Mild cognitive impairment in de novo Parkinson's disease: A neuromelanin MRI study in locus coeruleus

Abstract

Background We aimed to investigate neuromelanin‐sensitive magnetic resonance imaging (NM‐MRI) features in the locus coeruleus of de novo Parkinson's disease patients with different cognitive states and to determine whether these features are associated with cognitive impairment. Methods Three groups of subjects were recruited in this study, including patients with de novo PD with mild cognitive impairment (n = 23), patients with de novo PD without cognitive impairment (n = 48), and control subjects (n = 32). All subjects underwent clinical evaluations, as well as MRI scanning. The contrast‐to‐noise ratio of the locus coeruleus in the neuromelanin‐sensitive MRI images and cortical thickness were measured. Results The contrast‐to‐noise ratio of the locus coeruleus in PD patients with mild cognitive impairment was significantly lower than that of controls (P = 0.016). The contrast‐to‐noise ratio of the locus coeruleus for PD patients without cognitive impairment was intermediate between that of controls and PD patients with mild cognitive impairment. Furthermore, multiple linear regression analysis showed that the contrast‐to‐noise ratio of the locus coeruleus was negatively associated with performance on the Trail Making Test B in all PD patients, controlling for age, sex, years of education, the Unified Parkinson's Disease Rating Scale motor scores from right upper limb, Geriatric Depression Rating Scales scores, Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire scores, and cortical thickness. Conclusions Dysfunction of the locus coeruleus neurons may partly contribute to the decline in executive function in early de novo PD. In the future, the locus coeruleus‐norepinephrine system might be targeted for early‐intervention strategies in PD patients. © 2019 International Parkinson and Movement Disorder Society

Locus Coeruleus Malfunction Is Linked to Psychopathology in Prodromal Dementia With Lewy Bodies

“…The LC reveals degeneration and a loss of noradrenergic cells in alpha-synucleinopathies such as DLB (Iseki et al, 2001;Mori et al, 2002;Brunnström et al, 2011;Haglund et al, 2016, Table 1). The noradrenergic LC system often becomes degenerated early in both alpha-synucleinopathies such as Parkinson's disease (PD) (Solopchuk et al, 2018;Li et al, 2019), and ß-amyloidopathies like Alzheimer's disease (AD) (Zarow et al, 2003;Hou et al, 2021). Both diseases are closely related to Lewy body pathology, as mixed pathologies can coexist in patients with cognitive impairment (Coughlin et al, 2020).…”

“…The pathomechanism might be similar in both alphasynucleinopathies at an early stage in terms of the amount, type, and spread of Lewy bodies within the LC region. Via neuromelanin-sensitive MRI, a recent study (Li et al, 2019) showed that the LC's contrast-to-noise ratio in 23 PD patients with mild cognitive impairment was lower than in control subjects. They observed a negative relationship between reduced contrast to the LC and measures of executive dysfunction in these patients (Li et al, 2019) implying an early contribution by the LC-noradrenaline system to symptomatology in PD patients.…”

The Noradrenergic System in Parkinson’s Disease

“…Although dementia in PD is related to a substantial reduction in cortical cholinergic markers, there is also evidence for a more severe loss of noradrenergic input from the LC to cortical areas (Chan-Palay and Asan, 1989). The severity of dementia has been linked to the loss of LC neurons in some studies (Zweig et al, 1993;Del Tredici and Braak, 2013;Li et al, 2019).…”

Locus Coeruleus Magnetic Resonance Imaging in Neurological Diseases

“…Such a strict correlation with LC-MRI features was not observed for cognitive and dysautonomic symptoms. In fact, in PD patients suffering from mild cognitive impairment (PD-MCI), LC intensity was reduced compared to HC, but there were no differences between cognitively unimpaired PD patients and PD-MCI ones [74,76]. Similar results were observed in parkinsonian subjects suffering from dysautonomic dysfunctions [74].…”

“…In PD, several authors have shown the occurrence of significant reduction of LC-MRI intensity [16,[69][70][71][72][73][74][75][76]. Noteworthy, and in line with post-mortem pathological observations [13], in PD patients, LC-MRI alteration is even more severe than the SN-MRI one [72,73].…”