Affiliations: [a] Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, UK
| [b] Neurodegeneration Imaging Group, University of Exeter Medical School, London, UK
Correspondence:
[*]
Correspondence to: Marios Politis, Neurodegeneration Imaging Group, University of Exeter Medical School, London, UK. E-mail: m.politis@exeter.ac.uk.
Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf
Abstract: Background:The roles of amyloid-β and tau in the degenerative process of Alzheimer’s disease (AD) remain uncertain. [18F]AV-45 and [18F]AV-1451 PET quantify amyloid-β and tau pathology, respectively, while diffusion tractography enables detection of their microstructural consequences. Objective:Examine the impact of amyloid-β and tau pathology on the structural connectome and cognition, in mild cognitive impairment (MCI) and AD. Methods:Combined [18F]AV-45 and [18F]AV-1451 PET, diffusion tractography, and cognitive assessment in 28 controls, 32 MCI, and 26 AD patients. Results:Hippocampal connectivity was reduced to the thalami, right lateral orbitofrontal, and right amygdala in MCI; alongside the insula, posterior cingulate, right entorhinal, and numerous cortical regions in AD (all p < 0.05). Hippocampal strength inversely correlated with [18F]AV-1451 SUVr in MCI (r = –0.55, p = 0.049) and AD (r = –0.57, p = 0.046), while reductions in hippocampal connectivity to ipsilateral brain regions correlated with increased [18F]AV-45 SUVr in those same regions in MCI (r = –0.33, p = 0.003) and AD (r = –0.31, p = 0.006). Cognitive scores correlated with connectivity of the right temporal pole in MCI (r = –0.60, p = 0.035) and left hippocampus in AD (r = 0.69, p = 0.024). Clinical Dementia Rating Scale scores correlated with [18F]AV-1451 SUVr in multiple areas reflecting Braak stages I-IV, including the right (r = 0.65, p = 0.004) entorhinal cortex in MCI; and Braak stages III-VI, including the right (r = 0.062, p = 0.009) parahippocampal gyrus in AD. Conclusion:Reductions in hippocampal connectivity predominate in the AD connectome, correlating with hippocampal tau in MCI and AD, and with amyloid-β in the target regions of those connections. Cognitive scores correlate with microstructural changes and reflect the accumulation of tau pathology.
Keywords: Alzheimer’s disease, amyloid, connectome, diffusion tensor imaging, 18F-AV-1451, 18F-AV-45, magnetic resonance imaging, mild cognitive impairment, positron emission tomography, tau protein
