Abstract Details

Title Tracking Neurostructural Preclinical Predictors of Alzheimer’s Disease: Linking Clinical Markers to the Size of the Ventral Tegmental Area and Other Subcortical Nuclei

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-030

Objective To test the link between clinical indices of Alzheimer’s disease (AD) and neuronal loss in subcortical nuclei: Ventral Tegmental Area (VTA), Substantia Nigra (SN), Locus Coeruleus (LC), Nucleus Basalis of Meynert (NBM) and Red Nucleus (RN).

Background Recent evidence demonstrated that atrophy and diminished connectivity of the VTA predicted hippocampal volume loss and memory performance. Early impairments in other subcortical nuclei, such as the LC and the NBM have traditionally been associated with AD onset. It is unclear which nucleus is affected earliest in AD.

Design/Methods Structural MRI scans and neuropsychological scores were acquired in 256 non-demented adults (177 healthy and 79 with MCI prodromal to AD). Nuclei volumes were quantified and nonparametric correlations were run to test associations between each nucleus volume, hippocampal size, and scores on memory and other cognitive tests (p< 0.005), controlling for education, MMSE and global grey-matter signal. Nuclei structural covariance was also computed.

Results In MCI memory and hippocampal size were associated with the size of the NBM and memory was associated with LC size. In healthy adults, memory was associated with VTA, SN and RN size, reasoning with VTA and SN size, and hippocampal size with VTA size. Structural covariance of VTA extended to hippocampus, other limbic regions and areas in temporal, parietal and prefrontal cortex bilaterally. Structural covariance of the other nuclei was confined to the nuclei themselves.

Conclusions These findings replicate and extend in an independent and larger cohort earlier evidence suggesting that early VTA shrinkage is linked to structural and cognitive features of AD, strongly suggesting that decline in this subcortical structure might be a preclinical indicator of impending AD, prior to any involvement of LC and NBM. Tests of new learning were confirmed as a strong cognitive proxy of this structural abnormality.

Authors/Disclosures
Matteo De Marco, PhD (University of Sheffield) PRESENTER	No disclosure on file
Annalena Venneri, PhD (Brunel University London)	No disclosure on file

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