Magnetic Resonance Imaging Atrophy Research Articles

Imaging Approaches in Dementia: A Retrospective Cohort Study of Cross-sectional Imaging in the Indian Population

Introduction: Dementia is a broad medical term that describes the progressive cognitive decline of brain function due to disease or impairment, resulting in interference with daily activities. Magnetic Resonance Imaging (MRI) is commonly used for the clinical diagnosis of dementia by identifying cerebral atrophy and structural alterations. Furthermore, Magnetic Resonance Spectroscopy (MRS) can detect biochemical abnormalities in dementia patients, which may be beneficial for early diagnosis and treatment. Aim: To provide a comprehensive protocol and a guidance tool for radiologists to effectively diagnose dementia and its subtypes {Alzheimer’s Disease (AD), frontotemporal lobe dementia, etc.} based on radiological findings coupled with volumetry, spectroscopy, and Arterial Spin Labelling (ASL) findings. Materials and Methods: A retrospective observational study was conducted in the Department of Radiology, Nanavati Max Superspeciality Hospital, Mumbai, Maharashtra, India, between June 2022 and June 2023. A total of 125 patients were analysed to observe the correlation between whole brain volume, Intracranial Volume (ICV) of different cortical regions, hippocampal atrophy, and MRS findings. Descriptive statistics were used, and results were expressed as means and standard deviations for continuous variables, and as frequencies and percentages for categorical variables. Results: Out of 125 patients, 71 (56.8%) were males, and 54 (43.2%) were females, with ages ranging from 41 to 96 years. The majority presented with Mild Cognitive Impairment (MCI) 36 patients (28.8%) and Vascular Dementia (VaD) (18 patients - 14.4%). Some clinical features and imaging findings overlapped, resulting in some cases being a combination of different types of dementia. MRI, MRS, and Medial Temporal Atrophy (MTA) played a crucial role in allowing clinicians to perform a differential diagnosis. Conclusion: The use of MR volumetry and spectroscopy aids in classifying the type of dementia, which, in turn, gives treating clinicians a better perspective for further treatment and its outcomes.

A Rare Cause of Paroxysmal Movement Disorder Associated with TBC1D24 Gene Mutation in Two Siblings.

A Rare Cause of Paroxysmal Movement Disorder Associated with TBC1D24 Gene Mutation in Two Siblings.

Prosopagnosia, Other Specific Cognitive Deficits, and Behavioral Symptoms: Comparison between Right Temporal and Behavioral Variant of Frontotemporal Dementia.

Right temporal variant of frontotemporal dementia (rtv-FTD) represents an uncommon and recently described frontotemporal dementia (FTD) entity presenting with symptoms in many ways comparable to those of the frontal or behavioral variant of FTD (bv-FTD). The aims of this study were to explore the timing of cognitive and behavioral symptoms of rtv-FTD, and to compare the distinct cognitive deficits including prosopagnosia and behavioral symptoms of rtv-FTD patients with those observed in bv-FTD patients. We reviewed the records of 105 patients clinically diagnosed with FTD. A total of 7 patients (5 men/2 women) with FTD and marked right temporal atrophy in magnetic resonance imaging (MRI) were detected. Clinical features were compared with those observed in a group of 22 age-matched patients (16 men/6 women) with FTD and predominant frontal lobe atrophy. The main presenting symptoms of rtv-FTD were prosopagnosia, apathy, and episodic memory impairment. In contrast, social awkwardness and compulsive behaviors were dominant in later stages of the disease together with disinhibition and loss of insight with a marked personality change. Although the cognitive and behavioral profiles of patients with right temporal or frontal lobes atrophy present substantial similarities, each subtype has a number of distinct characteristics. It appears that prosopagnosia, obsessive behaviors, and psychotic symptoms are more prominent in rtv-FTD patients.

Divergent magnetic resonance imaging atrophy patterns in Alzheimer’s disease and primary age‐related tauopathy

