Changes in the language system as amyloid-β accumulates.

Area of Science:

• Neuroscience
• Neurology
• Cognitive Science

Background:

• Language dysfunction is a common symptom of Alzheimer's disease (AD).
• Early detection and understanding of preclinical AD are crucial for intervention.
• The preclinical phase of AD involves pathological changes before cognitive decline is evident.

Purpose of the Study:

• To investigate the association between amyloid accumulation and functional changes in the language network.
• To examine how longitudinal functional MRI changes relate to tau load in cognitively intact individuals.
• To identify early alterations in brain circuitry related to language in asymptomatic Alzheimer's disease.

Main Methods:

• Longitudinal study design over 5-6 years in 35 cognitively intact older adults.
• Amyloid accumulation measured using Positron Emission Tomography (PET).
• Functional changes in the language network assessed using task-related functional MRI; tau load measured with 18F-AV1451 PET.

Main Results:

• Amyloid accumulation correlated with increased response amplitude in the right superior temporal sulcus cortex during a semantic task.
• Amyloid accumulation was associated with decreased response amplitude in the left inferior frontal sulcus and right dorsomedial prefrontal cortex.
• No association was found between cross-sectional tau load and longitudinal functional MRI changes in this cohort.

Conclusions:

• Neocortex surrounding the posterior superior temporal sulcus plays a key role in the earliest stages of Alzheimer's disease.
• Amyloid accumulation affects cognitive brain circuitry during the asymptomatic phase of Alzheimer's disease.
• These findings highlight the impact of early amyloid pathology on language network function in cognitively normal individuals.