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Antiphospholipid Syndrome and Cognitive Dysfunction – Top 10 Series

Top 10 Points Patients Should Know About How Antiphospholipid Syndrome Can Affect Their Cognition

By Marion Sadoul, Medical Student; Marjorie Toussaint, Medical Student; Elizabeth Kozora, PhDDoruk Erkan, MD, MPH

Antiphospholipid syndrome (APS) patients may experience neurological problems, including cognition (for example, memory) problems. The following questions may help you better understand the different ways that APS may affect your memory. However, you should always speak with your doctor about symptoms and management of your disease.

  1. What is antiphospholipid syndrome?
  2. What is cognition and cognitive dysfunction?
  3. What are the common causes of cognitive dysfunction?
  4. How is cognitive dysfunction generally diagnosed?
  5. What is the frequency of cognitive dysfunction in antiphospholipid syndrome patients?
  6. What are the mechanisms of cognitive dysfunction in antiphospholipid syndrome?
  7. How do you treat cognitive dysfunction in antiphospholipid syndrome patients?
  8. How can cognitive dysfunction in antiphospholipid syndrome patients be prevented?
  9. Does antiphospholipid antibody positivity affect cognition in systemic lupus erythematosus patients?
  10. What is the next step if you think you suffer from cognition dysfunction?

1. What is antiphospholipid syndrome?

Antiphospholipid syndrome is a systemic autoimmune disease characterized by the production of antibodies – antiphospholipid antibodies (aPL) – that “attack” the person’s own body, resulting mainly mainly blood clots (thickened blood) and/or pregnancy complications.

The three most common medical tests to detect aPL are:

  • lupus anticoagulant (LA) test
  • anticardiolipin antibody (aCL) test
  • anti-Beta-2-glycoprotein-I (aβ2GPI) antibody test

People who are aPL-positive, that is, those who produce aPL, may or may not develop clinical problems. Different types of clinical problems aPL-positive patients experience include:

  • blood clots such as a deep vein thrombosis (a clot that forms in the vein usually in a leg), a pulmonary embolus (when the clot travels to the lung), or a stroke (when a clot forms in an artery)
  • pregnancy complications such as miscarriages, early delivery, intrauterine growth restriction, or preeclampsia (high blood pressure and protein in the urine during pregnancy)
  • neurological problems such as cognition problems (see below for further definition) or transient ischemic attack (like a stroke but reversible within a short period)
  • other clinical problems such as low platelet counts or heart valve disease

2. What is cognition and cognitive dysfunction?

Cognition is the brain process involved in thinking, learning, acquiring knowledge and understanding our environment. When your brain functions well, your cognitive system allows you to think, control your movements and communicate with others. These functions involve different parts of the brain.

Cognitive dysfunction is a significant deficit in any or all of the brain functions, such as planning, organizing, learning, recall or speaking (verbal fluency). A patient who suffers from cognitive dysfunction can:

  • forget different things, such as a phone number or a person’s name
  • be disoriented in time or space, that is, does not know where he/she is, or today’s date
  • have trouble in talking fluently, for example, may forget some words or does not use the appropriate word
  • have trouble in organizing

3. What are the common causes of cognitive dysfunction?

The most common causes of cognitive dysfunction in the general population are:

  • progressive central nervous system disorders (Alzheimer’s disease, Parkinson’s disease)
  • strokes and seizures
  • major mood disorders (depression and anxiety)

Other potential acute causes of cognitive dysfunction are:

  • infections such as pneumonia, urinary tract infection or meningitis
  • environmental exposures such as carbon monoxide poisoning or solvents
  • medications such as opioids, muscle relaxants, anxiety drugs or antiseizure drugs
  • hypotension (low blood pressure)
  • hypoglycemia or hyperglycemia (low or high level of blood sugar)
  • dehydration (when the body does not have enough water)
  • behavioral factors such as pain and fatigue

Other potential chronic causes of cognitive dysfunction are:

  • neurological diseases such as multiple sclerosis, epilepsy, movement disorders or brain tumor
  • brain trauma
  • chronic conditions such as hypothyroidism diabetes mellitius, vitamin B12 deficiency
  • chronic alcohol or substance (such as cocaine, opioids) abuse
  • sleep disorders (obstructive sleep apnea, insomnia)
  • Other autoimmune disorders – such as systemic lupus erythematosus (SLE or “lupus”), fibromyalgia, Sjogren’s, rheumatoid arthritis
  • history of developmental disorders or learning disabilities

4) How is cognitive dysfunction generally diagnosed?