AbstractBackgroundPrimary age‐related tauopathy (PART) is a pathological disorder characterized by the presence of tau‐positive neurofibrillary tangles (NFTs) and no amyloid‐beta (Aβ) deposition (“definite PART”). Currently, the diagnosis of PART is histologically assessed by the presence of tau positive NFT with Braak staging and a Consortium to Establish a Registry for Alzheimer’s disease (CERAD) Aβ stage of 0.MethodOur study compared brain magnetic resonance imaging (MRI) with neuropathological findings in patients with PART and AD, while assessing the relationship between brain atrophy and clinical impairment. We analysed 233 participants: 32 with no plaques (“definite” PART ‐ CERAD 0), and 201 cases within the AD spectrum, with 25 with sparse (CERAD 1), 76 with moderate (CERAD 2) and 100 with severe (CERAD 3) degree of neuritic plaques.ResultUpon correcting for age, sex and age difference at MRI and death, there were significantly higher levels of atrophy in CERAD 3 compared to CERAD 1‐2 and a trend compared to CERAD 0. In the anterior temporal region, there was a trend for higher levels of atrophy in CERAD 0 compared to CERAD 1. We then assessed the correlation between regional brain atrophy and CDR‐sum‐of‐boxes score for PART and AD, and found that overall cognition deficits are directly correlated with regional atrophy in the AD continuum, but not in definite PART. We further observed correlation between regional brain atrophy with multiple neuropsychological metrics in AD, while PART showed only specific correlations between language deficits and anterior temporal atrophy.ConclusionOverall, these findings support PART as an independent pathologic process from AD.

Divergent magnetic resonance imaging atrophy patterns in Alzheimer's disease and primary age-related tauopathy

Our study compared brain MRI with neuropathological findings in patients with primary age-related tauopathy (PART) and Alzheimer's disease (AD), while assessing the relationship between brain atrophy and clinical impairment. We analyzed 233 participants: 32 with no plaques (“definite” PART—BRAAK stage higher than 0 and CERAD 0), and 201 cases within the AD spectrum, with 25 with sparse (CERAD 1), 76 with moderate (CERAD 2), and 100 with severe (CERAD 3) degrees of neuritic plaques. Upon correcting for age, sex, and age difference at MRI and death, there were significantly higher levels of atrophy in CERAD 3 compared to CERAD 1–2 and a trend compared to PART (p = 0.06). In the anterior temporal region, there was a trend for higher levels of atrophy in PART compared to Alzheimer's disease spectrum cases with CERAD 1 (p = 0.08). We then assessed the correlation between regional brain atrophy and CDR sum of boxes score for PART and AD, and found that overall cognition deficits are directly correlated with regional atrophy in the AD continuum, but not in definite PART. We further observed correlations between regional brain atrophy with multiple neuropsychological metrics in AD, with PART showing specific correlations between language deficits and anterior temporal atrophy. Overall, these findings support PART as an independent pathologic process from AD.

An Automated Toolbox to Predict Single Subject Atrophy in Presymptomatic Granulin Mutation Carriers.

Magnetic resonance imaging (MRI) measures may be used as outcome markers in frontotemporal dementia (FTD). To predict MRI cortical thickness (CT) at follow-up at the single subject level, using brain MRI acquired at baseline in preclinical FTD. 84 presymptomatic subjects carrying Granulin mutations underwent MRI scans at baseline and at follow-up (31.2±16.5 months). Multivariate nonlinear mixed-effects model was used for estimating individualized CT at follow-up based on baseline MRI data. The automated user-friendly preGRN-MRI script was coded. Prediction accuracy was high for each considered brain region (i.e., prefrontal region, real CT at follow-up versus predicted CT at follow-up, mean error ≤1.87%). The sample size required to detect a reduction in decline in a 1-year clinical trial was equal to 52 subjects (power = 0.80, alpha = 0.05). The preGRN-MRI tool, using baseline MRI measures, was able to predict the expected MRI atrophy at follow-up in presymptomatic subjects carrying GRN mutations with good performances. This tool could be useful in clinical trials, where deviation of CT from the predicted model may be considered an effect of the intervention itself.

Evaluation of the relationship between retinal nerve layer thickness and corpus callosum atrophy in MRI with memory impairment in patients with multiple sclerosis.

ABSTRACTIntroduction:Multiple sclerosis (MS) is a chronic neurological disease in which demyelination and loss of axons lead to disruption of communication between neurons in the central nervous system. Cognitive impairment occurs in a significant proportion of patients with MS. Therefore, the aim of this study was to investigate the relationship between retinal nerve fiber layer (RNFL) thickness and corpus callosum atrophy in magnetic resonance imaging with memory disorders in patients with MS.Methods:This descriptive analytical study was performed on patients with a diagnosis of relapsing–remitting multiple sclerosis referred to the clinic of Ali Ibn Abi Talib Hospital in Zahedan, Iran. An information form that includes a Mini–Mental State Examination was first prepared, by which the patient’s memory impairment is measured. After recording the data, the data were collected using an information form and finally analyzed by SPSS software version 22 using an independent t-test.Results:In this study, 80 patients with MS primary progressive multiple sclerosis were included in the study, of which 53 were female and 27 were male. The mean age of patients was 45.1 ± 5.9 years, which did not show a statistically significant difference (P = 0.536). The mean RNFL thickness in patients with memory impairment was significantly lower than that in patients without memory impairment. The mean corpus callosum thickness was found to be significantly lower in patients with memory impairment than in patients without memory impairment.Conclusion:All in all, the results of this study showed that the thickness of RNFL and the corpus callosum in patients with memory impairment was significantly lower than that in patients without memory impairment.

