P50 gating deficit in Alzheimer dementia correlates to frontal neuropsychological function

BACKGROUND Cognitive inhibition processes were found to be deficient early in the clinical course of Alzheimer's disease (AD). The inhibition of redundant information is a precondition for efficient cognitive processing and presumably modulated by prefrontal attentional networks. Deficits in the suppression of the evoked potential P50 response to paired clicks are well known in schizophrenic patients and undergo cholinergic modulation. In this study, we aimed to investigate inhibitory gating deficits of P50 in AD and their relation to neuropsychological measures. METHOD P50 suppression was assessed in 19 AD-patients in comparison to a young and elderly control group (n=17 each) and related to MMSE and specific neuropsychological assessments. RESULTS Patients showed reduced sensory gating compared to healthy elderly (p<0.021) and exhibited significantly higher N40-P50-amplitudes. There were no age or gender effects in controls. Frontal neuropsychological tests (TMT-B, verbal fluency) and working memory requiring inhibition, but not declarative memory functions, were significantly correlated with inhibitory gating and test amplitude in both, AD-patients and controls. CONCLUSIONS The results support an early inhibitory deficit interfering with executive functions and working memory in AD independent from physiological aging. P50 gating might be applicable as a marker for inhibition deficits and thereby be important for prognosis estimation.

[1]  Iiro P. Jääskeläinen,et al.  Cholinergic modulation of preattentive auditory processing in aging , 2005, NeuroImage.

[2]  Oleg Korzyukov,et al.  Generators of the intracranial P50 response in auditory sensory gating , 2007, NeuroImage.

[3]  V. Jousmäki,et al.  Habituation of auditory N100 correlates with amygdaloid volumes and frontal functions in age-associated memory impairment , 1995, Physiology & Behavior.

[4]  A. Wiser,et al.  Normalization of auditory physiology by cigarette smoking in schizophrenic patients. , 1993, The American journal of psychiatry.

[5]  Paolo Bergonzi,et al.  Sensory Gating Deficit Assessed by P50/Pb Middle Latency Event Related Potential in Alzheimer’s Disease , 2006, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[6]  H Bratzke,et al.  Neuropathological hallmarks of Alzheimer's and Parkinson's diseases. , 1998, Progress in brain research.

[7]  F. Joseph McClernon,et al.  Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization , 2006, Psychopharmacology.

[8]  C. Reynolds,et al.  Wechsler memory scale-revised , 1988 .

[9]  G. Fein,et al.  The auditory P50 response is normal in Alzheimer's disease when measured via a paired click paradigm. , 1994, Electroencephalography and clinical neurophysiology.

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

[11]  Michael Krause,et al.  Auditory sensory gating in hippocampus and reticular thalamic neurons in anesthetized rats , 2003, Biological Psychiatry.

[12]  J. Morris,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assesment of Alzheimer's disease , 1989, Neurology.

[13]  M Scherg,et al.  Is frontal lobe involved in the generation of auditory evoked P50? , 2001, Neuroreport.

[14]  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.

[15]  J S Buchwald,et al.  Midlatency auditory evoked responses: differential abnormality of P1 in Alzheimer's disease. , 1989, Electroencephalography and clinical neurophysiology.

[16]  R Freedman,et al.  Schizophrenia, sensory gating, and nicotinic receptors. , 1998, Schizophrenia bulletin.

[17]  Hitoshi Shinotoh,et al.  Preserved acetylcholinesterase activity in aged cerebral cortex , 1998, The Lancet.

[18]  F. Jessen,et al.  Sensory gating deficit expressed by a disturbed suppression of the P50 event-related potential in patients with Alzheimer's disease. , 2001, The American journal of psychiatry.

[19]  H. Davis,et al.  Age-related change in neural processing of time-dependent stimulus features. , 2005, Brain research. Cognitive brain research.

[20]  B. Turetsky,et al.  P50 abnormalities in schizophrenia: relationship to clinical and neuropsychological indices of attention , 1998, Schizophrenia Research.

[21]  Peter Schönknecht,et al.  Prevalence and natural course of aging-associated cognitive decline in a population-based sample of young-old subjects. , 2005, The American journal of psychiatry.

