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BACKGROUND AND PURPOSE Fractal dimension (FD) is an index of structural complexity of cortical gray matter (GM) and white matter (WM). Application of FD to pontocerebellar degeneration has revealed cerebellar changes. However, so far, possible concurrent cerebral changes and progression of changes in brain complexity have not been investigated. METHODS We computed FD of cerebellar and cerebral cortex and WM derived from longitudinal brain MRI of patients with spinocerebellar ataxia type 2 (SCA2), which is an inherited cause of pontocerebellar degeneration. Nine SCA2 patients and 16 age-matched healthy controls were examined twice (3.6 ± .7 and 3.3 ± 1.0 years apart, respectively) on the same 1.5T MR scanner with T1-weighted imaging. Cortical GM and WM of the cerebrum and cerebellum were segmented using FreeSurfer and FD of these segmentations were computed. RESULTS At baseline, FD values of cerebellar GM and WM were significantly (P < .001) lower in SCA2 patients (2.48 ± .04 for GM and 1.74 ± .09 for WM) than in controls (2.56 ± .02 for GM and 2.22 ± .19 for WM). Also, FD values of cerebral GM were significantly (P < .05) lower in SCA2 patients (2.39 ± .03) than in controls (2.43 ± .02). No significant differences were observed for FD of the cerebral WM. The rate of change of FD values was not significantly different between SCA2 patients and controls. CONCLUSIONS The structural complexity of the cerebellum and cerebral cortex is reduced in SCA2 patients. Fractal analysis seems not to be able to demonstrate progression of changes associated with degeneration in SCA2.

Background and purpose Disruption of cortical-subcortical circuits related to small vessel disease (SVD) may predispose to depression in the elderly. We aimed to determine the independent association between white matter (WM) microstructural damage, evaluated with diffusion tensor imaging (DTI), and depressive symptoms in a cohort of elderly subjects with mild cognitive impairment (MCI) and SVD. Methods The vascular mild cognitive impairment (VMCI)-Tuscany Study is an observational multicentric longitudinal study that enrolled patients with MCI and moderate to severe degrees of WM hyperintensities on MRI. Lacunar infarcts, cortical atrophy, medial temporal lobe atrophy, microbleeds, and DTI-derived indices (mean diffusivity, MD and fractional anisotropy, FA) were evaluated on baseline MRI. Geriatric Depression Scale (GDS) (score 0–15) was used to assess depressive symptoms. An extensive neuropsychological battery, Instrumental Activities of Daily Living scale, and the Short Physical Performance Battery were used for cognitive, functional, and motor assessments, respectively. Results Seventy-six patients (mean age: 75.1 ± 6.8 years) were included. Univariate analyses showed a significant association between GDS score and both DTI-derived indices (MD: r = 0.307, p = 0.007; FA: r = −0.245; p = 0.033). The association remained significant after adjustment for age, WM hyperintensities severity, global cognitive, functional and motor performances, and antidepressant therapy (MD: r = 0.361, p = 0.002; FA: r = −0.277; p = 0.021). Conclusions These results outline the presence of an association between WM microstructural damage and depressive symptoms in MCI patients with SVD. This relationship does not seem to be mediated by disability, cognitive, and motor impairment, thus supporting the vascular depression hypothesis. Copyright © 2015 John Wiley & Sons, Ltd.

Purpose To investigate the impact of cerebrospinal fluid (CSF) contamination on metabolite evaluation in the superior cerebellar vermis with single-voxel 1H-MRS in normal subjects and patients with degenerative ataxias. Materials and Methods Twenty-nine healthy volunteers and 38 patients with degenerative ataxias and cerebellar atrophy were examined on a 1.5 Tesla scanner. Proton spectra of a volume of interest placed in the superior vermis were acquired using a four TE PRESS technique. We calculated N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and NAA/Cho ratios, T2 relaxation times and concentrations of the same metabolites using the external phantom method. Finally, concentrations were corrected taking into account the proportion of nervous tissue and CSF, that was determined as Volume Fraction (VF). Results In healthy subjects, a significant difference was observed between metabolite concentrations with and without correction for VF. As compared to controls, patients with ataxias showed significantly reduced NAA/Cr and NAA concentrations, while only corrected Cr concentration was significantly increased. The latter showed an inverse correlation with VF. Conclusion CSF contamination has a not negligible effect on the estimation of brain metabolites. The increase of Cr concentration in patients with cerebellar atrophy presumably reflects the substitutive gliosis which takes place along with loss of neurons. J. Magn. Reson. Imaging 2009;30:11–17. © 2009 Wiley-Liss, Inc.

