Differentiation of dementia with Lewy bodies from Alzheimer's disease using a dopaminergic presynaptic ligand

Background: Dementia with Lewy bodies (DLB) is one of the main differential diagnoses of Alzheimer's disease (AD). Key pathological features of patients with DLB are not only the presence of cerebral cortical neuronal loss, with Lewy bodies in surviving neurones, but also loss of nigrostriatal dopaminergic neurones, similar to that of Parkinson's disease (PD). In DLB there is 40–70% loss of striatal dopamine. Objective: To determine if detection of this dopaminergic degeneration can help to distinguish DLB from AD during life. Methods: The integrity of the nigrostriatal metabolism in 27 patients with DLB, 17 with AD, 19 drug naive patients with PD, and 16 controls was assessed using a dopaminergic presynaptic ligand, 123I-labelled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane (FP-CIT), and single photon emission tomography (SPET). A SPET scan was carried out with a single slice, brain dedicated tomograph (SME 810) 3.5 hours after intravenous injection of 185 MBq FP-CIT. With occipital cortex used as a radioactivity uptake reference, ratios for the caudate nucleus and the anterior and posterior putamen of both hemispheres were calculated. All scans were also rated by a simple visual method. Results: Both DLB and PD patients had significantly lower uptake of radioactivity than patients with AD (p<0.001) and controls (p<0.001) in the caudate nucleus and the anterior and posterior putamen. Conclusion: FP-CIT SPET provides a means of distinguishing DLB from AD during life.

[1]  S. Gacinovic,et al.  Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]‐FP‐CIT SPECT imaging: The [123I]‐FP‐CIT study group , 2000, Movement disorders : official journal of the Movement Disorder Society.

[2]  S. Asenbaum,et al.  Measurement of the dopaminergic degeneration in Parkinson's disease with [123I] beta-CIT and SPECT. Correlation with clinical findings and comparison with multiple system atrophy and progressive supranuclear palsy. , 1997, Journal of neural transmission. Supplementum.

[3]  S. Asenbaum,et al.  [123I]β-CIT and SPECT in essential tremor and Parkinson's disease , 1998, Journal of Neural Transmission.

[4]  J D Speelman,et al.  [123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson's disease. , 1997, Journal of neurology, neurosurgery, and psychiatry.

[5]  J. Hughes,et al.  Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. , 1992, Journal of neurology, neurosurgery, and psychiatry.

[6]  E. Perry,et al.  Psychiatric morbidity in dementia with Lewy bodies: a prospective clinical and neuropathological comparative study with Alzheimer's disease. , 1999, The American journal of psychiatry.

[7]  R. Lipton,et al.  Validity of clinical criteria for the diagnosis of dementia with Lewy bodies , 1999, Neurology.

[8]  P. Lantos,et al.  Validity of current clinical criteria for Alzheimer's disease, vascular dementia and dementia with Lewy bodies , 1999, British Journal of Psychiatry.

[9]  Jan Booij,et al.  Iodine-123-N-ω-Fluoropropyl-2β-Carbomethoxy-3β-(4-Iodophenyl)Tropane SPECT in Healthy Controls and Early-Stage, Drug-Naive Parkinson's Disease , 1998 .

[10]  W. Poewe,et al.  123I-beta-CIT and 123I-IBZM-SPECT scanning in levodopa-naive Parkinson's disease. , 1998, Movement disorders : official journal of the Movement Disorder Society.

[11]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[12]  F. Huppert,et al.  CAMDEX: A Standardised Instrument for the Diagnosis of Mental Disorder in the Elderly with Special Reference to the Early Detection of Dementia , 1986, British Journal of Psychiatry.

[13]  D. Dickson,et al.  Sensitivity and specificity of three clinical criteria for dementia with Lewy bodies in an autopsy‐verified sample , 1999, International journal of geriatric psychiatry.

[14]  [123I]β-CIT SPECT Visualizes Dopamine Transporter Loss in de novo Parkinsonian Patients , 1998, European Neurology.

[15]  L. Berg.  Clinical Dementia Rating (CDR). , 1988, Psychopharmacology bulletin.

[16]  Murat Emre,et al.  Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study , 2000, The Lancet.

[17]  D. Galasko,et al.  Neurotransmitters in basal ganglia and cortex of Alzheimer's disease with and without Lewy bodies , 1993, Neurology.

