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Background Parkinson’s disease (PD) increases risk for dementia and cascading adverse outcomes. The eight-item Montreal Parkinson Risk of Dementia Scale (MoPaRDS) is a rapid, in-office dementia screening tool. We examine predictive validity and other characteristics of the MoPaRDS in a geriatric PD cohort by testing a series of alternative versions and modelling risk score change trajectories. Methods Participants were 48 initially non-demented PD patients (Mage = 71.6 years, range = 65–84) from a three-year, three-wave prospective Canadian cohort study. A dementia diagnosis at Wave 3 was used to stratify two baseline groups: PD with Incipient Dementia (PDID) and PD with No Dementia (PDND). We aimed to predict dementia three years prior to diagnosis using baseline data for eight indicators that harmon-ized with the original report, plus education. Results Three MoPaRDS items (age, orthostatic hypotension, mild cognitive impairment [MCI]) discriminated the groups both independently and as a composite three-item scale (area under the curve [AUC] = 0.88). The eight-item MoPaRDS reliably discriminated PDID from PDND (AUC = 0.81). Education did not improve predictive validity (AUC = 0.77). Performance of the eight-item MoPaRDS varied across sex (AUCfemales = 0.91; AUCmales = 0.74), whereas the three-item configuration did not (AUCfemales = 0.88; AUCmales = 0.91). Risk scores of both configurations increased over time. Conclusions We report new data on the application of the MoPaRDS as a dementia prediction tool for a geriatric PD cohort. Results support the viability of the full MoPaRDS, and indicate that an empirically determined brief version is a promising complement.

Background: Quantitative susceptibility mapping (QSM) demonstrates elevated iron content in Parkinson’s disease (PD) patients within the basal ganglia, though it has infrequently been studied in relation to gait difficulties including freezing of gait (FOG). Our purpose was to relate QSM of basal ganglia and extra-basal ganglia structures with qualitative and quantitative gait measures in PD. Methods: This case–control study included PD and cognitively unimpaired (CU) participants from the Comprehensive Assessment of Neurodegeneration and Dementia study. Whole brain QSM was acquired at 3T. Region of interests (ROIs) were drawn blinded manually in the caudate nucleus, putamen, globus pallidus, pulvinar nucleus of the thalamus, red nucleus, substantia nigra, and dentate nucleus. Susceptibilities of ROIs were compared between PD and CU. Items from the FOG questionnaire and quantitative gait measures from PD participants were compared to susceptibilities. Results: Twenty-nine participants with PD and 27 CU participants were included. There was no difference in susceptibility values in any ROI when comparing CU versus PD (p > 0.05 for all). PD participants with gait impairment (n = 23) had significantly higher susceptibility in the putamen (p = 0.008), red nucleus (p = 0.01), and caudate nucleus (p = 0.03) compared to those without gait impairment (n = 6). PD participants with FOG (n = 12) had significantly higher susceptibility in the globus pallidus (p = 0.03) compared to those without FOG (n = 17). Among quantitative gait measures, only stride time variability was significantly different between those with and without FOG (p = 0.04). Conclusion: Susceptibilities in basal ganglia and extra-basal ganglia structures are related to qualitative measures of gait impairment and FOG in PD.

Author(s): Pilotto, Andrea; Romagnolo, Alberto; Scalvini, Andrea; Masellis, Mario; Shimo, Yasushi; Bonanni, Laura; Camicioli, Richard; Wang, Lily L; Dwivedi, Alok K; Longardner, Katherine; Rodriguez-Porcel, Federico; DiFrancesco, Mark; Vizcarra, Joaquin A; Montanaro, Elisa; Maule, Simona; Lupini, Alessandro; Ojeda-Lopez, Carmen; Black, Sandra E; Delli Pizzi, Stefano; Gee, Myrlene; Tanaka, Ryota; Yamashiro, Kazuo; Hatano, Taku; Borroni, Barbara; Gasparotti, Roberto; Rizzetti, Maria C; Hattori, Nobutaka; Lopiano, Leonardo; Litvan, Irene; Espay, Alberto J; Padovani, Alessandro; Merola, Aristide | Abstract: ObjectiveTo evaluate whether orthostatic hypotension (OH) or supine hypertension (SH) is associated with brain atrophy and white matter hyperintensities (WMH), we analyzed clinical and radiologic data from a large multicenter consortium of patients with Parkinson disease (PD) and dementia with Lewy bodies (DLB).MethodsSupine and orthostatic blood pressure (BP) and structural MRI data were extracted from patients with PD and DLB evaluated at 8 tertiary-referral centers in the United States, Canada, Italy, and Japan. OH was defined as a systolic/diastolic BP fall ≥20/10 mm Hg within 3 minutes of standing from the supine position (severe ≥30/15 mm Hg) and SH as a BP ≥140/90 mm Hg with normal sitting BP. Diagnosis-, age-, sex-, and disease duration-adjusted differences in global and regional cerebral atrophy and WMH were appraised with validated semiquantitative rating scales.ResultsA total of 384 patients (310 with PD, 74 with DLB) met eligibility criteria, of whom 44.3% (n = 170) had OH, including 24.7% (n = 42) with severe OH and 41.7% (n = 71) with SH. OH was associated with global brain atrophy (p = 0.004) and regional atrophy involving the anterior-temporal (p = 0.001) and mediotemporal (p = 0.001) regions, greater in severe vs nonsevere OH (p = 0.001). The WMH burden was similar in those with and without OH (p = 0.49). SH was not associated with brain atrophy (p = 0.59) or WMH (p = 0.72).ConclusionsOH, but not SH, was associated with cerebral atrophy in Lewy body disorders, with prominent temporal region involvement. Neither OH nor SH was associated with WMH.