Pasien Spinocerebellar Ataxia 3 (SCA3) dengan neuropati perifer di Indonesia : laporan kasus

Abstract Rationale: Spinocerebellar ataxia (SCA) 3, also known as Machado-Joseph Disease (MJD), is a neurodegenerative disease which involves cerebellum and its afferent and efferent pathways. Generally, the initial symptoms were gait disturbance, double vision, dysarthria, and vertigo.Patient concerns: a 43-year-old male, with known SCA3, presented hereditary ataxia had mild numbness in his both palms since two years ago. Sensory examination found no abnormality. Nerve Conduction Studies (NCS) showed severe axonal demyelinating sensorimotor peripheral neuropathy. In magnetic resonance imaging atrophy cerebellum with cerebral multiple lacunar infarction were seen. Diagnoses: SCA3 was diagnosed on the basis of clinical features, family pedigree, physical examination, electrophysiology study, neuroimaging, nerve biopsy, and genetic testing results. The electrophysiological manifestations revealed profound axonal demyelinating lesion in peripheral nerves. Genetic analysis was not done yet due to lack of availability of genetic testing in our country at this moment although it is the gold standard for diagnosis.Lessons: SCA3 with peripheral neuropathy represents a specific clinical entity that so far has never been described previously in Indonesia.Abbreviations: SCA3 = Spinocerebellar ataxia, MJD = Machado-Joseph Disease, NCS = Nerve Conduction Studies

Striatal Atrophy and Hypometabolism in Drug-Resistant Non-Ketotic Hyperglycemic Chorea-Ballism.

Non-ketotic hyperglycemic chorea-ballism (NKHCB) is a rare movement disorder associated with poorly controlled type-2 diabetes,1 in the majority of cases characterized by: unilateral hemicorea-hemiballism, contralateral striatum hyperintensity on T1-weighted magnetic resonance imaging (MRI), and clinical and radiological improvement after blood glucose correction.2 Herein, we present a case of NKHCB with following evidence of striatal atrophy. A 56-year-old woman presented to the emergency department of another hospital because of sudden onset of involuntary movements of the left limbs attenuated during rest. She had a recent history of type-2 diabetes mellitus treated with poor glycemic control. A computed tomography scan showed striatal hyperdensity. Routine laboratory findings were normal, despite a fasting blood glucose level of 167 mg/dL and glycate hemoglobin level of 130 mmol/mol (14%). MRI scan showed striatal T1-weighted hyperintensity with a corresponding hyperintensity in T2-weighted (Fig. 1A and B) and fluid attenuated inversion recovery (FLAIR) scans. The patient was diagnosed with NKHCB. Glucose control was optimized and anti-choreic therapy was started with haloperidol 5 mg/day and tetrabenazine 25 mg/day with a slight clinical benefit. The patient arrived at our attention 4 months after symptom onset for diagnostic re-evaluation. The motor impairment persisted and involuntary movements worsened insidiously. The neurological examination showed choreoatetosic and ballic movements of the left body side. Involuntary movements increased with distraction maneuvers and resolved during rest at bed. Blood fasting glucose was 126 mg/dL and glycated hemoglobin was 62 mmol/mol (7.8%). MRI scan showed the resolution of the striatal alteration, but highlighted atrophic evolution (Fig. 1C and D). A fluorodeoxyglucose positron emission tomography scan showed an intense hypometabolism consistent with morphological MRI atrophy findings (Fig. 1E and F). Haloperidol was discontinued and clinical improvement was obtained with tetrabenazine 25 mg thrice/day, piracetam 3 g/day and topiramate 25 mg twice/day. The comparison of MRI volumes at the two timepoints showed, on the right side, a decrease in caudate head and putamen volumes and an increase in the lateral ventricle volume. The two main pathophysiological mechanisms proposed for NKHCB are related to metabolic dysfunction and to microvascular damage.3, 4 Our findings may be explained by irreversible metabolic or vascular damage. The microvascular hypothesis might explain the prevalent unilateral clinical onset. The prognostic implication of our observation is related to the high variability in outcomes.1 Extended lesions at MRI were associated with prolonged involuntary movements.5 Our findings of focal atrophy strengthen these results, suggesting a role of the pathological disease severity, in-vivo assessed by MRI, to determine the persistence of the disorder. We hypothesize that a mild disorder, solved with anti-chorea treatment, might be associated with a lower degree of atrophy, unrecognized without a volumetric analysis. In conclusion, our case of NKHCB showed focal striatal atrophy and hypometabolism after radiological resolution in a 4-month follow-up, associated with poor response to glucose-control and anti-chorea treatment. To date, for the first time we documented nuclear volume changes with a quantitative approach demonstrating irreversible pathological changes in NKHCB, explaining drug-resistant cases. (1) Research project: A. Conception, B. Organization, C. Execution. (2) Statistical Analysis: A. Design, B. Execution, C: Review and Critique. (3) Manuscript: A. Writing of the first draft, B. Review and Critique. P.G.S.: 1A, 1B, 1C, 2A, 2B, 3A F.A.: 1A, 1B, 2C, 3B N.A.: 1C, 3B M.A.V.: 1A, 1B, 1C, 2C, 3B M.F.: 1A, 1B, 2C, 3B This study has been approved by the Ethics Committee of IRCCS San Raffaele Hospital and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The patient provided written informed consent to be anonymously included in this report. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. No funding was received for this work and the authors have no conflicts of interest to report. P.G. Scamarcia, N. Anzalone, and M.A. Volontè have nothing to disclose. F. Agosta is Section Editor of NeuroImage: Clinical; has received speaker honoraria from Philips, Novartis and Biogen Idec; and receives or has received research supports from the Italian Ministry of Health, AriSLA (Fondazione Italiana di Ricerca per la SLA), and the European Research Council. M. Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Outcomes of patients with cobalamin C deficiency: A single center experience.

