MRI-Based Quantitative Assessment of Normal-Appearing White & Gray Matter Demyelination in MS, Parkinson, LC, & Normal Aging, 2026, Khodanovich

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MRI-Based Quantitative Assessment of Normal-Appearing White and Gray Matter Demyelination in Multiple Sclerosis, Parkinson’s Disease, Long COVID, and Normal Aging

Khodanovich, Marina; Svetlik, Mikhail; Kamaeva, Daria; Usova, Anna; Anan’ina, Tatyana; Wasserlauf, Irina; Shadrina, Maria; Pashkevich, Valentina; Moshkina, Marina; Obukhovskaya, Victoria; Kataeva, Nadezhda; Levina, Anastasia; Alifirova, Valentina; Titova, Marina; Zhukova, Irina; Vasilieva, Svetlana; Schastnyy, Evgeny; Tumentceva, Yana A.; Yarnykh, Vasily

Abstract
Background/Objectives
: Normal-appearing white (WM) and gray (GM) matter outside focal demyelinating lesions (WMH) has been found impaired in many diseases and normal aging.
The present study aimed to compare global GM and WM alterations in patients with multiple sclerosis (MS), Parkinson’s disease, long COVID (LC) and normal aging.

Methods: The study population comprised 196 participants including patients with MS (n = 42), PD (n = 16), LC (n = 75), and healthy volunteers (n = 63).
All participants underwent MR scanning using the fast macromolecular fraction (MPF) mapping protocol and routine clinical sequences.
MPF in global normal-appearing WM, GM, and mixed WM-GM was measured after exclusion of segmented focal lesions.
To eliminate the influence of gender, age, and brain atrophy on the results, the corresponding covariates were included in the analysis.

Results: Significant WMH volume increase and MPF decrease in global WM, WM-GM, and GM were found both in normal aging (75–85 years) and MS, PD, and LC patients (except for WM and WMH volume in LC patients).
The greatest MPF decrease was observed in MS patients.
The youngest (18–24 years) controls had a significant MPF decrease in global WM, WM-GM, and GM compared to middle-aged (35–44 years) participants.
Among LC patients, the greatest global MPF reduction was found in patients with depression and insomnia as COVID-19 complications.
In healthy controls, the peak age of myelination was estimated as 42.2 years for WM, 46.5 years for WM-GM, and 45.4 years for GM.
Significant correlations were found between MPF and EDSS in MS patients (r = −0.71 in GM, r = −0.58 in WM-GM, r = −0.44 in WM) and stage of PD in PD patients (r = −0.58 in GM, r = −0.55 in WM-GM, r = −0.52 in WM).

Conclusions: MPF mapping showed high sensitivity to age-related and disease-related differences in brain myelination, particularly in GM.
Our results confirm the feasibility of using MPF mapping in large-scale clinical studies.

Web | DOI | PMC | PDF | Biomedicines | Open Access
 
For the LC patients, additional inclusion criteria were: previously positive COVID-19 PCR test, persistence of post-COVID neuropsychiatric complications at the time of the study, and the absence of neurological or psychiatric diagnoses prior to COVID-19.
LC patients were newly diagnosed by board-certified neurologists and psychiatrists, and the following symptom types were recorded: clinical depression, chronic headache, insomnia, asthenia, mild cognitive impairment, anosmia/hyposmia, ageusia, panic disorder, bipolar disorder, anxiety disorder, autonomic neuropathy, myalgia, dorsalgia, arthralgia, vestibular disorder, cervicobrachial syndrome, and disorder of the autonomic nervous system.
Most of these complications are common for LC
 
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