Background: Cerebral amyloid angiopathy (CAA) is associated with cognitive decline. CAA has diverse impacts on brain structure and function; however, the brain lesions that mediate the association of CAA with cognition are not understood well. Aims: To determine the degree to which CAA neuroimaging biomarkers mediate the association of CAA with cognitive dysfunction. Methods: We analyzed cross-sectional data of patients with probable CAA and controls without cognitive impairment from the Functional Assessment of Vascular Reactivity study. Neuropsychological tests were grouped into domains of memory, executive function, and processing speed. Candidate CAA neuroimaging biomarkers were pre-specified based on prior literature, consisting of white matter hyperintensity volume, peak width of skeletonized mean diffusivity (PSMD) on diffusion tensor magnetic resonance imaging (MRI), cerebrovascular reactivity (CVR), cortical thickness, and cortical thickness in a meta-region of interest typically affected by Alzheimer’s disease (AD). Cognitive scores and neuroimaging markers were standardized and reported in relation to values in controls. Mediation analysis was used to estimate the total effect of CAA on cognition and the proportion of the total effect that was mediated by neuroimaging biomarkers, controlling for age, sex, and education. Results: There were 131 participants (67 CAA and 64 controls). Mean age was 72.1 ± 7.7 years, and 54.2% were women. As expected, compared to controls, CAA was associated with lower cognition. In mediation analyses, CAA had direct unmediated effects of 48%, 46%, and 52% on all three cognitive domains. The association of CAA with memory was partially mediated by CVR and PSMD, accounting for 18% and 36% of the total effect of CAA. The association of CAA with executive function was partially mediated by PSMD and mean cortical thickness in the AD meta-region of interest (ROI), accounting for 33% and 31% of the total effect of CAA. The association of CAA with processing speed was partially mediated by CVR and PSMD, accounting for 8% and 34% of the total effect of CAA. Among CAA participants, the presence of cortical superficial siderosis was associated with lower processing speed. Conclusion: Altered white matter diffusivity (i.e. PSMD), CVR, and atrophy, taken together, account for about half the effect of CAA on cognition.

Background and ObjectivesReduced cerebrovascular reactivity is proposed to be a feature of cerebral amyloid angiopathy (CAA) but has not been measured directly. Employing a global vasodilatory stimulus (hypercapnia), this study assessed the relationships between cerebrovascular reactivity and MRI markers of CAA and cognitive function.MethodsIn a cross-sectional study, individuals with probable CAA, mild cognitive impairment, or dementia due to Alzheimer disease and healthy controls underwent neuropsychological testing and an MRI that included a 5% carbon dioxide challenge. Cerebrovascular reactivity was compared across groups controlling for age, sex, and the presence of hypertension, and its associations with MRI markers of CAA in participants with CAA and with cognition across all participants were determined using multivariable linear regression adjusting for group, age, sex, education, and the presence of hypertension.ResultsCerebrovascular reactivity data (mean ± SD) were available for 26 participants with CAA (9 female; 74.4 ± 7.7 years), 19 participants with mild cognitive impairment (5 female; 72.1 ± 8.5 years), 12 participants with dementia due to Alzheimer disease (4 female; 69.4 ± 6.6 years), and 39 healthy controls (30 female; 68.8 ± 5.4 years). Gray and whiter matter reactivity averaged across the entire brain was lower in participants with CAA and Alzheimer disease dementia compared to healthy controls, with a predominantly posterior distribution of lower reactivity in both groups. Higher white matter hyperintensity volume was associated with lower white matter reactivity (standardized coefficient [β], 95% CI −0.48, −0.90 to −0.01). Higher gray matter reactivity was associated with better global cognitive function (β 0.19, 0.03–0.36), memory (β 0.21, 0.07–0.36), executive function (β 0.20, 0.02–0.39), and processing speed (β 0.27, 0.10–0.45) and higher white matter reactivity was associated with higher memory (β 0.22, 0.08–0.36) and processing speed (β 0.23, 0.06–0.40).ConclusionsReduced cerebrovascular reactivity is a core feature of CAA and its assessment may provide an additional biomarker for disease severity and cognitive impairment.

