Intrinsic Brain Activity of Inferior Temporal Region Increased in Prodromal Alzheimer's Disease With Hearing Loss

Abstract

Background and ObjectiveHearing loss (HL) is one of the modifiable risk factors for Alzheimer's disease (AD). However, the underlying mechanism behind HL in AD remains elusive. A possible mechanism is cognitive load hypothesis, which postulates that over-processing of degraded auditory signals in the auditory cortex leads to deficits in other cognitive functions. Given mild cognitive impairment (MCI) is a prodromal stage of AD, untangling the association between HL and MCI might provide insights for potential mechanism behind HL.MethodsWe included 85 cognitively normal (CN) subjects with no hearing loss (NHL), 24 CN with HL, 103 mild cognitive impairment (MCI) patients with NHL, and 23 MCI with HL from the ADNI database. All subjects underwent resting-state functional MRI and neuropsychological scale assessments. Fractional amplitude of low-frequency fluctuation (fALFF) was used to reflect spontaneous brain activity. The mixed-effects analysis was applied to explore the interactive effects between HL and cognitive status (GRF corrected, voxel p-value <0.005, cluster p-value < 0.05, two-tailed). Then, the FDG data was included to further reflect the regional neuronal abnormalities. Finally, Pearson correlation analysis was performed between imaging metrics and cognitive scores to explore the clinical significance (Bonferroni corrected, p < 0.05).ResultsThe interactive effects primarily located in the left superior temporal gyrus (STG) and bilateral inferior temporal gyrus (ITG). Post-hoc analysis showed that NC with HL had lower fALFF in bilateral ITG compared to NC with NHL. NC with HL had higher fALFF in the left STG and decreased fALFF in bilateral ITG compared to MCI with HL. In addition, NC with HL had lower fALFF in the right ITG compared to MCI with NHL. Correlation analysis revealed that fALFF was associated with MMSE and ADNI-VS, while SUVR was associated with MMSE, MoCA, ADNI-EF and ADNI-Lan.ConclusionHL showed different effects on NC and MCI stages. NC had increased spontaneous brain activity in auditory cortex while decreased activity in the ITG. Such pattern altered with disease stage changing and manifested as decreased activity in auditory cortex along with increased activity in ITG in MCI. This suggested that the cognitive load hypothesis may be the underlying mechanism behind HL.

Effects of APOE ε2 allele on basal forebrain functional connectivity in mild cognitive impairment

“…The vascular etiology is an important part of the disease process, 79 such as the hypoperfusion and dysfunction of blood brain barrier 80 . Additionally, visual and auditory impairments have been found in MCI or AD patients and correlate with cognitive function 81,82 . Moreover, it is clear that the gut‐brain axis plays a vital role in neurodegenerative diseases.…”

“…80 Additionally, visual and auditory impairments have been found in MCI or AD patients and correlate with cognitive function. 81,82 Moreover, it is clear that the gut-brain axis plays a vital role in neurodegenerative diseases. And constipation has been considered to be a factor of cognitive decline in AD and MCI patients.…”

Cognitive and behavioral effects of hearing loss

“…The ‘cognitive load’ hypothesis attempts to explain the relationship between hearing loss and cognition as a function of cognitive resources necessary when someone is training to hear and process degraded auditory signals, which may lead to deficits in other cognitive functions. Hong et al [27] conducted a prospective study attempting to explore this relationship using functional magnetic resonance imaging and cognitive scores. Their study identified an interactive effect between hearing loss and cognitive status; those with cognitive impairment demonstrated decreased spontaneous activity in the auditory cortex and increased activity in regions used to process visuospatial information and multimodal sensory integration.…”