Recent cohort studies suggest a potential association between atopic dermatitis and dementia, though the evidence remains conflicting. This study aims to elucidate the association between atopic dermatitis and dementia employing systematic review, meta-analysis, and Mendelian randomization (MR). A comprehensive search was performed to select eligible cohort studies using Medline, Embase, Scopus, ScienceDirect, and the Web of Science database. In MR analysis, genomic data from the Genome Wide Association Study (GWAS) (864,982 European individuals) for atopic dermatitis cases and dementia cases were obtained from the MRBase. Statistical analyses included the inverse-variance weighted (IVW) method, sensitivity tests, and MR-PRESSO for outliers. The adjustment accounted for various factors, including sex, age, smoking status, and other medical comorbidities, along with several additional variables. In the systematic review and meta-analysis, 5 longitudinal cohort studies (12,576,235 participants) indicated a significant association between atopic dermatitis and all-cause dementia (adjusted hazard ratio: 1.15, 95% CI: 1.07-1.23). Subgroup analyses revealed an adjusted hazard ratio of 1.18 (95% CI: 1.08-1.27) for Alzheimer's disease in patients with atopic dermatitis, and an adjusted hazard ratio of 1.37 (95% CI: 1.21-1.55) for all-cause dementia in patients with moderate-to-severe atopic dermatitis. However, MR analysis showed no significant causal link between atopic dermatitis and dementia, Alzheimer's disease, vascular dementia, or cognitive performance. While the meta-analysis revealed a significant association, MR analysis did not substantiate a significant causal link. Future research should consider demographic variables and medication influences in unravelling the intricate atopic dermatitis-dementia interplay.