Highlights • We assessed the relationships between MRI measurements and clinical symptoms in PD. • Using longitudinal data (3 year follow-up) from 50 PD patients and 45 controls. • SN atrophy and WMHs were associated with additional motor deficits in PD patients. • WMHs and hippocampal atrophy were associated with cognitive deficit in PD patients. • Both grey and white matter damage contribute to motor and cognitive deficits in PD., Introduction Previous studies have found associations between grey matter atrophy and white matter hyperintensities (WMH) of vascular origin with cognitive and motor deficits in Parkinson’s disease (PD). Here we investigate these relationships in a sample of PD patients and age-matched healthy controls. Methods Data included 50 PD patients and 45 age-matched controls with T1-weighted and FLAIR scans at baseline, 18-months, and 36-months follow-up. Deformation-based morphometry was used to measure grey matter atrophy. SNIPE (Scoring by Nonlocal Image Patch Estimator) was used to measure Alzheimer’s disease-like textural patterns in the hippocampi. WMHs were segmented using T1-weighted and FLAIR images. The relationship between MRI features and clinical scores was assessed using mixed-effects models. The motor subscore of the Unified Parkinson's Disease Rating Scale (UPDRSIII), number of steps in a walking trial, and Dementia Rating Scale (DRS) were used respectively as measures of motor function, gait, and cognition. Results Substantia nigra atrophy was significantly associated with motor deficits, with a greater impact in PDs (p

Purpose Freezing of gait is a major source of disability associated with the progression of Parkinson's disease (PD). Our objective was to determine whether evolving changes in nigral iron content in association with declining motor function in early PD differentiates subjects who develop freezing from those who do not. Methods A cohort of previously untreated individuals with early PD (n = 19) was followed for 36 months clinically and with MRI. The cohort was divided into two groups based on the development of freezing during follow-up. A multiple gradient echo MRI sequence provided an index of basal ganglia iron content. Results There were significant baseline differences between those who developed freezing (n = 7) and those who did not (n = 12) in Unified Parkinson's Disease Rating Scale motor scores, time to complete a 14 m walk and timed up and go. There was a significant correlation between the measured change in transverse relaxation in the lateral substantia nigra pars compacta and the change in motor score from baseline to 36 months (p = 0.002). The freezing group showed a greater change in motor score and iron content than did the non-freezing group. Conclusions Individuals destined to develop freezing early in PD have more motor impairment at baseline, more rapid deterioration in motor function, and pars compacta changes suggestive of increased iron content in comparison to those who do not.

Objective To determine whether, in patients with early Parkinson's disease (PD), longitudinal changes in midbrain iron content are associated with declining motor function over a period of three years. Methods Nineteen untreated subjects with early PD and 13 age- and sex-matched controls were followed clinically for 36 months. MRI with a 3 T magnet was performed at baseline, 18 months and 36 months with a multiple gradient echo sequence designed for rapid single-scan mapping of the proton transverse relaxation rate R 2 *. R 2 * was calculated for midbrain and forebrain basal ganglia regions. Results A difference in R 2 * between patients and controls was observed at baseline ( p = 0.035) but not at 18 or 36 months in the lateral substantia nigra pars compacta (SNc). Linear regression indicated significant correlations between the change in R 2 * in the lateral SNc and the change score in UPDRS III ( p = 0.008) and the PDQ-39 -mobility sub-score ( p = 0.03) from baseline to 36 months. R 2 * tended to increase in those with more advanced disease and to decrease in those with milder disease. Conclusions High field MRI demonstrates lateral SNc abnormalities that progress over 3 years in early PD consistent with increased iron content in those with more advanced disease, corresponding to the known distribution of neuronal loss occurring in this disorder, and correlating with motor symptomatology. Larger and longer investigations with more precise mapping of iron-containing midbrain structures are needed to fully evaluate the potential of R 2 * as a biomarker of disease progression in PD.

Parkinson's disease (PD) patients are treated with levodopa (L-dopa) to help stabilize their impaired motor abilities; however, L-dopa leads to increased homocysteine (Hcy) levels, which may have a deleterious effect on brain structure and function. The purpose of this study was to examine the impact of increased Hcy concentration on global brain atrophy as determined by magnetic resonance imaging in PD patients and controls. The effect of high Hcy level on ventricular dilatation (percentage of intracranial volume [%ICV]) and total tissue volume (%ICV) was examined at baseline and longitudinally at 36 months. Age, sex, education, and L-dopa duration (in PD patients) were included as covariates. Elevated Hcy levels correlated positively with ventricular dilatation (%ICV) in the whole sample (P = 0.004) and in the PD group (P = 0.008). At baseline, adults with a high Hcy level (>14 μmol/L) had higher ventricular volume (%ICV) than adults with a low Hcy level (≤ 14 μmol/L) in the whole sample (P = 0.006) and in the PD group (P = 0.03), which persisted over 36 months in both the whole sample (P = 0.004) and the PD group (P = 0.03). PD patients with high Hcy concentrations had a greater rate of ventricular enlargement (%ICV) over time compared with those with low Hcy concentration (P = 0.02). Elevated Hcy concentration was associated with increased ventricular dilatation (%ICV) in PD patients. A larger sample with a broader age range and longer follow-up is needed to establish the consequences of high Hcy level, including interactions with genetic and environmental risk factors, in PD.

