Dementia refers to a condition where there is a loss of intellectual function (cognition).
It is usually a progressive condition that interferes with normal social and occupational
Patients with frontal lobe dementia (FLD) suffer from a destruction of the brain cells found
in the frontal lobe of the brain. Loss of frontal lobe neurons can cause changes in
personality, such as aggressiveness, agitation, and depression. In addition, patients with
FLD may have difficulty planning tasks and may have a loss of motivation.
Researchers believe that the cells lost in the frontal lobe of the brain are responsible for
producing a chemical called serotonin. Serotonin is a neurotransmitter, which means it is
used by neurons to communicate with other neurons. Researchers are inclined to believe that
by replacing the missing serotonin, symptoms of FLD may be relieved.
Drugs known as serotonin uptake inhibitors, help to maintain high levels of serotonin in the
body. They have been used successfully to treat patients with depression and patients with
violent / impulsive behaviors. Sertraline is a serotonin reuptake blocker that is
relatively easy to give (once daily), is safer than most other serotonin reuptake blockers
(very little effect on vital enzyme systems [cytochrome P-450]), and has few interactions
with other drugs.
This study is designed to test the effectiveness of Sertraline for the treatment of symptoms
associated with FLD. Patients participating in the study will receive Sertraline for 6
weeks and a placebo "inactive sugar pill" for 6 weeks. During the study, researchers will
test psychological and neurological functions to measure the effects of the drug.
Degeneration of frontal serotonin-containing neurons occurs in frontal lobe dementia (FLD).
The associated loss of serotonin transmission may contribute to the frontal lobe dysfunction
associated with this disorder. FLD patients will undergo a controlled clinical trial of an
orally administered serotonergic agent (Sertraline) which acts centrally to selectively
block serotonin uptake to treat patients' cognitive and behavioral frontal dysfunction.
Study subjects will be evaluated at regular intervals with a battery of neuropsychological
and behavioral tests designed to assess frontal and other cognitive functions. In addition,
compliance and levels of the medication will be measured in the blood and when possible in
the cerebrospinal fluid (CSF).
Characterized as having behavioral manifestations using a standardized neuropsychiatric
scale and interview.
FLD patients' frontal cognitive sysfunctions characterized using a short neurobehavioral
Patients must be able to be tested and cooperative with the procedures required in this
No contraindications to the use of Sertraline.
No medical conditions that can reasonably be expected to subject the patient to
unwarranted risk (e.g., cancer) or require frequent changes in medication.
Well-controlled medical conditions such as hypertension and diabetes will not be excluded.
Patients must not be pregnant or nursing and must be using effective contraception, if
still at child-bearing age.
No history of prior severe traumatic brain injury or other severe neurologic or
psychiatric condition, such as psychosis, stroke, multiple sclerosis, or spinal cord
Not using any psychotropic medication which cannot be stopped 4 weeks before the study.