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Do Neuronal Autoantibodies Contribute to Cognitive Impairment in Patients With Lung Cancer?


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In a German prospective cross-sectional study reported in JAMA Oncology, Bartels et al found that a high proportion of patients with lung cancer had neuronal antibodies that may be associated with increased risk of cognitive impairment.

As stated by the investigators, “Paraneoplastic neurological syndromes are associated with neuronal autoantibodies, and some of these autoantibodies are associated with neuropsychological symptoms. The most common underlying tumor is lung cancer. The association of neuronal autoantibodies with cognitive deficits has not been systematically investigated in patients with small cell lung cancer (SCLC) and non–small cell lung cancer (NSCLC).”

Study Details

This prospective, cross-sectional study included 167 consecutive patients with SCLC (n = 40) or NSCLC (n = 127) recruited at a single lung cancer center (Evangelische Lungenklinik) in Berlin between June 2015 and April 2016. Neuropsychological testing was performed in a selected subgroup of 97 patients, excluding patients aged > 80 years, those with brain metastases or a history of severe neurologic or psychiatric disorders, and those who had received brain radiotherapy or who had surgery < 5 days before enrollment.

In this prospective, cross-sectional study, more than one-third of patients with lung cancer had neuronal autoantibodies that were found to be associated with cognitive impairment. These autoantibodies might represent a potentially treatable mechanism of immune-mediated cognitive impairment among patients with lung cancer.
— Bartels et al

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Cognitive function was assessed with a battery of standardized neuropsychological tests for verbal memory, visuospatial memory, working memory, attention, and executive function. Cognitive impairment was defined, using International Cognition and Cancer Task Force criteria, as a test score of two or more standard deviations below the test-specific reference cohort on one or more test(s) of a cognitive domain. Investigators were blinded to patient autoantibody status and cognitive test results.

Key Findings

Brain-directed autoantibodies were detected in 61 (36.5%) of 167 patients, with 33 (19.8%) having known autoantibodies and 28 (16.8%) having autoantibodies against currently unknown antigens detected through immunohistochemical analysis. The prevalence of autoantibodies was 45.0% in patients with SCLC and 33.9% in those with NSCLC, and 69.6% in male and 63.4% in female patients.

Among patients with SCLC, the odds ratio for cognitive impairment with presence vs absence of autoantibodies was 11.0 (95% credible interval [CrI] = 1.2–103.6), with the increased risk being independent of age, sex, and neurologic deficit.

Among patients with NSCLC, those with immunoglobulin A autoantibodies targeting the N-methyl-D-aspartate receptor, the most common type identified, had an odds ratio for verbal memory deficit of 182.8 (95% CrI = 3.1–10,852.4). Patients with autoantibodies against currently unknown antigens had an odds ratio for cognitive impairment of 2.8 (95% CrI = 0.6–12.1).

The investigators concluded, “In this prospective, cross-sectional study, more than one-third of patients with lung cancer had neuronal autoantibodies that were found to be associated with cognitive impairment. These autoantibodies might represent a potentially treatable mechanism of immune-mediated cognitive impairment among patients with lung cancer.”

Carsten Finke, MD, of the Department of Neurology, Charite–Universitatsmedizin Berlin, is the corresponding author for the JAMA Oncology article.

Disclosure: This study was funded by grants from the German Ministry of Education and Research and German Research Foundation. For full disclosures of the study authors, visit jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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