Background Parkinson's disease (PD), characterized by motor dysfunction and cognitive decline, may demonstrate specific patterns of brain atrophy. Although cross-sectional magnetic resonance imaging (MRI) studies show correlation between regional brain volume loss and cognitive impairment, there is only scarce evidence from longitudinal studies validating the link between cognition and brain anatomy in PD. Objective To test the relationship between magnitude and spatial extent of atrophy in PD patients with progressive, significant cognitive decline and dementia (PDD). Methods We followed thirty-three initially non-demented patients with prevalent PD for three years while monitoring cognitive function and brain atrophy. Longitudinally acquired T1-weighted magnetic resonance images were analyzed in the voxel-based morphometry framework of SPM. Results Groups did not differ significantly with respect to age or gender. More males developed PDD (7 males, 3 females) compared to those remaining intact (12 males, 11 females). Clusters of lower grey matter volume were found in PDD compared to PD in left uncus at baseline and an expanded region that included the left hippocampus and parahippocampal gyrus at 36 months. The cognitive status by scan interaction showed differential changes between groups in the right insula. At a more liberal statistical threshold we observed changes in the right insula and bilateral hippocampi as well as the right cuneus additional to the lower brain stem. Conclusions Region specific atrophy, consistent with the pattern of cortical Lewy body deposition seen in autopsy studies, can be detected with MRI in PD patients with significant cognitive decline. MRI may be useful for tracking cognitive decline in PD.

Age-related ventricular enlargement is accelerated in Alzheimer's disease, but its relationship to cognitive decline in Parkinson's disease is less clear, even though dementia is common in Parkinson's disease. Our goals were to determine if greater enlargement of the ventricles and gray or white matter atrophy occurred in Parkinson's disease patients developing cognitive decline. Older nondemented patients with Parkinson's disease (33) and age- and sex-matched controls (39) were recruited and prospectively assessed for the development of significant cognitive decline over 36 months. Magnetic resonance imaging was obtained every 18 months, and ventricular volume and total brain gray and white matter volumes were measured using reliable segmentation of T1-weighted volumetric scans. Subjects with incidental intracranial abnormalities, an atypical course, and stroke as well as dropouts were excluded from a cohort of 52 patients and 50 controls. Among 33 patients and 39 controls, 10 patients and 3 controls developed significant cognitive impairment or dementia. Ventricular change and Parkinson's disease status were significantly associated with dementia. Ventricular change was significantly correlated with change in Mini-Mental Status Examination in the Parkinson's disease with dementia group (r = 0.87, P = .001). Gray matter atrophy was greater in Parkinson's disease with dementia, with similar change over time in both Parkinson's disease and Parkinson's disease with dementia. White matter volumes were not significantly different between Parkinson's disease and Parkinson's disease with dementia; however, the decrease over time might be greater in Parkinson's disease with dementia. Ventricular dilatation occurs early in the course of significant cognitive decline in patients with Parkinson's disease, possibly reflecting both cortical gray and white matter loss. © 2011 Movement Disorder Society

The purpose of this study was to determine if focal cortical abnormalities may occur in early Parkinson's disease (PD). We studied 26 untreated patients with early PD and 14 healthy control subjects, with cognitive screening and magnetic resonance imaging (MRI). Voxel-based morphometry was used to assess for the presence of localized cortical grey matter (GM) and/or subcortical white matter (WM) changes. Patient and control groups showed no differences in age or gender distribution. Females had a greater GM% than males (P = 0.001). Comparison of patients and controls revealed no difference in local GM volumes. In PD, however, there was decreased WM volume in the anterior right fusiform gyrus and superior temporal gyrus. There were no correlations between the California Verbal Learning Test long delay free recall, Judgment of Line Orientation, Trail Making A or B and either the GM or WM localized volumes. These results suggest that right anterior temporal lobe changes occur in untreated patients with PD. The earliest changes may occur in subcortical white matter rather than temporal cortex.

Although motor symptoms of Parkinson's disease (PD) are initially responsive to dopamine replacement therapy, nonresponsive features develop over time, suggesting that impaired dopaminergic function alone may not be wholly responsible for all the motor features of the disease. Previous studies suggest impaired function in the presupplementary motor area (pre-SMA) in PD. Our objective was to determine whether pre-SMA abnormalities are present in untreated patients with early disease. We measured N-acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios in pre-SMA in 26 untreated patients with early PD (disease duration 3.0 ± 2.0 yr) and 15 control subjects with single voxel magnetic resonance spectroscopy. Neither NAA/Cr nor Cho/Cr ratios differed significantly between groups. These observations suggest that, although pre-SMA function is impaired in moderately advanced PD, it is relatively spared in early disease. We suggest that pre-SMA dysfunction is in part responsible for the dopamine nonresponsive features associated with disease progression. © 2008 Movement Disorder Society

