As eyecare providers (ECPs), cataracts are one of the most common pathological ocular conditions we diagnose, monitor, refer for treatment, and co-manage after surgery. It is estimated that 94 million people are blind or visually impaired worldwide, and a cataract is the most common cause.1
In the US, though cataracts are not the leading cause of blindness, the condition affects more than 20.5 million Americans over age 40.1 Furthermore, 6.1 million Americans have already had cataract surgery.2
Cataracts develop because of aging, oxidative stress, and other modifiable risk factors like ultraviolet (UV) exposure, medication use, and smoking.2 A cataract is associated with a decrease in quality of life and a reduction in life expectancy. As the risks of cataract surgery have reduced, the number of candidates for surgery has grown.1
Overview of dementia
Dementia is a syndrome characterized by the deterioration of cognitive function beyond what is expected from the normal biological aging process.3 The World Health Organization (WHO) estimates that 55 million worldwide are affected by dementia, with the number expected to reach approximately 78 million by 2030 and 139 million by 2050.3
In the US, the CDC estimates that 5.8 million people have Alzheimer’s disease and related dementias, and the number of cases is expected to increase to 14 million by 2060.4
Signs, symptoms, and manifestations of dementia
Dementia, also called major neurocognitive disorder, is characterized as a chronic progressive loss of cognitive function in the absence of fluctuating consciousness. It is primarily a geriatric syndrome that may be caused by several underlying conditions.
Alzheimer’s disease (AD) is the leading cause and the usual form of dementia. It presents gradually, subtly, and results in progressive cognitive impairment with increasing severity over a period of years.5
The disease manifests as a disorder of higher brain functions, including learning and memory, complex attention, executive function, language, motor perception, and social cognition, which affect the patient’s ability to perform everyday activities.3 Like any other condition, the risk factors are both genetic and environmental.
Risk factors involve hypertension, diabetes, hyperlipidemia, metabolic syndrome, unhealthy diet, smoking, and physical inactivity.6 Because there is a lack of effective treatments for patients with dementia, finding risk factors to stop or delay dementia has become a priority in treatment.7
Diagnosis of dementia
Diagnosis of the disease is difficult and is frequently subjective.6 There is no single diagnostic test, and doctors use a variety of methods, including physical examination and brain scans, such as computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET), to rule out other causes for the patient’s symptoms.
A definitive diagnosis only occurs at death, where the abnormal accumulation of β-amyloid peptides (Aβ) extracellular aggregates, β-amyloid plaques, and protein tau intracellular twisted strands (neurofibrillary tangles, NFTs) can be observed.6
Currently, early diagnosis is based on the early recognition of various signs and symptoms; the most common sign being memory loss. Scientists have proposed that noninvasive eye scans and ocular biomarkers may be a diagnostic technique in the detection of early AD.6
The eye provides a window to the brain by way of the retina. Studies have reported the presence of β-amyloid plaques in the retina of AD patients, opening the possibility of detecting AD through a noninvasive eye scan. Furthermore, study data have revealed both degenerative changes and retinal neuron damage in the retina/eye of AD animal models. Labs are developing retinal imaging platforms able to detect β-amyloid plaques in the retinas of AD patients.6
Ophthalmic manifestations of dementia
Dementia can involve changes to structures in both the anterior and posterior segments.
Anterior segment biomarkers
The tear film could be a potential source for biomarkers of dementia. One study found that the combination of four tear proteins lipocalin-1, dermcidin, lysozyme C, and lacritin, had 81% sensitivity and 77% specificity for AD.6 Abnormal tear functions and reduced corneal sensitivity have been described with many neurodegenerative diseases.
Further, pupillary responses are associated with changes in brain impairment, including light reflex amplitude, which is reduced in AD. Of note, β-amyloid, found in AD patients, has been detected in the human lens of AD patients, and a correlation has been found between cortical cataract formation and AD degeneration.6
Posterior segment signs
The aqueous humor also has higher levels of proteins involved in AD pathology, such as β-amyloid peptides; and a series of chemokines, including eotaxin, eotaxin 3, and interleukin IL-8.
Inoue et al. suggested that open-angle glaucoma patients presented elevated levels of various biomarkers of AD in the aqueous humor, including apolipoprotein (Apo) AI, ApoCIII, ApoE, transthyretin (TTR), complement factor H, complement C3, and α2-macroglobulin (α2M).6
There is also data to suggest that ocular biomarkers related to neurodegenerative disorders may play an important role in the development of retinal impairment or loss of visual function. Retinal thickness is correlated to cortical atrophy and both the choroid and nerve fiber layer (NFL) demonstrate thinning in AD patients.
AD patients also show retinal ganglion cell (RGC) loss, and patients with AD, as well as AD animal models, display both Aβ and tau protein accumulation in the inner retinal layers.6
Identifying AD/dementia with ophthalmic imaging
Noninvasive optical imaging of the retina and optic nerve head (OHN) has been used to assess the optic nerve in AD and can be used as an effective screening tool in cognitive aging. In vivo detection of amyloid deposits in AD and the retinas of patients with AD were reported using OCT, and findings included perimacular and perivascular spots in the outer plexiform layer (OPL) and ganglion cell layer (GCL) and thinning of the NFL.6
Investigators hypothesize that changes in retina microvasculature may precede the changes in cerebral microcirculation seen in AD. Using imaging, investigators intend to evaluate markers of reduced capillary blood flow and nonperfusion in the superficial and deep retinal vascular plexuses and choriocapillaris imaging using OCT angiography (OCTA) that would complement established retinal-structural markers and increase their sensitivity and specificity in early detection.6
Various studies found that patients with AD have less density of retinal microvascular networks than normal, so retinal vessel reaction to flicker stimulation may be a promising noninvasive and widely available future test for the diagnosis and monitoring of AD.6
However, at the present time, the ocular biomarkers utilizing fundus photography, OCT, and OCTA have shown poor to moderate accuracy. Therefore, future longitudinal studies are needed to investigate whether changes in OCT and OCTA measurements over time are more accurate predictors of AD onset.8
Tips for co-managing patients with AD/dementia
No standard of care currently exists for an ocular protocol for dementia patients.6
Here are some tips for improving the exam for your patients:
- Schedule the exam during the best time of the day for the AD patients.
