a better understanding of the high rate of comorbidity reported between AD and glaucoma [2, 3]. In a nursing home-based study in Germany, the prevalences of glaucoma (as defined by characteristic optic nerve or visual field changes) were reported to be 25.9% in patients with AD and 5.2% in controls . In another study, Tamura et al. found that the prevalence of open-angle glaucoma (OAG) in Japanese patients with AD was 23.8%, which was significantly higher than that of the control subjects (9.9%) . There was no significant difference between intraocular pressures (IOPs) in AD patients with OAG and without OAG, and almost all AD patients with OAG showed normal tension. Furthermore, in a retrospective case-control study, Berdahl et al. reported the intriguing new observation that mean CSFP was 33% lower in subjects with primary open-angle glaucoma (POAG) (9.2 mmHg) compared with that of nonglaucomatous controls (13.0 mmHg; P < 0.00005) . The authors noted that their observation supports the concept that an abnormally high trans-lamina cribrosa pressure difference plays an important role in glaucomatous optic nerve damage, whether the result of elevated IOP, reduced CSFP or both. Considering the above data, it seems reasonable to speculate that there may be a causal relationship between AD and glaucoma that may be explained by low CSFP in patients with AD. This obviously needs to be confirmed by future research.
It should be stressed that other factors might also explain the link between AD and glaucoma. For example, Tamura et al. evaluated the APOE ε4 allele as a common genetic risk factor for AD and OAG . However, the percentage of AD patients with OAG who carried an APOE ε4 allele was not significantly different to that of AD patients without OAG, suggesting that APOE ε4 polymorphism may not be a common risk factor predisposing to both disorders . Recently, Helicobacter pylori infection has also been suggested to be involved in the pathogenesis of both AD and glaucoma . To investigate whether primary open-angle glaucoma is associated with increased risk of developing AD, Kessing et al. carried out a nationwide case register study comparing the rate of subsequent AD for patients with POAG (including normal tension glaucoma) with the rate for patients with primary angle-closure glaucoma (PACG), cataract, and osteoarthritis (OA) and with the rate for the general population . All patients included in the study were identified at hospital admission or outpatient contact during the period 1977 to 2001 in Denmark. However, the hypothesis that patients with POAG have increased risk of developing AD was not supported by the results .
In conclusion, we have summarized supportive evidence from the observations of Silverberg et al. that suggest that more advanced AD may be associated with a decrease in CSFP. The finding of a 24.1% occurrence of reduced CSFP among 174 patients with AD could be linked to the high rate of comorbidity between AD and glaucoma, since it has been shown that mean CSFP is lower in subjects with POAG. This could result in an abnormally high trans-lamina cribrosa pressure difference and lead to glaucomatous damage.
We are particularly grateful for the personal communication with Dr. Gerald D. Silverberg, Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA, and for permission to use his figure.
We have had permission from Dr. Silverberg to use personal communication and permission to use the figure (Frequency histogram showing the distribution of CSFP in all AD subjects) from his article entitled "Elevated cerebrospinal fluid pressure in patients with Alzheimer's disease" published in Cerebrospinal Fluid Research.
- Silverberg G, Mayo M, Saul T, Fellmann J, McGuire D: Elevated cerebrospinal fluid pressure in patients with Alzheimer's disease. Cerebrospinal Fluid Res. 2006, 3: 7-10.1186/1743-8454-3-7.PubMed CentralView ArticlePubMed
- Tamura H, Kawakami H, Kanamoto T, Kato T, Yokoyama T, Sasaki K, Izumi Y, Matsumoto M, Mishima HK: High frequency of open-angle glaucoma in Japanese patients with Alzheimer's disease. J Neurol Sci. 2006, 246: 79-83. 10.1016/j.jns.2006.02.009.View ArticlePubMed
- Bayer AU, Ferrari F, Erb C: High occurrence rate of glaucoma among patients with Alzheimer's disease. Eur Neurol. 2002, 47: 165-168. 10.1159/000047976.View ArticlePubMed
- Berdahl JP, Allingham RR, Johnson DH: Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology. 2008, 115: 763-768. 10.1016/j.ophtha.2008.01.013.View ArticlePubMed
- Silverberg GD, Huhn S, Jaffe RA, Chang SD, Saul T, Heit G, Von Essen A, Rubenstein E: Downregulation of cerebrospinal fluid production in patients with chronic hydrocephalus. J Neurosurg. 2002, 97: 1271-1275. 10.3171/jns.2002.97.6.1271.View ArticlePubMed
- Silverberg GD, Mayo M, Saul T, Fellmann J, Carvalho J, McGuire D: Continuous CSF drainage in AD: results of a double-blind, randomized, placebo-controlled study. Neurology. 2008, 71: 202-209. 10.1212/01.wnl.0000316197.04157.6f.View ArticlePubMed
- Kountouras J, Zavos C, Gavalas E, Boziki M, Chatzopoulos D, Katsinelos P: Normal- tension glaucoma and Alzheimer's disease: Helicobacter pylori as a possible common underlying risk factor. Med Hypotheses. 2007, 68: 228-229. 10.1016/j.mehy.2006.07.008.View ArticlePubMed
- Kessing LV, Lopez AG, Andersen PK, Kessing SV: No increased risk of developing Alzheimer disease in patients with glaucoma. J Glaucoma. 2007, 16: 47-51. 10.1097/IJG.0b013e31802b3527.View ArticlePubMed
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