15 Mar 2022

While scientists know that age-related hearing loss increases a person’s risk of dementia, their view of how vision loss affects cognition is fuzzy. It may be coming into focus, though. Recently, scientists reported that people who had surgery to remove cataracts were 30 percent less likely to be diagnosed with dementia than those who went untreated. Recent meta-analyses of observational studies suggest that fading eyesight increases dementia risk up to twofold. Could simply preserving or restoring people's vision and hearing lower the incidence of dementia? Prospective trials addressing this possibility are ongoing.

Alas, the connection between sensory loss and dementia is not straightforward. People with failing eyes or ears struggle taking cognitive tests, even if they don’t have dementia, yet scientists lack consensus on how to reckon with this confound in dementia studies. Are they missing opportunities to more accurately diagnose and prevent dementia?

“There needs to be greater consistency in how studies account for participants who have problems with hearing and/or vision at the time of cognitive testing,” wrote Phillip Hwang, Boston University, to Alzforum.

Willa Brenowitz, University of California, San Francisco, agreed, noting that age-related hearing and vision impairments receive too little attention. “Showing that they have broad health effects, including increased risk for dementia, could lead to more effective treatment strategies,” she wrote to Alzforum (comment below). Both Hwang and Brenowitz study the effect of age-related hearing or vision loss on dementia.

Diminishing Perception. As people age, their eyes and ears weaken. [Courtesy of Kuo et al., JAMA Network Open, 2021.]

Sharp Senses, Sharp Mind?
More than half of Americans 70 or older have impaired sight or hearing, and 11 percent of people over 80 have both (Lin et al., 2011; Swenor et al., 2013). Multiple reviews and meta-analyses have reported that people whose hearing was failing were 1.25- to 2.5-fold likelier to subsequently get dementia (reviewed by Ford et al., 2018; Loughrey et al., 2018; Feb 2011 news). In fact, a Lancet Commission pegged mid-life hearing loss as the largest modifiable risk factor for dementia (Aug 2020 conference news; Aug 2017 conference news). The report did not address poor eyesight because no meta-analysis was available at the time.

Since then, analysis of 12,300 U.K. Biobank participants aged 55 to 73 found that dementia incidence was higher in people who had macular degeneration, a cataract, or eye disease (Shang et al., 2021). Another large cross-sectional study of 3,375 Americans 65 and older in the Cardiovascular Health Study found that cataracts, macular degeneration, or diabetic retinopathy were likelier to be associated with dementia (Hwang et al., 2021). Three meta-analyses of observational studies did, as well. One calculated 35 percent greater odds of cognitive impairment, and 47 percent greater risk of dementia, in people with impaired vision (Shang et al., 2021). A second found those odds to be 66 and 109 percent higher, respectively (Vu et al., 2021). A third, focusing on eye diseases, found that cataracts and diabetic retinopathy bumped up dementia risk by 17 and 34 percent, respectively, while glaucoma and macular degeneration had no effect (Kuźma et al., 2021).

“These meta-analyses confirm that vision impairment is an epidemiological risk factor, and many people are optimistic that it will be included in future Lancet Commission updates,” Heather Whitson, Duke University School of Medicine, Durham, North Carolina, wrote to Alzforum.

Much the same conclusion came from a recent prospective study of almost 70,000 participants 60 and older from the U.K. Biobank and the European Prospective Investigation into Cancer‑Norfolk cohorts (Littlejohns et al., 2021). Researchers led by Elżbieta Kuźma, University of Hamburg, Germany, compared the dementia incidence over 15 years in visually impaired volunteers and controls. Those with severe impairment were twice as likely to develop dementia.

Another observational study tied certain aspects of vision loss to specific cognitive domains. Among 1,200 participants in the Baltimore Longitudinal Study of Aging, those with weak visual acuity or depth perception scored worse on memory and language tests. People with poor contrast sensitivity, i.e., the ability to distinguish an object from background, struggled on memory, language, attention, and visuospatial tasks (Varadaraj et al., 2021). 

What about the double whammy of failing eyes and ears? In a recent longitudinal analysis among 7,500 people 65 and older in the U.S. National Health and Aging Trends Study, those whose eyesight and hearing was bad were 50 percent likelier to be diagnosed with dementia over seven years than unimpaired participants (Kuo et al., 2021). 

“The data from observational studies overwhelmingly converge to support the claim that vision and hearing impairment are both risk factors for subsequent dementia,” Whitson wrote. Kuźma agreed. “Although there are still many questions to be answered, sensory impairment is a very promising target for dementia prevention,” she wrote (full comment below).