[18]  I Litvan,et al.  Accuracy of four clinical diagnostic criteria for the diagnosis of neurodegenerative dementias , 1999, Neurology.

[19]  S. E. Kim,et al.  SPECT measurement of iodine-123-beta-CIT binding to dopamine and serotonin transporters in Parkinson's disease: correlation with symptom severity. , 1999, Neurological research.

[20]  D. Brooks,et al.  Core assessment program for intracerebral transplantations (CAPIT) , 1992, Movement disorders : official journal of the Movement Disorder Society.

[21]  I G McKeith,et al.  Striatal dopaminergic markers in dementia with Lewy bodies, Alzheimer's and Parkinson's diseases: rostrocaudal distribution. , 1999, Brain : a journal of neurology.

[22]  L. Reneman,et al.  Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers , 2000, European Journal of Nuclear Medicine.

[23]  R. Schiffer,et al.  Lewy body disease: can we diagnose it? , 1998, The Journal of neuropsychiatry and clinical neurosciences.

[24]  J. P. Seibyl,et al.  [sup 123 I] beta-CIT/SPECT imaging demonstrates bilateral loss of dopamine transporters in hemi-Parkinson's disease , 1996, Neurology.

[25]  M. Ichise,et al.  SPECT imaging of pre- and postsynaptic dopaminergic alterations in l-dopa–untreated PD , 1999, Neurology.

[26]  C. Katona,et al.  Dementia with Lewy bodies: a study of post-synaptic dopaminergic receptors with iodine-123 iodobenzamide single-photon mission tomography , 1997, European Journal of Nuclear Medicine.

[27]  A. Swann,et al.  Prospective validation of Consensus criteria for the diagnosis of dementia with Lewy bodies , 2000, Neurology.

[28]  W. Kukull,et al.  The validity of 3 clinical diagnostic criteria for Alzheimer's disease , 1990, Neurology.

[29]  L. Thal,et al.  The Lewy body variant of Alzheimer's disease , 1990, Neurology.

[30]  G. Alexopoulos,et al.  Cornell scale for depression in dementia , 1988, Biological Psychiatry.

[31]  H. Arai,et al.  18F-fluorodopa PET study of striatal dopamine uptake in the diagnosis of dementia with Lewy bodies , 2000, Neurology.

[32]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[33]  Robert B. Innis,et al.  Graphical, Kinetic, and Equilibrium Analyses of in vivo [123I]β-CIT Binding to Dopamine Transporters in Healthy Human Subjects , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[34]  W. Poewe,et al.  123I‐β‐CIT and 123I‐IBZM‐SPECT scanning in levodopa‐naive Parkinson's disease , 1998 .

[35]  B. Hyman,et al.  Clinicopathologic correlates in temporal cortex in dementia with Lewy bodies , 1999, Neurology.

[36]  J. C. Stoof,et al.  Drug-naive patients with Parkinson’s disease in Hoehn and Yahr stages I and II show a bilateral decrease in striatal dopamine transporters as revealed by [123I]β-CIT SPECT , 1997, Journal of Neurology.

[37]  H. Przuntek,et al.  Delayed motor response correlates with striatal degeneration in Parkinson's disease , 1999, Acta neurologica Scandinavica.

[38]  J. C. Stoof,et al.  Iodine-123-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iod ophenyl)tropane SPECT in healthy controls and early-stage, drug-naive Parkinson's disease. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[39]  M. Hoehn,et al.  Parkinsonism , 1967, Neurology.

[40]  Robert H. Perry,et al.  Senile dementia of Lewy body type A clinically and neuropathologically distinct form of Lewy body dementia in the elderly , 1990, Journal of the Neurological Sciences.

[41]  R. Levy,et al.  Accuracy of clinical diagnosis of Alzheimer's disease. , 1990, BMJ.

[42]  S H Ferris,et al.  Behavioral symptoms in Alzheimer's disease: phenomenology and treatment. , 1987, The Journal of clinical psychiatry.

[43]  Eileen O. Smith,et al.  Decreased single‐photon emission computed tomographic {123I}β‐CIT striatal uptake correlates with symptom severity in parkinson's disease , 1995, Annals of neurology.

[44]  A. Lang,et al.  Lewy body disease and dementia. A review. , 1996, Archives of internal medicine.