Overview of NC-tb for the detection of  AD-PP

The detection of the neurodegeneration and the effects on the processing of cognition that is associated with Alzheimer’s disease (AD) at the presymptomatic stage, is of critical importance, as it will guide future treatments strategies that will delay the onset of clinical AD by many years. The presymptomatic stage may precede the clinical stage of AD by more than a decade and has been termed the AD-Pathophysiological Process (AD-PP), as it emphasises the progressive neurodegeneration that occurs prior to the clinical diagnosis. AD-PP comprises of three pathological stages which are marked by progressive synaptic and neuronal dysfunction, due to the abnormal accumulation and action of beta-amyloid and tau proteins. In the first two stages of AD-PP, episodic memory impairment is not apparent on behavioural tests. However, as the pathology that marks stages 1 and 2 originates in medial temporal cortical regions, an area that is known to be critical for episodic memory, there is putatively sufficient interference in the processing required for memory to be detected by electrophysiological methods. Further, as episodic memory is dependent on a large distributed network of areas that control and interact with the MTL areas, then it can be predicted that dysfunction in one part of the network has some effect on other parts of that network. In the episodic memory network this has been shown to include hyperactivations in the pre-frontal cortex that may signify compensatory processes.

 

Electrophysiological measures of neural activity, which includes quantative electroencephalography (qEEG), event related potentials (ERPs) and source modelling techniques provide a relatively simple and cost effective method of detecting these changes. As the success of detection depends on a high discriminatory index of the tests, a series of tests or test battery would seem to offer more potential than single tasks. Our objective therefore is to test a series of ERP episodic memory correlates, to produce a reliable, valid and highly discriminatory test battery that could be applied effectively in clinical practice and detect AD at preclinical stages 1 and 2. The outcome of this would provide early diagnosis and direct treatment strategies.