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A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia

From the Cognitive Neuroscience Section (E.D.H., J.G.), NINDS; and Geriatric Psychiatry Branch (K.T.P.), NIMH, Bethesda, MD.

Address correspondence and reprint requests to Dr. Edward D. Huey, Clinical Fellow, Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, CRC, Room 5C206, Bethesda, MD 20892; e-mail: hueye{at}ninds.nih.gov

Objective: To evaluate neurotransmitter deficiencies and neurotransmitter-based treatments for frontotemporal dementia (FTD).

Methods: The authors conducted a systematic review of the literature on the mechanism and treatment of FTD and a meta-analysis of treatment studies of antidepressants for the behavioral symptoms of FTD.

Results: Patients with FTD show deficiencies in the serotonin and dopamine neurotransmitter systems, while the acetylcholine system appears relatively intact. Antidepressant treatment significantly improves behavioral symptoms in FTD, but most studies are small and uncontrolled. Serotonergic treatments appear to improve the behavioral but not cognitive symptoms of FTD.

Conclusions: Studies of neurotransmitter deficiencies in frontotemporal dementia (FTD) can be helpful in developing treatments. Treatment studies on FTD are scarce, given the prevalence and severity of this illness. Larger, well-controlled treatment studies are required to reach more definitive conclusions about treatment efficacy. Multicenter studies are likely the best way to complete treatment studies in a timely manner.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the January 10 issue to find the title link for this article.

Supported by the Intramural Research Programs of the NIH, National Institute of Neurological Disorders and Stroke, and NIMH.

Disclosure: K.T.P. has served as a consultant for Pfizer and received fees in excess of $10,000. The authors report no conflicts of interest.

Received April 4, 2005. Accepted in final form September 21, 2005.

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