Cataract Surgery Prevents Dementia
Cataracts offer an opportunity to test this idea. In the United States, more than half of people older than 80 have a cataract or have had one removed, according to the National Eye Institute. Eric Larson, Kaiser Permanente Washington Health Research Institute, Seattle, wondered if dementia incidence fell after this brief surgery. As reported in the December 6, 2021, JAMA Internal Medicine, first author Cecilia Lee of the University of Washington, Seattle, tested this by analyzing medical records of 3,766 cognitively normal participants in the Adult Changes in Thought study, which began in 1994. The ACT recruits healthy people older than 65 from around Seattle and assesses them twice a year. Those who score 85 percent or lower on the Cognitive Abilities Screening Instrument undergo clinical evaluation for dementia. Most participants in this cohort are Caucasian.

As surgery controls, Lee included 728 glaucoma patients. Though less common than cataracts, glaucoma is a leading cause of blindness in aging. It damages the optic nerve by causing a buildup of pressure that can be relieved by draining the fluid in the eyeball. One hundred and five people had this procedure, while about half of the 3,038 people with a cataract had it removed. Of the people who had cataracts at the start of the study, 853, or 28 percent, developed dementia, 709 of them AD. Among the glaucoma cases, 230, or 32 percent, developed dementia, including 184 AD cases.

Did restoring sight reduce dementia incidence? Of the 1,382 people who had a cataract removed, 23 percent developed dementia, versus 30 percent of the 1,656 who opted not to have the surgery. All told, Lee calculated that people who had their cataracts removed were 30 percent less likely to develop all-cause or AD dementia (see image below). The glaucoma pressure treatment did not reduce dementia risk. “This reassured us that the decreased dementia risk is specific to cataract removal, and not just being healthy enough to undergo eye surgery,” Lee said.

When calculating dementia risk, she accounted for age at cataract or glaucoma diagnosis, and common risk factors, including sex, race, years of education, APOE genotype, and smoking history. The study not only supports the idea that vision impairment increases a person’s risk for dementia, but that correcting vision could stave it off.

No Cataract, No Dementia? In the ACT cohort, cataract surgery reduced the risk of developing all-cause dementia. Only being APOE4 negative was more protective. Data for AD were similar (not shown). [Courtesy of Lee et al., JAMA Internal Medicine, 2021.]

Putting Sensory Restoration to the Test
Jennifer Deal, Johns Hopkins University, Baltimore, applauded the bias controls in Lee’s study but noted that it was observational and relied on medical records. “We still don’t know if sensory loss causes dementia, just that many studies show associations and that some observational data suggest sensory restoration may be beneficial,” she told Alzforum.

In fact, the association can cut both ways. Analysis of medical records of 141,000 old people in Finland found that people who already have dementia are less likely to have their cataracts removed than cognitively healthy people (Hokkinen et al., 2022). The Finnish researchers found this concerning, because cataract removal might improve quality of life.

Deal highlighted the need for prospective studies that directly test if treating poor eyesight or hearing would prevent dementia. One randomized controlled trial measuring functional and quality-of-life changes over six months among 122 people with AD who either had or did not have their cataracts removed has completed, but results are not yet published. As it stands, a few trials hint that correcting sensory deprivation slows memory loss.

After a pilot study of 40 cognitively normal elders suggested hearing aids slightly improve memory over six months, Deal, along with Frank Lin and Josef Coresh at JHU, in 2018 began a randomized controlled trial to see if hearing aids could slow cognitive decline and prevent dementia over three years (Deal et al., 2017; Deal et al., 2018). Called Aging and Cognitive Health Evaluation in Elders Study (ACHIEVE), it includes 977 dementia-free 70- to 84-year-olds from the Atherosclerosis Risk in Communities cohort who had mild to moderate untreated hearing loss. Half got a pair of hearing aids and four training sessions over 10 weeks to ensure they knew how to use them, while the rest met with a health counselor four times over the same period to learn how to prevent age-related diseases. Outcomes include cognition, social engagement, and mental and physical health every six months. Time to a diagnosis of dementia or mild cognitive impairment is one of the secondary outcomes. Deal said the trial will wrap up this year and report results in 2023.

Some observational studies have also found that older adults’ executive function improves once they begin using hearing aids (reviewed by Sanders et al., 2021). To broaden access to these devices, the FDA recently proposed that people be allowed to buy them without having a medical exam or audiologist fitting (FDA 2021 press release). Both Larson and Brenowitz consider this promising. “Hearing aids and vision corrections are underutilized, often being ignored until severe stages of sensory impairment,” Brenowitz wrote.

