Amantadine for Executive Dysfunction Syndrome in Patients With Dementia -- Drayton et al. 45 (3): 205 -- Psychosomatics
Amantadine for Executive Dysfunction Syndrome in Patients With Dementia -- Drayton et al. 45 (3): 205 -- Psychosomatics
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHOD
RESULTS
DISCUSSION
REFERENCES
Executive dysfunction syndrome, also known as "frontal lobe syndrome," is commonly seen in patients with brain diseases from many causes.1 Executive dysfunction syndrome has been associated with damage to "frontal-subcortical" brain circuits believed to be the anatomical basis of executive control function.2 A variety of neuropsychiatric symptoms indicative of executive dysfunction have been associated with damage to these circuits, including cognitive disturbance, personality change, mood symptoms, and a series of challenging behaviors. Among patients with degenerative dementia, especially advanced dementia, symptoms of executive dysfunction syndrome are common and present a challenging clinical dilemma. While executive dysfunction syndrome occurs with some frequency in patients with Alzheimer's disease,3,4 it is one of the cardinal clinical manifestations of frontotemporal degeneration. Frontotemporal degeneration is a group of disorders with a common histopathology5,6 that involves the degeneration of the frontal and anterior temporal lobes.5,6 This disease has been referred to in the literature by various names, including non-Alzheimer's dementia, semantic dementia, or Pick's disease.5,6 The prevalence of frontotemporal degeneration among all cases of dementia has been estimated to range between 3% and 22%. Frontotemporal degeneration usually presents during the fifth to seventh decades of life and has a strong familial link.5,6 The symptoms of executive dysfunction syndrome usually precede cognitive decline in patients with frontotemporal degeneration.6 Behavioral disinhibition, decreased judgment, and poor insight are common. Executive functioning is usually selectively impaired during the early stages of frontotemporal degeneration. However, in an older person with dementia, it is very difficult to distinguish executive dysfunction syndrome due to Alzheimer's disease from that due to frontotemporal degeneration on clinical grounds, other than by careful history taking.7
The treatment of executive dysfunction syndrome, especially in the context of frontotemporal degeneration, has been very challenging and mostly unsuccessful.1 Reports have suggested that selective serotonin reuptake inhibitors, bromocriptine, carbamazepine, lithium, and other agents may have efficacy in treating executive dysfunction syndrome. However, there is a dearth of controlled trials in this area, and there have been only a few case series reported. In general, treatments have focused on manipulation of the dopamine, serotonin, or cholinergic neurotransmitter systems that are thought to be modulators of the frontal-subcortical loops involved in the pathogenesis of executive dysfunction syndrome.1
We report here the results from an open, uncontrolled chart review study of our experience using the antiviral drug amantadine to treat executive dysfunction syndrome in patients with dementia. Several years ago, clinicians on our team began to use amantadine empirically, outside its labeled use, for the treatment of these symptoms without a formal protocol. This was based on a report that amantadine helped executive dysfunction syndrome in patients with traumatic brain injury8 and by a case series suggesting that dopamine "augmentation" with bromocriptine reduces problem behaviors related to executive dysfunction syndrome.9 The precise mechanism of amantadine's brain action is unknown. It appears to have dopamine-modulating activity in the peripheral and CNS by augmenting the release and inhibiting the cellular reuptake of dopamine.10 Amantadine is also a N-methyl-D-aspartic acid receptor antagonist, which may indirectly enhance dopaminergic transmission and confer neuroprotective effects, similar to its analogue, memantine.11 Moreover, amantadine is known to alter the function of nicotinic acetylcholine receptors in muscle and has a weak antagonist effect on mammalian hippocampal nicotinic acetylcholine receptors. This may signify protective effects in neurodegenerative disorders or in cholinergic toxicity.12
Interesting. Bromocriptine also heals insulin resistance, in addition to apparently helping executive dysfunction
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHOD
RESULTS
DISCUSSION
REFERENCES
Executive dysfunction syndrome, also known as "frontal lobe syndrome," is commonly seen in patients with brain diseases from many causes.1 Executive dysfunction syndrome has been associated with damage to "frontal-subcortical" brain circuits believed to be the anatomical basis of executive control function.2 A variety of neuropsychiatric symptoms indicative of executive dysfunction have been associated with damage to these circuits, including cognitive disturbance, personality change, mood symptoms, and a series of challenging behaviors. Among patients with degenerative dementia, especially advanced dementia, symptoms of executive dysfunction syndrome are common and present a challenging clinical dilemma. While executive dysfunction syndrome occurs with some frequency in patients with Alzheimer's disease,3,4 it is one of the cardinal clinical manifestations of frontotemporal degeneration. Frontotemporal degeneration is a group of disorders with a common histopathology5,6 that involves the degeneration of the frontal and anterior temporal lobes.5,6 This disease has been referred to in the literature by various names, including non-Alzheimer's dementia, semantic dementia, or Pick's disease.5,6 The prevalence of frontotemporal degeneration among all cases of dementia has been estimated to range between 3% and 22%. Frontotemporal degeneration usually presents during the fifth to seventh decades of life and has a strong familial link.5,6 The symptoms of executive dysfunction syndrome usually precede cognitive decline in patients with frontotemporal degeneration.6 Behavioral disinhibition, decreased judgment, and poor insight are common. Executive functioning is usually selectively impaired during the early stages of frontotemporal degeneration. However, in an older person with dementia, it is very difficult to distinguish executive dysfunction syndrome due to Alzheimer's disease from that due to frontotemporal degeneration on clinical grounds, other than by careful history taking.7
The treatment of executive dysfunction syndrome, especially in the context of frontotemporal degeneration, has been very challenging and mostly unsuccessful.1 Reports have suggested that selective serotonin reuptake inhibitors, bromocriptine, carbamazepine, lithium, and other agents may have efficacy in treating executive dysfunction syndrome. However, there is a dearth of controlled trials in this area, and there have been only a few case series reported. In general, treatments have focused on manipulation of the dopamine, serotonin, or cholinergic neurotransmitter systems that are thought to be modulators of the frontal-subcortical loops involved in the pathogenesis of executive dysfunction syndrome.1
We report here the results from an open, uncontrolled chart review study of our experience using the antiviral drug amantadine to treat executive dysfunction syndrome in patients with dementia. Several years ago, clinicians on our team began to use amantadine empirically, outside its labeled use, for the treatment of these symptoms without a formal protocol. This was based on a report that amantadine helped executive dysfunction syndrome in patients with traumatic brain injury8 and by a case series suggesting that dopamine "augmentation" with bromocriptine reduces problem behaviors related to executive dysfunction syndrome.9 The precise mechanism of amantadine's brain action is unknown. It appears to have dopamine-modulating activity in the peripheral and CNS by augmenting the release and inhibiting the cellular reuptake of dopamine.10 Amantadine is also a N-methyl-D-aspartic acid receptor antagonist, which may indirectly enhance dopaminergic transmission and confer neuroprotective effects, similar to its analogue, memantine.11 Moreover, amantadine is known to alter the function of nicotinic acetylcholine receptors in muscle and has a weak antagonist effect on mammalian hippocampal nicotinic acetylcholine receptors. This may signify protective effects in neurodegenerative disorders or in cholinergic toxicity.12
Interesting. Bromocriptine also heals insulin resistance, in addition to apparently helping executive dysfunction
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