OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with high morbidity and mortality. There are about 5%-15% of ALS patients combining with frontotemporal lobe degeneration (FTLD) at the same time and 50% of patients combing with cognitive function changes. The analysis of cortical thickness based on MRI is an important imaging method to evaluate brain structure. The aim of the study was to explore the changes of brain structure in ALS patients by cortical thickness analysis, and to explore the correlation between the brain structure and cognitive function. METHODS: In the study, 18 ALS patients treated in Department of Neurology, Peking University Third Hospital and 18 normal controls (age, gender and education level matched) were included. 3D magnetization prepared rapid gradient echo imaging (MPRAGE) sequence MRI was performed and the cortical thickness was analyzed. At the same time, all the ALS patients took neuropsychology assessments, including: mini-mental state examination (MMSE), verbal fluency test (VFT), Stroop color word test (SCWT), prospective memory (PM), emotional picture perception and recognition, and faux pas story test. RESULTS: After cognitive assessment, two ALS patients had cognitive impairment. One was in accordance with ALS-frontotemporal dementia (FTD) diagnosis and the other one was in accordance with ALS cognitive impairment (ALSci) diagnosis. In all the 18 ALS patients and 18 normal controls, the cortical thickness of the left medial orbitofrontal lobe and the medial temporal lobe were significantly reduced (P < 0.05) in ALS group by the vertex-wise comparison. Cortical thickness of the left entorhinal cortex, the left inferior temporal gyrus, the left medial orbitofrontal lobe and the left insular lobe was significantly reduced (P < 0.05) by the region-wise comparison. However, when only concluded the 16 ALS non-cognitive impairment patients, there was no significant difference between the two groups (P>0.05). There were correlations between the scores of prospective memory, emotional picture perception and recognition, faux pas story test and the cortical thickness of their corresponding regions (P < 0.05). CONCLUSION The cortical thickness of ALS patients are correlated with neuropsychological scores which may reflect the changes of cortical structure corresponding to the cognitive assessment, and may provide help for the early diagnosis of cognitive changes in ALS patients.
Humans ; Amyotrophic Lateral Sclerosis/diagnostic imaging* ; Neurodegenerative Diseases ; Frontotemporal Dementia/psychology* ; Neuropsychological Tests ; Cognitive Dysfunction/etiology* ; Magnetic Resonance Imaging/methods*

PURPOSE: Obtaining brain tissue is critical to definite diagnosis and to furthering understanding of neurodegenerative diseases. The present authors have maintained the National Neuropathology Reference and Diagnostic Laboratories for Dementia in South Korea since 2016. We have built a nationwide brain bank network and are collecting brain tissues from patients with neurodegenerative diseases. We are aiming to facilitate analyses of clinic-pathological and image-pathological correlations of neurodegenerative disease and to broaden understanding thereof. MATERIALS AND METHODS: We recruited participants through two routes: from memory clinics and the community. As a baseline evaluation, clinical interviews, a neurological examination, laboratory tests, neuropsychological tests, and MRI were undertaken. Some patients also underwent amyloid PET. RESULTS: We recruited 105 participants, 70 from clinics and 35 from the community. Among them, 11 died and were autopsied. The clinical diagnoses of the autopsied patients included four with Alzheimer's disease (AD), two with subcortical vascular dementia, two with non-fluent variant primary progressive aphasia, one with leukoencephalopathy, one with frontotemporal dementia (FTD), and one with Creutzfeldt-Jakob disease (CJD). Five patients underwent amyloid PET: two with AD, one with mixed dementia, one with FTD, and one with CJD. CONCLUSION: The clinical and neuropathological information to be obtained from this cohort in the future will provide a deeper understanding of the neuropathological mechanisms of cognitive impairment in Asia, especially Korea.
Alzheimer Disease ; Amyloid ; Aphasia, Primary Progressive ; Asia ; Brain* ; Cognition Disorders ; Cohort Studies ; Creutzfeldt-Jakob Syndrome ; Dementia ; Dementia, Vascular ; Diagnosis ; Frontotemporal Dementia ; Humans ; Korea* ; Leukoencephalopathies ; Magnetic Resonance Imaging ; Memory ; Neurodegenerative Diseases ; Neurologic Examination ; Neuropathology ; Neuropsychological Tests

BACKGROUND AND PURPOSE: Behavioral variant frontotemporal dementia (bvFTD) is a subtype of frontotemporal dementia, which has clinical symptoms of progressive personality and behavioral changes with deterioration of social cognition and executive functions. The pathology of bvFTD is known to be tauopathy or TDP-43 equally. We analyzed the 18F-THK5351 positron emission tomography (PET) scans, which were recently developed tau PET, in patients with clinically-diagnosed bvFTD. METHODS: Forty-eight participants, including participants with behavioral variant frontotemporal dementia (bvFTD, n=3), Alzheimer's disease (AD, n=21) and normal cognition (NC, n=24) who completed 3T magnetic resonance images, 18F-THK5351 PET scans, and detailed neuropsychological tests were included in the study. Voxel-wise statistical analysis and region of interest (ROI)-based analyses were performed to evaluate the retention of THK in bvFTD patients. RESULTS: In the voxel-based and ROI-based analyses, patients with bvFTD showed greater THK retention in the prefrontal, medial frontal, orbitofrontal, anterior cingulate, insula, anterior inferior temporal and striatum regions compared to NC participants. Left-right asymmetry was noted in the bvFTD patients. A patient with extrapyramidal symptoms showed much greater THK retention in the brainstem. CONCLUSIONS: The distribution of THK retention in the bvFTD patients was mainly in the frontal, insula, anterior temporal, and striatum regions which are known to be the brain regions corresponding to the clinical symptoms of bvFTD. Our study suggests that 18F-THK5351 PET imaging could be a supportive tool for diagnosis of bvFTD.
Alzheimer Disease ; Brain ; Brain Stem ; Cognition ; Diagnosis ; Executive Function ; Frontotemporal Dementia* ; Gyrus Cinguli ; Humans ; Neuropsychological Tests ; Pathology ; Positron-Emission Tomography ; Tauopathies

