Language dysfunction and related amyloid-β in Alzheimer's disease mediated by brain functional connectivity changes

Area of Science:

• Neuroscience
• Neurology
• Cognitive Science

Background:

• Language dysfunction is an early symptom of Alzheimer's disease (AD).
• The relationship between amyloid-β pathology and language impairment in AD is not fully understood.
• Functional connectivity (FC) within language networks is crucial for maintaining language function.

Purpose of the Study:

• To investigate whether altered functional connectivity (FC) in fronto-temporal language regions mediates the association between amyloid-β burden and language dysfunction in Alzheimer's disease (AD).
• To explore the specific role of fronto-temporal FC in the progression of language deficits associated with amyloid-β accumulation.

Main Methods:

• Recruited 110 participants (44 cognitively unimpaired, 24 mild cognitive impairment, 42 AD patients).
• Assessed language function using acoustic and semantic features from speech recordings (cookie-theft picture description).
• Utilized resting-state functional MRI and 18F-florbetapir PET to measure fronto-temporal FC and amyloid-β burden.

Main Results:

• AD patients exhibited prolonged silence durations and hesitation in speech, correlated with semantic content.
• Average silence duration positively correlated with global amyloid-β burden (r=0.30, p=0.015).
• Reduced fronto-temporal FC was observed in AD patients. Mediation analysis showed reduced FC between left rpSTS and right dIFG mediated the link between amyloid-β burden and speech silence duration (a*b=0.19, p=0.026).

Conclusions:

• Reduced fronto-temporal functional connectivity mediates the relationship between amyloid-β burden and language dysfunction in Alzheimer's disease.
• The left rostroposterior superior temporal sulcus (rpSTS) appears particularly vulnerable to amyloid-β burden, potentially leading to impaired connectivity with other language network regions.