SynthesisDrugs & aging2026
Gabapentinoid Use and Risk of Alzheimer's Disease-Related Dementias: A Systematic Review and Meta-analysis of Observational Studies.
Synthesis in Drugs & aging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
14 authors.
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Abstract
BACKGROUND AND
objectiveGabapentinoids, particularly gabapentin and pregabalin, are widely prescribed for neuropathic pain and other chronic conditions, including in populations at risk for cognitive decline. Their long-term cognitive safety and potential association with Alzheimer's disease and related dementias (ADRD) remain uncertain. We examined whether gabapentinoid use is associated with ADRD risk and assessed between-study heterogeneity and potential study-level modifiers.
methodsPubMed, Embase, and the Cochrane Library were searched from inception through November 2025. We included observational studies comparing gabapentinoid users with non-users or non-gabapentinoid comparators and reporting incident ADRD. Risk of bias was assessed using ROBINS-E. A random-effects meta-analysis was performed using odds ratios. Subgroup and meta-regression analyses explored study-level modifiers. Certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). The protocol was registered in PROSPERO (CRD420251240055).
resultsFive observational studies (325,245 participants) were included. Gabapentinoid use was associated with modestly higher estimated odds of ADRD (odds ratio, 1.28; 95% confidence interval 1.10-1.50; P = 0.002), with high heterogeneity (I
conclusionsGabapentinoid use was associated with modestly higher estimated odds of ADRD in pooled observational data. High heterogeneity, residual confounding, and confounding by indication preclude causal inference. These findings support cautious prescribing, particularly for off-label and long-term use, and underscore the need for prospective studies. CLINICAL
trial registrationPROSPERO protocol number: CRD420251240055.
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