Phosphorus chemical shift and 31P,31P spin-spin coupling tensors have been characterized for pentaphenylphosphinophosphonium tetrachlorogallate, [Ph3P-PPh2][GaCl4], using solid-state 31P NMR spectroscopy. Spectra obtained with magic-angle spinning yield the isotropic value of the indirect spin-spin coupling, |1J(31P,31P)iso|, 323 ± 2 Hz, while 2D spin-echo and rotational resonance experiments provide the effective dipolar coupling constant, Reff, 1.70 ± 0.02 kHz, and demonstrate that Jiso is negative. Within experimental error, the effective dipolar coupling constant and Jiso are unchanged at –120°C. The anisotropy in 1J(31P,31P), ΔJ, has been estimated by comparison of Reff and the value of the dipolar coupling constant, RDD, calculated from the P—P bond length as determined by X-ray diffraction. It is concluded that |ΔJ| is small, with an upper limit of 300 Hz. Calculations of 1J(31P,31P) for model systems H3P-PH+2 and (CH3)3P-P(CH3)+2 using density functional theory as well as multiconfigurational self-consistent field theory (H3P-PH+2) support this conclusion. The experimental spin-spin coupling parameters were used to analyze the 31P NMR spectrum of a stationary powder sample and provide information about the phosphorus chemical shift tensors. The principal components of the phosphorus chemical shift tensor for the phosphorus nucleus bonded to three phenyl groups are δ11 = 36 ppm, δ22 = 23 ppm, and δ33 = –14 ppm with an experimental error of ±2 ppm for each component. The components are oriented such that δ33 is approximately perpendicular to the P—P bond while δ11 forms an angle of 31° with the P—P bond. For the phosphorus nucleus bonded to two phenyl groups, the principal components of the phosphorus chemical shift tensor are δ11 = 23 ppm, δ22 = –8 ppm, and δ33 = –68 ppm with experimental errors of ±2 ppm. In this case, δ33 is also approximately perpendicular to the P—P bond; however, δ22 is close to the P—P bond for this phosphorus nucleus, forming an angle of 13°. The dihedral angle between the δ33 components of the two phosphorus chemical shift tensors is 25°. Results from ab initio calculations are in good agreement with experiment and suggest orientations of the phosphorus chemical shift tensors in the molecular frame of reference.Key words: Nuclear magnetic resonance spectroscopy, phosphorus chemical shift tensors, 31P-31P J-coupling tensors, density functional theory, multiconfigurational self-consistent field theory, phosphinophosphonium salts.

A series of organic hydrochloride salts has been investigated using solid-state 35Cl and 37Cl NMR spectroscopy at applied magnetic field strengths of 9.4 and 18.8 T. Magic-angle spinning, static Hahn-echo, and quadrupolar Carr−Purcell Meiboom−Gill (QCPMG) echo experiments have been applied to investigate the chlorine electric field gradient (EFG) and chemical shift (CS) tensors for l-tyrosine hydrochloride, l-cysteine methyl ester hydrochloride, l-cysteine ethyl ester hydrochloride, quinuclidine hydrochloride, and tris sarcosine calcium chloride. Chlorine-35 nuclear quadrupolar coupling constants for these compounds range from 2.23 to 5.25 MHz, and isotropic chemical shifts range from approximately 9 to 53 ppm relative to the chloride ion in aqueous solution. The results demonstrate the feasibility and benefits of high-field 35/37Cl NMR studies of organic chloride salts. A discussion of the data in the context of the known X-ray or neutron diffraction structures for these compounds suggests that the chlor...

An extensive ab initio molecular orbital study of the (27)Al nuclear spin-rotation and nuclear quadrupolar coupling constants in aluminum hydride, AlH, has been performed. The (27)Al nuclear spin-rotation constant (C( perpendicular)), calculated to be approximately 300 kHz, was neglected in a previous analysis of the hyperfine structure in the microwave spectrum (M. Goto and S. Saito, Astrophys. J. 452, L147-148 (1995)). Unfortunately, the ab initio calculations do not provide a definitive value for the aluminum nuclear quadrupolar coupling constant, but suggest a value of -49+/-4 MHz. It is apparent that the microwave study of AlH should be repeated. Copyright 2001 Academic Press.

Despite the large known chemical shift (CS) range for boron and the large number of 11B NMR studies of glasses, no boron CS tensors have been characterized to date. We report the application of solid-state NMR techniques at moderate (9.4 T) and high (17.63 T) applied magnetic field strengths to the characterization of the boron CS tensors in trimesitylborane (BMes3) and triphenyl borate (B(OPh)3). The boron CS tensor of the former compound exhibits a remarkably large span, Ω = 121 ± 1 ppm, which encompasses the known range of isotropic chemical shifts for tricoordinate boron compounds. Conversely, the effect of the boron CS tensor on the 11B NMR spectra of B(OPh)3 is difficult to observe and quantify even at field strengths as high as 17.63 T; we find Ω ≤ 10 ppm. This marked difference in the boron nuclear magnetic shielding tensors is reproduced accurately by a series of ab initio and DFT calculations with a range of basis sets. The difference is rationalized in the context of Ramsey's theory of nuclear ...

