The fractional amplitude of low-frequency fluctuations signals related to amyloid uptake in high-risk populations—A pilot fMRI study

BackgroundPatients with type 2 diabetes mellitus (T2DM) and subjective cognitive decline (SCD) have a higher risk to develop Alzheimer's Disease (AD). Resting-state-functional magnetic resonance imaging (rs-fMRI) was used to document neurological involvement in the two groups from the aspect of brain dysfunction. Accumulation of amyloid-β (Aβ) starts decades ago before the onset of clinical symptoms and may already have been associated with brain function in high-risk populations. However, this study aims to compare the patterns of fractional amplitude of low-frequency fluctuations (fALFF) maps between cognitively normal high-risk groups (SCD and T2DM) and healthy elderly and evaluate the association between regional amyloid deposition and local fALFF signals in certain cortical regions.Materials and methodsA total of 18 T2DM, 11 SCD, and 18 healthy elderlies were included in this study. The differences in the fALFF maps were compared between HC and high-risk groups. Regional amyloid deposition and local fALFF signals were obtained and further correlated in two high-risk groups.ResultsCompared to HC, the altered fALFF signals of regions were shown in SCD such as the left posterior cerebellum, left putamen, and cingulate gyrus. The T2DM group illustrated altered neural activity in the superior temporal gyrus, supplementary motor area, and precentral gyrus. The correlation between fALFF signals and amyloid deposition was negative in the left anterior cingulate cortex for both groups. In the T2DM group, a positive correlation was shown in the right occipital lobe and left mesial temporal lobe.ConclusionThe altered fALFF signals were demonstrated in high-risk groups compared to HC. Very early amyloid deposition in SCD and T2DM groups was observed to affect the neural activity mainly involved in the default mode network (DMN)

The default mode network is disrupted in Parkinson's disease with visual hallucinations.

BACKGROUND: Visual hallucinations (VH) are one of the most striking nonmotor symptoms in Parkinson's disease (PD), and predict dementia and mortality. Aberrant default mode network (DMN) is associated with other psychoses. Here, we tested the hypothesis that DMN dysfunction contributes to VH in PD. METHODS: Resting state functional data was acquired from individuals with PD with VH (PDVH) and without VH (PDnonVH), matched for levodopa drug equivalent dose, and a healthy control group (HC). Independent component analysis was used to investigate group differences in functional connectivity within the DMN. In addition, we investigated whether the functional changes associated with hallucinations were accompanied by differences in cortical thickness. RESULTS: There were no group differences in cortical thickness but functional coactivation within components of the DMN was significantly lower in both PDVH and PDnonVH groups compared to HC. Functional coactivation within the DMN was found to be greater in PDVH group relative to PDnonVH group. CONCLUSION: Our study demonstrates, for the first time that, within a functionally abnormal DMN in PD, relatively higher "connectivity" is associated with VH. We postulate that aberrant connectivity in a large scale network affects sensory information processing and perception, and contributes to "positive" symptom generation in PD.Contract grant sponsor: Research Grant Council of Hong Kong (General Research Fund awarded to Chua and McAlonan); Infrastructural support: National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and [Institute of Psychiatry] King's College London (McAlonan); Wellcome Trust; Contract grant number: 088324 (Rowe); National Institute for Health Research Cambridge Biomedical Research Centre (Suckling).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/hbm.2257

Clinical associations and prognostic value of MRI-visible perivascular spaces in patients with ischemic stroke or TIA: a pooled analysis

BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH

Advanced magnetic resonance imaging techniques in the diagnosis of Alzheimer's disease (AD), and evaluation of AD pathogenesis in an aging brain

