An executive in the music industry aged 74 years with mild hypercholesterolemia treated with atorvastatin 20 mg/day but otherwise in good health was referred by his primary care provider (PCP) for neuropsychiatric evaluation because of mild cognitive impairment for the past 2 years. Baseline MRI demonstrated minimal diffuse gray matter loss without acute findings, and fluorodeoxyglucose positron emission tomography (FDG-PET) identified a reduction in glucose metabolism in the parieto-temporal region. Because of his professional responsibilities and the presumption of mild cognitive impairment (MCI) progression over time, his neurologist suggested treatment with monoclonal antibody (mAb)-based amyloid targeting therapy. Over the next 5 months, he received 6 monthly infusions of aducanumab with some measurable improvement in cognition and no adverse effects. A brain magnetic resonance imaging (MRI) before the 5th dose was unchanged from baseline. However, 2 weeks after the 6th dose, he experienced the relatively sudden onset of dizziness, vertigo, and a mildly ataxic gait. MRI revealed sulcal T2-fluid-attenuated inversion recovery (T2 FLAIR) hyperintensities in the leptomeningeal space.