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Brainstem substructures and cognition in prodromal Alzheimer's disease
Shubir Dutt1,2, Yanrong Li3, Mara Mather1,2
1Department of Psychology, University of Southern California, Los Angeles, CA, USA.
Brain Imaging and Behavior
|March 1, 2021
Summary
Smaller brainstem volumes, particularly the midbrain and locus coeruleus, are linked to attention and executive function deficits in mild cognitive impairment (MCI). This suggests early Alzheimer's disease (AD) brainstem degeneration impacts cognition.
Area of Science:
- Neuroscience
- Neuropathology
- Cognitive Neurology
Background:
- Neuropathological studies suggest Alzheimer's disease (AD) tau pathology may initiate in brainstem nuclei.
- The specific impact of brainstem nuclei degeneration on cognitive impairment in prodromal AD remains unclear.
Purpose of the Study:
- To investigate the relationship between brainstem substructure volumes and cognitive performance in individuals with and without mild cognitive impairment (MCI).
- To determine if tau-mediated degeneration of brainstem nuclei contributes to cognitive deficits in early-stage Alzheimer's disease.
Main Methods:
- Region-of-interest and voxel-level analyses were used to assess brainstem, midbrain, pons, and locus coeruleus volumes in cognitively normal adults and those with MCI.
- Multiple linear regression models, corrected for relevant covariates, examined the association between brainstem volumes and cognitive function.
- Cerebrospinal fluid (CSF) AD biomarker characterization was performed on subsamples.
Main Results:
- Smaller midbrain and locus coeruleus volumes were significantly associated with poorer attention and executive function in participants with MCI.
- The association between locus coeruleus volume and executive function remained significant in MCI participants with confirmed AD biomarkers.
- Brainstem volumes did not show significant relationships with memory performance.
Conclusions:
- Degeneration of the midbrain and locus coeruleus is implicated in attention and executive deficits observed in MCI.
- These findings, combined with prior neuropathological data, suggest a link between early AD-related brainstem degeneration and cognitive impairments in prodromal AD.
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