Associations Between POAG, Alzheimer's and Vascular Dementia
Associations Between POAG, Alzheimer's and Vascular Dementia
Aims The potential association between primary open angle glaucoma (POAG) and Alzheimer's disease (AD) is uncertain and has implications for understanding disease pathogenesis, referral and treatments. The aim was to determine whether individuals diagnosed with POAG are at higher risk of subsequently developing AD or vascular dementia.
Methods A POAG cohort of 87 658 people was constructed from English National Health Service linked hospital episode statistics from 1999 to 2011. An AD cohort (251 703 people), vascular dementia cohort (217 302 people) and reference cohort (>2.5 million people) were constructed in similar ways. Risk of dementia following POAG was determined: rate ratios were calculated based on standardised rates of dementia in the POAG cohort.
Results The risk of AD following a diagnosis of POAG was not elevated: the rate ratio was 1.01 (95% CI 0.96 to 1.06). The risk of vascular dementia after POAG was modestly elevated, with rate ratio 1.10 (1.05 to 1.16). The likelihood of a hospital record of POAG following AD or vascular dementia was very low, with rate ratios 0.28 (0.24 to 0.31) and 0.32 (0.28 to 0.37), respectively.
Conclusions POAG and AD are neurodegenerative conditions that share some pathological features. However, considering AD after POAG, their coexistence at the individual level is no different from that expected by chance. By contrast, a diagnosis of POAG is modestly associated with later development of vascular dementia, presumably owing to shared vascular risk factors. People with dementia in England are much less likely to be admitted subsequently with POAG, perhaps through poor access to hospital eye services and diagnostic challenges.
Primary open angle glaucoma (POAG) and Alzheimer's disease (AD) are neurodegenerative diseases strongly associated with increased age. POAG and AD exhibit similarities in some histopathological features: retinal ganglion cells are lost in both conditions, and hyperphosphorylated τ is found in the AD brain and the glaucomatous retina. In addition, abnormal retinal deposition of amyloid-β has been observed in animal models of glaucoma. However, differences are observed between the two conditions in some of their systemic risk factors; for example, cigarette smoking is thought to increase risk of AD but not of POAG. The genetic risk factors for the two conditions also appear distinct. The major genetic variant for AD is at APOE; the ε4 allele carries higher risk of AD, but in most studies does not influence POAG risk.
Considerable interest has grown in recent years over the potential relationship between POAG and AD. This has important implications for understanding disease pathophysiology in the two conditions, and may provide insights into whether existing drugs against targets in one disease (eg, antiamyloid-β drugs) may be effective against the other disease. Ongoing laboratory and clinical trials in this area have been reviewed recently, including strategies based around targeting plaque formation, inflammation, oxidative stress and neuroprotection. In addition, considerable interest has grown in the potential for using retinal changes as a biomarker for AD. Finally, a positive association might also suggest that patients diagnosed with one condition should be screened for the other.
However, definitive evidence for an epidemiological association has been lacking. Several studies have observed increased prevalence of glaucoma in patients with AD, though methodological weaknesses and small study sizes may limit their interpretation. By contrast, other studies have suggested that patients with POAG are not at increased risk of developing AD.
We have previously examined the potential association between age-related macular degeneration (AMD) and AD using record linkage. Similarly, the main purpose of the current study was to use record linkage to determine whether individuals admitted to hospital with POAG were significantly more or less likely than others to develop AD in subsequent years. In addition, the risk of developing vascular dementia in subsequent years was examined, given ongoing interest in potential links between POAG and vascular disease.
Abstract and Introduction
Abstract
Aims The potential association between primary open angle glaucoma (POAG) and Alzheimer's disease (AD) is uncertain and has implications for understanding disease pathogenesis, referral and treatments. The aim was to determine whether individuals diagnosed with POAG are at higher risk of subsequently developing AD or vascular dementia.
Methods A POAG cohort of 87 658 people was constructed from English National Health Service linked hospital episode statistics from 1999 to 2011. An AD cohort (251 703 people), vascular dementia cohort (217 302 people) and reference cohort (>2.5 million people) were constructed in similar ways. Risk of dementia following POAG was determined: rate ratios were calculated based on standardised rates of dementia in the POAG cohort.
Results The risk of AD following a diagnosis of POAG was not elevated: the rate ratio was 1.01 (95% CI 0.96 to 1.06). The risk of vascular dementia after POAG was modestly elevated, with rate ratio 1.10 (1.05 to 1.16). The likelihood of a hospital record of POAG following AD or vascular dementia was very low, with rate ratios 0.28 (0.24 to 0.31) and 0.32 (0.28 to 0.37), respectively.
Conclusions POAG and AD are neurodegenerative conditions that share some pathological features. However, considering AD after POAG, their coexistence at the individual level is no different from that expected by chance. By contrast, a diagnosis of POAG is modestly associated with later development of vascular dementia, presumably owing to shared vascular risk factors. People with dementia in England are much less likely to be admitted subsequently with POAG, perhaps through poor access to hospital eye services and diagnostic challenges.
Introduction
Primary open angle glaucoma (POAG) and Alzheimer's disease (AD) are neurodegenerative diseases strongly associated with increased age. POAG and AD exhibit similarities in some histopathological features: retinal ganglion cells are lost in both conditions, and hyperphosphorylated τ is found in the AD brain and the glaucomatous retina. In addition, abnormal retinal deposition of amyloid-β has been observed in animal models of glaucoma. However, differences are observed between the two conditions in some of their systemic risk factors; for example, cigarette smoking is thought to increase risk of AD but not of POAG. The genetic risk factors for the two conditions also appear distinct. The major genetic variant for AD is at APOE; the ε4 allele carries higher risk of AD, but in most studies does not influence POAG risk.
Considerable interest has grown in recent years over the potential relationship between POAG and AD. This has important implications for understanding disease pathophysiology in the two conditions, and may provide insights into whether existing drugs against targets in one disease (eg, antiamyloid-β drugs) may be effective against the other disease. Ongoing laboratory and clinical trials in this area have been reviewed recently, including strategies based around targeting plaque formation, inflammation, oxidative stress and neuroprotection. In addition, considerable interest has grown in the potential for using retinal changes as a biomarker for AD. Finally, a positive association might also suggest that patients diagnosed with one condition should be screened for the other.
However, definitive evidence for an epidemiological association has been lacking. Several studies have observed increased prevalence of glaucoma in patients with AD, though methodological weaknesses and small study sizes may limit their interpretation. By contrast, other studies have suggested that patients with POAG are not at increased risk of developing AD.
We have previously examined the potential association between age-related macular degeneration (AMD) and AD using record linkage. Similarly, the main purpose of the current study was to use record linkage to determine whether individuals admitted to hospital with POAG were significantly more or less likely than others to develop AD in subsequent years. In addition, the risk of developing vascular dementia in subsequent years was examined, given ongoing interest in potential links between POAG and vascular disease.
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