Introduction The molecular mechanism of neurodegeneration, including tau and neurite complexity, is an important topic in Alzheimer's disease (AD) research. Methods We recruited 27 amyloid‐positive individuals identified through 11 C‐Pittsburgh compound B (PiB) positron emission tomography (PET) and 31 amyloid‐negative individuals with normal cognition. All participants underwent 11 C‐PiB and 18 F‐THK5351 PET and magnetic resonance imaging (MRI) with neurite orientation dispersion and density imaging (NODDI) protocol. The neurite density index (NDI), orientation dispersion index (ODI), and PET images were analyzed to calculate voxel‐wise correlations among the imaging modalities and correlations with cognitions. Results In the amyloid‐positive participants, there were significant negative correlations between 18 F‐THK5351 and NDI and between 18 F‐THK5351 and ODI. The bilateral mesial and lateral temporal lobes were mainly involved. Regarding cognition, 18 F‐THK5351 showed more marked associations with all cognitive domains than the other modalities. Discussion Tau and neuroinflammation in AD may reduce the neurite density and orientation dispersion, particularly in the mesial and lateral temporal lobes.

IntroductionAlzheimer's disease (AD) is characterized by accumulation of extracellular amyloid‐β and intracellular tau neurofibrillary tangles. The recent advent of tau positron emission tomography (PET) has enabled in vivo assessment of tau pathology. The aim of this study was to explore whether tau deposition influences the structural connectivity in amyloid‐negative and amyloid‐positive groups, and further explore the difference between the groups.MethodsWe investigated 18 patients with amnestic mild cognitive impairment/mild AD (AD‐spectrum group) and 35 cognitively normal older adults (CN group) using diffusion MRI, amyloid, and tau PET imaging. Diffusion connectometry was performed to identify white matter pathways correlated with each of the six variables of tau deposition in the bilateral hippocampi, temporal lobes, posterior and anterior cingulate cortices, precunei, orbitofrontal lobes, and entire cerebrum.ResultsThe CN group showed increased connectivity along with an increased tau deposition in the bilateral hippocampi, temporal lobes, and entire cerebrum, whereas the AD‐spectrum group showed decreased connectivity in the bilateral hippocampi, temporal lobes, anterior and posterior cingulate cortices, precunei, and entire cerebrum.ConclusionThese findings suggest that tau deposition in the CN group seems to induce a compensatory response against early neuronal injury or chronic inflammation associated with normal aging, whereas the coexistence of amyloid and tau in the AD‐spectrum group seems to outweigh the compensatory response leading to decreased connectivity, suggesting that amyloid plays a crucial role in alternating structural connectivity.

Background Diffusional kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) metrics provide more specific information regarding pathological changes than diffusion tensor imaging (DTI). Purpose To detect microstructural abnormalities in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS) patients by using DKI and NODDI metrics. Study Type Prospective. Population Twenty ME/CFS patients and 23 healthy controls were recruited. Field Strength/Sequence Three‐b value DWI (b‐values = 0, 1000, and 2000 sec/mm2) and 3D T1‐weighted images were at 3.0T. Assessment Mean kurtosis (MK), neurite density index (NDI), orientation dispersion index (ODI), fractional anisotropy (FA), and mean diffusivity (MD) were calculated. Statistical Testing The two‐sample t‐test analysis in SPM12 software was used to compare the differences between ME/CFS and control groups. Results In the ME/CFS patients, we observed significant FA decreases in the genu of the corpus callosum and the anterior limb of the right internal capsule (P < 0.05), but no significant difference in MD (P = 0.164); there were also significant MK decreases in the right frontal area, anterior cingulate gyrus, superior longitudinal fasciculus (SLF), and left parietal area (P < 0.05). Significant NDI decreases were observed in the right posterior cingulate gyrus, SLF, and left frontal area of the ME/CFS patients (P < 0.05). Significant ODI decreases were seen in the bilateral occipital areas, right superior temporal gyrus, the anterior limb of internal capsule, and the posterior cingulate gyrus (P < 0.05), and significant ODI increases were revealed in the bilateral occipital and right temporal areas (P < 0.05). Data Conclusion Right SLF abnormalities may be a diagnostic marker for ME/CFS. Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:818–824.

