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Glaucoma Associated With Vascular Dementia

POAG, Alzheimer’s and Dementia

Primary open angle glaucoma (POAG) and Alzheimer’s are both neurodegenerative diseases that have some features in common and other features that are distinct. Retinal ganglion cells are lost in both conditions, for example. The modified tau proteins that make up the tangles or twisted fibers in Alzheimer’s are also found in the retina of those with POAG. In addition, abnormal retinal deposits of amyloid-beta have been seen in animal models of glaucoma as well as the amyloid plaque found in the brains of Alzheimer’s patients.

On the other hand, the two conditions differ in some of their risk factors; cigarette smoking is thought to increase risk of Alzheimer’s for instance, but not of POAG. The genetic risk factors for the two conditions also appear distinct. The major genetic variant for Alzheimer’s is at apolipoprotein E, with carriers of the E4 allele having a higher Alzheimer’s risk. But in most studies E4 allele does not influence POAG risk.

Is there a connection between these two diseases? Previous epidemiologic studies looking at their potential relationship have had inconsistent results, leading a team of UK researchers to further study whether individuals diagnosed with POAG are at greater risk of subsequently developing Alzheimer’s (1).

The investigators also examined whether the risk of developing vascular dementia in subsequent years was linked to POAG, as there has been ongoing interest in potential associations between POAG and vascular disease.

Study Design

In this record linkage study, A POAG cohort of 87,658 people was constructed from English National Health Service-linked hospital statistics from 1999 to 2011. An Alzheimer’s cohort (251,703 people), a vascular dementia cohort (217,302 people) and a reference cohort (>2.5 million people) were similarly constructed. Risk of dementia following POAG was determined; rate ratios were calculated based on standardized rates of dementia in the POAG cohort.

Results

The researchers found no elevated risk of developing Alzheimer’s following a diagnosis of POAG. The rate ratio was 1.01 (95% CI 0.96 to 1.06).

However, a modest but significant positive association was seen between POAG and vascular dementia, with a rate ratio of 1.10 (95% CI 1.05 to 1.16). They also found that the likelihood of a hospital record of POAG following Alzheimer’s or dementia diagnosis was very low, with rate ratios of 0.28 (0.24 to 0.31) and 0.32 (0.28 to 0.37), respectively.

Comments

The potential relationship between POAG and vascular dementia is interesting, and further study is warranted. If this observed association is confirmed, it could have important implications for understanding disease pathophysiology in the two conditions, and provide insights into whether treatment strategies for one disease might be effective against the other.

Also, the finding that Alzheimer’s and dementia patients do not commonly have a record of developing POAG could represent a genuine deficit in ophthalmic care for people with a loss of mental ability.

Possible explanations for the observed link may include risk factors that are shared between POAG and vascular dementia. For example, diabetes and hypertension are strong risk factors for vascular dementia, and also increase the risk of POAG. In addition, previous research has shown that patients with POAG have reduced cerebrovascular blood flow and vaso-reactivity compared with controls.

As some glaucoma experts are now asking, could damage from glaucoma be the ocular manifestation of more widespread vascular problems involving the brain, rather than a separate process isolated only to the eye (2)?

References

1. Keenan TDL, et al. Associations between primary open angle glaucoma, Alzheimer’s disease and vascular dementia: record linkage study. Br J Ophthalmol; 99:524–27, 2015.
2. Harris A, et al. Cerebral blood flow in glaucoma patients. J Glaucoma 22:546-48, 2013.