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Objective Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the clinical impact of amyloid PET imaging is still under investigation. The aim of this study was to evaluate the diagnostic impact and clinical utility in patient management of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer’s disease (AD). We also aimed to determine the cutoffs for amyloid positivity for quantitative measures by investigating the agreement between quantitative and visual assessments. Methods Ninety-nine patients suspected of having AD underwent 18F-florbetapir PET at five institutions. Site-specialized physicians provided a diagnosis of AD or non-AD with a percentage estimate of their confidence and their plan for patient management in terms of medication, prescription dosage, additional diagnostic tests, and care planning both before and after receiving the amyloid imaging results. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by four board-certified nuclear medicine physicians. The PET images were also quantitatively analyzed using the standardized uptake value ratio (SUVR) and Centiloid (CL) scale. Results Visual interpretation obtained 48 positive and 51 negative PET scans. The amyloid PET results changed the AD and non-AD diagnosis in 39 of 99 patients (39.3%). The change rates of 26 of the 54 patients (48.1%) with a pre-scan AD diagnosis were significantly higher than those of 13 of the 45 patients with a pre-scan non-AD diagnosis (χ2 = 5.334, p = 0.0209). Amyloid PET results also resulted in at least one change to the patient management plan in 42 patients (42%), mainly medication (20 patients, 20%) and care planning (25 patients, 25%). Receiver-operating characteristic analysis determined the best agreement of the quantitative assessments and visual interpretation of PET scans to have an area under the curve of 0.993 at an SUVR of 1.19 and CL of 25.9. Conclusion Amyloid PET using 18F-florbetapir PET had a substantial clinical impact on AD and non-AD diagnosis and on patient management by enhancing diagnostic confidence. In addition, the quantitative measures may improve the visual interpretation of amyloid positivity.

Background/Aims: Depression and cognitive decline are reported to be interrelated. Depression of older adults with memory complaints who seek medical help have not been well documented. This study was carried out to test the hypothesis that a relatively high level of depressive symptoms associated with brain structure is characteristic of people who visited a memory clinic unaccompanied (UA). Method: We retrospectively compared Center for Epidemiologic Studies Depression Scale (CES-D, for evaluation of depressive symptoms) scores of UA subjects (n = 21) with those of people who were accompanied (n = 75). Within each groups, we further examined the association between brain morphology and the CES-D scores using FreeSurfer software. Results: We found that the relatively high CES-D scores of UA subjects were inversely associated with the normalized volumes of bilateral superior temporal gyrus (STG). Conclusion: Our results suggest that depressive symptoms of UA subjects demonstrated by the relatively high levels of CES-D scores were primary, because of the inverse association with the normalized volume of bilateral STG. Thus, focusing on the depressive symptoms may be a suitable approach to satisfy potential medical needs of UA subjects with or without memory impairment.

Tauopathies differ in terms of the brain regions that are affected. In Alzheimer's disease, basal forebrain and hippocampus are mainly involved, while frontotemporal lobar degeneration affects the frontal and temporal lobes and subcortical nuclei including striatum. Over 90% of human cases of tauopathies are sporadic, although the majority of established tau-transgenic mice have had mutations. This prompted us to establish transgenic mice expressing wild-type human tau (Tg601). Old (>14 months old) Tg601 mice displayed decreased anxiety in the elevated plus maze test and impaired place learning in the Morris water maze test. Immunoblotting of brain tissue identified that soluble tau multimer was increased with aging even though insoluble tau was not observed. In the striatum of old Tg601, the level of AT8- or AT180-positive tau was decreased compared with that of other regions, while PHF-1-positive tau levels remained equal. Phosphorylated tau-positive axonal dilations were present mainly in layers V and VI of the prefrontal cortex. Loss of synaptic dendritic spine and decreased immunohistochemical level of synaptic markers were observed in the nucleus accumbens. In vivo 2-[(18)F]fluoro-2-deoxy-d-glucose positron emission tomography analysis also showed decreased activity exclusively in the nucleus accumbens of living Tg601 mice. In Tg601 mice, the axonal transport defect in the prefrontal cortex-nucleus accumbens pathway may lead to decreased anxiety behavior. Differential distribution of hyperphosphorylated tau may cause region-specific neurodegeneration.

The mechanisms that render tau a toxic agent are still unclear, although increasing evidence supports the assertion that alterations of tau can directly cause neuronal degeneration. In addition, it is unclear whether neurodegeneration in various tauopathies occurs via a common mechanism or that specific differences exist. The aim of this review is to provide an overview of tauopathies from bench to bedside. The review begins with clinicopathological findings of familial and sporadic tauopathies. It includes a discussion of the similarities and differences between these two conditions. The second part concentrates on biochemical alterations of tau such as phosphorylation, truncation and acetylation. Although pathological phosphorylation of tau has been studied for many years, recently researchers have focused on the physiological role of tau during development. Finally, the review contains a summary of the significance of tauopathy model mice for research on neurofibrillary tangles, axonopathies, and synaptic alteration.

