Possible Increase in Prevalence of Alzheimer Disease Found in Patients With Myasthenia Gravis

There was a significant increase in the prevalence of Alzheimer disease (AD) in patients with previously diagnosed myasthenia gravis (MG), suggesting that MG is an independent risk factor of the disease, according to the results of a study published in Neurologica.

Both MG and AD are similar in that they compromise acetylcholine function. In MG, this occurs at the level of the neuromuscular junction due to autoimmune disorder, while in AD, this occurs in the central nervous system following neurodegeneration, the study authors wrote. Despite these similarities, there have been no studies up until now that have reported a possible link between MG and AD. Therefore, the investigators aimed to analyze a potential relationship between the two by examining the OR and prevalence of AD among patients who have MG.

The multicenter, retrospective, observational study was conducted using data from the electronic medical records of patients of a health care system in Spain. Clinical data were obtained on 3,181,485 patients between January 1, 2011, and May 10, 2020, obtained, and only patients older than 60 years were included (N = 970,503 patients).

Concept of Alzheimer disease

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Of these patients, 1208 had MG (4.28%), while 44 patients also had AD, with an average age of 79.3 (95% CI, 77.1-81.3) years. In patients who were older than 60 years and did not have MG (n = 969,475 patients), 27,350 also had a diagnosis of AD (2.82%), with an average age of 81.1 (95% CI, 81.7-81.9) years, the results of the study show.

Upon examining these data, the investigators observed an increase in the prevalence of AD in the cohort with MG vs the general population (4.28% vs. 2.82%), the results show. There was a significant statistical difference among the 2 populations, and an OR of 1.54 (95% CI, 1.13-2.08; P = .0051).

The authors noted that there was not a statistically significant difference in important risk factors of AD such as age, hypertension status, gender, hyperlipidemia, and type 2 diabetes. However, they note that the association between MG and AD does not indicate causality, and that future investigations should aim to provide insight into this matter.

Although available evidence suggests that vascular risks can play a large role in the development of AD, the investigators adjusted for risk factors in each group, and there was no statistical difference between the groups with and without MG when comparing these risk factors, the study authors wrote. They concluded that there is a stronger argument for the consideration of MG as an independent factor for AD.

The investigators proposed a series of hypotheses that could explain the association between MG and AD. One hypothesis supports a direct relationship between MG and AD, suggesting that patients with MG present cognitive problems more frequently than the general population; however, there have been conflicting studies on the matter.

Further, previous evidence indicates autoimmune diseases may be associated with a higher risk of AD. Other explanations include the physical and mental weakness that is associated with chronic diseases, which could cause cognitive defects, and the possible correlation between corticoid consumption and a higher risk of developing AD, the study authors wrote.

They cautioned that these hypotheses are speculative and require further investigation. They also noted that the study had some limitations, including it being an observational, retrospective study that could have led to bias when collecting data.

“This association does not demonstrate causality, but this opens the possibility of a potential pathophysiological relationship between both diseases,” the study authors concluded.

Reference

Morales-Casado M I, Diezma-Martin A M, Munoz-Escudero F, et al. Association between myasthenia gravis and Alzheimer’s disease. Neurologica. 2024;78(2):41-46. doi:10.33588/rn.7802.2023120