Biallelic variants in MMACHC results in the combined methylmalonic aciduria and homocystinuria, called cobalamin (cbl) C (cblC) deficiency. We report 26 patients with cblC deficiency with their phenotypes, genotypes, biochemical parameters, and treatment outcomes, who were diagnosed and treated at our center. We divided all cblC patients into two groups: group 1: SX group: identified after manifestations of symptoms (n = 11) and group 2: NB group: identified during the asymptomatic period via newborn screening (NBS) or positive family history of cblC deficiency (n = 15). All patients in the SX group had global developmental delay and/or cognitive dysfunction at the time of the diagnosis and at the last assessment. Seizure, stroke, retinopathy, anemia, cerebral atrophy, and thin corpus callosum in brain magnetic resonance imaging (MRI) were common in patients in the SX group. Global developmental delay and cognitive dysfunction was present in nine patients in the NB group at the last assessment. Retinopathy, anemia, and cerebral atrophy and thin corpus callosum in brain MRI were less frequent. We report favorable outcomes in patients identified in the neonatal period and treated pre‐symptomatically. Identification of cblC deficiency by NBS is crucial to improve neurodevelopmental outcomes.

Association of tau accumulation and atrophy in mild cognitive impairment: a longitudinal study.

To examine the patterns of longitudinal tau accumulation and cortical atrophy and their association in subjects with mild cognitive impairment (MCI). We collected 23 participants (60-89years old, 11 males/12 females) with MCI from the Alzheimer's Disease Neuroimaging Initiative database. All participants underwent 18F flortaucipir (FTP) positron emission tomography (PET) and structural magnetic resonance imaging (MRI) scans at the baseline and follow-up visits (12-36months). General linear models with covariates (baseline age, sex) were used to detect brain areas of significant tau accumulation and atrophy over time. Mediation analysis was employed to explore the potential reason for sequential biomarker changes in MCI progression, adjusting for baseline age, sex, and education level. Voxel-wise tau accumulation in MCI subjects was predominantly located in the inferior temporal cortex, middle temporal cortex, parietal cortex, posterior cingulate, precuneus, and temporoparietal regions (P < 0.001), and MRI atrophy included the inferior-middle temporal lobe, parietal lobe, and precuneus (P < 0.001). Longitudinal FTP accumulation was moderately associated with annualized MRI cortical atrophy (r = 0.409, 95% CI: 0.405-0.414, P < 0.01). Regional analyses indicated significant bivariate associations between annualized MRI cortical atrophy and FTP accumulation (baseline FTP cortical uptake and longitudinal FTP change). The results of the mediation analysis showed that the relationship between baseline FTP uptake and longitudinal cortical atrophy was partly mediated by the longitudinal FTP cortical change (indirect effect: 0.0107, P = 0.04). Our findings provide a preliminary description of the patterns of longitudinal FTP accumulation and annualized cortical atrophy in MCI progression, and MCI subjects with high tau binding levels show an increase risk of longitudinal tau accumulation, atrophy, and cognitive decline. Trial registration NCT00106899. Registered 1 April 2005, https://clinicaltrials.gov/ct2/show/study/NCT00106899.