Phosphorus chemical shift and spin−spin coupling tensors have been characterized for tetramethyldiphosphine disulfide (TMPS) by analysis of 31P CP NMR spectra obtained at 4.7 T for a single crystal. In addition, 31P CP NMR spectra of stationary powder and magic angle spinning (MAS) samples have been acquired at two applied magnetic fields (4.7 and 9.4 T) and analyzed independently using the dipolar-chemical shift method. A 2D spin-echo NMR spectrum was also obtained to independently determine the effective 31P−31P dipolar coupling constant. The crystal structure of TMPS (space group C2/m) consists of six molecules per unit cell. For two of the six molecules, the two phosphorus nuclei are related by an inversion center (site 1), while the remaining four molecules possess mirror planes containing the S−P−P−S bonds (site 2). The differences between the two sites are very subtle, as revealed by a redetermination of the X-ray crystal structure. The phosphorus chemical shift tensors obtained from both single-cr...

Phosphorus-31 1D NMR spectra of a stationary powder sample of a phosphole tetramer containing two phosphorus spin pairs have been obtained at 4.7 T and 9.4 T. In order to separate 31P-31P spin-spin coupling from anisotropic chemical shielding, 2D spin-echo NMR spectra have been acquired. Phosphorus-31 CPMAS NMR experiments indicate that the two spin pairs of the tetramer are equivalent and each may be treated as an isolated spin pair. Within a given spin pair, the difference between the isotropic chemical shifts of two directly bonded phosphorus nuclei is 1.7 ppm. As well, they are spin-spin coupled by both the indirect and direct interactions, 1J(31P, 31P) = -362 Hz and RDD = 1.80 kHz, respectively. The principal components and relative orientation of the two phosphorus chemical shielding tensors have been determined using the dipolar-chemical shift technique; however, since the dipolar tensor is axially symmetric, ambiguities in the chemical shielding tensor orientation relative to the molecular framework result. Using ab initio calculations and simulations of the 2D spin-echo spectra, many of these ambiguities have been resolved. The spans and skews of the phosphorus shielding tensors for all four three-coordinate phosphorus nuclei are the same within experimental error, 115 ppm and 0.70, respectively. Combined experimental and theoretical results indicate that the phosphorus shielding tensor orientations are dictated by the local environment. For both shielding tensors, the most shielded component, δ33, is approximately 78° from the P-P bond and in the phosphole ring plane. The relative orientation of the δ33 components is described by a dihedral angle of 82°, similar to the dihedral angle of approximately 76° defining the twist of the phosphole rings about the bridging P-P bond.Key words: solid-state 31P NMR, phosphorus chemical shielding tensors, phosphole tetramer, 31P—31P spin pairs, ab initio calculations.

Using accurate 35/37Cl spin−rotation data and the chlorine chemical shift of HCl(g) with respect to the chloride ion in aqueous solution, δ = 28 ± 3 ppm, a more reliable chlorine absolute shielding...

We consider a pair of polygons on the simple cubic lattice forming a link of specified type. We investigate the mean writhe of the polygons as a function of the number of edges in each polygon, and of the link type. Although two unknotted polygons which are linked as a Hopf link have zero mean writhe, we show that other torus links induce writhe in the polygons. We also consider non-torus links, including a link in which one polygon is knotted.

Parkinson's disease (PD) patients are treated with levodopa (L-dopa) to help stabilize their impaired motor abilities; however, L-dopa leads to increased homocysteine (Hcy) levels, which may have a deleterious effect on brain structure and function. The purpose of this study was to examine the impact of increased Hcy concentration on global brain atrophy as determined by magnetic resonance imaging in PD patients and controls. The effect of high Hcy level on ventricular dilatation (percentage of intracranial volume [%ICV]) and total tissue volume (%ICV) was examined at baseline and longitudinally at 36 months. Age, sex, education, and L-dopa duration (in PD patients) were included as covariates. Elevated Hcy levels correlated positively with ventricular dilatation (%ICV) in the whole sample (P = 0.004) and in the PD group (P = 0.008). At baseline, adults with a high Hcy level (14 μmol/L) had higher ventricular volume (%ICV) than adults with a low Hcy level (≤ 14 μmol/L) in the whole sample (P = 0.006) and in the PD group (P = 0.03), which persisted over 36 months in both the whole sample (P = 0.004) and the PD group (P = 0.03). PD patients with high Hcy concentrations had a greater rate of ventricular enlargement (%ICV) over time compared with those with low Hcy concentration (P = 0.02). Elevated Hcy concentration was associated with increased ventricular dilatation (%ICV) in PD patients. A larger sample with a broader age range and longer follow-up is needed to establish the consequences of high Hcy level, including interactions with genetic and environmental risk factors, in PD.