- Showing individual letters versus lines or sentences may provide a better measure of visual acuity. While Snellen testing may measure their acuity, it is unlikely to capture their visual function or be an indicator of their real-world performance.
- If available, perform contrast sensitivity testing which may be a better measure of visual performance than visual acuity.
- Perform testing, including visual field and/or OCT to manage other disease processes.
- Monitor patients more frequently to assess the change in cataract status (e.g., 3 to 6 months).
- Look for updated research on the protocol for managing the patient with AD.
- Caregivers may not always inform their doctors that patients have AD, so conveying this information to the surgeon when referring for cataract surgery may improve outcomes.
What is the sensory deprivation hypothesis?
It is worth noting that 20% of Americans older than 65 years of age experience significant sensory impairment, including vision or hearing.7,9 Numerous prospective studies have shown an association between sensory impairment and cognitive decline.7
Sensory impairment is thought to contribute to social isolation and/or a decline in activity or exercise, which may result in a decline in cognitive stimulation, increasing the risk of dementia. It has been proposed that correcting sensory loss may be a modifiable risk factor for the prevention of dementia later in life.9
Cataracts could be a target for intervention, as they act as a potential source of visual sensory deprivation. Therefore, cataract surgery could be an important intervention if it can be shown to be a protective factor against the risk of developing dementia.7
Studies on cataract surgery and dementia
Though the exact mechanism between cataract surgery and dementia is not fully understood, researchers have suggested several ideas.
First, a cataract may decrease neuronal input, which could accelerate neurodegeneration or amplify the effect of neurodegeneration through brain atrophy.9 Studies show the visual cortex changes structurally with vision loss.
Patients with neovascular age-related macular degeneration (nAMD) show an associated visual cortex atrophy and an increase in gray matter volume has been observed after cataract surgery.9 Furthermore, it is possible the brain tries to compensate for the visual deficit, which may increase cognitive load and exacerbate the brain’s decline.9
The literature also demonstrates an association between cataract extraction and an increase in the quantity and quality of light. Intrinsically photosensitive retinal ganglion cells (ipRGCs) are sensitive to short-wavelength (blue) light, which has been shown to be associated with cognitive function, circadian rhythm, and Alzheimer’s.9
The ipRGCs are linked to multiple areas of the brain, and their activation may trigger brain activity. The yellow hue of the lens caused by a cataract may block the blue light, which activates these retinal cells.9
A systematic review and meta-analysis of 245,299 people in four trials, conducted in 2023 by Zhang et al., concluded cataract surgery may be a protective factor against the onset of all-cause dementia and can reduce the economic and family burden caused by all-cause dementia worldwide. The team noted that because the etiology of different types of dementia varies cataract surgery may not reduce all types of dementia.7
The connection between eye diseases/vision loss and dementia
Numerous recent studies have connected glaucoma and AD, as both diseases have common risk factors and pathophysiological mechanisms, suggesting that Alzheimer's disease and glaucoma should be considered age-related neurodegenerative diseases.6
AD and AMD also share common pathological signaling defects and disease mechanisms at the genetic level. Study evidence suggests that β-amyloid, the main component of senile plaques and the hallmark sign of AD, is also a vital component of drusen, the main marker of AMD.6
Though AMD is a retinal disease, AD damages the brain cells as well as the retina. Further, the two conditions share commonalities, including abnormal extracellular deposits, metabolic and oxidative stress, neuroinflammation, and microvascular abnormalities.6
The link between cataract removal and decreased dementia risk
Multiple studies have found cataract removal is significantly associated with a lower risk of developing dementia. A 2022 study compared glaucoma surgery with cataract surgery, and the report found glaucoma surgery, which doesn’t improve vision, did not lower the risk of developing dementia; however, cataract surgery, which does improve vision, did.9
Findings show that having cataract surgery can reverse the risk of dementia, suggesting that reversible visual impairment could be a modifiable risk factor for the disease. Compared with patients with cataracts who did not receive cataract surgery, the risk of dementia in adults receiving cataract surgery was reduced by 50%.10
In conclusion
Emerging evidence supports the potential cognitive benefits of cataract surgery. Research suggests a correlation between improved visual acuity post-surgery and a reduced risk of dementia.
While the exact mechanisms remain unclear, researchers point to enhanced sensory input, reduced cognitive load, and potential neuroprotective effects as potential mechanisms. As such, cataract surgery may be a modifiable factor in the prevention or delay of cognitive decline.
Timely intervention by ECPs may preserve both visual and cognitive health among our aging patients. Further studies are needed to better understand the precise mechanism and identify both biomarkers and imaging findings that allow for earlier identification of the disease.