There are different tests that can be used to diagnose cognitive dysfunction.

Relatively quick screening tests (mental status evaluations) are based on simple questions such as patient’s name and date of birth, today’s date, or the name of the hospital. There are also quick 5- to 10-minute standardized screening measures such as the Mini Mental Status Examination and the Montreal Cognitive Assessment, which can be administered and scored.

More sophisticated evaluations are performed by a trained neuropsychologist and provide detailed information about the patient’s cognitive function based on their gender, age, educational level and ethnicity. These tests evaluate different cognition-related functions handled by your brain. Here are some examples:

  • attention and concentration (ability to pay selective attention to something while ignoring other things, ability of a person to stay focused on a topic or event)
  • learning (acquisition) and memory (delayed recall) of new information
  • ability to understand auditory and written verbal material
  • thinking of the names of things and verbal fluency
  • perceptual disorders such as the ability to recognize symbols, for example, geometrical figures or country’s flags
  • problem solving, decision making and organizing

5) What is the frequency of cognitive dysfunction in antiphospholipid syndrome patients?

There are different types of cognitive dysfunction, depending on the severity of clinical manifestations. We can summarize them as:

  • mild cognitive impairment
  • moderate cognitive impairment
  • severe cognitive impairment

The most common form in the general population, and more commonly in elderly, is mild cognitive impairment. The frequency in the American population ranges between 7% to 25% and increases with the age.

It is difficult to estimate the true frequency of cognitive dysfunction in APS patients because other conditions (listed above) can be the cause of, or contribute to, cognitive dysfunction in a person who also happens to have APS. For instance, many APS patients with cognitive dysfunction also have lupus or a history of strokes. Although the literature is limited, studies report the frequency of cognitive dysfunction, defined as significant deficits in any or all of the cognitive functions regardless of severity, as 20% to 80% in aPL-positive patients. Based on these studies, we estimate the frequency of cognitive dysfunction in different subgroups of aPL-positive patients as:

  • patients with positive aPL but without APS/lupus: 20% to 40%
  • patients with APS but without lupus: 40% to 80%
  • lupus patients with positive aPL only or APS: 20% to 55%

6) What are the mechanisms of cognitive dysfunction in antiphospholipid syndrome?

Possible mechanisms include:

  • Blood clots – such as stroke or multiple small blood clots – can deprive the brain of oxygen, which can cause damage to brain cells in the form of lesions. Eventually, these lesions can cause a person to have cognitive dysfunction.
  • Other mechanisms, independent of blood clots, include:
    • Impairment of the blood-brain barrier (a semipermeable membrane that separates the blood from the brain’s fluid and which functions as a barrier to the passage of cells, particles and large molecules into the brain) caused by aPL. This can result in antiphospholipid antibodies and other substances to pass into the brain and bind to the brain cells. For example, when aPL are injected in mices brains, the animals display impaired motor coordination as well as hyperactivity that manifests as increased stair-climbing).
    • Direct aPL interference with the function of brain cells.
    • Psychological and behavioral factors associated with having APS (such as depression, anxiety, pain, fatigue).

7) How do you treat cognitive dysfunction in antiphospholipid syndrome patients?

Treatment of cognitive dysfunction in APS patient is not yet well established.

Firstly, we have to make sure that the cognitive dysfunction is due to APS, and that all the treatable causes are excluded.

Secondly, symptoms may be ameliorated by cognitive behavioral therapy. The goal here is to adapt a patient’s behavior to manage daily tasks in which memory is used. Behavioral therapy is tailored based on the patient’s symptoms, helping patient identify problems better, and finding a way to face them. Exercises, intellectual stimulations, diet, improving the sleep quality, and social interaction can also improve the cognitive function (further discussed below). Mindfulness (meditation activities) may also be useful particularly for attention and concentration problems.

