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Dementia in hippocampal sclerosis resembles frontotemporal dementia more than Alzheimer disease

From the Departments of Psychiatry and Behavioral Sciences (Drs. Blass, Brandt, Rao, Steinberg, and Rabins), Pathology, Neurology (Dr. Troncoso), Medicine, Mental Health, and Health Policy and Management (Dr. Rabins), The Johns Hopkins University School of Medicine, Baltimore, MD; and Department of Pathology (Dr. Hatanpaa), University of Texas Southwestern Medical School.

Address correspondence and reprint requests to Dr. David M. Blass, Johns Hopkins Hospital, Department of Psychiatry and Behavioral Sciences, 600 North Wolfe Street, Meyer 279, Baltimore, MD 21287–7279; e-mail: dmblass{at}jhmi.edu

Objective: To characterize the clinical course of pathologically diagnosed hippocampal sclerosis dementia (HSD).

Background: Dementia associated with HSD is incompletely characterized. Previous studies suggest similarities to both Alzheimer disease (AD) and frontotemporal dementia (FTD).

Methods: Case-control analysis of the clinical course of patients with HSD, FTD, and AD from a neuropathology autopsy series conducted by a university hospital. Case histories were reviewed. Cumulative prevalence of behavioral, cognitive, psychiatric, and language symptoms were compared between groups, as was time of symptom onset. Clinical diagnostic criteria for FTD and AD were applied to case histories. Sensitivity and specificity of clinical FTD diagnostic criteria (Report of the Work Group on FTD and Pick’s disease) were computed.

Results: Cumulative prevalence of symptoms in HSD was most similar to that of FTD and differed from AD. Behavioral abnormalities such as decreased grooming and inappropriate behavior were more prevalent in HSD and FTD than AD. Hyperorality, inappropriate behavior, and decreased interest had earlier onset in HSD and FTD. Cognitive symptoms of disorientation, dyscalculia, apraxia, and agnosia were more prevalent in AD, as were psychiatric symptoms of hallucinations, delusions, and aggression. Most HSD patients met diagnostic criteria for FTD. Criteria sensitivity was 64.0% and specificity was 73.7%.

Conclusions: FTD is a clinical syndrome associated with heterogeneous neuropathology. The clinical course of HSD is more similar to that of FTD than AD. These findings, together with the neuropathologic data presented in the accompanying article, support expanding the scope of FTD (Pick complex) to include HSD.

Received August 28, 2003. Accepted in final form April 20, 2004.

See also pages 414 and 538

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