It has been reported that patients with Dementia are sleepier and that daytime sleepiness is associated with worse cognitive performance. Inflammatory markers may be elevated in patients with cognitive impairment and have been proposed as mediators of excessive daytime sleepiness (EDS). The aim of this large, controlled study was to examine the association of sleepiness with cognitive performance and peripheral markers of inflammation in patients with dementia. A sub-sample of 46 patients with mild-to-moderate Dementia [mean age:80.3 (SD=5.6) years, 40% males] and 85 cognitively intact controls(NI) [mean age :73.0(SD=7.4) years, 37% males], were recruited from a large, population-based cohort in the island of Crete, Greece of 3,140 older adults (≥60yrs). All participants underwent medical history/physical examination, extensive neuropsychiatric and neuropsychological evaluation, 3-day 24-h actigraphy and a single morning measure of IL-6 and TNFα plasma levels. Comparisons of sleep parameters and inflammation markers between Dementia and NI, and between nappers and non-nappers within each diagnostic group, were made using ANOVA controlling for demographics. Associations between inflammatory markers, sleep variables, and neuropsychological performance were assessed within each group using Partial Correlation analysis controlling for demographics, depression, use of psychotropic medications, and sleep apnea symptoms. Dementia patients compared to NI had marginally significant longer nap total sleep time (TST) (76.7±7.0min vs. 60.9±8min, respectively, p=0.2). Also, within Dementia patients, nappers compared to non-nappers had significantly worse performance in autobiographic memory scale (p=0.002), digits reverse (p=0.007), AVLT retention (p=0.010), and assessment of daily function (p=0.012). Finally, IL-6 levels were significantly associated with nap TST within Dementia patients (r=0.500, p=0.01). , while no significant associations were found between IL-6 and sleepiness within the NI group These data indicate that IL-6 plasma levels in patients with Dementia are associated with increased daytime sleepiness. In demented patients, objective sleepiness may be a biologic marker of the severity of the disease. National Strategic Reference Framework (ESPA) 2007-2013, Program: THALES, University of Crete, title: “A multi-disciplinary network for the study of Alzheimer’s Disease” (Grant :MIS 377299)