Deficit in Central Auditory Processing as a Biomarker of Pre-Clinical Alzheimer's Disease

Abstract

Prevention of dementia due to Alzheimer's disease (d/AD) requires interventions that slow the disease process prior to symptom onset. To develop such interventions, one needs metrics that assess pre-symptomatic disease progression. Familiar measures of progression include cerebrospinal fluid (CSF) biochemical and imaging analyses, as well as cognitive testing. Changes in the latter can sometimes be difficult to distinguish from effects of "normal" aging. A different approach involves testing of "central auditory processing" (CAP), which enables comprehension of auditory stimuli amidst a distracting background (e.g., conversation in a noisy bar or restaurant). Such comprehension is often impaired in d/AD. Similarly, effortful or diminished auditory comprehension is sometimes reported by cognitively healthy elders, raising the possibility that CAP deficit may be a marker of pre-symptomatic AD. In 187 cognitively and physically healthy members of the aging, AD family history-positive PREVENT-AD cohort, we therefore evaluated whether CAP deficits were associated with known markers of AD neurodegeneration. Such markers included CSF tau concentrations and magnetic resonance imaging volumetric and cortical thickness measures in key AD-related regions. Adjusting for age, sex, education, pure-tone hearing, and APOEɛ4 status, we observed a persistent relationship between CAP scores and CSF tau levels, entorhinal and hippocampal cortex volumes, cortical thickness, and deficits in cognition (Repeatable Battery for Assessment of Neuropsychological Status total score, and several of its index scales). These cross-sectional observations suggest that CAP may serve as a novel metric for pre-symptomatic AD pathogenesis. They are therefore being followed up longitudinally with larger samples.

Keywords: Biomarkers; central auditory processing disorder; cognitive function; pre-clinical Alzheimer’s disease; prevention; sensorineural assessment.

Fig.1

Whole brain cortical thickness measures associated with SSI-ICM. The figure displays a color map representing results of whole brain random-field theory cortical thickness analysis. The images, in sequence from top left, show left-lateral, dorsal, right-lateral, left-mesial, ventral, and right-mesial views, while the lower images show coronal views from rostral (left) and caudal (right) perspectives. Analyses adjusted for age, gender, education, APOE ɛ4 status, and tone test. The adjusted SSI-ICM score displayed a positive relationship with right Heschl’s gyrus at the peak level (indicated by red colored point). SSI-ICM score showed a positive relationship with thickness of the left and right precuneus, with extension to adjacent inferior parietal and occipital cortices. Also of interest are positive associations with right parahippocampal and entorhinal cortices, as well as left inferior and mid temporal gyri. All these areas are displayed as blue colored areas and are statistically significant as clusters.

Fig.2

Whole brain cortical thickness measures associated with DSI-REA. Color map showing association of DSI-REA score with cortical thickness estimated using whole brain random-field theory analysis. The different image perspectives are as explained in Fig. 1. After adjustment for age, gender, education, APOE ɛ4 status, and tone test, DSI-REA score (representing presumed degeneration of transcortical auditory pathways) showed an inverse relationship with thickness of the right dorsomedial and inferior frontal cortices, as indicated in pale blue. Also shown are associations with thickness of left superior and transverse temporal cortices as well as bilateral inferior temporal gyri, right anterior temporal pole, and right precuneus. Analyses are significant at the cluster level, as shown. No significant peaks are observed.