Objective: To study changes in microstructural integrity of white matter tracts associated with apathy in patients with early Parkinson’s disease (PD) and hyposmia

Background: Smells may generate specific emotions. Apathy and smell dysfunction may share evolutionary pathways. Clinically, these have been associated late in the disease course in PD (1). Neuroanatomically, microstructural changes in the cingulate cortex, corona radiata, and corpus callosum have been strongly associated with apathy in patients with more advanced PD (2).

Method: We used the Parkinson’s Progression Markers Initiative (PPMI) database that studies patients with de-novo PD. We analyzed PD patients with smell dysfunction who were followed for 5 years, did not have apathy at the initial visit, and had completed a baseline diffusion MRI (dMRI) at the baseline and 48-month follow-up visits, as per study protocol.

Smell dysfunction was defined as a University of Pennsylvania Smell Identification Test score below the 10th percentile at baseline. We defined apathy as a Movement Disorders Society United Parkinson’s Disease Rating Scale part 1A item 1.5 with a score of 1 or more.

The FMRIB Software Library (FSL)’s Diffusion Toolkit (FDT) was used for preprocessing, weighted least-squares tensor fitting and voxel-wise FA estimation of diffusion images We measured fractional anisotropy (FA) at the genu and body of the corpus callosum, bilateral anterior corona radiata, left superior corona radiata, and left cingulate cortex at the baseline visit dMRI and compared to the 48 months follow up scan.

Results: We analyzed data on 40 MRI Brain scans at baseline visit and at 4 years. There was a significant decrease in FA in the right anterior corona radiata (p<.0001), left anterior corona radiata (p=0.0244), genu (p=0.0012) and body of the corpus callosum (p=0.0228) between baseline and follow up at 4 years. The left cingulate cortex (p=1) and the superior corona radiata (p=1), known to be associated with hyposmia (3,4), did not demonstrate any changes in FA over time.

Conclusion: Our analysis showing decline in microstructural integrity in white matter in regions with known association with apathy in PD patients highlights the need for greater research for causality between hyposmia and apathy, with validated clinical outcomes.

References: 1. Cramer CK, Friedman JH, Amick MM. Olfaction and apathy in Parkinson’s disease. Parkinsonism Relat Disord. 2010 Feb;16(2):124–6.
2. Zhang Y, Wu J, Wu W, Liu R, Pang L, Guan D, et al. Reduction of white matter integrity correlates with apathy in Parkinson’s disease. Int J Neurosci. 2018 Jan;128(1):25–31.
3. Sobhani S, Rahmani F, Aarabi MH, Sadr AV. Exploring white matter microstructure and olfaction dysfunction in early parkinson disease: diffusion MRI reveals new insight. Brain Imaging Behav. 2019 Feb;13(1):210–9.
4. Du S, Wang Y, Li G, Wei H, Yan H, Li X, et al. Olfactory functional covariance connectivity in Parkinson’s disease: Evidence from a Chinese population. Front Aging Neurosci. 2022;14:1071520.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/does-hyposmia-induce-apathy-in-early-parkinsons-disease-lessons-from-structural-brain-connectivity/