Brain iron deposition is linked with cognitive severity in Parkinson’s disease

Abstract

BackgroundDementia is common in Parkinson’s disease (PD) but measures that track cognitive change in PD are lacking. Brain tissue iron accumulates with age and co-localises with pathological proteins linked to PD dementia such as amyloid. We used quantitative susceptibility mapping (QSM) to detect changes related to cognitive change in PD.MethodsWe assessed 100 patients with early-stage to mid-stage PD, and 37 age-matched controls using the Montreal Cognitive Assessment (MoCA), a validated clinical algorithm for risk of cognitive decline in PD, measures of visuoperceptual function and the Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 (UPDRS-III). We investigated the association between these measures and QSM, an MRI technique sensitive to brain tissue iron content.ResultsWe found QSM increases (consistent with higher brain tissue iron content) in PD compared with controls in prefrontal cortex and putamen (p<0.05 corrected for multiple comparisons). Whole brain regression analyses within the PD group identified QSM increases covarying: (1) with lower MoCA scores in the hippocampus and thalamus, (2) with poorer visual function and with higher dementia risk scores in parietal, frontal and medial occipital cortices, (3) with higher UPDRS-III scores in the putamen (all p<0.05 corrected for multiple comparisons). In contrast, atrophy, measured using voxel-based morphometry, showed no differences between groups, or in association with clinical measures.ConclusionsBrain tissue iron, measured using QSM, can track cognitive involvement in PD. This may be useful to detect signs of early cognitive change to stratify groups for clinical trials and monitor disease progression.

The impact of brain iron accumulation on cognition: A systematic review

“…Higher iron in CN predicted lower dementia rating scale score (r = -0.7, p = 0.0232; Rho = -0.56, p = 0.0944); Lower arithmetic score correlated higher iron in CN (r = −0.64, p = 0.0481; Rho = −0.70, p = 0.0359) and putamen (r = −0.78, p = 0.0077; Rho = −0.65, p = 0.0495); TH iron was predictive of Digit Symbol output (r = 0.77, p = 0.0088; Rho = 0.57, p = 0.0865), time taken to complete the test (r = −0.79, p = 0.0069; Rho = −0.56, p = 0.0909), and MMSE scores (r = 0.66, p = 0.0397; Rho = 0.47, p = 0.1611); In the two choice test CN iron correlated with longer reaction time by the left (r = 0.56, p = 0.0918) and right (r = 0.79, p = 0.0062) hands, higher GP iron correlated with longer reaction time by the right hand (r = 0.65, p = 0.0421) and higher PU iron correlated with longer movement time by the left (r = 0.70, p = 0.024) hand; Fine finger movement speed showed no significant relationship with iron estimates in any region; In the Digit Symbol grid, CN and TH iron accounted for 80% of the variance; Low TH iron (p = 0.0096) was a unique predictor of performance over the caudate iron measure (p = 0.5192) Sun et al, 2017 [61] svMCI group had significantly lower composite, attention-executive, memory and language z scores than controls; significantly higher susceptibility in svMCI group over controls in R-HP (p<0.01), L-HP (p<0.01), R-PU (p<0.05); svMCI group had significantly negative correlation between sus in R-HP and memory z sore (p = 0.012); susceptibility in R-HP of svMCI group was positively correlated to language z score (p = 0.026); susceptibility in R-PU in the svMCI group was significantly negatively correlated to attention-executive z score (p = 0.033); composite z score not related to susceptibility Thomas et al, 2020 [62] Increase in QSM in PD compared to controls in prefrontal cortex, R-PU and Rtemporal cortex (p<0.05); Increased QSM in SN in PD compared to controls (p = 0.004); In PD patients there was susceptibility increase with decreasing MoCA scores in HP, TH, CN, caudal regions of ventromedial prefrontal cortex, regions of basal forebrain, R-PU and R-insular cortex; Increased absolute susceptibility with increased dementia risk score in PD patients (p<0.05); widespread QSM increases in patients with poor visual performance (p<0.05); PD group showed significant increase in susceptibility (p<0.05) with UPDRS-III in right PU…”

Impairment of the visuospatial working memory in the patients with Parkinson’s Disease: an fMRI study

“…Recently, various neuroimaging studies are focusing on PD-MCI to examine which type of pathology is a dominant cause of cognitive impairment. Some studies using quantitative susceptibility mapping have indicated that brain iron deposition is linked with cognitive severity in PD [22,23]. Thomas Herein, we discuss about the deactivation of the MFG and IPL.…”

Neurological update: neuroimaging in dementia

“…This technique is sensitive to iron, calcium and other magnetic substances [ 80 ]. The deposition of iron measured using QSM has been linked with cognition in Alzheimer’s disease [ 81 ] and Parkinson’s disease [ 82 ]. In Alzheimer’s disease, iron is found in the plaques and tangles that characterise the disease, though there is still some work required to establish what exactly is being identified, for example whether ferrous or ferric iron is picked up by QSM.…”