The association of gabapentin use and change of cognitive and functional status in older adults with normal cognition

Background Although gabapentin has been increasingly prescribed to older adults, the relationship between gabapentin and cognition/functional status is not well studied. Therefore, we aimed to examine the association of gabapentin use and cognitive/functional change in older adults. Methods A retrospective cohort study was conducted using National Alzheimer’s Coordinating Center Uniform Data Set (2005‐March 2021). Gabapentin new users with normal cognition at the visit of gabapentin initiation (i.e., index visit) were included. New‐users were matched on year of first enrollment and time of gabapentin initiation since enrollment to randomly select nonusers with replacement. The decline of cognitive/functional status, including Clinical Dementia Rating global score (CDRGLOB), Clinical Dementia Rating sum of boxes (CDRSUM), Mini‐Mental State Examination (MMSE), sum of Functional Activities Questionnaire (FAQ), and mean of FAQ, was assessed from index to index+1 and index+2 visits. The criteria of cognitive/functional status decline were any increase of CDRGLOB, 1 point increase of CDRSUM, 1 point decrease of MMSE, 3 point increase of sum of FAQ, and 0.3 point increase of mean of FAQ. To mitigate confounding and selection bias, stabilized inverse probability of treatment weights and stabilized inverse probability of censoring weights were used. Generalized estimating equations with an exchangeable working correlation structure were used to account for within‐participant correlations and obtain robust standard errors. Results We included 496 new‐users (mean age [SD]: 78.0 [7.1]; male 35.9%) and 4,464 nonusers (77.4 [7.1]; 35.1%) with normal cognition at index. Among the participants who had information of seizure history (57.1% of new‐users and 58.0% of nonusers), 2.2% and 1.6% of new‐users and nonusers, respectively, reported having seizure history, indicating that gabapentin is widely prescribed off‐label in older adults. Gabapentin use was significantly associated with cognitive/functional status decline with outcomes, including CDRGLOB at index+1 visit (odds ratio [95% confidence interval]: 1.57 [1.08, 2.31]); CDRSUM at index+1 visit (1.89 [1.16, 3.06]) and at index+2 visit (1.66 [1.05, 2.63]); and mean of FAQ at index+2 visit (2.23 [1.22, 4.07]) (Figure 1). Conclusions Gabapentin use was significantly associated with decline in cognitive and functional status among older adults with initially normal cognition. Further studies are needed to examine the association.