Surface-based analysis of cortical thickness and volume loss in Alzheimer’s disease

Background and Hypothesis: Magnetic resonance imaging (MRI) has become a useful tool in monitoring the progression of Alzheimer's disease. Previous surface-based analysis has focused on changes in cortical thickness associated with the disease1. The objective of this study is to analyze MRI-derived cortical reconstructions for patterns of atrophy in terms of both cortical thickness and cortical volume. We hypothesize that Alzheimer’s Disease progression will be associated with a more significant change in volume than thickness.&#x0D; Experimental Design or Project Methods: MRI data was obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). All subjects with baseline and two-year 3T MRI scans were included. Segmentation of MRIs into gray and white matter was performed with FreeSurfer2,3,4,5. Subjects whose scans did not segment accurately were excluded. Surfaces were then registered to a common atlas with Ciftify6, and anatomically-constrained Multimodal Surface Matching (aMSM) was used to analyze longitudinal changes in each subject7. This produced continuous surface maps showing changes in cortical surface area and thickness. These maps were multiplied to create cortical volume maps8. Permutation Analysis of Linear Models (PALM) was used to perform two-sample t-tests comparing the maps of the Alzheimer’s and control groups9.&#x0D; Results: Preliminary analysis of nine Alzheimer’s subjects and nine control subjects produced surface maps displaying patterns that were expected given previous research findings10,11. There was increased volume and thickness loss in Alzheimer’s subjects relative to controls, with relatively high loss in structures of the medial temporal lobe. Future analysis of a larger sample will determine whether statistically significant differences exist between the Alzheimer’s and control groups in terms of thickness loss and volume loss.&#x0D; Conclusion and Potential Impact: If significant results are found, surface-based analysis of cortical volume may allow for detection of atrophy at an earlier stage in disease progression than would be possible based on cortical thickness.&#x0D; &#x0D; References&#x0D; 1. Clarkson MJ, Cardoso MJ, Ridgway GR, Modat M, Leung KK, Rohrer JD, Fox NC, Ourselin S. A comparison of voxel and surface based cortical thickness estimation methods. NeuroImage. 2011 Aug 1; 57(3):856-65.&#x0D; 2. Dale AM, Fischl B, Sereno MI. Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage. 1999;9:179194.&#x0D; 3. Fischl B, Sereno M, Dale A. Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system. Neuroimage. 1999;9:195–207. &#x0D; 4. Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, van der Kouwe A, Killiany R, Kennedy D, Klaveness S, Montillo A, Makris N, Rosen B, Dale AM. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 2002;33:341-355.&#x0D; 5. Fischl B, Salat DH, van der Kouwe AJ, Makris N, Segonne F, Quinn BT, Dale AM. Sequence-independent segmentation of magnetic resonance images. Neuroimage 2004;23 Suppl 1:S69-84.&#x0D; 6. Glasser MF, Sotiropoulos SN, Wilson JA, Coalson TS, Fischl B, Andersson JL, Xu J, Jbabdi S, Webster M, Polimeni JR, Van Essen DC, Jenkinson M, WU-Minn HCP Consortium. The minimal preprocessing pipelines for the Human Connectome Project. Neuroimage. 2013 Oct 15;80:105-24.&#x0D; 7. Robinson EC, Garcia K, Glasser MF, Chen Z, Coalson TS, Makropoulos A, Bozek J, Wright R, Schuh A, Webster M, Hutter J, Price A, Cordero Grande L, Hughes E, Tusor N, Bayly PV, Van Essen DC, Smith SM, Edwards AD, Hajnal J, Jenkinson M, Glocker B, Rueckert D. Multimodal surface matching with higher-order smoothness constraints. Neuroimage. 2018;167:453-65.&#x0D; 8. Marcus DS, Harwell J, Olsen T, Hodge M, Glasser MF, Prior F, Jenkinson M, Laumann T, Curtiss SW, Van Essen DC. Informatics and data mining tools and strategies for the human connectome project. Front Neuroinform 2011;5:4.&#x0D; 9. Winkler AM, Ridgway GR, Webster MA, Smith SM, Nichols TE. Permutation inference for the general linear model. NeuroImage, 2014;92:381-397&#x0D; 10. Matsuda, H. MRI morphometry in Alzheimer’s disease. Ageing Research Reviews. 2016 Sep;30:17-24.&#x0D; 11. Risacher SL, Shen L, West JD, Kim S, McDonald BC, Beckett LA, Harvey DJ, Jack CR Jr, Weiner MW, Saykin AJ. Alzheimer's Disease Neuroimaging Initiative (ADNI). Longitudinal MRI atrophy biomarkers: relationship to conversion in the ADNI cohort. Neurobiol Aging. 2010 Aug;31(8):1401-18.