Sirs, Posterior cortical atrophy (PCA) is a presenile dementia that presents primarily with signs and symptoms of cortical visual dysfunction [1]. The most common associated pathologic findings of PCA are amyloid plaques and neurofibrillary tangles predominantly affecting the visual association areas [8]. Although [C] Pittsburgh compound B (PIB) PET studies of amnestic Alzheimer’s disease (AD) have been conducted [2, 3, 5], the link between amyloid-b (Ab) and regional brain dysfunction remains controversial. However, two PIB studies of PCA supported the possible link between Ab deposition and clinical features [7, 10]. Here, we describe a patient with PCA who showed left homonymous hemianopsia and uncoupling between PIB uptake and glucose metabolism in the right occipital lobe. A 63-year-old woman consulted our hospital with a 5-year history of poor vision. She first noticed that characters on posters appeared to be shaking. One year later, she found difficulty in reading subtitles in movies and then she became unable to read books. On neurological examination, she showed left homonymous hemianopsia. A Goldmann dynamic visual field examination demonstrated macular-sparing left homonymous hemianopsia. Visual acuity was normal and bilateral light reflexes were prompt. Other neurological examinations were normal. On neuropsychological evaluations, she showed visuospatial dysfunction and dyscalculia. MMSE score was 26 of 30. Memory function was preserved. She demonstrated disturbed recognition of superimposed figures. Face and color recognition were normal. Cerebrospinal fluid (CSF) Ab42 was decreased (297 pg/ ml) and in normal controls, the levels are 874 ± 293 pg/ml (mean ± SD, INNOTEST b-AMYLOID(1-42), Innogenetics, Ghent, Belgium). CSF tau protein phosphorylated at serine 199 was increased (1.36 pM). In normal controls, these levels are 0.6 ± 0.4 pM [4]. [F] fluorodeoxyglucose (FDG) PET image was acquired for 6 min starting 45 min after the injection of 150 MBq of tracer. The accumulation of [C] PIB was evaluated by a standardized uptake value ratio (SUVR) on a summing image obtained 40–60 min after injection of 500 MBq of tracer taking the cerebellar cortex as a reference region. [F] FDG PET showed hypometabolism in the temporo-parieto-occipital lobe predominantly on the right (Fig. 1d–f). [C] PIB PET demonstrated increased uptake in the bilateral frontal lobes and parietal and occipital cortices with more intense uptake on the right (Fig. 1g–i). In the right occipital lobe, FDG uptake showed lower metabolism in the lateral occipital cortex (Fig. 1d, e, arrow) than in the calcarine cortex (Fig. 1d, e, arrowhead). In contrast, amyloid imaging demonstrated high PIB uptake in the right calcarine cortex (Fig. 1g, h, arrowhhead) while the adjacent lateral occipital cortex showed normal PIB uptake (Fig. 1g, h, arrow). It was shown that macular sparing occurred when the posterior part of the calcarine cortex was spared in patients with striate cortical disease such as infarction, neoplasm and cerebromalacia, while macular splitting occurred when the occipital pole and operculum were involved [6]. Neuroimaging studies of our patient demonstrated that in the occipital lobe, there were two regions showing different T. Kambe Y. Motoi (&) N. Hattori Department of Neurology, Juntendo University School of Medicine, 2-1-1, Hongo Bunkyo-ku, Tokyo 113-8421, Japan e-mail: motoi@juntendo.ac.jp

We report a 78-year-old woman with rheumatoid arthritis who developed recurrent embolic cerebellar strokes associated with vertical atlantoaxial subluxation (AAS). On contrast angiography, the bilateral vertebral arteries (VAs) were occluded between the C1 and C2 levels, and the distal parts of bilateral VA were supplied by the collateral circulations. Dynamic cerebral angiography and carotid duplex ultrasonography showed that blood flow was substantially decreased in the left VA and left posterior inferior cerebellar artery on cervical anteflexion. It is suggested that vertical AAS reduced the blood flow of collateral circulation in the left VA with cervical anteflexion and might be a cause of recurrent ischemic stroke.

Late neurosyphilis tends to affect the brain and spinal cord parenchyma, typically presenting as dementia, tabes dorsalis, general paresis, sensory ataxia, or bowel/ bladder dysfunction. We present a case of neurosyphilis with manifestations of vivid visual hallucinations as the initial symptom. Only later did the patient develop agitation, auditory hallucinations, and monopolizing conversation. In patients with neurosyphilis, auditory hallucinations are common, but visual hallucinations have rarely been reported.

Background Posterior reversible encephalopathy syndrome (PRES) is a transient clinical and neuroradiologic syndrome caused by cerebral vasogenic edema. Various reversible neurologic symptoms were shown in patients with PRES. Freezing of gait (FOG) is mainly observed in neurodegenerative diseases. Case presentation We report a 43-year-old man, with undergoing hemodialysis therapy for chronic renal failure, had mild elevation of blood pressure. His consciousness level suddenly deteriorated, and brain MRI demonstrated hyperintense lesions in the bilateral basal ganglia on fluid-attenuated inversion recovery images, diffusion-weighted images, and apparent diffusion coefficient maps. After improvement of disturbance of consciousness, he showed FOG accompanied by bradykinesia and postural instability. His FOG spontaneously improved concurrently with alleviation of basal ganglionic lesions on follow-up MRI. Conclusions It is suggested that vasogenic edema on bilateral basal ganglia associated with PRES can cause acute transient FOG.