Background: The impact of Alzheimer’s disease (AD) on society’s resources and manpower has been forecasted for more than a decade, and recent statistics across the globe reveal that it is forthcoming. Pioneering work since 1980s confirmed the pathological hallmarks of the disease, such as neuritic plaques, neurofibrillary tangles, amyloid-β peptides, and microtubule-associated tau proteins. There are many gaps in the full appraisal of this complex disease, which possibly begins early in life in susceptible individuals and present at different severity and speed. In current thesis, advanced magnetic resonance imaging (MRI) techniques were evaluated for their efficacy in diagnosis, and in exploring AD pathogenesis. Methods: In MRI volumetry/perfusion and diffusion studies, 20 and 18 AD subjects (different cohorts) were recruited respectively from the memory clinic of a University hospital, while 20 and 18 cognitively normal older adults (CN) were recruited respectively from elderly centers, community and university volunteers, as well as 17 young adults in the diffusion study. In MR Spectroscopy (MRS), 30 healthy volunteers of 3 different age ranges (20-39, 40-59, 60-89) were recruited. All studies were performed using a 3-tesla MRI scanner. For MRI volumetry, a standardized T1-weighted 3D volumetric Fast Field Echo sequence, and for pulsatile Arterial Spin Labeling (ASL), a Look-Locker-based echo-planar imaging sequence was employed. Single-shot echo-planar diffusion weighted imaging was used to examine white matter (WM) integrity; diffusion sensitizing gradients (b = 800 s/mm2) applied in 16 directions, and one additional image without diffusion gradient (b0 = 0 s/mm2). Single voxel MRS was performed in the limbic regions, with point resolved spectroscopy for volume selection and excitation for water suppression. Results: Voxel Based Morphometry with Diffeomorphic Anatomical Registration using Exponentiated Lie algebra and standard registration has similarly high efficacies as manual hippocampal volumetry in discriminating AD from CN. Using pulsatile ASL, we found impairment of hemodynamic parameters other than cerebral blood flow (CBF) in moderate AD, indicative of underlying vascular abnormality. Combined MR hippocampal volumetry and ASL CBF was superior to single measure in AD diagnosis. Using diffusion tensor imaging (DTI) techniques, parallel evidence of anterior WM disintegrity in normal elderly, and more extensively in the AD was found. AD showed further loss of WM integrity in the posterior brain regions, and such WM disintegrity may result from demyelination. In aging, we found increased choline and creatine, and N-acetyl-aspartate in cingulate gyri, which might suggest glial proliferation and neuronal hypertrophy respectively. Discussion: A ‘one-stop-shop’ study combining structural and perfusion MRI has improved efficacy in discriminating AD from CN. DTI showed possible WM retrogenesis in normal aging and AD, although ischemic effect on WM cannot be ruled out. Our MRS study highlighted metabolic changes with age, which could be compensatory to an increased energy demand coupled with a lower CBF. Neuroimaging is likely to have a great impact on early diagnosis of AD, which will benefit patient care, prognostication and future therapy. Hopefully, insights into the physiology of normal aging and pathophysiology of AD derived from neuroimaging can guide future basic science and clinical research.published_or_final_versionDiagnostic RadiologyMasterDoctor of Medicin

The Use of Diffusion Kurtosis Imaging for the Differential Diagnosis of Alzheimer’s Disease Spectrum

Structural and diffusion kurtosis imaging (DKI) can be used to assess hippocampal macrostructural and microstructural alterations respectively, in Alzheimer’s disease (AD) spectrum, spanning from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) and AD. In this study, we explored the diagnostic performance of structural imaging and DKI of the hippocampus in the AD spectrum. Eleven SCD, thirty-seven MCI, sixteen AD, and nineteen age- and sex-matched normal controls (NCs) were included. Bilateral hippocampal volume, mean diffusivity (MD), and mean kurtosis (MK) were obtained. We detected that in AD vs. NCs, the right hippocampal volume showed the most prominent AUC value (AUC = 0.977); in MCI vs. NCs, the right hippocampal MD was the most sensitive discriminator (AUC = 0.819); in SCD vs. NCs, the left hippocampal MK was the most sensitive biomarker (AUC = 0.775). These findings suggest that, in the predementia stage (SCD and MCI), hippocampal microstructural changes are predominant, and the best discriminators are microstructural measurements (left hippocampal MK for SCD and right hippocampal MD for MCI); while in the dementia stage (AD), hippocampal macrostructural alterations are superior, and the best indicator is the macrostructural index (right hippocampal volume)

