The Auditory Afferent Pathway as a Clinical Marker of Alzheimer’s Disease

Alzheimer’s disease (AD) is a degenerative neurological condition that causes brain cells to die and the brain to shrink (atrophy). AD is the most prevalent cause of dementia and is defined as a progressive deterioration in cognitive, behavioral, and social skills that impair a person’s ability to function independently. AD affects around 5.8 million people in the United States aged 65 and above. 80% of those are 75 or older. The early symptoms of disease include forgetting recent events or discussions. A person with AD will develop severe memory impairment and lose the capacity to do daily chores as the disease develops. Memory impairments worsen as the disease advances and new symptoms emerge. Medications may improve or reduce the course of symptoms temporarily. There is no cure for AD or medication that affects the progression of the disease in the brain. Complications from significant loss of brain function, such as dehydration, starvation, or infection, result in death in the advanced stages of the condition. According to recent research, both peripheral and central auditory system impairment occurs in the symptomatic stages of AD and this may be early indications of the disease. Furthermore, loss of auditory ability leads to communication problems, social isolation, and poor living standards for Alzheimer’s patients and families. Before the apparent neuronal loss in AD, neural pathways and nuclei in the brain stem may be disrupted.

In a new paper published in Journal of Alzheimer’s Disease Australian scientists, Professor Kaneez Fatima Shad from the University of Technology Sydney together with Wissam Soubra and Dr. Dennis Cordato from Ingham Institute for Applied Medical Research proposed new biomarkers that are reliable and yet accessible. The neuroscientists with many years of experience noticed that AD inevitably causes degeneration of various tracts in the brain stem. Therefore, examination of these pathways with the help of magnetic resonance spectroscopy (MRS), brain stem auditory evoked potentials (BAEPs), and event-related potentials (ERPs) could be a reliable way to improve the diagnostic accuracy of AD. These approaches are economical as compared to recent and advanced techniques which measure amyloid and Tau PET and CSF of amyloid-β (Aβ) 42/40 ratio and CSF tau. Authors wanted to prove how functional losses appear before structural problems in Alzheimer’s disease (AD) and how this can help in early diagnosis of disease. To achieve their objectives, authors examined the 1H-MRS findings of the inferior colliculus in 54 males (27 healthy controls and 27 MCI patients aged 50-70). All patients were subjected to neuropsychological testing, which included the Mini-Mental State Examination and the Clinical Dementia Rating. The Point Resolved Spectroscopy (PRESS) technique was used for sequencing 1H-MRS of the inferior colliculus, using both multi and single voxels with varying voxel sizes (from 7-15) to get consistent findings with little noise. Authors chose to focus on the auditory route since it is the most external of the sensory routes and one of the last sensory pathways to be clinically diagnosed as being impaired in Alzheimer’s disease. Additionally, they also hypothesized that degenerative changes in the auditory pathway might be recognized much earlier than visible atrophy of the cortex.

In their findings, authors observed that in subjects with Mini-Mental State Examination scores greater than 24 and no signs of atrophy in their MRI of the medial temporal lobe, imaging of the inferior colliculi using magnetic resonance spectroscopy showed a significant decrease in the neuronal markers N acetyl aspartate/creatine ratio and an increase in the glial marker myo-Inositol. In cognitive decline, particularly Alzheimer’s disease, abnormalities in auditory event-related potentials (ERPs) have been identified. The study also validated the use of 1H-MRS in MCI for detecting neuronal alterations in the brain stem. Patients with mild MCI have a higher risk of progression to AD and in such situations 1H-MRS can serve as a useful diagnostic procedure. The researchers also discovered a substantial drop in amplitude and increased in latency within the first 10 ms of auditory evoked potentials recorded on electroencephalography (EEG), indicating a slower brainstem auditory response. EEG spectral power measured in the brain is also linked to neuronal activity in the inferior colliculi. Authors hypothesized that a non-invasive functional assessment of auditory afferent pathways, like brain stem auditory, evoked potentials, magnetic resonance spectroscopy, and event-related potentials, could increase AD diagnosis accuracy.

Although measuring hearing loss and using it as a biomarker for the diagnosis and even monitoring the progress of AD is not a new concept, but the hypothesis by Professor Kaneez Fatima Shad and colleagues is more way of objective assessment of hearing loss and focusing on the degenerative changes in the neural pathways. Thus, the report proposes the use of MRS, BAEPs, and ERPs to measure the severity of the disease condition. In addition, since using the individual tests may not be sufficient to predict the course of AD, the Australian researchers propose developing a hybrid algorithm that can utilize the results of multiple tests. Such a hybrid test can have relatively good sensitivity and specificity. This approach might lead to the creation of a new hybrid algorithm that could operate as a potential non-invasive biomarker of early cognitive decline and be used to detect persons at risk of dementia, notably AD.