A Comparison of Substantia Nigra T1 Hyperintensity in Parkinson's Disease Dementia, Alzheimer's Disease and Age-Matched Controls: Volumetric Analysis of Neuromelanin Imaging.

OBJECTIVE: Neuromelanin loss of substantia nigra (SN) can be visualized as a T1 signal reduction on T1-weighted high-resolution imaging. We investigated whether volumetric analysis of T1 hyperintensity for SN could be used to differentiate between Parkinson's disease dementia (PDD), Alzheimer's disease (AD) and age-matched controls. MATERIALS AND METHODS: This retrospective study enrolled 10 patients with PDD, 18 patients with AD, and 13 age-matched healthy elderly controls. MR imaging was performed at 3 tesla. To measure the T1 hyperintense area of SN, we obtained an axial thin section high-resolution T1-weighted fast spin echo sequence. The volumes of interest for the T1 hyperintense SN were drawn onto heavily T1-weighted FSE sequences through midbrain level, using the MIPAV software. The measurement differences were tested using the Kruskal-Wallis test followed by a post hoc comparison. RESULTS: A comparison of the three groups showed significant differences in terms of volume of T1 hyperintensity (p < 0.001, Bonferroni corrected). The volume of T1 hyperintensity was significantly lower in PDD than in AD and normal controls (p < 0.005, Bonferroni corrected). However, the volume of T1 hyperintensity was not different between AD and normal controls (p = 0.136, Bonferroni corrected). CONCLUSION: The volumetric measurement of the T1 hyperintensity of SN can be an imaging marker for evaluating neuromelanin loss in neurodegenerative diseases and a differential in PDD and AD cases.

Synergistic effects of longitudinal amyloid and vascular changes on lobar microbleeds.

OBJECTIVE: To determine whether amyloid and hypertensive cerebral small vessel disease (hCSVD) changes synergistically affect the progression of lobar microbleeds in patients with subcortical vascular mild cognitive impairment (svMCI). METHODS: Among 72 patients with svMCI who underwent brain MRI and [11C] Pittsburgh compound B (PiB)-PET, 52 (72.2%) completed the third year of follow-up. These patients were evaluated by annual neuropsychological testing, brain MRI, and follow-up PiB-PET. RESULTS: Over 3 years, 31 of 52 patients (59.6%) had incident cerebral microbleeds (CMBs) in the lobar and deep regions. Both baseline and longitudinal changes in lacune numbers were associated with increased numbers of lobar and deep microbleeds, while baseline and longitudinal changes in PiB uptake ratio were associated only with the progression of lobar microbleeds, especially in the temporal, parietal, and occipital areas. Regional white matter hyperintensity severity was also associated with regional lobar CMBs in the parietal and occipital regions. There were interactive effects between baseline and longitudinal lacune number and PiB retention on lobar microbleed progression. Increased lobar, but not deep, CMBs were associated with decreased scores in the digit span backward task and Rey-Osterrieth Complex Figure Test. CONCLUSIONS: Our findings suggest that amyloid-related pathology and hCSVD have synergistic effects on the progression of lobar microbleeds, providing new clinical insight into the interaction between amyloid burden and hCSVD on CMB progression and cognitive decline with implications for developing effective prevention strategies.

Pathogenesis of cerebral microbleeds: In vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment.

OBJECTIVE: Cerebral microbleeds (CMBs) are a neuroimaging marker of small vessel disease (SVD) with relevance for understanding disease mechanisms in cerebrovascular disease, cognitive impairment, and normal aging. It is hypothesized that lobar CMBs are due to cerebral amyloid angiopathy (CAA) and deep CMBs are due to subcortical ischemic SVD. We tested this hypothesis using structural magnetic resonance imaging (MRI) markers of subcortical SVD and in vivo imaging of amyloid in patients with cognitive impairment. METHODS: We included 226 patients: 89 with Alzheimer disease-related cognitive impairment (ADCI) and 137 with subcortical vascular cognitive impairment (SVCI). All subjects underwent amyloid imaging with [(11) C] Pittsburgh compound B (PiB) positron emission tomography, and MRI to detect CMBs and markers of subcortical SVD, including the volume of white matter hyperintensities (WMH) and the number of lacunes. RESULTS: Parietal and occipital lobar CMBs counts were higher in PiB(+) ADCI with moderate WMH than PiB(+) ADCI with minimal WMH, whereas PiB(-) patients with SVCI (ie, "pure" SVCI) showed both lobar and deep CMBs. In multivariate analyses of the whole cohort, WMH volume and lacuna counts were positively associated with both lobar and deep CMBs, whereas amyloid burden (PiB) was only associated with lobar CMBs. There was an interaction between lacuna burden and PiB retention on lobar (but not deep) CMBs (p<0.001). INTERPRETATION: Our findings suggest that although deep CMBs are mainly linked to subcortical SVD, both subcortical SVD and amyloid-related pathologies (eg, CAA) contribute to the pathogenesis of lobar CMBs, at least in subjects with mixed lobar and deep CMBs. Furthermore, subcortical SVD and amyloid-related pathologies interact to increase the risk of lobar CMBs.

