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OBJECTIVE To investigate brain structure, cerebral vasculature and cognitive function in a cohort of patients with late-onset Pompe disease, with particular reference to the differences from those with the classic-infantile phenotype, where extensive white matter abnormalities and impaired cognition on long-term enzyme-treatment are reported in a subset of patients. METHODS Brain imaging (T1, T2, T2 FLAIR, SWI and MRA-TOF) was combined with extensive cognitive testing of general intelligence (Wechsler IQ Test, Montreal Cognitive Assessment) and specific neuropsychological domains (verbal fluency, cognitive flexibility, attention, memory, visuospatial abilities). RESULTS We included 19 patients with late-onset Pompe disease (age range 11-56 years). Two patients showed mild punctate white matter abnormalities within normal range for age, with a Fazekas score of 1-2. Magnetic resonance angiography revealed a slight vertebrobasilar dolichoectasia in two patients, yet did not show any aneurysms or vascular dissections. Most patients had age adjusted scores within the normal range for the Wechsler index scores (verbal comprehension, perceptual reasoning, working memory, processing speed) and combined total intelligence (IQ) score (median 101, IQR 91-111; one patient had a below average score for total IQ), as well as for the specific domains verbal fluency, attention, and memory. A subset of patients performed suboptimally on the Rey Complex Figure Test (9/14 patients) or cube-copying/clock drawing test of the MoCA (8/10 patients). INTERPRETATION Our study showed no brain abnormalities, other than minor microvascular lesions considered within normal range for age, nor general cognitive impairment in late-onset Pompe patients. These findings are in sharp contrast with the widespread white matter abnormalities and cognitive problems found in some classic-infantile patients. This article is protected by copyright. All rights reserved.