Objective: To characterize the clinical and neuropsychological features of pure and mixed hippocampal sclerosis dementia (HS) compared to Alzheimer9s disease (AD). Background HS dementia accounts for about 10% of cases of dementia in the elderly. At present it is diagnosed only at autopsy, as it lacks distinctive clinical features. It is often found along with neurodegenerative conditions including AD, Lewy body and fronto-temporal dementias, labeled 9mixed9 HS dementia. A proportion of HS is found without concomitant classical neurodegenerative pathology, and is labeled 9pure9 HS. There is a need to clinically characterize HS in relation to dementia, as its underlying etiology and subsequent treatment might be expected to differ from other neurodegenerative dementias. Design/Methods: Retrospective case control study comparing the clinical and neuropsychological profile of a series of pure HS cases and a series of mixed HS/AD with matched samples of neuropathologically confoirmed pure AD cases. Each series was matched on gender, age at death, and interval from last MMSE to death. The groups were compared in MMSE, Mattis DRS (total and subscales), and a panel of psychometric tests. Results: At first presentation, pure HS subjects (n=17) differed from matched AD patients (n=102) only regarding relatively preserved logical memory immediate recall (p=0.02). At last clinical examination prior to death, pure HS subjects had a significantly higher mean MMSE and DRS memory subscale scores compared to matched AD cases. Mixed HS+AD subjects (n=22) did not differ in any of the cognitive measures compared to matched AD cases (n=66) at initial examination or at last examination prior to death. Conclusions: Relative deterioration of learning and delayed recall, and slower progression of cognitive decline may help to distinguish pure HS dementia from AD. Mixed HS dementia appeared indistinguishable from AD. Disclosure: Dr. Pillai has nothing to disclose. Dr. Edland has nothing to disclose. Dr. Gahagan has nothing to disclose. Dr. Salmon has received personal compensation for activities with Bristol Myer Squibb as a consultant. Dr. Galasko has received personal compensation for activities with United BioSource Corporation, Elan Pharmaceuticals and Janssen Pharmaceuticals(DSMB) as a consultant. Dr. Galasko has received personal compensation in an editorial capacity for Alzheimer9s Disease Research and Treatment, published by Biomed Central. Dr. Galasko has received research support from Pfizer Pharmaceuticals and Eli Lilly, Inc.