Cerebellar atrophy in patients with subcortical-type vascular cognitive impairment.

Recent studies suggest that the role of the cerebellum extends into cognitive regulation and that subcortical vascular dementia (SVaD) can result in cerebellar atrophy. However, there has been no evaluation of the cerebellar volume in the preclinical stage of SVaD. We aimed to compare cerebellar volume among patients with amnestic mild cognitive impairment (aMCI) and subcortical vascular mild cognitive impairment (svMCI) and evaluate which factors could have contributed to the cerebellar volume. Participants were composed of 355 patients with aMCI, svMCI, Alzheimer's disease (AD), and SVaD. Cerebellar volumes were measured using automated methods. A direct comparison of the cerebellar volume in SVaD and AD groups showed that the SVaD group had a statistically smaller cerebellar volume than the AD group. Additionally, the svMCI group had a smaller cerebellar volume than the aMCI group, with the number of lacunes (especially in the supratentorial regions) being associated with cerebellar volume. Cerebellar volumes were associated with some neuropsychological tests, digit span backward and ideomotor apraxia. These findings suggest that cerebellar atrophy may be useful in differentiating subtypes of dementia and the cerebellum plays a potential role in cognition.

Ocular vestibular evoked myogenic potentials induced by air-conducted sound in patients with acute brainstem lesions.

OBJECTIVE: The ocular vestibular-evoked myogenic potential (oVEMP), a recently documented otolith-ocular reflex, is considered to reflect the central projections of the primary otolithic afferent fibers to the oculomotor nuclei. The aim of our study is to define air-conducted sound oVEMP abnormality in patients with acute brainstem lesions and to determine the brainstem structures involved in the generation of oVEMPs. METHODS: In response to air-conducted tone burst sounds (ACS), oVEMP was measured in 52 patients with acute brainstem lesions. Individualized brainstem lesions were analyzed by means of MRI-based voxel-wise lesion-behavior mapping, and the probabilistic lesion maps were constructed. RESULTS: More than half (n=28, 53.8%) of the patients with acute brainstem lesions showed abnormal oVEMP in response to ACS. The majority of patients with abnormal oVEMPs had lesions in the dorsomedial brainstem that contains the medial longitudinal fasciculus (MLF), the crossed ventral tegmental tract (CVTT), and the oculomotor nuclei and nerves. CONCLUSION: MLF, CVTT, and the oculomotor nuclei and nerves appear to be responsible for otolith-ocular responses in the brainstem. SIGNIFICANCE: Complemented to cervical VEMP for the uncrossed otolith-spinal function, oVEMP to ACS may be applied to evaluate the crossed otolith-ocular function in central vestibulopathies.

The relationships between extent and microstructural properties of the midsagittal corpus callosum in human brain.

Recent quantitative analyses of the corpus callosum (CC) have tried to assess the interhemispheric connectivity. Based on histological results showing an expansion of callosal extent at the midsagittal plane, without fiber density alterations, callosal extent was interpreted as an index of interhemispheric connectivity. The microstructural properties of the CC have also been investigated extensively using diffusion tensor imaging, to assess interhemispheric connectivity. The relationships between axonal density and callosal extent need to be investigated to understand how these parameters reflect interhemispheric connectivity. We used a semi-automated CC segmentation scheme in T1-weighted magnetic resonance image and fractional anisotropy (FA) image, respectively. The parameterization method of the segmented CC was applied to 47 right-handed healthy adult subjects. The callosal extent and microstructural properties were measured using the callosal thickness and diffusion indices (FA, mean diffusivity, and axial and radial diffusivity), respectively. Our results revealed a correlation between callosal thickness and FA on the posterior body and isthmus of the CC, which suggests that these regions are more sensitive to fiber alterations than other regions. Based on this result, we suggest that both the extent of the CC and its microstructural properties should be considered together in the estimation of interhemispheric connectivity in healthy adult populations.