jats:titleAbstract</jats:title>jats:secjats:titleBackground</jats:title>jats:pCommon genetic variance in apolipoprotein E (jats:italicAPOE</jats:italic>), β‐glucocerebrosidase (jats:italicGBA</jats:italic>), microtubule‐associated protein tau (jats:italicMAPT</jats:italic>), and α‐synuclein (jats:italicSNCA</jats:italic>) has been linked to cognitive decline in Parkinson's disease (PD), although studies have yielded mixed results.</jats:p></jats:sec>jats:secjats:titleObjectives</jats:title>jats:pTo evaluate the effect of genetic variants in jats:italicAPOE</jats:italic>, jats:italicGBA</jats:italic>, jats:italicMAPT</jats:italic>, and jats:italicSNCA</jats:italic> on cognitive decline and risk of dementia in a pooled analysis of six longitudinal, non‐selective, population‐based cohorts of newly diagnosed PD patients.</jats:p></jats:sec>jats:secjats:titleMethods</jats:title>jats:p1002 <jats:styled-content style="fixed-case">PD</jats:styled-content> patients, followed for up to 10 years (median 7.2 years), were genotyped for at least one of <jats:styled-content style="fixed-case">jats:italicAPOE</jats:italic></jats:styled-content>‐ε4, <jats:styled-content style="fixed-case">jats:italicGBA</jats:italic></jats:styled-content> mutations, <jats:styled-content style="fixed-case">jats:italicMAPT</jats:italic> H1</jats:styled-content>/<jats:styled-content style="fixed-case">H2</jats:styled-content>, or <jats:styled-content style="fixed-case">jats:italicSNCA</jats:italic></jats:styled-content> rs356219. We evaluated the effect of genotype on the rate of cognitive decline (Mini‐Mental State Examanation, <jats:styled-content style="fixed-case">MMSE</jats:styled-content>) using linear mixed models and the development of dementia (diagnosed using standardized criteria) using Cox regression; multiple comparisons were accounted for using <jats:styled-content style="fixed-case">Benjamini−Hochberg</jats:styled-content> corrections.</jats:p></jats:sec>jats:secjats:titleResults</jats:title>jats:pCarriers of jats:italicAPOE</jats:italic>‐ε4 (n = 281, 29.7%) and jats:italicGBA</jats:italic> mutations (n = 100, 10.3%) had faster cognitive decline and were at higher risk of progression to dementia (jats:italicAPOE</jats:italic>‐ε4, HR 3.57, jats:italicP</jats:italic> < 0.001; jats:italicGBA</jats:italic> mutations, HR 1.76, jats:italicP</jats:italic> = 0.001) than non‐carriers. The risk of cognitive decline and dementia (HR 5.19, jats:italicP</jats:italic> < 0.001) was further increased in carriers of both risk genotypes (n = 23). No significant effects were observed for jats:italicMAPT</jats:italic> or jats:italicSNCA</jats:italic> rs356219.</jats:p></jats:sec>jats:secjats:titleConclusions</jats:title>jats:p<jats:styled-content style="fixed-case">jats:italicGBA</jats:italic></jats:styled-content> and <jats:styled-content style="fixed-case">jats:italicAPOE</jats:italic></jats:styled-content> genotyping could improve the prediction of cognitive decline in <jats:styled-content style="fixed-case">PD</jats:styled-content>, which is important to inform the clinical trial selection and potentially to enable personalized treatment © 2022 The Authors. jats:italicMovement Disorders</jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society</jats:p></jats:sec>