The case is not cut-and-dried, though. Correcting hearing and vision loss after a dementia diagnosis has yielded mixed results (reviewed by Dawes et al., 2019). For example, in a randomized controlled trial of 51 people with AD and hearing loss, hearing aids did not slow cognitive decline over six months as per ADAS-Cog scores (Nguyen et al., 2017; reviewed by Mamo et al., 2018). In contrast, deaf people with mild cognitive impairment fared better after cochlear implants were surgically placed inside their ears to directly stimulate auditory nerves. In a small observational study of 70 older adults, cognition remained stable for seven years in 19 of the 31 who had MCI before the surgery, and it even returned to normal in another 10 of them (Mosnier et al., 2018; reviewed by Dawes, 2019). 

A simple reason for restoring a person's sight and hearing is it will ease their social isolation, which is linked to increased risk for dementia. The European SENSE-Cog randomized control trial is assessing this by giving hearing aids or glasses to 354 adults with mild to moderate dementia and hearing or vision loss (Regan et al., 2019). They receive home check-ins to ensure they are using their aids regularly. The primary outcome is change in Dementia Quality of Life score, while secondary outcomes include change in Montreal Cognitive Assessment, various activities of daily living, and the Neuropsychiatric Inventory. A previous pilot of 19 participants found that, after two months, they felt less alone, more socially engaged, and more independent with daily activities (Hooper et al., 2019; Leroi et al., 2020). 

Can You Hear Me Now?
If people don't see or hear well, do they score worse on cognitive tests even if their cognition is fine? One prospective study found that old people with hearing loss scored worse on the auditory Modified Telephone Interview for Cognitive Status, but did just fine on the visual Hopkins Verbal Learning Test or verbal fluency task (Goodwin et al., 2021). 

With this in mind, Deal and Bonnielin Swenor, also at JHU, wondered how scientists deal with this problem when measuring cognition in aging, including people being evaluated for dementia. As reported in the February 1 Alzheimer’s & Dementia, co-first authors Chelsea Liu of the Harvard T.H. Chan School of Public Health, Boston, and Niranjani Nagarajan of JHU asked leaders of 192 cognitive aging studies if and how they account for hearing and vision loss. The authors chose ongoing or recently completed prospective studies of at least 200 people older than 60 that included two or more types of cognitive assessment. They did not require the cohorts to study MCI or dementia, nor did they look at the primary goal of each study.

Of 85 responses, 77 had measured hearing loss, 78 had measured vision loss, 75 had measured both, and five neither. Most did so subjectively, via patient self-reporting or physician evaluation. Some objectively assessed the senses: 32 cohort studies ran hearing tests, and 45 tested vision. During cognitive testing, only one-third of the studies equipped participants who had a sensory impairment with an aid, such as a magnifying glass, a screen with a large font, or a headset.

Overall, there was little consensus in the way researchers assessed for hearing and vision loss or adjusted protocols accordingly, prompting Liu and Nagarajan to call for standardization in the field. Hwang and Kuźma agreed. “Harmonization of protocols across cohorts would greatly improve the quality and comparability of studies and validation of results, ultimately leading to a much better understanding of cognitive changes and dementia,” Kuźma wrote.

Liu and Nagarajan believe that, without proper standards, researchers overestimate dementia prevalence, essentially mistaking vision or hearing deficits for cognitive decline.

Looking Ahead
Though research in this area has been picking up of late, much remains unknown. At conference held by the National Institute on Aging and the American Geriatrics Society, scientists defined three main research gaps: understanding the mechanisms that link sensory loss and cognition, finding better measures to quantify those links, and identifying interventions (Whitson et al., 2018). 

Sense and Cognition. Hearing, vision, and cognition are linked but scientists need to learn exactly what changes in aging . [Courtesy of Whitson et al., Journal of the American Geriatrics Society, 2018.]

Researchers have a few theories about how hearing or vision loss may lead to dementia (see image above; reviewed by Griffiths et al., 2020; Uchida et al., 2019; Rutherford et al., 2018). The “use it or lose it” hypothesis posits that people who lose sight or hearing withdraw from mentally stimulating tasks, leading to depression and social withdrawal. “People with sensory impairment are not able to fully engage the world, which expedites these dementia risk factors,” Lee said.

Another idea is that waning senses stress the brain by hijacking neurons that would otherwise perform cognitive tasks into helping interpret sights and sounds (reviewed by Martini et al., 2014). “Garbled sound makes the brain work harder, which may pull resources away from other activities, such as forming memories,” Deal suggested. Researchers think the same may be true in cases of poor vision.

