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Published on: July 30, 2017
Reduced monoaminergic nuclei MRI signal detectable in pre-symptomatic older adults with future memory decline
Annalena Venneri1, Matteo De Marco2
1Department of Neuroscience, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK. a.venneri@sheffield.ac.uk.
Abstract:
Evidence from murine models and human post-mortem studies indicates that monoaminergic nuclei undergo degeneration at the pre-symptomatic stage of Alzheimer's disease (AD). Analysing 129 datasets from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and relying on the Clinical Dementia Rating as group-defining instrument, we hypothesised that the MRI signal of monoaminergic nuclei would be a statistically significant predictor of memory decline in participants initially recruited in ADNI as healthy adults. As opposed to a group of cognitively stable participants, participants developing memory decline had reduced signal in the ventral tegmental area at baseline, before any evidence of functional decline emerged. These findings indicate that monoaminergic degeneration predates the onset of memory decline in an AD-centred initiative, with a crucial involvement of very-early changes of a dopaminergic region. This translates into potential informative avenues for pharmacological treatment of pre-symptomatic AD.
Insights
Early degeneration in brain
Area of Science:
- Neuroscience
- Neurology
- Alzheimer's Disease Research
Background:
- Monoaminergic nuclei degeneration is observed in early Alzheimer's disease (AD) stages through animal and human studies.
- Identifying pre-symptomatic AD biomarkers is crucial for timely intervention.
- The ventral tegmental area's role in early AD is under investigation.
Purpose of the Study:
- To investigate if MRI signal changes in monoaminergic nuclei predict memory decline in cognitively normal individuals.
- To determine if monoaminergic degeneration precedes functional decline in Alzheimer's disease.
- To explore the involvement of dopaminergic regions in pre-symptomatic AD.
Main Methods:
- Analysis of 129 datasets from the Alzheimer's Disease Neuroimaging Initiative (ADNI).
- Utilizing the Clinical Dementia Rating scale for participant group definition.
- Comparing baseline MRI signal in monoaminergic nuclei between cognitively stable participants and those who later develop memory decline.
Main Results:
- Participants who developed memory decline showed reduced MRI signal in the ventral tegmental area at baseline.
- This reduction was observed before any clinical evidence of functional decline.
- Monoaminergic nuclei degeneration, particularly in a dopaminergic region, is a predictor of future memory decline.
Conclusions:
- Monoaminergic degeneration, specifically in the ventral tegmental area, predates memory decline in Alzheimer's disease.
- These early changes in dopaminergic regions are significant indicators of pre-symptomatic AD.
- Findings suggest potential targets for early pharmacological interventions in Alzheimer's disease.
