Marriage, Actually…Doesn’t Prevent Dementia?!?

An Interview with Dr. Selin Karakose

Your study challenges previous research & the long-held belief that marriage offers protective benefits against dementia. So I'm curious, what led you to explore the relationship between marital status and dementia risk?

Our research team investigates the role of various psychosocial protective and risk factors in cognitive health, including dementia risk. Given the evolving role of marriage in society and the increasing number of unmarried individuals (divorced, widowed, or never married), understanding their potential vulnerability to dementia is critical for identifying high-risk groups and providing targeted monitoring and support. Therefore, we aimed to extend prior work by examining whether unmarried individuals have an elevated risk of dementia, using a large sample (NACC) of over 20,000 older adults followed for up to 18 years with annual evaluations at specialized dementia clinics across the United States.

The findings indicate that never-married and divorced individuals had a lower risk of developing dementia compared to married individuals. Were you surprised to see that? Could you elaborate on the potential factors or mechanisms that might explain this trend?

Yes, we were surprised. Accounting for age and sex, we found that widowed, divorced, and never-married individuals had about 50%* or lower dementia risk relative to their married counterparts. Notably, this effect was similar across male and female participants and younger and older adults.

*When hazard ratio [HR] is below 1, the percentage of reduction is calculated as (1/HR)x100. So, for widowed: 1/0.73=37%, divorced: 1/0.66=52%, and never married: 1/0.60=66%).

Despite the commonly held belief that marriage is protective for health, recent research has not found disadvantages of being unmarried compared to married, including in cognitive outcomes. For example, a recent study by Hanes and Clouston (2024) indicated that participants experienced slower rates of cognitive decline following divorce, which could potentially lead to a lower risk of dementia over time.

Several factors could potentially contribute to these results. There is some evidence that divorce can lead to greater happiness and life satisfaction, and widowed individuals may experience an increase in close network size in the years following widowhood, which could potentially protect against dementia risk. Older married individuals, on the other hand, may have a smaller social network, tend to be less self-reliant, and may experience stressful conditions such as caregiving, which could contribute to the lower risk of dementia. Another important possible explanation is that the findings could suggest a delayed diagnosis among unmarried individuals. More research is needed to identify the mechanisms linking marital status and incident dementia.

Since people who aren't married might get diagnosed with dementia later than those who are, how did you handle that in your study? And how might it affect the conclusions we draw from the results?

We examined the average age of dementia onset and the severity at onset: Our findings suggested that while the widowed were diagnosed at an older age and with slightly more severe symptoms compared to the other groups, the never married and divorced did not differ from the married on the age or severity of impairment at the time of diagnosis. 

Individuals may be unaware of their symptoms, particularly in the early stages of dementia. The subtle prodromal changes associated with cognitive impairment and dementia, such as memory, personality, and behavior changes are frequently first reported by partners/spouses. Thus, married individuals might be more likely to seek dementia evaluation and to be diagnosed at an earlier stage compared to those who are unmarried.

However, the participants in the NACC study were evaluated each year with rigorous standardized testing at clinics specialized in dementia diagnosis. Thus, it is unlikely that there are substantial delays in diagnosis for the NACC participants. A delay in diagnosis might be more of an issue for prior studies that relied on health records, which partly depend on individual self-referral to their doctor, which may introduce biases in the timing of diagnosis.

The results of previous studies showing that marriage was protective could be explained by a delayed diagnosis for the married. For example, compared to unmarried individuals who need to be self-reliant to live independently, partners can compensate for cognitive impairment, delaying seeking care, which would result in delayed diagnosis.

Given that social connection is a known protective factor for cognitive health, do you think the observed differences in dementia risk are more about social support and relationship quality than marital status per se?

Within marriage, the health benefits appear to be present only in high-quality marriages. Indeed, in a study by Lawrance and colleagues (2019) individuals who are unhappy in their marriage, an indicator of marital quality, are more likely to have equal or worse health and mortality risk compared to those who are widowed, divorced, or never-married counterparts. In line with this, a recent study from our research team found that on days when participants were more satisfied with their relationships, they felt healthier and reported sharper minds, better memory, and clearer thinking. Examining the association by considering marital status duration (e.g., timing of marital loss) and incorporating other relationship factors (e.g., relationship satisfaction) is needed to fully understand the connection between marital status and risk of dementia.

What are the broader implications of your findings for public health or dementia prevention strategies? (Could these results shift how we think about social connection and cognitive aging beyond marital status?)

Our findings highlight that marriage itself may not be a universally protective factor for health, as traditionally believed. Given that nearly half of all dementia cases worldwide could be prevented or delayed by addressing 14 modifiable risk factors, it is critical to identify older adults who are vulnerable to developing dementia. Our findings suggest that married individuals may be at higher (not lower) risk and could benefit from closer monitoring and support.

What other questions are you currently exploring in your research? Are there follow-up studies or related areas of aging and brain health you're particularly excited about?

Our recent research focuses on investigating the link between life satisfaction, a crucial component of well-being, and the risk of dementia among older adults. We provided consistent evidence that life satisfaction is associated with a lower risk of dementia, and that this protective effect is robust across world regions, persisting even after accounting for well-established dementia risk factors (e.g., age, sex, education, depression, diabetes, smoking). Our next step is to investigate the association between marital status and dementia in other samples to replicate and evaluate the generalizability of the findings. Additionally, since the health benefits of marriage appear to occur only in high-quality relationships, we aim to examine the role of relationship quality on cognitive outcomes.

Dr. Karakose conducts research at Florida State University.

You can read the full study here.

