Objective: To explore diffusion-based MRI assessments of the nucleus basalis of Meynert (nbM) as a neuroimaging biomarker of cognitive abilities and longitudinal cognitive changes in Parkinson’s disease (PD).

Background: The nbM provides a major cholinergic input to the cortex and is an early site of degeneration in Alzheimer’s disease.¹ In PD, diffusion tensor imaging (DTI) assessments of the nbM were previously shown to distinguish and predict cognitive impairment;² however, no previous studies have assessed how free-water (FW) compares with DTI for these outcomes and if longitudinal changes in diffusion-based assessments correlate with changes in cognition. FW quantifies extracellular water within a voxel that likely reflects tissue atrophy and/or inflammation.^{3, 4} In the substantia nigra, FW is more sensitive to longitudinal changes than DTI in PD.^5-7 We evaluated how nbM FW compares with DTI for cognition outcomes in PD patients from the Parkinson’s Progression Markers Initiative (PPMI).

Method: A total of 149 PD patients (mean disease duration=6.9 months) from PPMI with valid Baseline DTI data were analyzed (downloaded April 2018).  Utilizing the same definitions as the previously mentioned PPMI study,² cognitive impairment at Baseline was defined as a Montreal Cognitive Assessment (MoCA) score ≤25, while modified Level 2 criteria mild cognitive impairment (MCI) was defined as a MoCA ≤25 with at least two cognitive test scores >1.5 standard deviations below the standardized mean score.⁸  MoCA was selected for the longitudinal analyses based on previous results showing sensitivity to change.⁹  The b=0 image from each MRI acquisition was non-linearly registered in MNI space using the Advanced Normalization Tools software package.  The nbM was defined using a histologically-defined atlas.  The diffusion tensor was calculated using both single tensor and bi-tensor models, with the later providing an estimate of free-water (FW) and FW-corrected DTI.³

Results: [Table 1]
[Table 2]
[Table 3]

Conclusion: NbM FW is more sensitive than DTI for distinguishing and predicting cognitive impairment and longitudinally reflecting cognitive changes in early Parkinson’s disease.  These qualities support nbM FW as a promising cognition-progression biomarker in PD that could help identify cognition protective therapies in clinical trials.

References: 1. Schmitz TW, Nathan Spreng R, Alzheimer’s Disease Neuroimaging I. Basal forebrain degeneration precedes and predicts the cortical spread of Alzheimer’s pathology. Nature communications 2016;7:13249. 2. Schulz J, Pagano G, Fernandez Bonfante JA, Wilson H, Politis M. Nucleus basalis of Meynert degeneration precedes and predicts cognitive impairment in Parkinson’s disease. Brain 2018;141:1501-16. 3. Pasternak O, Sochen N, Gur Y, Intrator N, Assaf Y. Free water elimination and mapping from diffusion MRI. Magn Reson Med 2009;62:717-30. 4. Pasternak O, Shenton ME, Westin CF. Estimation of extracellular volume from regularized multi-shell diffusion MRI. Med Image Comput Comput Assist Interv 2012;15:305-12. 5. Ofori E, Pasternak O, Planetta PJ, et al. Longitudinal changes in free-water within the substantia nigra of Parkinson’s disease. Brain 2015;138:2322-31. 6. Burciu RG, Ofori E, Archer DB, et al. Progression marker of Parkinson’s disease: A 4-year multisite imaging study. Brain 2017;140:2183–92. 7. Guttuso T, Jr., Bergsland N, Hagemeier J, Lichter DG, Pasternak O, Zivadinov R. Substantia Nigra Free Water Increases Longitudinally in Parkinson Disease. AJNR Am J Neuroradiol 2018;39:479-84. 8. Weintraub D, Simuni T, Caspell-Garcia C, et al. Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson’s disease. Mov Disord 2015;30:919-27. 9. Caspell-Garcia C, Simuni T, Tosun-Turgut D, et al. Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease. PLoS One 2017;12:e0175674.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/nucleus-basalis-of-meynert-free-water-distinguishes-and-predicts-cognitive-impairment-and-longitudinally-correlates-with-cognitive-changes-in-early-parkinsons-disease/