Diagnostic Usefulness of Cognitive Auditory Event-Related P300 Subcomponents in Patients With Alzheimers Disease?

Summary: Early diagnosis of Alzheimers disease (AD) would be of great clinical value. Auditory event-related P300 mainly generated in temporoparietal regions is related to the pathophysiology of AD. A former study revealed that reliable separation of P300 subcomponents by dipole source analysis increased sensitivity (86.7%) and specificity (76.7%) in correctly detecting AD patients from healthy subjects. Aim of the present study was to replicate this interesting finding on a different sample. Auditory event-related P300 was recorded in unmedicated patients with mild to moderate AD and age- and sex-matched healthy volunteers. The subcomponents of the P300, P3a and P3b, were determined by dipole source analysis (Brain Electric Source Analysis program). As in the first study, AD patients were again characterized by a diminished P3b amplitude and longer P3a latency and reaction time. Using these three parameters, sensitivity was 81.3% to detect patients with AD from healthy controls with a specificity of 83.3%. This successful replication of the first study suggests that recording and determining P300 subcomponents together with other putative neurobiological markers may be useful to enhance the individual diagnostic accuracy in AD at an early stage.

[1]  Bruce J. Fisch,et al.  Fisch and Spehlmann's Eeg Primer: Basic Principles of Digital and Analog Eeg , 1999 .

[2]  P300 and neuropsychological function in normal aging and dementia. , 1995, Electroencephalography and clinical neurophysiology. Supplement.

[3]  M. Rowan,et al.  Clinical application of electrophysiological markers in the differential diagnosis of depression and very mild Alzheimer's disease. , 1996, Journal of neurology, neurosurgery, and psychiatry.

[4]  A. Hofman,et al.  Incidence of dementia and major subtypes in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. , 2000, Neurology.

[5]  Frank Padberg,et al.  Value of event-related P300 subcomponents in the clinical diagnosis of mild cognitive impairment and Alzheimer's Disease. , 2002, Psychophysiology.

[6]  Cholinergic, serotonergic, and GABAergic effects on the ERP. , 1995, Electroencephalography and clinical neurophysiology. Supplement.

[7]  A Pfefferbaum,et al.  Clinical application of the P3 component of event-related potentials. I. Normal aging. , 1984, Electroencephalography and clinical neurophysiology.

[8]  K. Squires,et al.  Long latency event-related components of the auditory evoked potential in dementia. , 1978, Brain : a journal of neurology.

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

[10]  H Shibasaki,et al.  Auditory long latency event-related potentials in Alzheimer's disease and multi-infarct dementia. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[11]  A. Hofman,et al.  Prevalence of dementia and major subtypes in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. , 2000, Neurology.

[12]  K. Blennow,et al.  Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer’s disease: a community based follow up study , 1998, Journal of neurology, neurosurgery, and psychiatry.

[13]  A Hofman,et al.  Prognosis with stroke in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. , 2000, Neurology.

[14]  J. Ashford,et al.  “Preclinical” AD revisited , 2000, Neurology.

[15]  J. Polich,et al.  EEG and ERP assessment of normal aging. , 1997, Electroencephalography and clinical neurophysiology.

[16]  N Tanizaki,et al.  Semi-automatic ROI placement system for analysis of brain PET images based on elastic model: application to diagnosis of Alzheimer's disease. , 2000, The Keio journal of medicine.

[17]  M. Folstein,et al.  Accuracy of Clinical Diagnosis of Alzheimer Disease and Clinical Features of Patients with Non-Alzheimer Disease Neuropathology , 1996, Alzheimer disease and associated disorders.

[18]  P. Tariot.  Maintaining Cognitive Function in Alzheimer Disease: How Effective are Current Treatments? , 2001, Alzheimer disease and associated disorders.

[19]  E. Donchin,et al.  Is the P300 component a manifestation of context updating? , 1988, Behavioral and Brain Sciences.

[20]  K. Blennow,et al.  Evaluation of CSF-tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice. , 2001, Archives of neurology.

[21]  Ulrich Hegerl,et al.  Dipole source analysis of P300 component of the auditory evoked potential: a methodological advance? , 1997, Psychiatry Research: Neuroimaging.

[22]  F E Bloom,et al.  P300 assessment of early Alzheimer's disease. , 1990, Electroencephalography and clinical neurophysiology.

[23]  J T O'Brien,et al.  Temporal lobe magnetic resonance imaging can differentiate Alzheimer's disease from normal ageing, depression, vascular dementia and other causes of cognitive impairment , 1997, Psychological Medicine.