[22]  H. Braak,et al.  Vulnerability of Select Neuronal Types to Alzheimer's Disease , 2000, Annals of the New York Academy of Sciences.

[23]  S. Barth,et al.  Neuropsychologische Profile in der Demenzdiagnostik: Eine Untersuchung mit der CERAD-NP-Testbatterie , 2005 .

[24]  R. Reitan Validity of the Trail Making Test as an Indicator of Organic Brain Damage , 1958 .

[25]  P. Fossier,et al.  Cholinergic modulation of the cortical neuronal network , 2003, Pflügers Archiv.

[26]  Robert Freedman,et al.  Neurophysiological and neuropsychological evidence for attentional dysfunction in schizophrenia , 1993, Schizophrenia Research.

[27]  Aysenil Belger,et al.  Comparison of four components of sensory gating in schizophrenia and normal subjects: a preliminary report , 1999, Psychiatry Research.

[28]  M. Geyer,et al.  Multiple site evaluation of P50 suppression among schizophrenia and normal comparison subjects , 1998, Schizophrenia Research.

[29]  T. Demiralp,et al.  The effects of interstimulus interval on sensory gating and on preattentive auditory memory in the oddball paradigm Can magnitude of the sensory gating affect preattentive auditory comparison process? , 2007, Neuroscience Letters.

[30]  Nick F. Ramsey,et al.  Effects of Aging on BOLD fMRI during Prosaccades and Antisaccades , 2006, Journal of Cognitive Neuroscience.

[31]  M. D'Andrea,et al.  Targeting the alpha 7 nicotinic acetylcholine receptor to reduce amyloid accumulation in Alzheimer's disease pyramidal neurons. , 2006, Current pharmaceutical design.

[32]  Robert Freedman,et al.  The genetics of sensory gating deficits in schizophrenia , 2003, Current psychiatry reports.

[33]  A. Baddeley,et al.  The multi-component model of working memory: Explorations in experimental cognitive psychology , 2006, Neuroscience.

[34]  J. E. O'Neill,et al.  Nicotinic receptor desensitization and sensory gating deficits in schizophrenia , 1998, Biological Psychiatry.

[35]  Robert W. Buchanan,et al.  An open-labeled trial of adjunctive donepezil for cognitive impairments in patients with schizophrenia , 2003, Schizophrenia Research.

[36]  Carmen Martin-Ruiz,et al.  Nicotinic receptor abnormalities in Alzheimer’s disease , 2001, Biological Psychiatry.

[37]  E. Golob,et al.  Auditory cortical activity in amnestic mild cognitive impairment: relationship to subtype and conversion to dementia. , 2007, Brain : a journal of neurology.

[38]  Edward J. Golob,et al.  Sensory cortical interactions in aging, mild cognitive impairment, and Alzheimer’s disease , 2001, Neurobiology of Aging.

[39]  A. Starr,et al.  Auditory brain-stem, middle- and long-latency evoked potentials in mild cognitive impairment , 2005, Clinical Neurophysiology.

[40]  A. Baddeley,et al.  Attentional control in Alzheimer's disease. , 2001, Brain : a journal of neurology.

[41]  Ann Summerfelt,et al.  Review of clinical correlates of P50 sensory gating abnormalities in patients with schizophrenia. , 2005, Schizophrenia bulletin.

[42]  E. Bramon,et al.  Meta-analysis of the P300 and P50 waveforms in schizophrenia , 2004, Schizophrenia Research.

[43]  Robert Freedman,et al.  Proof-of-Concept Trial of an α7 Nicotinic Agonist in Schizophrenia , 2006 .

[44]  Paige E. Scalf,et al.  Training-induced plasticity in older adults: Effects of training on hemispheric asymmetry , 2007, Neurobiology of Aging.

[45]  J. Hodges,et al.  Attention and executive deficits in Alzheimer's disease. A critical review. , 1999, Brain : a journal of neurology.

[46]  Hélène Amieva,et al.  Inhibitory functioning in Alzheimer's disease. , 2004, Brain : a journal of neurology.

[47]  A. Belger,et al.  Midlatency evoked potentials attenuation and augmentation reflect different aspects of sensory gating , 1999, Biological Psychiatry.

[48]  R. Knight,et al.  Prefrontal deficits in attention and inhibitory control with aging. , 1997, Cerebral cortex.