Purpose To explore gender, age-related, and regional differences of magnetization transfer ratio (MTR) of brain cortical and subcortical gray matter (GM). Materials and Methods In all, 102 healthy subjects (51 women and 51 men; range 25–84 years) were examined with 3-mm thick MT images. We assessed MTR in automatically segmented GM structures including frontal, parietal-insular, temporal, and occipital cortex, caudate, pallidus and putamen, and cerebellar cortex. A general linear model analysis was conducted to ascertain the linear and quadratic relationship among the MTR and gender, age, and anatomical structure. Results The effect of gender was borderline (P = 0.07) in all GM structures (with higher MTR values in men), whereas age showed a significant linear as well as quadratic effect in all cortical and subcortical GM structures (P ≤ 0.001). Quadratic age-related decrease in MTR began at about 40 years of age. Mean and standard deviation (SD) of MTR had the following decreasing order: thalamus (58.3 + 0.8), pallidus (56.8 ± 1.3), caudate (55.5 ± 1.6) and putamen (54.6 ± 1.1); temporal (56.8 ± 0.9), parietal-insular (56.8 ± 1.1), frontal (56.5 ± 1.1), occipital (55.4 ± 1.0) and cerebellar (53.2 ± 1.0) cortex. In post-hoc testing, all regional pairwise differences were statistically significant except pallidus vs. temporal or parietal-insular cortex, caudate vs. occipital cortex, frontal vs. parietal-insular or temporal cortex. Conclusion MTR of the cortical and subcortical brain GM structures decreases quadratically after midlife and shows significant regional differences. J. Magn. Reson. Imaging 2014;40:360–366 © 2013 Wiley Periodicals, Inc.

Voxel-based morphometry (VBM) enables an unbiased in-vivo whole-brain quantitative analysis of differences in gray matter (GM), white matter (WM) and cerebro-spinal fluid (CSF) volumes. We assessed with VBM 20 spinocerebellar ataxia Type 2 (SCA2) patients with mild or moderate cerebellar deficit and 20 age and sex-matched healthy controls. SCA2 patients showed a significant (P 0.01) correlation was observed between the GM and WM loss and severity of the neurological deficit. In SCA2 patients with mild to moderate cerebellar deficit, GM and WM volume loss and CSF volume increase are confined to the posterior cranial fossa.

The 37-43 amino acid Abeta peptide is the principal component of beta-amyloid deposits in Alzheimer's disease (AD) brain, and is derived by serial proteolysis of the amyloid precursor protein (APP) by beta- and gamma-secretase. gamma-Secretase also cleaves APP at Val50 in the Abeta numbering (epsilon cleavage), resulting in the release of a fragment called APP intracellular domain (AICD). The aim of this study was to determine whether amino acid substitutions in the APP transmembrane domain differentially affect Abeta and AICD generation. We found that the APPV715F substitution, which has been previously shown to dramatically decrease Abeta40 and Abeta42 while increasing Abeta38 levels, does not affect in vitro generation of AICD. Furthermore, we found that the APPL720P substitution, which has been previously shown to prevent in vitro generation of AICD, completely prevents Abeta generation. Using a fluorescence resonance energy transfer (FRET) method, we next found that both the APPV715F and APPL720P substitutions significantly increase the distance between the N- and C-terminus of presenilin 1 (PS1), which has been proposed to contain the catalytic site of gamma-secretase. In conclusion, both APPV715F and APPL720P change PS1 conformation with differential effects on Abeta and AICD production.