[24]  E. Halgren,et al.  Generators of the late cognitive potentials in auditory and visual oddball tasks. , 1998, Electroencephalography and clinical neurophysiology.

[25]  Y. Mimori,et al.  The P300 event-related potentials in dementia of the Alzheimer type. Correlations between P300 and monoamine metabolites. , 1990, Electroencephalography and clinical neurophysiology.

[26]  T W Picton,et al.  Separation and identification of event-related potential components by brain electric source analysis. , 1991, Electroencephalography and clinical neurophysiology. Supplement.

[27]  J. Yesavage,et al.  Automatic and Effortful Processing in Aging and Dementia: Event-Related Brain Potentials , 1997, Neurobiology of Aging.

[28]  D. Blackwood,et al.  P300, a state and a trait marker in schizophrenia , 2000, The Lancet.

[29]  Ulrich Hegerl,et al.  Neurochemical Substrates and Neuroanatomical Generators of the Event-Related P300 , 1999, Neuropsychobiology.

[30]  K. Squires,et al.  Age-related variations in evoked potentials to auditory stimuli in normal human subjects. , 1978, Electroencephalography and clinical neurophysiology.

[31]  Jaime Kulisevsky,et al.  Usefulness of P300 in Subjective Memory Complaints: A Prospective Study , 2005, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[32]  A. Starr,et al.  Latency variability of the components of auditory event-related potentials to infrequent stimuli in aging, Alzheimer-type dementia, and depression. , 1988, Electroencephalography and clinical neurophysiology.

[33]  Ove Almkvist,et al.  Early diagnosis of Alzheimer dementia based on clinical and biological factors , 1999, European Archives of Psychiatry and Clinical Neuroscience.

[34]  J. Polich,et al.  P300 as a clinical assay: rationale, evaluation, and findings. , 2000, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[35]  R. Verleger.  Event-related potentials and cognition: A critique of the context updating hypothesis and an alternative interpretation of P3 , 1988, Behavioral and Brain Sciences.

[36]  A Pfefferbaum,et al.  Clinical utility of long latency 'cognitive' event-related potentials (P3): the cons. , 1990, Electroencephalography and clinical neurophysiology.

[37]  T. Robbins,et al.  Neuropsychology--dementia and affective disorders. , 1996, British medical bulletin.

[38]  C. Ballard,et al.  Advances in the Treatment of Alzheimer’s Disease: Benefits of Dual Cholinesterase Inhibition , 2002, European Neurology.

[39]  H. Möller,et al.  P300 subcomponents reflect different aspects of psychopathology in schizophrenia , 1999, Biological Psychiatry.

[40]  B. Hyman,et al.  The Neuropathological Diagnosis of Alzheimer’s Disease: Clinical-Pathological Studies , 1997, Neurobiology of Aging.

[41]  R. Ihl,et al.  Event-related potentials and psychopharmacology. Cholinergic modulation of P300. , 1994, Pharmacopsychiatry.

[42]  M. Scherg,et al.  Two bilateral sources of the late AEP as identified by a spatio-temporal dipole model. , 1985, Electroencephalography and clinical neurophysiology.

[43]  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.

[44]  B L Holman,et al.  The scintigraphic appearance of Alzheimer's disease: a prospective study using technetium-99m-HMPAO SPECT. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[45]  M. Molnár,et al.  On the origin of the P3 event-related potential component. , 1994, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[46]  T Dierks,et al.  Functional imaging procedures in dementias: mapping of EEG and evoked potentials , 1992, Acta neurologica Scandinavica. Supplementum.

[47]  T W Picton,et al.  The P300 Wave of the Human Event‐Related Potential , 1992, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[48]  K. Meador,et al.  Cholinergic modulation of human P3 event‐related potentials , 1987, Neurology.

[49]  Georg Juckel,et al.  P300 and symptom improvement in schizophrenia , 2001, Psychopharmacology.

[50]  J. Ford,et al.  Clinical application of the P3 component of event-related potentials. II. Dementia, depression and schizophrenia. , 1984, Electroencephalography and clinical neurophysiology.

[51]  R. Verleger,et al.  Event-related EEG potentials in mild dementia of the Alzheimer type. , 1992, Electroencephalography and clinical neurophysiology.

[52]  H. Bickel.  [Dementia in advanced age: estimating incidence and health care costs]. , 2001, Zeitschrift fur Gerontologie und Geriatrie.