A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia

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.

[1]  A. Moosa,et al.  Evidence for an association between the CSF HVA:5-HIAA ratio and aggressiveness in frontotemporal dementia but not in Alzheimer's disease. , 2004 .

[2]  M. Primeau,et al.  Quantitative Electroencephalography in Frontotemporal Dementia with Methylphenidate Response: A Case Study , 2004, Clinical EEG and neuroscience.

[3]  Trey Sunderland,et al.  Decreased beta-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. , 2003, JAMA.

[4]  Adolf Pfefferbaum,et al.  Neuroimaging studies of schizophrenia , 1991, Schizophrenia Research.

[5]  Nick C Fox,et al.  Vulnerability to neuroleptic side effects in frontotemporal lobar degeneration , 2003, International journal of geriatric psychiatry.

[6]  M. Ikeda,et al.  Efficacy of Fluvoxamine as a Treatment for Behavioral Symptoms in Frontotemporal Lobar Degeneration Patients , 2004, Dementia and Geriatric Cognitive Disorders.

[7]  D. Ciraulo The American Psychiatric Publishing Textbook of Psychopharmacology , 2004 .

[8]  Daniela Perani,et al.  Glucose metabolism and serotonin receptors in the frontotemporal lobe degeneration , 2005, Annals of neurology.

[9]  Yan Yang Schmitt Frontotemporal dementia : evidence for impairment of ascending serotoninergic but not noradrenergic innervation Immunocytochemical and quantitative study using a graph method , 2022 .

[10]  K. Blennow,et al.  Decreased monoamine metabolites in frontotemporal dementia and Alzheimer’s disease , 1998, Neurobiology of Aging.

[11]  J. Simpson,et al.  Neurochemical observations in a case of Pick's disease , 1980, Journal of the Neurological Sciences.

[12]  N. Hattori,et al.  Bromocriptine treatment for perseveration in demented patients. , 1998, Alzheimer disease and associated disorders.

[13]  D. Sparks,et al.  Neurochemical and Histopathologic Alterations Characteristic of Pick's Disease in a Non-demented Individual , 1994, Journal of neuropathology and experimental neurology.

[14]  K. Blennow,et al.  Biological Correlates of Clinical Subgroups of Alzheimer’s Disease , 2002, Dementia and Geriatric Cognitive Disorders.

[15]  W. Meier-Ruge,et al.  Neurochemical enzyme changes in Alzheimer's and Pick's disease. , 1984, Archives of gerontology and geriatrics.

[16]  P S Goldman-Rakic,et al.  Widespread origin of the primate mesofrontal dopamine system. , 1998, Cerebral cortex.

[17]  J. Merrilees,et al.  Long-term care of patients with frontotemporal dementia. , 2003, Journal of the American Medical Directors Association.

[18]  S. Reske,et al.  FTDP‐17: An early‐onset phenotype with parkinsonism and epileptic seizures caused by a novel mutation , 1999, Annals of neurology.

[19]  J. Constantinidis,et al.  Pick’s Disease , 1974 .

[20]  Sharon K. McDowell,et al.  Differential effect of a dopaminergic agonist on prefrontal function in traumatic brain injury patients. , 1998, Brain : a journal of neurology.

[21]  J. T. Coull,et al.  Theα2 antagonist idazoxan remediates certain attentional and executive dysfunction in patients with dementia of frontal type , 1996, Psychopharmacology.

[22]  Y. Lampl,et al.  Efficacy of acetylcholinesterase inhibitors in frontotemporal dementia , 2004, The Annals of pharmacotherapy.

[23]  D. Bowen,et al.  NEOCORTICAL CHOLINERGIC NEURONS IN ELDERLY PEOPLE , 1977, The Lancet.

[24]  P. Blier,et al.  Is there a role for 5-HT1A agonists in the treatment of depression? , 2003, Biological Psychiatry.