Could fading eyesight directly affect neural circuitry? Cataracts are usually yellow, hence filter blue light. Lee thinks this might prevent stimulation of intrinsically photosensitive retinal ganglion cells. ipRGCs help regulate circadian rhythm and have been tied to cognitive function and AD. "Lower risk for developing dementia following cataract extraction may also be associated with increased stimulation of ipRGCs by blue light," Lee and colleagues wrote in their December 6 paper.

Deal agrees that sensory deprivation may directly change the brain. The temporal lobe, the home of the primary auditory cortex, shrinks faster in people with hearing loss (reviewed by Ralli et al., 2019). Whitson is leading an observational study to test this further, monitoring brain-structure changes in people with macular degeneration.

Lastly, researchers don't know how amyloid plaques or neurofibrillary tangles fit into the interplay between dementia and poor senses. “Is the brain losing the ability to distinguish sophisticated sounds because of dementia pathology?” asked Larson. If so, could hearing aids still help improve cognition?

Whitson also thinks more work is needed to understand how dementia and sensory deprivation dovetail. “It’s unknown to what degree age-related vision and hearing loss directly cause or unmask dementia, or whether sensory impairment and dementia frequently co-occur because they share similar risk factors,” Whitson wrote.—Chelsea Weidman Burke

Comments

1. • Phillip Hwang
     Boston University
   • Posted: 15 Mar 2022

   These four studies help to raise more awareness about the impact of hearing and visual impairments on the development of dementia and cognitive dysfunction. The article by Lee et al. is very interesting as it provides initial evidence that vision loss may be causally related to dementia, since cataract extraction was associated with reduced risk of dementia. More studies need to be done to confirm this finding, with special attention paid to addressing limitations associated with an observational study design and ascertainment of cataract diagnoses and surgery. But the observed findings are intriguing and can motivate further studies to examine whether visual impairment is a causal risk factor for dementia and to test potential interventions to address vision loss.

   I was also struck by the results reported by Liu et al., who showed the heterogeneity in how hearing and vision problem are accounted for during cognitive testing. This is an important descriptive paper because one of the main questions in the field regarding the relationship between hearing and/or vision and cognition, including dementia, is to what degree is performance on cognitive testing influenced by poor hearing and vision, and how that might affect the interpretation of the results. To evaluate the body of evidence more accurately, we need greater consistency in how studies account for participants who have problems with hearing and/or vision at the time of cognitive testing and in what those procedures might be. Hopefully, this paper will stimulate discussion and action around this.

   View all comments by Phillip Hwang
2. • Willa Brenowitz
     UCSF
   • Posted: 15 Mar 2022

   I think it is still unclear what mechanisms are driving the association between sensory impairments and dementia risk. However, if sensory impairments are indeed risk factors for dementia, this would offer an important avenue for intervention. Hearing aids and vision corrections are underutilized, and often interventions occur in more severe stages. There is room to improve aspects of hearing and vision care, as well the accommodations that make it easier for those with impairments to navigate the world.

   But we really aren't quite able to say that sensory impairments cause dementia. There is some question around what cognitive tests are measuring in those with sensory impairment, and whether associations are due to reverse causation or shared risk factors (e.g., genes, vascular disease). As most studies just describe associations in older adults, it's very difficult to tease these issues apart.

   It's important we have more studies aimed at understanding the underlying biology, including those that can test specific mechanisms and different hypotheses. I think Lee et al.’s paper on cataract surgery is a nice attempt to account for some of the potential biases, since they include modeling approaches to reduce bias as well as examine a negative control (glaucoma).

   Overall, I'd say, there is a very intriguing connection between sensory loss and dementia. There is a lot we still don't know about these associations, and a need for further studies. One of the biggest limitations, highlighted by Liu et al., is that many studies don't include both objective sensory measurement and dementia outcomes (including cognitive, imaging, and biomarkers).

   Additionally, few studies include longitudinal sensory measures or measurement spanning the life course. This could be addressed by expanding sensory measures in aging cohorts.

   View all comments by Willa Brenowitz
3. • Elżbieta Kuźma
     Albertinen-Haus Centre for Geriatrics and Gerontology, University of Hamburg
   • Posted: 17 Mar 2022

   There is a growing interest in the relationship between sensory impairment and dementia risk. Hearing loss is an established dementia risk factor that has been highlighted as a key modifiable risk factor by both Lancet Commissions on dementia prevention, intervention, and care published in 2017 and 2020. Visual impairment has been studied less extensively. However, two recent meta-analyses suggested an increased risk of all-cause dementia associated with visual impairment (Shang et al., 2021; Kuźma et al., 2021). 

