Auditory P50: a potential biomarker of early Alzheimer's disease and relationship to cerebrospinal fluid beta-amyloid and tau

Alzheimer's disease (AD) is a growing health concern as the population and percentage of older adults continues to rise. The pathophysiological process underlying the disease is present for years before the onset of clinical symptoms, providing a potential window of opportunity to intervene before neural systems are irreparably damaged. The necessity for early intervention is one driving force in the search for biomarkers to indicate the presence or absence of disease or the likelihood of developing AD. Cerebrospinal fluid concentrations of beta amyloid (Aβ) and tau, linked to the pathogenesis of AD, have been the most extensively studied biomarkers. While promising, CSF biomarkers are invasive, costly and have limited accessibility. In contrast, electroencephalogram-derived event-related potential (ERP) techniques, as proposed in this study, are noninvasive, inexpensive and widely accessible. ERPs are capable of detecting abnormalities in brain activity that reflect underlying disease-related changes in the brain. Abnormal ERPs have long been observed in AD patients and in patients with mild cognitive impairment (MCI). More recently, several studies have shown the P50 ERP component differentiates AD patients from controls and may have utility predicting MCI conversion to dementia. The present study investigated the P50 ERP component as a potential AD biomarker in MCI patients and cognitively normal controls. Thirty-six patients with MCI were divided into two groups based on CSF evidence of amyloidosis. Twenty-seven age-matched controls were divided into groups using a median split of amyloid level. An auditory oddball paradigm was used to elicit the P50 response. Very few cognitively normal controls were amyloid positive and P50 amplitude was not found to differ as a function of Aβ level. Amyloid-positive MCI patients showed larger P50 amplitudes for all stimulus conditions relative to the amyloid-negative group. P50 amplitude was also a significant predictor of CSF status in the MCI patients. The best predictor conditions showed 94.7% sensitivity, 94.1% specificity and total model accuracy of 94.4% when classifying the MCI patients according to amyloid positivity. P50 amplitude did not differ between MCI patients and normal controls, providing support for a distinct relationship between P50 and AD pathology versus clinical symptoms due to another etiology. P50 may therefore have clinical utility as a prescreening measure to identify in vivo Alzheimer's pathology in pre-dementia stages of the disease. Findings across the literature implicate the prefrontal cortex in top-down modulation of the auditory cortical response. Larger, unrestrained P50 may reflect a deficit in this modulating activity, possibly via disrupted cortico-cortical pathways, alterations in cholinergic system function, or impairment in functional neural networks affected by early AD pathology.Ph.D., Psychology -- Drexel University, 201