Blood thinners can treat and prevent blood clots in APS patients but are not helpful in treating cognitive dysfunction. A small-scale study showed that Rituximab, a drug used to treat cancer, rheumatoid arthritis and vasculitis may improve some aPL-related clinical problems, including cognitive dysfunction. More specifically, improvement in attention, visuomotor speed (that is, the speed of coordination of movement and visual perception by the brain), and flexibility was noted in a small number of APS patients with cognitive dysfunction. It should be noted that these results must be confirmed by a large-scale controlled studies.

8) How can cognitive dysfunction in antiphospholipid syndrome patients be prevented?

Correcting risk factors such as diabetes, hypertension, and obesity has considerable impact on reducing the risk of cognitive dysfunction.

Moreover, several preventive factors have been identified for cognitive dysfunction in general, which include:

  • Education: The most important individual factor): Low level of education is correlated with a higher risk of developing cognitive dysfunction.
  • Intellectual stimulations: Those who keep stimulating their brain by mental exercises (such as crossword or Sudoku puzzles), learning a new language, or going out with their families and friends (instead of staying home watching TV) have the lowest risk of developing cognitive dysfunction.
  • Physical exercise: Benefits of physical exercise are well known for cognitive functions and general health. According to the Lancet Commission (2017), there is an inverse relationship between physical activity and the risk of developing a severe cognitive impairment. The benefits fluctuate depending on the type of physical exercises. In addition, the National Academics 2017 recommend physical exercise to decrease or delay cognitive dysfunction. Physical exercise also decreases the risk of developing chronic diseases such as diabetes and hypertension, which are important risk factors of cognitive dysfunction.
  • Diet: A real connection between diet and the risk of developing cognitive dysfunction exists. A balanced diet is recommended for all patients (that is, eating less meat and more fruits and vegetables, dried fruits and nuts). However, some vitamins such as Vitamin B12 or Vitamin B9 (folic acid) have a positive impact on prevention cognitive dysfunction, especially for patients with a high blood level of homocysteine.
  • Social interactions: Social interaction can prevent cognitive dysfunction. Isolation and loneliness have negative impacts on cognitive function. There are different theories for this connection. One theory is that loneliness can decrease sleep quality, increase the risk of depression, and eventually increase the risk of cognitive dysfunction.
  • Sleep: Sleep plays a crucial role in consolidating memory and eliminating toxic substances produced by the brain. Some studies have reported that bad sleep quality leads to significant metabolic and inflammatory changes in our body, and are related to an increased risk of cardiovascular diseases and cognition problems.

9) Does antiphospholipid antibody positivity affect cognition in systemic lupus erythematosus patients?

Cognitive dysfunction in lupus patients can develop independent of aPL. However, aPL positivity is more frequent in lupus patients with cognitive dysfunction, compared to those without cognitive dysfunction.

10) What is the next step if you think you suffer from cognition dysfunction?

You should talk to your physician if:

  • Your family notices problems with your memory.
  • You forgot recent facts.
  • You are forgetting your medications or important meetings or appointments.
  • It is hard for you to handle a conversation, such as understanding what people are saying or responding to questions.
  • You have trouble recognizing faces or remembering names of familiar people.
  • You are having difficulty solving simple problems or organizing activities.
  • You are getting lost when driving or walking even in familiar places.

Your doctor will investigate the reversible causes of cognitive dysfunction and, if needed, order a neuropsychological tests.


Marion Sadoul*
Medical Student, Academic Visitor, Hospital for Special Surgery, New York, NY

Marjorie Toussaint*
Medical Student, Academic Visitor, Hospital for Special Surgery, New York, NY

*Equally Contributed

Elizabeth Kozora, PhD
National Jewish Health, Denver, CO
Adjunct Scientist, Hospital for Special Surgery, New York, NY


Doruk Erkan, MD, MPH
Attending Rheumatologist, Hospital for Special Surgery
Professor of Medicine, Weill Cornell Medical College

