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Objective Using a large US claims database (MarketScan®), we investigated the controversy surrounding the role of statins in Parkinson’s disease (PD). Methods We performed a retrospective case-control analysis. First, we identified 2,322 incident PD cases having a minimum of 2.5 y of continuous enrollment prior to earliest diagnosis code or prescription of antiparkinson medication. Then, 2,322 Controls were matched individually by age, gender, and a “follow-up window” to explore the relationship of statin use with incident PD. Results Statin usage was significantly associated with PD risk, with the strongest associations being for lipophilic (OR=1.58, p<0.0001) vs. hydrophilic (OR=1.19, p=0.25) statins, statins plus non-statins (OR=1.95, p<0.0001), and for the initial period after starting statins (<1 y OR=.82, 1–2.5 y OR =1.75, and ≥2.5 y OR =1.37; ptrend<0.0001). Conclusion Use of statin (especially lipophilics) was associated with higher risk of PD, and the stronger association in initial use suggests a facilitating effect.

Background Cortical and subcortical gray matter (GM) atrophy may progress differently during the course of Parkinson's disease (PD). We delineated and compared the longitudinal pattern of these PD-related changes. Methods Structural MRIs and clinical measures were obtained from 76 PD with different disease durations and 70 Controls at baseline, 18- and 36-months. Both cortical and subcortical (putamen, caudate, and globus pallidus) GM volumes were obtained, compared, and associated with PD clinical measures at baseline. Their volumes and rates of change also were compared among Controls, PDs, and PD subgroups based on duration of illness [≤1 year (PDE), 1-5 years (PDM), and >5 years (PDL)]. Results Compared to Controls, PD subjects displayed smaller cortical GM and striatal (putamen, caudate, ps≤0.001), volumes at baseline. Cortical GM volumes were negatively associated with disease duration at baseline, whereas striatal volumes were not. PD subjects demonstrated accelerated volume loss in cortical GM (p=0.006), putamen (p=0.034), and caudate (p=0.008) compared to Controls. Subgroup analyses demonstrated that accelerated cortical atrophy reached statistical significance in PD subjects with duration of illness 1-5 years (PDM, ps<0.001) and the trend of accelerated atrophy seemed to persist until later stages, whereas striatal atrophy occurred in PD subjects with PDE (p=0.021 for putamen, p=0.005 for caudate) and PDM (p=0.002 for putamen, p=0.001 for caudate) that significantly slowed down in PDL (ps for PDL vs PDE or PDM: <0.01). Conclusions The pattern of GM loss in PD differs in cortical and subcortical regions, with striatal atrophy occurring earlier and extra-striatal cortical atrophy later.

Parkinson’s disease (PD) is marked pathologically by nigrostriatal dopaminergic terminal loss. Histopathological and in vivo labeling studies demonstrate that this loss occurs most extensively in the caudal putamen and caudate head. Previous structural studies have suggested reduced striatal volume and atrophy of the caudate head in PD subjects. The spatial distribution of atrophy in the putamen, however, has not been characterized. We aimed to delineate the specific locations of atrophy in both of these striatal structures. T1- and T2-weighted brain MR (3T) images were obtained from 40 PD and 40 control subjects having no dementia and similar age and gender distributions. Shape analysis was performed using doubly segmented regions of interest. Compared to controls, PD subjects had lower putamen (p=0.0003) and caudate (p=0.0003) volumes. Surface contraction magnitudes were greatest on the caudal putamen (p≤0.005) and head and dorsal body of the caudate (p≤0.005). This spatial distribution of striatal atrophy is consistent with the known pattern of dopamine depletion in PD and may reflect global consequences of known cellular remodeling phenomena.

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

Plasma low density lipoprotein (LDL) cholesterol has been associated both with risk of Parkinson’s disease (PD) and with age-related changes in cognitive function. This prospective study examined the relationship between baseline plasma LDL-cholesterol and cognitive changes in PD and matched Controls. Fasting plasma LDL-cholesterol levels were obtained at baseline from 64 non-demented PD subjects (62.7 ± 7.9 y) and 64 Controls (61.3 ± 6.8 y). Subjects underwent comprehensive neuropsychological testing at baseline, 18-, and 36-months. Linear mixed-effects modeling was used to assess the relationships between baseline LDL-cholesterol levels and longitudinal cognitive changes. At baseline, PD patients had lower scores of fine motor (p<0.0001), executive set shifting (p=0.018), and mental processing speed (p=0.049) compared to Controls. Longitudinally, Controls demonstrated improved fine motor and memory test scores (p=0.044, and p=0.003), whereas PD patients demonstrated significantly accelerated loss in fine motor skill (p=0.002) compared to Controls. Within the PD group, however, higher LDL-cholesterol levels were associated with improved executive set shifting (β=0.003, p<0.001) and fine motor scores (β=0.002, p=0.030) over time. These associations were absent in Controls (p>0.7). The cholesterol - executive set shifting association differed significantly between PDs and Controls (interaction p=0.005), whereas the cholesterol - fine motor association difference did not reach significance (interaction, p=0.104). In summary, higher plasma LDL-cholesterol levels were associated with better executive function and fine motor performance over time in PD, both of which may reflect an effect on nigrostriatal mediation. Confirmation of these results and elucidation of involved mechanisms are warranted, and might lead to feasible therapeutic strategies.

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Background and Purpose Both diffusion tensor imaging (DTI) and R2* have shown promise in differentiating Parkinson’s disease (PD) from atypical parkinsonism [particularly multiple system atrophy (MSA) and progressive supranuclear palsy (PSP)]. We assessed DTI, R2*, and their combination for differentiating PD, MSA, PSP, and controls. Materials and Methods A total of 106 subjects (36 controls, 35 PD, 16 MSA, and 19 PSP) were included. DTI and R2* measures from striatal, midbrain, limbic, and cerebellar regions were obtained and compared between groups. The discrimination performance of DTI and R2* among groups was assessed using elastic-net machine learning and receiver operating characteristic analysis. Results Compared to controls, PD patients showed significant R2* differences in the red nucleus. Compared to PD, both MSA and PSP patients showed more widespread changes, extending from the midbrain to striatal and cerebellar structures. The pattern of changes, however, was different between the two groups. For instance, MSA patients showed decreased FA and increased R2* in the subthalamic nucleus, whereas PSP patients showed increased MD in the hippocampus. Combined DTI and R2* were significantly better than DTI or R2* alone in separating controls from PD/MSA-P/PSP, controls from PD, PD from MSA-P/PSP, and PD from MSA-P, but not PD from PSP or MSA-P from PSP. Conclusion DTI and R2* provide different but complementary information for different parkinsonisms. Combined DTI and R2* may be a superior marker for PD differential diagnosis.