[25]  Calbindin D-28k and parvalbumin immunoreactivity in the frontal cortex in patients with frontal lobe dementia of non-Alzheimer type associated with amyotrophic lateral sclerosis. , 1993, Journal of neurology, neurosurgery, and psychiatry.

[26]  I. Ferrer Neurons and Their Dendrites in Frontotemporal Dementia , 1999, Dementia and Geriatric Cognitive Disorders.

[27]  F. Tagliavini,et al.  Basal nucleus of meynert A neuropathological study in Alzheimer's disease, simple senile dementia, Pick's disease and Huntington's chorea , 1983, Journal of the Neurological Sciences.

[28]  D. Sparks,et al.  Alterations in brain monoamine oxidase activity in aging, Alzheimer's disease, and Pick's disease. , 1991, Archives of neurology.

[29]  J R Hodges,et al.  The prevalence of frontotemporal dementia , 2002, Neurology.

[30]  G. Frisoni,et al.  Single photon emission computed tomography with [99Tc]‐HM‐PAO and [123I]‐IBZM in Alzheimer's disease and dementia of frontal type: preliminary results , 1994, Acta neurologica Scandinavica.

[31]  A. Paetau,et al.  A post-mortem comparison of the cortical cholinergic system in Alzheimer's disease and Pick's disease , 1983, Journal of the Neurological Sciences.

[32]  Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups. , 1994, Journal of neurology, neurosurgery, and psychiatry.

[33]  R. McIntyre,et al.  Mechanisms of antipsychotic-induced weight gain. , 2001, The Journal of clinical psychiatry.

[34]  I. Litvan Therapy and management of frontal lobe dementia patients , 2001, Neurology.

[35]  Markesbery Wr,et al.  Alterations in Brain Monoamine Oxidase Activity in Aging, Alzheimer's Disease, and Pick's Disease , 1991 .

[36]  D. Sparks,et al.  Altered serotonergic and cholinergic synaptic markers in Pick's disease. , 1991, Archives of neurology.

[37]  P. Francis,et al.  Preliminary neurochemical findings in non-Alzheimer dementia due to lobar atrophy. , 1993, Dementia.

[38]  Functional imaging, the frontal lobes, and dementia. , 1998, Dementia.

[39]  M. Laine,et al.  Striatal dopamine transporter and extrapyramidal symptoms in frontotemporal dementia , 2002, Neurology.

[40]  I. Kanazawa,et al.  Studies on neurotransmitter markers of the basal ganglia in Pick's disease, with special reference to dopamine reduction , 1988, Journal of the Neurological Sciences.

[41]  P. De Deyn,et al.  Evidence for an association between the CSF HVA:5-HIAA ratio and aggressiveness in frontotemporal dementia but not in Alzheimer's disease. , 2004, Journal of neurology, neurosurgery, and psychiatry.

[42]  M. Mendez,et al.  Goals in symptomatic pharmacologic management of frontotemporal lobar degeneration , 2002, American journal of Alzheimer's disease and other dementias.

[43]  M. Wilson,et al.  The organization of serotonergic projections to cerebral cortex in primates: Retrograde transport studies , 1991, Neuroscience.

[44]  F. Pasquier,et al.  Frontotemporal Dementia: A Randomised, Controlled Trial with Trazodone , 2004, Dementia and Geriatric Cognitive Disorders.

[45]  Kristine Yaffe,et al.  Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis. , 2003, JAMA.

[46]  P. Francis,et al.  Neurochemical Features of Frontotemporal Dementia , 1999, Dementia and Geriatric Cognitive Disorders.

[47]  Camellia P. Clark,et al.  Clinical and Physiological Consequences of Rapid Tryptophan Depletion , 2000, Neuropsychopharmacology.

[48]  Judith M. Rumsey,et al.  Cerebral glucose metabolism in adults with hyperactivity of childhood onset. , 1990 .

