Eyes Offer Window Into Cognitive Impairment

Cognitive impairment occurred more than twice as often in patients with normotensive glaucoma (NTG) as compared with high-tension glaucoma (HTG) and exhibited a trend toward greater impairment, a matched case-control study showed.

A telephone-based cognitive assessment questionnaire showed that 14.8% of patients with NTG met criteria for cognitive impairment versus 5.4% of patients with HTG. Patients with cognitive impairment trended toward lower highest-measured intraocular pressure (IOP). Otherwise no ocular parameters had associations with cognitive impairment in either group.

The study builds on existing evidence supporting an association between NTG and dementia, Sean Mullany, MD, of Flinders University in Adelaide, Australia, and coauthors reported in the British Journal of Ophthalmology.

“What we think is important about this study is that it demonstrates, on a small scale, that some of these patients with normal tension glaucoma have clinical features suggestive that nerve degeneration is occurring, not just in the eye, but elsewhere within the brain,” Mullany told MedPage Today via email. “That’s not to say that people with normal tension glaucoma will get dementia nor vice versa. To us it is more suggestive that there may be some shared risk features – be those genetic or environmental – which may contribute to nerve degeneration within the eye and within the brain.”

“This study is important as it provides some additional evidence of a possible relationship between glaucoma and dementia. We think that the takeaway message is that glaucoma is more than just a disease of eye pressure, and that further clinical advances in glaucoma may result from developing a better understanding of the neurological and systemic features of this disease.”

The data analysis included a relatively small number of participants (290) and multiple factors could have accounted for the differences observed, which the authors acknowledged, said Andrew Iwach, MD, of the Glaucoma Center of San Francisco, and a clinical spokesperson for the American Academy of Ophthalmology.

“To me the exciting point of all this is that with newer imaging technologies that were originally designed to help us monitor glaucoma patients and retinal disease, these same instruments now have such high resolution that we can detect earlier signs — we’ve always been able to see signs of high blood pressure or diabetes in the eye — but now potentially some of these other neurologic conditions,” said Iwach.

“I think [the study] adds to our body of knowledge, but I wouldn’t act on this data just yet,” he added. “We need a better study, a large study, because it may turn out that there were some other factors that influenced the end result.”

Several observational studies provided evidence of an association between primary open angle glaucoma (POAG) and dementia. However, the data have been inconsistent. A recent meta-analysis yielded a small positive association, but individual studies included in the analysis were heterogeneous, as were the results.

Understanding of the pathophysiology of NTG, a POAG subtype arising from retinal degeneration in the absence of ocular hypertension, remains incomplete. However, the discovery of an association between NTG and two genes implicated in frontotemporal dementia suggests the possibility of a shared neurodegenerative pathway, the authors noted as background for their research. Previous studies of NTG and dementia were limited by retrospective study design and small sample sizes.

“We hypothesized that NTG is associated with an increased prevalence of cognitive impairment and sought to elucidate this association through a cross-sectional comparison of cognition in older NTG and HTG participants randomly sampled from a large, multicenter glaucoma registry,” Mullany and coauthors stated.

Participants for the study came from the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG), which has a database comprising more than 7,000 patients, including 3,200 with POAG. Eligibility was limited to ANZRAG participants at least 65 years old. HTG was defined as a highest-recorded IOP of ≥25 mm Hg and NTG as a highest-recorded IOP ≤21 mm Hg.

Investigators identified 248 participants with NTG and an age- and sex-matched group of 349 with HTG. Cognitive function was assessed by means of the telephone version of the Montreal Cognitive Assessment (T-MoCA) with a maximum possible score of 22. Mullany and colleagues defined cognitive impairment as a score of <11.

A total of 290 participants completed the cognitive assessment. The results showed that 21 of 144 participants in the NTG group had T-MoCA scores <11 as compared with eight of 146 participants in the HTG group. The difference translated into an odds ratio of 2.2 for an association between NTG and cognitive impairment (95% CI 1.1-6.7, P=0.030). NTG had a non-significant association with lower absolute T-MoCA score as a continuous variable (P=0.108).

By multivariate analysis, NTG and cognitive impairment remained significantly associated (OR 2.6, 95% CI 1.1-6.7, P=0.034). Hypertension was the only other factor independently associated with cognitive impairment (OR 1.7, 95% CI 1.0-2.8, P=0.038). Participants with cognitive impairment had lower highest-measured IOP, but the difference did not achieve significance versus participants without impairment (P=0.16).