Parkinson's disease (PD) is a common progressive neurodegenerative movement disorder. Although motor symptoms are associated with focal loss of substantia nigra dopaminergic neurons, pathological changes in PD are widespread 1 . Dementia in patients with PD is common and patients with Parkinson's disease and dementia (PDD) have involvement of additional cortical regions compared with non- demented PD patients 2 .While PD is not known to directly affect white matter fiber tracts, changes in these tracts may reflect pathology within the neuronal cell bodies from which the axons arise and PDD patients may show different patterns of white matter involvement than PD patients. Diffusion tensor imaging (DTI) non-invasively measures the anisotropic mobility of water in the human brain 3 , which ABSTRACT: Background:InParkinson'sdisease(PD)celllossinthesubstantianigraisknowntoresultinmotorsymptoms;however widespread pathological changes occur and may be associated with non-motor symptoms such as cognitive impairment. Diffusion tensorimagingisaquantitativeimagingmethodsensitivetothemicro-structureofwhitemattertracts. Objective: Tomeasurefractional anisotropy (FA) and mean diffusivity (MD) values in the corpus callosum and cingulum pathways, defined by diffusion tensor tractography, in patients with PD, PD with dementia (PDD) and controls and to determine if these measures correlate with Mini-Mental Status Examination (MMSE) scores in parkinsonian patients. Methods: Patients with PD (17 Males (M),12 Females (F)), mild PDD (5 M,1F) and controls (8 M, 7F) underwent cognitive testing and MRI scans. The corpus callosum was divided into four regions and the cingulum into two regions bilaterally to define tracts using the program DTIstudio (Johns Hopkins University) using the fiber assignment by continuous tracking algorithm. Volumetric MRI scans were used to measure white and gray matter volumes. Results: Groups did not differ in age or education.There were no overall FA or MD differences between groups in either the corpus callosum or cingulum pathways. In PD subjects the MMSE score correlated with MD within the corpus callosum.These findings were independent of age, sex and total white matter volume. Conclusions: The data suggest that the corpus callosum or its cortical connections are associated with cognitive impairment in PD patients. RESUME: La tractographie du corps calleux et du cingulum dans la maladie de Parkinson. Contexte : Dans la maladie de Parkinson, il est bien

Age-related ventricular enlargement is accelerated in Alzheimer's disease, but its relationship to cognitive decline in Parkinson's disease is less clear, even though dementia is common in Parkinson's disease. Our goals were to determine if greater enlargement of the ventricles and gray or white matter atrophy occurred in Parkinson's disease patients developing cognitive decline. Older nondemented patients with Parkinson's disease (33) and age- and sex-matched controls (39) were recruited and prospectively assessed for the development of significant cognitive decline over 36 months. Magnetic resonance imaging was obtained every 18 months, and ventricular volume and total brain gray and white matter volumes were measured using reliable segmentation of T1-weighted volumetric scans. Subjects with incidental intracranial abnormalities, an atypical course, and stroke as well as dropouts were excluded from a cohort of 52 patients and 50 controls. Among 33 patients and 39 controls, 10 patients and 3 controls developed significant cognitive impairment or dementia. Ventricular change and Parkinson's disease status were significantly associated with dementia. Ventricular change was significantly correlated with change in Mini-Mental Status Examination in the Parkinson's disease with dementia group (r = 0.87, P = .001). Gray matter atrophy was greater in Parkinson's disease with dementia, with similar change over time in both Parkinson's disease and Parkinson's disease with dementia. White matter volumes were not significantly different between Parkinson's disease and Parkinson's disease with dementia; however, the decrease over time might be greater in Parkinson's disease with dementia. Ventricular dilatation occurs early in the course of significant cognitive decline in patients with Parkinson's disease, possibly reflecting both cortical gray and white matter loss.

New solid-state NMR (SSNMR) methods and applications continue to blossom such that a diverse array of physical, chemical, and biological problems are now being addressed using a variety of SSNMR experiments. While SSNMR is far from routine for chemists in the manner that a technique such as solution NMR is, there are nevertheless numerous applications of SSNMR which would be beneficial to many “non-specialists”, e.g., synthetic chemists seeking to characterize their materials. This article gathers together practical details for those one-dimensional experiments which, in a broad sense, are considered “routine” in a modern SSNMR laboratory. Emphasis is placed on providing information and over 300 key references in a manner which will be useful for the novice and the non-specialist. For practicing SSNMR spectroscopists, it is hoped that this article will serve as a valuable reference in the laboratory. In addition to providing a brief review of pulsed Fourier transform NMR, the article discusses experimental details relating to the study of solid samples containing spin- 1 nuclei, non-integer quadrupolar nuclei, and deuterium.

