Distinct cerebral cortical perfusion patterns in idiopathic normal-pressure hydrocephalus.

The aims of the study are to evaluate idiopathic normal-pressure hydrocephalus (INPH)-related cerebral blood flow (CBF) abnormalities and to investigate their relation to cortical thickness in INPH patients. We investigated cortical CBF utilizing surface-based early-phase 18 F-florbetaben (E-FBB) PET analysis in two groups: INPH patients and healthy controls. All 39 INPH patients and 20 healthy controls were imaged with MRI, including three-dimensional volumetric images, for automated surface-based cortical thickness analysis across the entire brain. A subgroup with 37 participants (22 INPH patients and 15 healthy controls) that also underwent 18 F-fluorodeoxyglucose (FDG) PET imaging was further analyzed. Compared with age- and gender-matched healthy controls, INPH patients showed statistically significant hyperperfusion in the high convexity of the frontal and parietal cortical regions. Importantly, within the INPH group, increased perfusion correlated with cortical thickening in these regions. Additionally, significant hypoperfusion mainly in the ventrolateral frontal cortex, supramarginal gyrus, and temporal cortical regions was observed in the INPH group relative to the control group. However, this hypoperfusion was not associated with cortical thinning. A subgroup analysis of participants that also underwent FDG PET imaging showed that increased (or decreased) cerebral perfusion was associated with increased (or decreased) glucose metabolism in INPH. A distinctive regional relationship between cerebral cortical perfusion and cortical thickness was shown in INPH patients. Our findings suggest distinct pathophysiologic mechanisms of hyperperfusion and hypoperfusion in INPH patients.

MRI-visible Dilated Perivascular Space in the Brain by Age: The Human Connectome Project.

Background Dilated perivascular spaces (dPVS) are associated with aging and various disorders; however, the effect of age on dPVS burden in young populations and normative data have not been fully evaluated. Purpose To investigate the dPVS burden and provide normative data according to age in a healthy population, including children. Materials and Methods In this retrospective study, three-dimensional T2-weighted brain MRI scans from the Human Connectome Project data sets were used for visual grading (grade 0, 1, 2, 3, 4 for 0, 1-10, 11-20, 21-40, and >40 dPVS on a single section of either hemispheric region) and automated volumetry of dPVS in basal ganglia (BGdPVS) and white matter (WMdPVS). Linear and nonlinear regression were performed to assess the association of dPVS volume with age. Optimal cutoff ages were determined with use of the maximized continuous-scale C-index. Participants were grouped by cutoff values. Linear regression was performed to assess the age-dPVS volume relationship in each age group. Normative data of dPVS visual grades were provided per age decade. Results A total of 1789 participants (mean age, 35 years; age range, 8-100 years; 1006 female participants) were evaluated. Age was related to dPVS volume in all regression models (R2 range, 0.41-0.55; P < .001). Age-dPVS volume relationships were altered at the mid-30s and age 55 years; BGdPVS and WMdPVS volumes negatively correlated with age until the mid-30s (ß, -1.2 and -7.8), then positively until age 55 years (ß, 3.3 and 54.1) and beyond (ß, 3.9 and 42.8; P < .001). The 90th percentile for dPVS grades was grade 1 for age 49 years and younger, grade 2 for age 50-69 years, and grade 3 for age 70 years and older (overall, grade 2) for BGdPVS, and grade 3 for age 49 years and younger and grade 4 for age 50 years and older (overall, grade 3) for WMdPVS. Conclusion Dilated perivascular spaces (dPVS) showed a biphasic volume pattern with brain MRI, lower volumes until the mid-30s, then higher afterward. Grades of 3 or higher and 4 might be considered pathologic dPVS in basal ganglia and white matter, respectively. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Bapuraj and Chaudhary in this issue.

Cortical Thickness from MRI to Predict Conversion from Mild Cognitive Impairment to Dementia in Parkinson Disease: A Machine Learning-based Model.

Background Group comparison results associating cortical thinning and Parkinson disease (PD) dementia (PDD) are limited in their application to clinical settings. Purpose To investigate whether cortical thickness from MRI can help predict conversion from mild cognitive impairment (MCI) to dementia in PD at an individual level using a machine learning-based model. Materials and Methods In this retrospective study, patients with PD and MCI who underwent MRI from September 2008 to November 2016 were included. Features were selected from clinical and cortical thickness variables in 10 000 randomly generated training sets. Features selected 5000 times or more were used to train random forest and support vector machine models. Each model was trained and tested in 10 000 randomly resampled data sets, and a median of 10 000 areas under the receiver operating characteristic curve (AUCs) was calculated for each. Model performances were validated in an external test set. Results Forty-two patients progressed to PDD (converters) (mean age, 71 years ± 6 [standard deviation]; 22 women), and 75 patients did not progress to PDD (nonconverters) (mean age, 68 years ± 6; 40 women). Four PDD converters (mean age, 74 years ± 10; four men) and 20 nonconverters (mean age, 67 years ± 7; 11 women) were included in the external test set. Models trained with cortical thickness variables (AUC range, 0.75-0.83) showed fair to good performances similar to those trained with clinical variables (AUC range, 0.70-0.81). Model performances improved when models were trained with both variables (AUC range, 0.80-0.88). In pair-wise comparisons, models trained with both variables more frequently showed better performance than others in all model types. The models trained with both variables were successfully validated in the external test set (AUC range, 0.69-0.84). Conclusion Cortical thickness from MRI helped predict conversion from mild cognitive impairment to dementia in Parkinson disease at an individual level, with improved performance when integrated with clinical variables. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Port in this issue.