An interview with Dr. Reut Shor, Dr. Marko Popovic, Dr. Rajeev Runi, Dr. Andrew Mihalache

Can you tell our readers a little about yourself and the work you do? What prompted you to investigate a potential link between the popular weight-loss drugs (GLP-1 receptor agonists) and the serious eye condition called wet macular degeneration (also known as Neovascular Age-Related Macular Degeneration or AMD)?

We are a group of physicians, researchers and methodologists who all have an interest in ocular (eye) health. Investigating the potential toxicities of systemic medications on retinal health is one of our areas of interest. Neovascular AMD is fundamentally a disease of pathological angiogenesis (new blood vessel formation), and several of its risk factors overlap with those seen in patients who often use GLP-1 receptor agonists, such as those with chronic heart failure, chronic kidney disease, and diabetes.

In addition, there have been growing reports of ocular adverse events with GLP-1 receptor agonists, but no clear consensus regarding their impact on AMD progression. This made me very curious to explore this relationship using real-world, population-level data.

For those unfamiliar, can you describe what neurovascular age-related macular degeneration (nAMD) is and why it is significant for patients with diabetes (Type 2?)

Age-related macular degeneration is a condition that affects the retina (which is similar to the film in a camera) at the back of the eye. It is the most common cause of vision loss in those aged 50 and older in the developed world. Age-related macular degeneration exists in two main forms: the early form called dry AMD, and the more advanced form called wet AMD or neovascular AMD (nAMD). In nAMD, abnormal blood vessels grow beneath the retina and leak, leading to rapid and potentially severe vision loss. This condition is particularly relevant for patients with type 2 diabetes, mainly because GLP-1 receptor agonists are commonly prescribed for diabetes management, but also because both diabetes and nAMD share key risk factors such as aging, impaired blood circulation, and chronic inflammation.

Your study found a twofold increased risk of nAMD in patients with diabetes using GLP-1 Receptor Agonists (RAs). How clinically significant is this increase? (How should patients and/or clinicians interpret it?)

While the absolute risk remains low—about 2 in 1,000 for GLP-1 RA users compared to 1 in 1,000 for non-users—the twofold increase in a matched population is clinically meaningful. It suggests a potential biological link between the medication and the disease. additionaly, older age and a history of stroke were both associated with an even higher risk of nAMD in the context of GLP-1 receptor agonist use. For these higher-risk patients, clinicians may want to exercise additional caution. Regardless of age or comorbidities, it’s important for clinicians to be aware of potential ocular risks and to promptly refer patients to ophthalmology if they report visual symptoms or concerns. Close collaboration between prescribing clinicians and eye care providers will be key as we continue to learn more.

Do we know why GLP-1 RAs might be associated with increased risk of nAMD? Are there any working theories?

GLP-1 receptor agonists appear to have several different adverse effects on the eye, and it seems that the net effect may be harmful in the context of neovascular AMD.

On one hand, we know that GLP-1 receptor agonists are very effective at improving blood glucose control. Some studies have suggested that the increase in ocular adverse events could be related to the sudden and sharp drop in blood glucose upon initiating these agents. If this is true, we would hypothesize that after longer-term use, once blood sugar levels stabilize, the risk of nAMD with GLP-1 receptor agonist use might decline. However, in our study, we observed that the risk actually increased with prolonged exposure.

When we looked further into the potential direct effects of GLP-1 receptor activation on the eye, we found that GLP-1 receptors are expressed in the retina, specifically, in the retinal ganglion cells, retinal pigment epithelial cells and endothelial cells, which may trigger different cascades. For example, an animal study in mice showed that activation of these receptors can induce a hypoxic effect on the retina. This could represent one possible mechanism contributing to the increased risk we observed.

Of course, more research is needed to fully understand these pathways, but these findings offer some important clues.

Are specific GLP-1 RAs more implicated than others—or was the increased risk consistent across the class?

97.5% of the prescribed GLP-1 drugs in our study were semaglutide (Ozempic), while lixisenatide (Adlyxin) accounted for only 2.5% of prescriptions. This is likely because semaglutide was the more widely available and indicated formulation during the study period. Thus, the results reflect the overall class effect observed. To draw conclusions regarding specific GLP-1 agents, more granular data would be required in future studies.

These drugs are widely used for diabetes and weight loss. In your opinion, how should this finding influence prescribing decisions, if at all, education for patients or label warnings?

I wouldn’t say it should cause alarm, but it should encourage awareness. GLP-1 receptor agonists provide significant benefits for cardiovascular and kidney outcomes, and those benefits remain very important. However, patients, especially those at higher risk for AMD (such as older adults or those with a history of stroke), should be monitored carefully, and clinicians should remain vigilant for any new visual symptoms in these patients. Patients who are prescribed these drugs that experience vision issues should be promptly referred to an ophthalmologist for further evaluation.

What kind of follow-up studies are needed to understand this risk more clearly? (In those with diabetes, but I'm also curious about risk in those with obesity without diabetes.)

The next steps for this research involve moving beyond observational findings to more definitive study designs. To establish causality, prospective cohort studies will be needed to confirm the association between GLP-1 receptor agonist use and neovascular AMD. In parallel, further investigation into the underlying biological mechanisms, through both basic science and translational research, will be essential to understand how these drugs may influence retinal health. Finally, as GLP-1 RAs are increasingly prescribed to non-diabetic individuals for weight loss, it will be important to study these populations as well, to determine whether the observed ocular risks extend beyond diabetic patients.

Are you doing any more research in this area or what sort of research are you doing next, if any?

Our next step will be to explore whether similar ocular risks are present in non-diabetic individuals, particularly given the growing use of GLP-1 receptor agonists for weight loss.

To read the full study and learn more about the study authors, click here.