[49]  Alan A. Wilson,et al.  Equivalent occupancy of dopamine D1 and D2 receptors with clozapine: differentiation from other atypical antipsychotics. , 2004, The American journal of psychiatry.

[50]  D. Price,et al.  Pick's disease (lobar sclerosis) , 1983, Neurology.

[51]  A. Bava,et al.  Olanzapine as a treatment of neuropsychiatric disorders of Alzheimer's disease and other dementias: A 24-month follow-up of 68 patients , 2003, American journal of Alzheimer's disease and other dementias.

[52]  C. Lyketsos,et al.  Amantadine for executive dysfunction syndrome in patients with dementia. , 2004, Psychosomatics.

[53]  R. Curtis,et al.  Case of pick's central lobar atrophy with apparent stabilization of cognitive decline after treatment with risperidone. , 2000, Journal of clinical psychopharmacology.

[54]  A. Bava,et al.  Effects of selegiline on fronto‐temporal dementia: a neuropsychological evaluation , 2002, International journal of geriatric psychiatry.

[55]  G. Pilleri The Klüver-Bucy Syndrome in man. A clinico-anatomical contribution to the function of the medial temporal lobe structures. , 1966, Psychiatria et neurologia.

[56]  M. Åsberg,et al.  Neurotransmitters and Suicidal Behavior , 1997, Annals of the New York Academy of Sciences.

[57]  L. Gwyther,et al.  Dementia, Religion, and Spirituality , 2003 .

[58]  R. Coppola,et al.  The distribution of cerebral muscarinic acetylcholine receptors in vivo in patients with dementia. A controlled study with 123IQNB and single photon emission computed tomography. , 1991, Archives of neurology.

[59]  R. DeTeresa,et al.  Neocortical morphometry and cholinergic neurochemistry in Pick's disease. , 1988, American Journal of Pathology.

[60]  B L Miller,et al.  Dietary changes, compulsions and sexual behavior in frontotemporal degeneration. , 1995, Dementia.

[61]  J. S. Benton,et al.  Choline acetyltransferase activity and histopathology of frontal neocortex from biopsies of demented patients , 1982, Journal of the Neurological Sciences.

[62]  J. Coyle,et al.  Cortical Degeneration with Swollen Chromatolytic Neurons: Its Relationship to Pick's Disease , 1986, Journal of neuropathology and experimental neurology.

[63]  R. Inoue,et al.  A juvenile case of frontotemporal dementia: Neurochemical and neuropathological investigations , 1995, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[64]  T. Robbins,et al.  Methylphenidate (‘Ritalin’) can Ameliorate Abnormal Risk-Taking Behavior in the Frontal Variant of Frontotemporal Dementia , 2006, Neuropsychopharmacology.

[65]  B. Sahakian,et al.  Paroxetine does not improve symptoms and impairs cognition in frontotemporal dementia: a double-blind randomized controlled trial , 2004, Psychopharmacology.

[66]  R. Faber,et al.  Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. , 1999, Neurology.

[67]  V. Chan‐Palay,et al.  Alterations in Tyrosine Hydroxylase Immunoreactive Neurons of the Locus ceruleus in Pick's Disease , 1991 .

[68]  M. Rappley,et al.  Clinical practice. Attention deficit-hyperactivity disorder. , 2005, The New England journal of medicine.

[69]  Kristine Yaffe,et al.  Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. , 2005, JAMA.

[70]  A. Bava,et al.  Frontotemporal Dementia: Paroxetine as a Possible Treatment of Behavior Symptoms , 2002, European Neurology.

[71]  K. Kosaka,et al.  Alterations of muscarinic acetylcholine receptors in atypical Pick’s disease without Pick bodies , 2003, Journal of neurology, neurosurgery, and psychiatry.

[72]  Joseph James Duffy,et al.  Apathy: a treatable syndrome. , 1995, The Journal of neuropsychiatry and clinical neurosciences.