   Another study by Lee and colleagues suggested that cataract extraction is associated with lower dementia risk. This further adds to our understanding of the relationship between eye diseases and dementia risk. Our recent meta-analyses investigating visual impairment, eye diseases, and dementia risk suggested an increased risk of dementia and Alzheimer’s disease associated with cataracts (Kuźma et al., 2021). However, we identified only four prospective studies investigating these associations. I am very pleased to see another study on this topic that addresses key issues, e.g. reverse causation.

   I would like to highlight the systematic review by Liu and colleagues on the association between hearing and vision impairment in cohort studies collecting cognitive data in older adults. I want to emphasize their call for the development of standardized methods to collect cognitive data that consider sensory impairment. Studies involving older people who may have sensory impairment vary greatly in terms of the methodology used, e.g. sample selection, adjustment strategy, and ascertainment of sensory impairment and dementia, which makes comparisons difficult. Harmonization of protocols across cohorts would greatly improve the quality and comparability of studies, and validation of results, ultimately leading to a much better understanding of cognitive changes and dementia.

   Identifying modifiable risk factors for dementia that could inform the development of targeted interventions or help identify those at risk of developing dementia is of great importance given there is currently no cure for dementia. Given that most causes of sensory impairment are treatable or preventable, managing these problems could help improve the quality of life and reduce dementia risk.

   More research is needed to assess the potential to prevent dementia using interventions that reduce sensory impairment. More well-designed studies on dual sensory impairment with objective measurements are also needed as hearing and visual impairment often co-occur. Although there are still a lot of questions to be answered, especially in terms of mechanisms that could explain the sensory-dementia associations, sensory impairment is a very promising target for dementia prevention.

   References:

   Shang X, Zhu Z, Wang W, Ha J, He M. The Association between Vision Impairment and Incidence of Dementia and Cognitive Impairment: A Systematic Review and Meta-analysis. Ophthalmology. 2021 Jan 8; PubMed.

   Kuźma E, Littlejohns TJ, Khawaja AP, Llewellyn DJ, Ukoumunne OC, Thiem U. Visual Impairment, Eye Diseases, and Dementia Risk: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2021;83(3):1073-1087. PubMed.

   View all comments by Elżbieta Kuźma

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References

News Citations

1. Hearing Loss Linked to Incident Dementia 21 Feb 2011
2. Lancet Commission’s Dementia Hit List Adds Alcohol, Pollution, TBI 4 Aug 2020
3. Lancet Commission Claims a Third of Dementia Cases Are Preventable 11 Aug 2017

Paper Citations

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External Citations

1. randomized controlled trial
2. Aging and Cognitive Health Evaluation in Elders Study (ACHIEVE)
3. FDA 2021 press release
4. European SENSE-Cog

Further Reading

Papers

1. Naël V, Pérès K, Dartigues JF, Letenneur L, Amieva H, Arleo A, Scherlen AC, Tzourio C, Berr C, Carrière I, Delcourt C, Helmer C, Sense-Cog consortium. Vision loss and 12-year risk of dementia in older adults: the 3C cohort study. Eur J Epidemiol. 2019 Feb;34(2):141-152. Epub 2019 Jan 4 PubMed.
2. Jafari Z, Kolb BE, Mohajerani MH. Age-related hearing loss and tinnitus, dementia risk, and auditory amplification outcomes. Ageing Res Rev. 2019 Dec;56:100963. Epub 2019 Sep 23 PubMed.
3. Hubbard HI, Mamo SK, Hopper T. Dementia and Hearing Loss: Interrelationships and Treatment Considerations. Semin Speech Lang. 2018 Jul;39(3):197-210. Epub 2018 Jun 22 PubMed.
4. Andrusjak W, Barbosa A, Mountain G. Identifying and Managing Hearing and Vision Loss in Older People in Care Homes: A Scoping Review of the Evidence. Gerontologist. 2020 Apr 2;60(3):e155-e168. PubMed.

News

1. HHS Adds Goal of Alzheimer’s Prevention to National Plan 28 Dec 2021
2. Sharp Centenarians Shrug Off Effects of Alzheimer’s Pathology 2 Feb 2021
3. Resilience Redefined: Sharp at Age 100, Still Sharp at 102 4 Mar 2020
4. Are Subtle Memory Concerns a Sign of Future Dementia? 31 Jul 2013