No abstract

Background: In clinical practice, equivocal findings are inevitable in visual interpretation of whether amyloid positron emission tomography (PET) is positive or negative. It is therefore necessary to establish a more objective quantitative evaluation method for determining the indication for disease-modifying drugs currently under development.Aims: We aimed to determine cutoffs for positivity in quantitative analysis of 18F-flutemetamol PET in patients with cognitive impairment and suspected Alzheimer's disease (AD). We also evaluated the clinical efficacy of amyloid PET in the diagnosis of AD. This study was registered in the Japan Registry of Clinical Trials (jRCTs, 031180321).Methods: Ninety-three patients suspected of having AD underwent 18F-flutemetamol PET in seven institutions. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by two board-certified nuclear medicine physicians. If the two readers obtained different interpretations, the visual rating was rerun until they reached consensus. The PET images were quantitatively analyzed using the standardized uptake value ratio (SUVR) and standardized Centiloid (CL) scale with the whole cerebellum as a reference area.Results: Visual interpretation obtained 61 positive and 32 negative PET scans. Receiver operating characteristic analysis determined the best agreement of quantitative assessments and visual interpretation of PET scans to have an area under curve of 0.982 at an SUVR of 1.13 and a CL of 16. Using these cutoff values, there was high agreement between the two approaches (kappa = 0.88). Five discordant cases had SUVR and CL values ranging from 1.00 to 1.22 and from 1 to 26, respectively. In these discordant cases, either diffuse or mildly focal elevation of cortical activity confused visual interpretation. The amyloid PET outcome significantly altered the diagnosis of AD (χ2 = 51.3, p &lt; 0.0001). PET imaging elevated the proportions of the very high likelihood category from 20.4 to 46.2% and the very low likelihood category from 0 to 22.6%.Conclusion: Quantitative analysis of amyloid PET using 18F-flutemetamol can objectively evaluate amyloid positivity using the determined cutoffs for SUVR and CL. Moreover, amyloid PET may have added value over the standard diagnostic workup in dementia patients with cognitive impairment and suspected AD.

No abstract

In multiple system atrophy with predominant parkinsonism (MSA-P), several voxel-based morphometry (VBM) studies have revealed gray matter loss; however, the white matter volume changes have been rarely reported. We investigated the volume changes of white matter as well as gray matter by VBM. A retrospective MRI study was performed in 20 patients with MSA-P and 30 age-matched healthy controls. We applied VBM with statistical parametric mapping (SPM8) plus diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) to explore the regional atrophy of gray and white matter in all of the MSA-P patients, 14 patients with left-side dominant and 6 patients with right-side dominant onset as compared to controls. In all of the MSA-P patients, VBM revealed a significant volume reduction of gray matter in the bilateral putamina, cerebellums and dorsal midbrain. White matter loss was located in bilateral globus pallidi, external capsules extending to the midbrain, right subcortical to precentral area through internal capsule, the pons, bilateral middle cerebellar peduncles and left cerebellum. In left-side dominant MSA-P patients, the gray and white matter volume loss was detected predominantly on the right side and vice versa in right-side dominant MSA-P patients. A correlation with disease duration and severity was not detected. VBM using SPM8 plus DARTEL detected significant volume loss not only in the gray but also in the white matter of the area affected by MSA-P.

The recent advent of tau-specific positron emission tomography (PET) has enabled in vivo assessment of tau pathology in Alzheimer’s disease (AD). However, because PET scanners have limited spatial resolution, the measured signals of small brain structures or atrophied areas are underestimated by partial volume effects (PVEs). The aim of this study was to determine whether partial volume correction (PVC) improves the precision of measures of tau deposits in early AD. We investigated tau deposits in 18 patients with amyloid-positive early AD and in 36 amyloid-negative healthy controls using 18F-THK5351 PET. For PVC, we applied the SPM toolbox PETPVE12. The PET images were then spatially normalized and subjected to voxel-based group analysis using SPM12 for comparison between the early AD patients and healthy controls. We also compared these two groups in terms of brain atrophy using voxel-based morphometry of MRI. We found widespread neocortical tracer retention predominantly in the posterior cingulate and precuneus areas, but also in the inferior temporal lobes, inferior parietal lobes, frontal lobes, and occipital lobes in the AD patients compared with the controls. The pattern of tracer retention was similar between before and after PVC, suggesting that PVC had little effect on the precision of tau load measures. Gray matter atrophy was detected in the medial/lateral temporal lobes and basal frontal lobes in the AD patients. Interestingly, only a few associations were found between atrophy and tau deposits, even after PVC. In conclusion, PVC did not significantly affect 18F-THK5351 PET measures of tau deposits. This discrepancy between tau deposits and atrophy suggests that tau load precedes atrophy.