Introduction: Descriptions of Lyme disease and dementia are rare. Objective: To describe patients with dementia and a positive “intrathecal anti-Borrelia antibody index” (AI), specific for neuroborreliosis. Methods: Among 1,594 patients seen for dementia, we prospectively identified and studied 20 patients (1.25%) with dementia and a positive AI. Patients underwent a battery of neuropsychological tests brain, MRI, FDG-PET, and cerebrospinal fluid (CSF) analysis. An etiological diagnosis of the dementia was made at the end of the follow-up of 5.0 ± 2.9 years. Results: We found two groups of patients with dementia, the first (n = 7, 0.44%) with certain neuroborreliosis and stability or mild improvement of dementia after treatment by antibiotics and the second (n = 13, 0.81%) with progressive worsening of dementia, despite the antibiotics. In the second group, the final diagnoses were Alzheimer’s disease (AD) (n = 4), AD and Lewy body disease (LBD) (n = 3), LBD (n = 1), FTLD (n = 3), hippocampal sclerosis (n = 1), and vascular dementia (n = 1). We did not observe any differences in cognitive test between the two patient groups at baseline. Brain MRI showed more focal atrophy and FDG-PET showed more frontal hypometabolism in the second group. Tau, p-tau, and Aβ 42 concentrations in the CSF were normal in the neuroborreliosis group, and coherent with diagnosis in the second. Conclusion: Pure Lyme dementia exists and has a good outcome after antibiotics. It is advisable to do Lyme serology in demented patients, and if serology is positive, to do CSF analysis with AI. Neurodegenerative dementia associated with positive AI also exists, which may have been revealed by the involvement of Borrelia in the CNS.