Neuronal Autoantibodies May be Associated With Cognitive Impairment in Lung Cancer

The presence of neuronal autoantibodies in patients with lung cancer, specifically small cell lung cancer and non–small cell lung cancer, appears to be associated with cognitive impairment.

The presence of neuronal autoantibodies in patients with lung cancer could be associated with cognitive impairment, according to results from a prospective, cross-sectional study published in JAMA Oncology.

Neuronal autoantibodies were detected in 36.5% (95% CI, 29.2%-44.3%) of the patients with lung cancer included in the study population. Patients with small cell lung cancer (SCLC) had a higher prevalence of neuronal antibodies (45.0%; 95% CI, 29.3%-61.5%) compared with patients with non–small cell lung cancer (NSCLC; 33.9%; 95% CI, 25.7%-42.8%).

Of the patients who were selected for comprehensive standardized neuropsychological assessment, cognitive impairment was observed in 65 patients (67%) with lung cancer based on International Cognition and Cancer Task Force criteria. The most commonly observed cognitive domain deficits were executive function (45.8%) and attention (43.3%). Additionally, the odds of cognitive impairment among patients with SCLC who have neuronal autoantibodies were 11-fold higher than patients who were autoantibody-negative (OR, 11.0; 95% credible interval [CrI], 1.2-103.6).

“The association of autoantibodies with cognitive impairment was particularly notable in patients with SCLC and was mainly found among patients with [ anti-intracellular] autoantibodies (AICs) and associated with deficits in verbal memory, visuospatial memory, and attention,” the investigators wrote.

From June 2015 to April 2016, a total of 167 patients with lung cancer were recruited from 1 center in Berlin, Germany. A select subgroup of 97 patients underwent detailed neuropsychological testing. Investigators focused the research outcomes on the prevalence of neuronal autoantibodies their association with cognitive impairment.

The median patient age was 66 years (IQR, 59.0-72.0), with men accounting for 62.9% of the population. The majority of patients had stage 4 disease for both NSCLC (55.1%) and SCLC (57.5%).

Cognitive impairment occurrence was similar between patients with NSCLC (69.0%; 95% CI, 56.9%- 79.5%) and SCLC (61.5%; 95% CI, 40.6%-79.8%), as well as between male patients (69.6%; 95% CI, 55.9%-81.2%) and female patients (63.4%; 95% CI, 46.9%-77.9%).

Additionally, the presence of anti-intracellular (AIC) autoantibodies was associated with significantly increased odds of cognitive impairment (OR, 8.3; 95% CrI, 0.7- 92.5), verbal memory deficits (OR, 44.0; 95% CrI, 1.4- 1345.4), and attention deficits (OR, 36.8; 95% CrI, 2.9-474.1).

For NSCLC, an association was observed between the presence of immunoglobin A (IgA) N-methyl-D-aspartate receptor (NMDAR) autoantibodies and a significantly higher likelihood of verbal memory deficit (OR, 182.8; 95% CrI, 3.1-10,852.4). Moreover, no increase in the likelihood of cognitive impairment (OR, 0.7; 95% CrI, 0.1-4.9) or verbal memory deficit (OR, 0.4; 95% CrI, 0.02- 11.1) was observed compared with patients who were autoantibody-negative.

“A high prevalence of neuronal autoantibodies was observed among patients with lung cancer, and these neuronal autoantibodies were associated with clinically relevant cognitive impairment. These autoantibodies might represent a potentially treatable mechanism of immune-mediated cognitive impairment among patients with lung cancer,” the investigators concluded.

A major limitation of the research was the small sample size of the patient cohort. Additionally, the consecutive low power in subgroup analyses, including that of NSCLC and SCLC, as well as autoantibody types, was a study limitation.


Bartels F, Wandrey MM, Aigner A, et al. Association between neuronal autoantibodies and cognitive impairment in patients with lung cancer. JAMA Oncol. 2021;7(9):1302-1310. doi:10.1001/jamaoncol.2021.2049