Amyloid-Negative Dementia in the Elderly is Associated with High Accumulation of Tau in the Temporal Lobes

Background: We previously reported that among cases clinically diagnosed with Alzheimer’s disease, the proportion of amyloid beta (Aβ) -negative case increases in the elderly population. Tauopathy including Argyrophilic Grain Disease (AGD) and Neurofibrillary Tangle-Predominant Dementia (NFTPD), may be the leading causes of such dementia. Objective: To evaluate the involvement of tau, we studied tau accumulation in Amyloid-Negative Dementia Cases in the Elderly (ANDE) with Positron Emission Tomography (PET). Methods: Seven cases with slowly progressive dementia who were older than 80 years and were negative for Aβ were studied. In one case, autopsy obtained 2 years after the PET examination revealed neurofibrillary tangles limited around the parahippocampal gyrus. Four cases showed strong laterality in magnetic resonance imaging atrophy (clinical AGD), while the other three cases had no significant laterality in atrophy (clinical NFTPD). Age-corrected PET data of healthy controls (HC; n = 12) were used as control. Tau accumulation was evaluated with [11C]PBB3-PET. Results: High accumulation was found in the lateral temporal cortex in ANDE. In autopsy case, scattered neurofibrillary tangles were found in the parahippocampal gyrus. In addition, there was a very high accumulation of PBB3 in the large area of bilateral parietal lobes, although no corresponding tau component was found in the autopsied case. Conclusion: Relatively high burden of tau deposition was commonly observed in the lateral temporal cortex and parietal cortex of ANDE, part of which may explain dementia in these subjects. [11C]PBB3 may be useful in detecting tauopathy in ANDE.

Detecting frontotemporal dementia syndromes using MRI biomarkers.

BackgroundDiagnosing frontotemporal dementia may be challenging. New methods for analysis of regional brain atrophy patterns on magnetic resonance imaging (MRI) could add to the diagnostic assessment. Therefore, we aimed to develop automated imaging biomarkers for differentiating frontotemporal dementia subtypes from other diagnostic groups, and from one another.MethodsIn this retrospective multicenter cohort study, we included 1213 patients (age 67 ± 9, 48% females) from two memory clinic cohorts: 116 frontotemporal dementia, 341 Alzheimer's disease, 66 Dementia with Lewy bodies, 40 vascular dementia, 104 other dementias, 229 mild cognitive impairment, and 317 subjective cognitive decline. Three MRI atrophy biomarkers were derived from the normalized volumes of automatically segmented cortical regions: 1) the anterior vs. posterior index, 2) the asymmetry index, and 3) the temporal pole left index. We used the following performance metrics: area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. To account for the low prevalence of frontotemporal dementia we pursued a high specificity of 95%. Cross-validation was used in assessing the performance. The generalizability was assessed in an independent cohort (n = 200).ResultsThe anterior vs. posterior index performed with an AUC of 83% for differentiation of frontotemporal dementia from all other diagnostic groups (Sensitivity = 59%, Specificity = 95%, positive likelihood ratio = 11.8, negative likelihood ratio = 0.4). The asymmetry index showed highest performance for separation of primary progressive aphasia and behavioral variant frontotemporal dementia (AUC = 85%, Sensitivity = 79%, Specificity = 92%, positive likelihood ratio = 9.9, negative likelihood ratio = 0.2), whereas the temporal pole left index was specific for detection of semantic variant primary progressive aphasia (AUC = 85%, Sensitivity = 82%, Specificity = 80%, positive likelihood ratio = 4.1, negative likelihood ratio = 0.2). The validation cohort provided corresponding results for the anterior vs. posterior index and temporal pole left index.ConclusionThis study presents three quantitative MRI biomarkers, which could provide additional information to the diagnostic assessment and assist clinicians in diagnosing frontotemporal dementia.

FDG-PET hypometabolism is more sensitive than MRI atrophy in Parkinson's disease: A whole-brain multimodal imaging meta-analysis.

