Stage-dependent loss of cortical gyrification as Parkinson disease “unfolds”

Abstract

Objective: Nigrostriatal terminal losses are known to progress most rapidly in early-stage Parkinson disease (PD) and then plateau, whereas cortical pathology continues and may provide a better marker of PD progression in later stages. We investigated cortical gyrification indices in patients with different durations of PD, since cortical folding may capture complex processes involving transverse forces of neuronal sheets or underlying axonal connectivity.Methods: Longitudinal cohort structural MRI were obtained at baseline, 18 months, and 36 months from 70 patients with PD without dementia and 70 control participants. Cortical local gyrification index (LGI) was compared between controls and PD subgroups based upon duration of illness (DOI, ,1 year [PD E , n 5 17], 1-5 years [PD M , n 5 19], .5 years [PD L , n 5 24]) and adjusted using false discovery rate. Associations between LGI and clinical measurements were assessed using multiple linear regression. Areas having significantly reduced LGI also were analyzed using baseline data from a newly established cohort (PD n 5 87, control n 5 66) to validate our findings.Results: In the longitudinal cohort, PD L had significantly reduced overall gyrification, and bilaterally in the inferior parietal, postcentral, precentral, superior frontal, and supramarginal areas, compared to controls (p , 0.05). Longitudinally, loss of gyrification was accelerated in PD M participants, compared to controls.LGI showed robust correlations with DOI and also was correlated with PD-related clinical measurements. Similar results were obtained in the validation sample.Conclusions: Loss of cortical gyrification may be accelerated within the first few years after PD diagnosis, and become particularly prominent in later stages. Thus, it may provide a metric for monitoring progression in vivo. In Parkinson disease (PD), degeneration of dopamine terminals is thought to progress rapidly within the first few years after diagnosis and then plateau.1 Thus, in more advanced stages of disease, non-nigrostriatal brain changes may serve as better markers of PD progression. Evidence suggests that widespread pathologic changes occur in the cortex, including apoptotic signaling, Lewy pathology, reduction in other neurotransmitters, and interneuron loss. [2][3][4] It is unclear, however, how cell death relates to the pattern of cortical Lewy pathology, and whether cortical changes can be used to gauge PD progression. 5 Lewy pathology has been documented in specific cortical layers (i.e., preferentially in deep layers of high-order sensory association areas). 5,6 Some previous imaging studies have demonstrated decreased cortical thickness in PD, 7,8 but reported results have been inconsistent and have not shown robust associations with disease progression in the absence of dementia. These

Longitudinal changes of cortical microstructure in Parkinson's disease assessed with T1 relaxometry

“…In fact, the involvement of the cerebral cortex in PD has been repeatedly confirmed by conventional magnetic resonance imaging (MRI) studies reporting multiple cortical abnormalities such as regional cortical thinning (Mak et al, 2015), gray matter (GM) volume decline (Jia et al, 2015), increased atrophy rate (Tessa et al, 2014) and a loss of cortical gyrification (Sterling et al, 2016). Conventional MRI techniques allow volumetric measurements, but still, they are based on mixed signal contrasts which renders the interpretation of the underlying microstructural tissue processes impossible (Tofts, 2003).…”

“…Despite the increasing evidence for PD-related histopathological (Braak et al, 2003) and volumetric alterations in the cerebral cortex (Jia et al, 2015, Mak et al, 2015, Sterling et al, 2016, Tessa et al, 2014), only a few studies assessed cortical relaxation times in PD: one study reported no effect in T2* (Ulla et al, 2013), two studies focused on T2 values, reporting both regional T2 shortening (Mondino et al, 2002) and prolongation (Vymazal et al, 1999) in the prefrontal cortex. The only cross-sectional study using T1 relaxometry reported shortening of cortical T1 relaxation time in PD (Vymazal et al, 1999) which was attributed to the decrease of the cortical ferritin (Dexter et al, 1990).…”

Imaging of Motor Cortex Physiology in Parkinson's Disease

“…As for structural imaging measures, these may also help gauge disease progression in PD. A recent 3‐year progression study of PD without dementia showed reduced cortical gyrification in the precentral and postcentral areas in more advanced stages of the disease and a decline in this measure with disease progression . Although structural changes in M1 are not a hallmark of PD, they raise the hypothesis that functional cortical changes in PD could be followed by structural changes.…”

“…Alternatives to voxel‐based morphometry that allow the estimation of gray matter changes (eg, surface‐based morphometry), have revealed cortical thinning in the sensorimotor cortex in nondemented PD when compared with controls and reduced cortical gyrification in M1 in those PD patients with more advanced disease duration (Fig. ) . Although based on the majority of T1‐based studies structural changes in M1 are not a signature of PD, the latest results using surface‐based morphometry raise the possibility that changes in structure could occur once patients reach the more moderate to advanced stages of the disease and may explain emerging signs such as the progressive loss of balance and increasing gait difficulty.…”

“…Figure reprinted with permission from Sterling NW, Wang M, Zhang L, et al Stage‐dependent loss of cortical gyrification as Parkinson disease “unfolds”. Neurology 2016;86(12):1143‐1151 …”