Related articles


  1. Berman J, Erkan D, Lockshin MD. A patient’s guide to the antiphospholipid syndrome. Elsevier Science B.V. 2002; 437-444.
  3. Kozora E, Erkan D, Zhang L , et al. Cognitive dysfunction in antiphospholipid antibody (aPL)-negative systemic lupus erythematosus (SLE) versus aPL-positive non-SLE patients. Clin Exp Rheumatol 2013; 32: 34-40.
  4. Angela M, Sanford MD. Mild Cognitive Impairment. Clinics in Geriatric Medicine, 2017; 33: 325-337.
  5. Petersen RC, Lopez O, Armstrong MJ, 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; 90:126.
  6. Yelnik CM, Kozora E, Appenzeller S. Cognitive disorders and antiphospholipid antibodies. Autoimmun. Rev. 2016; 15: 1193-1198.
  8. Brey R, Muscal E, Chapman J. Antiphospholipid antibodies and the brain: a consensus report. Lupus 2011; 20: pp. 153-157.
  9. Katzav A, Ben-Ziv T, Blank M, et al. Antibody-specific behavioral effects: intracerebroventricular injection of antiphospholipid antibodies induces hyperactive behavior while anti-ribosomal-P antibodies induces depression and smell deficits in mice. J Neuroimmunol 2014; 15: pp. 10-15.
  10. Frauenknecht K, Katzav A, Weiss Lavi R, et al. Mice with experimental antiphospholipid syndrome display hippocampal dysfunction and a reduction of dendritic complexity in hippocampal CA1 neurones. Neuropathol Appl Neurobiol 2015; 41: pp. 657-671.
  11. Ziporen L, Shoenfeld Y, Levy Y, et al. Neurological dysfunction and hyperactive behavior associated with antiphospholipid antibodies. A mouse model. J Clin Invest 1997; 1: pp. 613-619.
  12. Fleetwood T, Cantello R, Comi C. Antiphospholipid Syndrome and the Neurologist: From Pathogenesis to Therapy. Front. Neurol. 2018; 9:1001.
  13. Erkan D, Vega J, Ramón G, et al. A pilot open-label phase II trial of rituximab for non-criteria manifestations of antiphospholipid syndrome. Arthritis Rheum 2013;65:464-71.
  14. Davis K. How does cognitive behavioral therapy work? Medical News Today 2018.
  15. Aube D. La santé cognitive, une nouvelle cible pour vieillir en santé, synthese des connaissances; Direction du développement des individus et des communautés. Institut national de santé publique Quebec 2017.
  16. Norton S, Matthews FE, Barnes BE, et al. Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data. The Lancet Neurology 2014; 13: 788-794.
  17. Rebok GW, Ball K, Guey LT, et al. Ten‐year effects of the advanced cognitive training for independent and vital elderly cognitive training trial on cognition and everyday functioning in older adults. J Am Geriatr Soc 2014; 62: 16-24.
  18. National Academies of Sciences, Engineering, and Medicine. Preventing cognitive decline and dementia. Washington, D.C.: National Academies Press; 2017
  19. Stern Y. The Concept of Cognitive Reserve: A Catalyst for Research. Journal of Clinical and Experimental Neuropsychology, 2003; 25: 589-593.
  20. Blazer DG, Yaffe K, Liverman CT. Cognitive Aging: Progress in Understanding and Opportunities for Action. Committee on the Public Health Dimensions of Cognitive Aging, Board on Health Sciences Policy, Institute of Medicine. Washington, DC: National Academies Press, 2015.
  21. Hikichi H, Kondo K, Takeda T, et al. Social interaction and cognitive decline: Results of a 7-year community intervention. Alzheimers Dement 2017; 3: 23-32.
  22. Hakim A. Préservez votre vitalité mentale : 7 règles pour prévenir la démence, Éditions de l’Homme. 2016; 240.
  23. Sanna G, Bertolaccini ML, Cuadrado MJ, et al. Neuropsychiatric manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid antibodies. J Rheumatol 2003; 30: 985-992.
  24. Hanly JG, Hong C, Smith S, et al. A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus. Arthritis Rheum 1999; 42: 728-34.
  25. Menon S, Jameson-Shortall E, Newman SP, et al. A longitudinal study of anticardiolipin antibody levels and cognitive functioning in systemic lupus erythematosus. Arthritis Rheum 1999; 42: 735-41.
  26. Ruiz-Irastorza G, Egurbide MV, Martinez-Berriotxoa A, et al. Antiphospholipid antibodies predict early damage in patients with systemic lupus erythematosus. Lupus 2004; 13: 900-905.

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