Recently, revised diagnostic criteria for Parkinson's disease (PD) were introduced (Postuma et al., 2015). Yet, except for well-established dopaminergic imaging, validated imaging biomarkers for PD are still missing, though they could improve diagnostic accuracy.We conducted systematic meta-analyses to identify PD-specific markers in whole-brain structural magnetic resonance imaging (MRI), [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) and diffusion tensor imaging (DTI) studies. Overall, 74 studies were identified including 2323 patients and 1767 healthy controls. Studies were first grouped according to imaging modalities (MRI 50; PET 14; DTI 10) and then into subcohorts based on clinical phenotypes. To ensure reliable results, we combined established meta-analytical algorithms - anatomical likelihood estimation and seed-based D mapping - and cross-validated them in a conjunction analysis.Glucose hypometabolism was found using FDG-PET extensively in bilateral inferior parietal cortex and left caudate nucleus with both meta-analytic methods. This hypometabolism pattern was confirmed in subcohort analyses and related to cognitive deficits (inferior parietal cortex) and motor symptoms (caudate nucleus). Structural MRI showed only small focal gray matter atrophy in the middle occipital gyrus that was not confirmed in subcohort analyses. DTI revealed fractional anisotropy reductions in the cingulate bundle near the orbital and anterior cingulate gyri in PD.Our results suggest that FDG-PET reliably identifies consistent functional brain abnormalities in PD, whereas structural MRI and DTI show only focal alterations and rather inconsistent results. In conclusion, FDG-PET hypometabolism outperforms structural MRI in PD, although both imaging methods do not offer disease-specific imaging biomarkers for PD.

Optical coherence tomography and magnetic resonance imaging visual pathway evaluation in Wolfram syndrome.

The aim of this study was to assess parameters of retinal morphology by using high-definition optical coherence tomography (OCT) in patients with Wolfram syndrome (WFS) and their relation to optic tract atrophy in magnetic resonance imaging (MRI). High-definition OCT and MRI parameters were evaluated in 12 patients with WFS (three males, nine females; median age at examination 12y 8mo, range 10y 2mo-15y 11mo) and referred to 30 individuals with type 1 diabetes (T1D) (12 males, 18 females; median age at examination 20y 5mo, range 16y 8mo-21y 4mo) and 33 typically developing comparison participants (10 males, 23 females; median age at examination 20y 7mo, range 13y-22y 4mo). Total thickness and quadrant thickness of the retinal nerve fibre layer (RNFL), macular full-thickness parameters and macular ganglion cell layer/inner plexiform layer, intraorbital and intracranial thickness of the optical nerve, as well as the optic chiasm and visual tracts were significantly reduced in patients with WFS compared with those having T1D and the typically developing comparison participants. Optic chiasm thickness correlated negatively in patients with WFS with both age (r=-0.79; p=0.002) and duration of diabetes (r=-0.62; p=0.032). Thickness of the intraorbital parts of the optic nerves in patients with WFS correlated positively with thickness of the superior RNFL (r=0.73; p=0.006). High-definition OCT in combination with MRI could become an important tool for evaluating the effectiveness of therapeutic trials in patients with WFS. Provides evidence of significant reduction of retinal parameters and optic nerves in patients with Wolfram syndrome (WFS). Shows correlations between magnetic resonance imaging parameters and retinal morphology parameters in patients with WFS.

Frontostriatal grey matter atrophy in amyotrophic lateral sclerosis A visual rating study.

ABSTRACTAmyotrophic lateral sclerosis (ALS) is characterised by frontostriatal grey matter changes similar to those in frontotemporal dementia (FTD). However, these changes are usually detected at a group level, and simple visual magnetic resonance imaging (MRI) cortical atrophy scales may further elucidate frontostriatal changes in ALS.Objective:To investigate whether frontostriatal changes are detectable using simple visual MRI atrophy rating scales applied at an individual patient level in ALS.Methods:21 ALS patients and 17 controls were recruited and underwent an MRI scan. Prefrontal cortex sub-regions of the medial orbitofrontal cortex (MOFC), lateral orbitofrontal cortex (LOFC) and anterior cingulate cortex (ACC), striatal sub-regions of the caudate nucleus (CN) and nucleus accumbens (NAcc) were rated using visual grey matter atrophy 5-point Likert scales.Results:Significantly higher atrophy ratings in the bilateral MOFC only in ALS patients versus controls was observed (p<.05). Patients with greater MOFC atrophy had significantly higher atrophy of the CN (p<.05) and LOFC (p<.05).Conclusion:Use of simple visual atrophy rating scales on an individual level reliably detects frontostriatal deficits specific to ALS, showing MOFC atrophy differences with associated CN and LOFC atrophy. This is an applicable method that could be used to support clinical diagnosis and management.

Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years.