Background: Parkinson disease (PD) is a progressive neurodegenerative disorder in which the major pathologic substrate is a loss of dopaminergic neurons from the lateral substantia nigra pars compacta (SNc). Our objective was to determine whether, in patients with early PD, SNc changes evident on MRI sequences sensitive to iron content corresponded anatomically to the pathologic changes reported previously, and to correlate these changes to the duration and severity of clinical manifestations of PD. Methods: Twenty-six untreated patients with early PD and 13 age- and gender-matched control subjects had MRI with a 3 tesla magnet using a multiple gradient echo sequence designed for rapid single-scan mapping of the proton transverse relaxation rate ( R 2 * ). R 2 * was calculated for midbrain and forebrain basal ganglia regions. Clinical features were rated with the Unified Parkinson9s Disease Rating Scale. Results: A difference in measured R 2 * values between patients and controls was observed in the lateral SNc ( p ≤ 0.005). Linear regression indicated a correlation between the lateralized motor score from the clinically most affected side and R 2 * values from the opposite lateral SNc ( p = 0.01). Conclusions: High field strength MRI demonstrates lateral substantia nigra pars compacta abnormalities in early Parkinson disease (PD) consistent with increased iron content and corresponding to the known distribution of neuronal loss occurring in this disorder. This may ultimately provide an imaging marker for disease progression in PD, although longitudinal studies are required. GLOSSARY: AC = anterior commissure; CN = caudate nucleus; GP = globus pallidus; LantGP = left anterior GP; LantPu = left anterior Pu; LlatSNc = left lateral SNc; LlatSNr = left lateral SNr; LmedSNc = left medial SNc; LmedSNr = left medial SNr; LpostGP = left posterior GP; LpostPu = left posterior Pu; PC = posterior commissure; PD = Parkinson disease; Pu = putamen; RantGP = right anterior GP; RantPu = right anterior Pu; RlatSNc = right lateral SNc; RlatSNr = right lateral SNr; RmedSNc = right medial SNc; RmedSNr = right medial SNr; RN = red nucleus; ROI = region of interest; RpostGP = right posterior GP; RpostPu = right posterior Pu; SNc = substantia nigra compacta; SNr = substantia nigra reticulata; TE = echo times; UPDRS = Unified Parkinson9s Disease Rating Scale.

Objectives To determine overall patterns of brain atrophy associated with memory, executive function (EF) and dopamine non-responsive motor measures in older parkinsonian patients. Design Forty-three older PD patients (≥65 years) and matched controls underwent a neurological examination (Unified Parkinson's Disease Rating Scale, separated into dopamine responsive and dopamine non-responsive signs) and neuropsychological testing (memory: California Verbal Learning Test (CVLT)) and a composite of index of executive function (EF): Stroop Interference, Trail Making Test Part B, and digit ordering. All underwent volumetric MRI scans analyzed using voxel-based morphometry (VBM). Group comparisons, and the correlations between MRI gray and white matter volume and motor and cognitive measures were controlled for age, sex and intracranial volume. Cerebellar volume was independently measured using a validated extraction method. Results Patients and controls were matched for demographics and global cognitive measures. VBM indicated significant gray matter (GM) atrophy in the cerebellum in PD and was confirmed independently. Poor memory was associated with GM atrophy in the left (uncus, middle temporal and fusiform gyri) and right temporal lobes and left putamen. Dopamine non-responsive motor signs and EF were associated with caudate atrophy. EF was also associated with GM atrophy in the middle temporal gyri, the left precuneus and cerebellum. Conclusions Cortical and striatal atrophy were associated with dopamine non-responsive motor signs and cognitive impairment and provide a morphologic correlate for progression of PD. Cerebellar atrophy was found in older PD patients.

The anterior cingulate (AC) gyrus and the presupplementary motor area (pre-SMA) show pathological changes in Parkinson's disease (PD). We examined if PD patients show magnetic resonance spectroscopy (MRS) changes in NAA/Cr in the AC, pre-SMA, or posterior cingulate (PC). Forty-four (27 male, 17 female) healthy nondemented PD patients and 38 controls (18 male, 20 female) 65 years of age and older were examined using the Unified Parkinson's Disease Rating Scale (UPDRS), Mini-Mental State Examination, Frontal Assessment Battery, and Geriatric Depression Scale. MRS was performed at 1.5 T. Voxels (8 cc; PRESS; TE = 80; TR = 1,600 ms) were placed mid-sagittally. Gray matter and white matter volumes were measured within voxels using SPM2. Spectra were analyzed using LC model to yield NAA/Cr and Cho/Cr. Demographic and cognitive measures did not differ between groups. Motor UPDRS was 17.7 +/- 8.8 for PD. Pre-SMA NAA/Cr was lower in PD (PD: 1.39 +/- 0.17; control: 1.47 +/- 0.16; P = 0.045) and correlated negatively with age (r = 0.39; P = 0.01), but not with UPDRS, disease duration, or dopamine equivalents. AC and PC NAA/Cr and Cho/Cr in any region did not differ (P > 0.05). In conclusion, pre-SMA NAA/Cr was selectively decreased in PD, consistent with neuronal dysfunction. This should be further examined as a biomarker of disease in PD.