Differential brainstem atrophy patterns in multiple sclerosis and neuromyelitis optica spectrum disorders

Background: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are central nervous system (CNS) inflammatory demyelinating disorders. It is clinically important to distinguish MS from NMOSD, as treatment and prognosis differ. Brainstem involvement is common in both disorders. Purpose: To investigate whether the patterns of brainstem atrophy on volumetric analysis in MS and NMOSD were different and correlated with clinical disability. Study Type: Case–control cross-sectional study. Subjects: In all, 17 MS, 13 NMOSD, and 18 healthy control (HC) subjects were studied. Field Strength/Sequence: T1-weighted and T2w spin-echo images were acquired with a 3T scanner. Assessment: Semiautomated segmentation and volumetric measurement of brainstem regions were performed. Anatomical information was obtained from whole brain T1w images using a 3D magnetization-prepared rapid gradient-echo (MPRAGE) imaging sequence (TR/TE/T: 7.0/3.2/800 msec, voxel size: 1 × 1 × 1 mm3, scan time: 10 min 41 sec). Statistical Tests: Independent samples t-test, Mann–Whitney U-test, partial correlation, and multiple regression analysis. Results: Baseline characteristics were similar across the three groups, without significant difference in disease duration (P = 0.354) and EDSS score (P = 0.159) between MS and NMOSD subjects. Compared to HC, MS subjects had significantly smaller normalized whole brainstem (−5.2%, P = 0.027), midbrain (−8.3%, P = 0.0001), and pons volumes (−5.9%, P = 0.048), while only the normalized medulla volume was significantly smaller in NMOSD subjects compared to HC (−8.5% vs. HC, P = 0.024). Normalized midbrain volume was significantly smaller in MS compared to NMOSD subjects (−5.0%, P = 0.014), whereas normalized medulla volume was significantly smaller in NMOSD compared to MS subjects (−8.1%, P = 0.032). Partial correlations and multiple regression analysis revealed that smaller normalized whole brainstem, pons, and medulla oblongata volumes were associated with greater disability on the Expanded Disability Status Scale (EDSS), Functional System Score (FSS)-brainstem and FSS-cerebellar in NMOSD subjects. Data Conclusion: Differential patterns of brainstem atrophy were observed, with the midbrain being most severely affected followed by pons in MS, whereas only the medulla oblongata was affected in NMOSD. Level of Evidence: 2. Technical Efficacy: Stage 3. J. Magn. Reson. Imaging 2018;47:1601–1609

Multimodal MRI of the hippocampus in Parkinson's disease with visual hallucinations

Visual hallucinations carry poor prognosis in Parkinson’s disease. Here we tested the hypothesis that the hippocampus and visuospatial memory impairment play a central role in the pathology of PD with visual hallucinations. Multimodal magnetic resonance imaging of the brain was carried out in 12 people with PD and visual hallucinations; 15 PD individuals without hallucinations; and 14 healthy controls. Age, gender, cognitive ability, and education level were matched across the three groups. PD patients were taking dopaminergic medication. Hippocampal volume, shape, mean diffusivity (MD), and functional connectivity within the whole brain were examined. Visuospatial memory was compared between groups, and correlations with hippocampal MD, functional connectivity, and the severity of hallucinations were explored. There were no macrostructural differences across groups, but individuals with hallucinations had higher diffusivity in posterior hippocampus than the other two groups. Visuospatial memory was poorer in both PD groups compared to controls, and was correlated with hallucinations. Finally, hippocampal functional connectivity in the visual cortices was lower in those with hallucinations than other groups, and this correlated with visuospatial memory impairment. In contrast, functional connectivity between the hippocampus and default mode network regions and frontal regions was greater in the PD hallucinators compared to other groups. We suggest that hippocampal pathology, which disrupts visuospatial memory, makes a key contribution to visual hallucinations in PD. These findings may pave the way for future studies of imaging biomarkers to measure treatment response in those with PD who are most at risk of poor outcomes.link_to_OA_fulltex