Current HIV treatments are successful at suppressing plasma HIV RNA to undetectable levels for most adherent patients. Yet, emerging evidence suggests that viral suppression will inadequately control inflammation and mitigate risk for progressive brain injury. We sought to quantify differences in longitudinal brain atrophy rates among older virally suppressed HIV-infected participants compared with that of healthy aging participants. We examined longitudinal structural brain magnetic resonance imaging atrophy rates using region of interest assessments and voxel-wise tensor-based morphometry in HIV-infected participants older than 60 years (n = 38) compared with age-matched HIV-uninfected healthy and cognitively normal controls (n = 24). The mean age of participants was 63 years, the mean estimated duration of infection was 21 years, and the median duration of documented viral suppression was 3.2 years. Average proximal and nadir CD4 counts were 550 and 166, respectively; 15/38 (39%) met criteria for HIV-associated neurocognitive disorder. In models adjusting for age and sex, HIV serostatus was associated with more rapid average annualized rates of atrophy in the cerebellum (0.42% vs. 0.02%, P = 0.016), caudate (0.74% vs. 0.03%, P = 0.012), frontal lobe (0.48% vs. 0.01%, P = 0.034), total cortical gray matter (0.65% vs. 0.16%, P = 0.027), brainstem (0.31% vs. 0.01%, P = 0.026), and pallidum (0.73% vs. 0.39%, P = 0.046). Among those with HIV, atrophy rates did not differ statistically by cognitive status. Despite persistent control of plasma viremia, these older HIV-infected participants demonstrate more rapid progressive brain atrophy when compared with healthy aging. Either HIV or other factors that differ between older HIV-infected participants and healthy controls could be responsible for these differences.

Cerebellopathy secondary to anti-peroxidase antibody-mediated toxicity. A special case of Hashimoto encephalopathy

ObjectiveThe aim of this case report is to highlight the importance of recognizing uncommon causes of cerebellar involvement. Case presentationA 45-year-old woman with no medical history who presented gait instability that appears suddenly and evolves rapidly in two weeks, causing frequent falls. Neurological examination revealed an inability to walk due to severe ataxia, accompanied by global hypotonia, appendicular dysmetria, opsoclonus and dysarthria. We studied this patient with cerebellar syndrome, obtaining as relevant findings global cerebellar atrophy in MRI (magnetic resonance imaging) and especially, considerably elevated levels of antibodies against thyroid peroxidase (TPO). The patient was treated with high doses of intravenous methylprednisolone for 5days. Six months after diagnosis and in treatment with low doses of prednisone, the patient is asymptomatic. ConclusionWe must considerer the cerebellar involvement secondary to steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) in a patient in whom other more frequent causes of isolated cerebellar disease have been ruled out.

SNAP IS PROBABLY NORMAL AGING: FINDINGS FROM BIOMARKERS SIGNATURE

Suspected non-Alzheimer pathophysiology (SNAP) is a biomarker-based entity characterized with neurodegeneration (suggested by high cerebrospinal fluid (CSF) Tau levels, magnetic resonance imaging atrophy in Alzheimer's disease (AD)-vulnerable regions, or positron emission tomography (PET) hypometabolism in AD-vulnerable regions) but lack of amyloidosis (defined by high PET radiotracer binding or low CSF fluid of Aβ levels), regardless of clinical status (clinically normal, mild cognitive impairment or dementia). SNAP is also a complement to the new National Institute on Aging–Alzheimer Association (NIA-AA) research criteria of preclinical AD. We aimed to explore the biomarkers in different clinical status with SNAP. We used the baseline data from Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) and collected the individuals with SNAP (clinically normal, mild cognitive impairment or dementia). The criteria were decreased CSF Aβ1–42 (<192pg/ml) and elevated CSF Tau (total Tau>93pg/ml, or phosphorylated Tau>23pg/ml). The data of biomarkers from CSF (e.g. Aβ, Tau, α-synuclein, sAPPβ, neurogranin, β-secretase, neurofilament, isoprostane, multiplex proteomics) and plasma (e.g. Aβ, Tau, neurofilament) were extracted. Mann-Whitney U tests were carried out between the groups of different clinical status, and P<0.05 was regarded as statistical significance. A total of 31 SNAP individuals were selected from ADNI1 cohort, with 18 clinically normal, 9 MCI and 4 dementia. APOE4 alleles were only 8%. In comparison with clinically normal, CSF CD40 (Mann-Whitney U test, Z=-2.024, P =0.046) and fibrinogen (Mann-Whitney U test, Z=-2.239, P =0.025) significantly changed in MCI, as well as CSF isoprostane (ISO8PGF2A) was elevated in dementia. In comparison with clinically normal, CSF isoprostane (ISO8PGF2A) (Mann-Whitney U test, Z=-2.315, P=0.020) was elevated in dementia. APOE4 is less common in SNAP. Only elevated ISO8PGF2A is observed in dementia in comparison with clinically normal and MCI, which is not found between clinically normal and MCI. Large-sample is required to confirm our findings and seek better biomarkers to differentiate the clinical status of SNAP. As the previous opinion “SNAP individuals are stable over time”, biomarkers signature suggests SNAP may be normal aging rather than pathological changes, in which brain atrophy and cognitive decline progress slowly.