Delayed orthostatic hypotension in Parkinson's disease.

Orthostatic hypotension (OH) is relatively common in the early stage of Parkinson's disease (PD). It is divided into delayed OH and classical OH. Classical OH in PD has been investigated widely, however, the clinical implications of delayed OH in PD have seldom been studied. The purpose of this study is to characterize delayed OH in PD. A total of 285 patients with early drug-naïve PD were enrolled and divided into three groups according to orthostatic change: no-OH, delayed OH, and classical OH. The disease severity in terms of motor, non-motor, and cognitive functions was assessed. The cortical thickness of 82 patients was analyzed with brain magnetic resonance imaging. The differences among groups and linear tendency in the order of no-OH, delayed OH, and classical OH were investigated. Seventy-seven patients were re-evaluated. Initial and follow-up evaluations were explored to discern any temporal effects of orthostasis on disease severity. Sixty-four (22.5%) patients were defined as having delayed OH and 117 (41.1%) had classical OH. Between-group comparisons revealed that classical OH had the worst outcomes in motor, non-motor, cognitive, and cortical thickness, compared to the other groups. No-OH and delayed OH did not differ significantly. Linear trends across the pre-ordered OH subtypes found that clinical parameters worsened along with the orthostatic challenge. Clinical scales deteriorated and the linear gradient was maintained during the follow-up period. This study suggests that delayed OH is a mild form of classical OH in PD. PD with delayed OH has milder disease severity and progression.

Cortical thinning pattern according to differential nigrosome involvement in patients with Parkinson's disease.

The pathological hallmark of Parkinson's disease (PD) is the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, where the dopaminergic neurons form five clusters called nigrosomes 1-5 (N1-N5). N1 is the largest and considered to be the most affected by PD, followed by N2, N4, N3, and N5. Recently, an MRI study suggested a sequential progression of loss from N1 to N4. As the extent of cortical thinning widens as PD progresses, we aimed to define cortical thinning patterns according to the differential involvement of N1 and N4 in PD patients. Cortical thickness was analyzed in 83 PD patients (29 with N1 loss on at least one side of the brain, but no N4 loss; and 54 with N4 loss on at least one side) and 35 healthy subjects with age, sex, disease duration, and intracranial volume as covariates. On patient-wise analysis, for areas with more cortical thinning than the controls, PD patients with N4 loss had wider cortical thinning involving more dorsolateral prefrontal cortex and temporal areas than PD patients with only N1 loss, but cortical thinning did not significantly differ between these two patient groups. However, cortical thinning was more apparent in hemisphere-level analysis with statistically significant clusters being found more in hemispheres with N4 loss than hemispheres with N1 loss in PD patients compared to normal hemispheres of the controls. Cortical thinning occurred in a similar propagation pattern to that seen with PD progression, supporting past hypotheses on the sequential progression of nigrosome loss from N1 to N4.

Blood pressure lability is associated with subcortical atrophy in early Parkinson's disease.

OBJECTIVE: Increased cerebral white matter intensities associated with blood pressure (BP) lability were reported in patients with Parkinson's disease. However, this type of cardiovascular dysautonomia has seldom been associated with disruptions in deep gray matter structures in Parkinson's disease. In the present study, the associations between BP lability and subcortical deep gray matter structures in early Parkinson's disease were evaluated. METHODS: The present study included 98 early nondemented Parkinson's disease patients. Supine and orthostatic BPs were measured using head-up tilt tests. BP variabilities, measured as standard deviations of 24-h daytime and nighttime BPs, were assessed using 24-h ambulatory BP monitoring. Every patient underwent brain MRI and measurement of deep gray matter volumes. The associations between BP lability and deep gray matter structures were analyzed. RESULTS: Parkinson's disease patients with orthostatic hypotension had smaller volumes of striatum, particularly caudate, than patients without OH after adjusting for covariates of age, sex, disease duration, and Mini-Mental Status Examination score. Nocturnal BP variability was inversely associated with thalamus, hippocampus, and globus pallidus volumes. CONCLUSION: The results from the present study showed that BP lability was adversely associated with structural changes in early Parkinson's disease. Different forms of BP fluctuations influenced distinct deep gray matter structures.