The anterior thalamic nuclei are important for spatial and episodic memory, however, surprisingly little is known about the status of these nuclei in neurological conditions that present with memory impairments, such as Down syndrome. We quantified neurons and glial cells in the anterior thalamic nuclei of four older patients with Down syndrome. There was a striking reduction in the volume of the anterior thalamic nuclei and this appeared to reflect the loss of approximately 70% of neurons. The number of glial cells was also reduced but to a lesser degree than neurons. The anterior thalamic nuclei appear to be particularly sensitive to effects of aging in Down syndrome and the pathology in this region likely contributes to the memory impairments observed. These findings reaffirm the importance of examining the status of the anterior thalamic nuclei in conditions where memory impairments have been principally assigned to pathology in the medial temporal lobe.