What Is Antiphospholipid Syndrome (APS) “Brain Fog”? If I Have APS “Brain Fog,” What Can I Do To Help?

The APS Program Community Q&A Series, written by Dr. Ray Zuo, was created to answer questions we receive from the APS Program community and will cover a variety of topics. In this month’s edition, Dr. Zuo provides some updates to a previous topic regarding brain fog and APS!

QUESTION: What is antiphospholipid syndrome (APS) “brain fog”? If I have APS “brain fog,” what can I do to help?

ANSWER: Cognitive dysfunction (what many refer to as "brain fog") can be experienced by those who have APS or lupus. One report assessed cognitive function among 143 patients with positive antiphospholipid antibody testing and found cognitive dysfunction in 3% of patients with low levels of antiphospholipid antibodies, but in 12% of patients with higher levels [1]. Another study found cognitive dysfunction in 42% of APS patients compared to 11% of healthy individuals matched for age, sex, and level of education [2]. The prevalence of cognitive problems has been reported as even higher in lupus, up to 88% in some studies [3].

Brain fog can take many different forms and affects each person differently. Some people notice difficulty finding the right words, trouble concentrating, or problems remembering small details, while others describe a general sense of mental slowness that makes everyday tasks harder. These symptoms can be confusing and deeply frustrating, especially because they often come and go. In APS, brain fog is typically episodic, meaning symptoms may worsen during periods of stress, illness, or fatigue and then improve again. Importantly, this type of cognitive difficulty does not usually progress to severe dementia, which is reassuring, even though the symptoms themselves can be very disruptive to daily life.

Despite how common and burdensome brain fog is for people with APS, its underlying cause remains poorly understood, representing a major knowledge gap in the field. Many patients experience brain fog even when brain imaging such as MRI appears normal, blood tests show no obvious abnormalities, and there is no history of stroke [4]. This makes APS-related cognitive symptoms particularly challenging to study. Several mechanisms have been proposed, including microscopic blood clots in the brain, disruption of the blood–brain barrier that normally protects the brain from harmful antibodies and inflammatory molecules, ongoing inflammation and immune activation, and psychological factors such as depression or anxiety [5]. However, none of these explanations fully account for what patients' experience.

A few recent studies provide important but incomplete clues. One study comparing brain MRI scans from approximately 200 APS patients to 69 healthy individuals found that people with APS were more likely to show brain volume loss, or atrophy, even in the absence of prior stroke, although the relationship between these changes and brain fog was not strong [6]. Another study in lupus patients, some of whom had antiphospholipid antibodies, showed that levels of calprotectin—a marker of neutrophil activation—were higher in those with cognitive dysfunction, and that changes in calprotectin tracked with changes in cognition over time [7]. These findings suggest that inflammation, particularly involving neutrophils, may contribute to cognitive symptoms, but much more research is needed to define the exact biological mechanisms.

Unfortunately, research on cognitive dysfunction in APS remains limited, and dedicated funding for this area is almost nonexistent. Because APS-related brain fog does not fit neatly into traditional categories such as stroke or dementia, it is often overlooked by major funding agencies. As a result, the biological mechanisms underlying APS brain fog remain poorly understood, and there are currently no targeted or effective treatments available. 

Recognizing how profound brain fog can affect quality of life for patients with APS, our laboratory has launched a self-funded research effort aimed at uncovering its underlying mechanisms. The work focuses on how antiphospholipid antibodies interact with key brain support cells, including astrocytes and oligodendrocytes, which are essential for brain signaling, energy balance, and protection of neurons. By studying how different types and concentrations of antiphospholipid antibodies alter the function of these cells, we hope to identify biological pathways that could one day be targeted for treatment. For those who feel moved to help advance this effort, we welcome and deeply appreciate any interest in supporting this research, as patient-directed contributions can play a meaningful role in moving this important work forward.

When considering APS-associated brain fog, it is important to first rule out other common causes of cognitive problems, such as Alzheimer’s disease, Parkinson’s disease, seizure disorders, poorly controlled chronic medical conditions like high blood pressure or diabetes, sleep disorders, and untreated or undertreated depression and anxiety [8-10]. At present, there are no APS-specific therapies for cognitive dysfunction, but symptom-focused strategies can help patients better manage daily life.

If you experience episodes of brain fog, don’t panic, but do bring this issue to your doctor’s attention. Meanwhile, here are some strategies that may help manage your life with APS brain fog:

1. Sleeping well: Not sleeping enough impairs our brain’s ability to eliminate toxic substances and is associated with cognitive dysfunction.
2. Reducing stress: Give your mind a chance to rest and relax. Set a time each day to reset yourself by meditating, listening to music, or taking a walk outside.
3. Applying cognitive pacing: Avoid multitasking. Break your mental work into shorter blocks and take regular breaks.
4. Challenging your mind: Exercise your mind and keep it stimulated (such as doing crossword puzzles, reading, learning a new language, interacting with new people, etc.).
5. Getting emotional support: A supportive environment is crucial for managing cognitive symptoms.
6. Taking care of your body: Take on a healthy diet and exercise regularly. Avoid alcohol and tobacco.

In summary, brain fog is a common and often debilitating symptom for patients with APS, but it does not typically progress to severe dementia. Its causes are likely complex and involve many interacting factors, and the lack of dedicated research has significantly slowed progress toward understanding and treating this condition. While targeted therapies are not yet available, adopting supportive lifestyle strategies can help patients regain a sense of control and confidence. Continued research, including self-funded efforts driven by patient needs, is essential to close this knowledge gap and ultimately develop effective treatments for APS-related cognitive dysfunction.

1. Erkan, D., et al., Moderate versus high-titer persistently anticardiolipin antibody positive patients: are they clinically different and does high-titer anti-beta 2-glycoprotein-I antibody positivity offer additional predictive information? Lupus, 2010. 19(5): p. 613-9.

2. 2. Tektonidou, M.G., et al., Cognitive deficits in patients with antiphospholipid syndrome: association with clinical, laboratory, and brain magnetic resonance imaging findings. Arch Intern Med, 2006. 166(20): p. 2278-84.

3. 3. Hanly, J.G., et al., Review: Nervous System Disease in Systemic Lupus Erythematosus: Current Status and Future Directions. Arthritis Rheumatol, 2019. 71(1): p. 33-42.

4. 4. Hassan, F., et al., Cognitive Impairment in Anti-Phospholipid Syndrome and Anti-Phospholipid Antibody Carriers. Brain Sci, 2022. 12(2).

5. 5. Ricarte, I.F., et al., Neurologic manifestations of antiphospholipid syndrome. Lupus, 2018. 27(9): p. 1404-1414.

6. 6. Naftali, J., et al., Brain atrophy is associated with antiphospholipid antibody syndrome with and without vascular pathology. J Neurol Sci, 2025. 472: p. 123460.

7. 7. Munoz-Grajales, C., et al., Association of Elevated Serum S100A8/A9 Levels and Cognitive Impairment in Patients With Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken), 2025. 77(11): p. 1303-1312.

8. 8. Norton, S., et al., Potential for primary prevention of Alzheimer's disease: an analysis of population-based data. Lancet Neurol, 2014. 13(8): p. 788-94.

9. 9. Petersen, R.C., et al., Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology, 2018. 90(3): p. 126-135.

10. 10. Langa, K.M. and D.A. Levine, The diagnosis and management of mild cognitive impairment: a clinical review. JAMA, 2014. 312(23): p. 2551-61.