The pathological features of Alzheimer's disease are senile plaques which are aggregates of β-amyloid peptides and neurofibrillary tangles in the brain. Neurofibrillary tangles are aggregates of hyperphosphorylated tau proteins, and these induce various other neurodegenerative diseases, such as progressive supranuclear palsy, corticobasal degeneration, frontotemporal lobar degeneration, frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and chronic traumatic encephalopathy. In the case of Alzheimer's disease, the measurement of neurofibrillary tangles associated with cognitive decline is suitable for differential diagnosis, disease progression assessment, and to monitor the effects of therapeutic treatment. This review discusses considerations for the development of tau ligands for imaging and summarizes the results of the first-in-human and preclinical studies of the tau tracers that have been developed thus far. The development of tau ligands for imaging studies will be helpful for differential diagnosis and for the development of therapeutic treatments for tauopathies including Alzheimer's disease.
Alzheimer Disease ; Brain ; Brain Injury, Chronic ; Chromosomes, Human, Pair 17 ; Diagnosis, Differential ; Disease Progression ; Frontotemporal Dementia ; Frontotemporal Lobar Degeneration ; Ligands ; Neurodegenerative Diseases ; Neurofibrillary Tangles ; Parkinsonian Disorders ; Peptides ; Plaque, Amyloid ; Supranuclear Palsy, Progressive ; tau Proteins ; Tauopathies

A 62-year-old man presented with a one-year history of word finding difficulty, impaired single word comprehension and personality changes including aggression, apathy and eating change. Brain MRIs showed severe atrophy in the left anterior temporal lobe. The clinical syndromic diagnosis was semantic variant primary progressive aphasia. He died at age 70 of pneumonia. At autopsy, transactive response DNA-binding protein (TDP) immunoreactive long dystrophic neurites were predominantly found in the cerebral cortices, which were compatible with frontotemporal lobar degeneration-TDP type C pathology.
Aggression ; Apathy ; Aphasia, Primary Progressive ; Atrophy ; Autopsy ; Brain ; Cerebral Cortex ; Comprehension ; Diagnosis ; Eating ; Frontotemporal Dementia ; Frontotemporal Lobar Degeneration ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Neurites ; Pathology ; Pneumonia ; Semantics ; TDP-43 Proteinopathies ; Temporal Lobe

OBJECTIVES: The aim of this study was to draw attention toward so called ‘behavioral variant frontotemporal dementia(bvFTD) phenocopy syndrome’, which is difficult to discriminate with the primary psychiatric disorders, showing poor response to conventional therapeutic drugs, leading to higher risk to misdiagnoses and legal problems. Furthermore, the author insisted that our interest and study on them must be continued. METHODS: English articles published during 2000 thru 2016 had been searched by internet with the combination of words such as ‘frontotemporal’, ‘phenocopy’ and ‘behavioral’, and reviewed. Besides, two clinical vignettes were described. RESULTS: Precise diagnosis is important because patients' behavioral symptoms can influence on their families and community. However, disease-modifying treatment for bvFTD are not developed until now, and recent therapeutic drugs are only good for specific symptoms, while deterioration progresses in spite of proper psychiatric management. The possible bvFTD patients are not progressed into probable bvFTD clinically, showing no decline of cogntive and social function, no decrease of activity function, longer survival time, and normal neuroimaging for several years. CONCLUSIONS: Rather than expected, there are much more patients having clinical symptoms, course and diagnostic findings including neuroimaging, which are atypical to classical frontotemporal dementia and primary psychiatric disorders. If our knowledge and discriminating ability is improved, discovery rate of that cases will be increased. However, the identity of these atypical features are not clarified until now, it must be further actively investigated.
Behavioral Symptoms ; Cognition ; Diagnosis ; Diagnostic Errors ; Frontotemporal Dementia* ; Humans ; Internet ; Neuroimaging

Many kinds of degenerative, psychiatric, and cerebrovascular diseases can mimic behavioral variant frontotemporal dementia. We present a 73-year-old woman who presented with apathy, inappropriate social behavior, and persecutory delusion. A neuropsychological examination revealed frontal/executive dysfunction with relative sparing of episodic memory. Magnetic resonance imaging and F-18 fluorodeoxyglucose positron-emission tomography produced normal findings. However, magnetic resonance angiography revealed severe right internal carotid stenosis. After carotid stenting, her behavioral symptoms disappeared and did not recur during an 18-month follow-up.
Aged ; Apathy ; Behavioral Symptoms ; Carotid Artery, Internal* ; Carotid Stenosis* ; Cerebrovascular Disorders ; Delusions ; Female ; Follow-Up Studies ; Frontotemporal Dementia* ; Humans ; Magnetic Resonance Angiography ; Magnetic Resonance Imaging ; Memory, Episodic ; Positron-Emission Tomography ; Social Behavior ; Stents

Anesthetic experience in frontotemporal dementia (FTD) with severe hypotension associated autonomic dysfunction has not yet been reported. Here in case, we report on the case of treatment with vasopressin to refractory hypotension in FTD patient. A 54-year-old male presented with a ten-year history of FTD with frequent syncope. The patient was scheduled to undergo subtotal gastrectomy for resection of stomach cancer. During the operation, sudden hypotension occurred and it was refractory to fluid and 1 unit of blood resuscitation and did not respond to catecholamine. Transesophageal echocardiography showed normal heart with adequate volume state. After intravenous administration of arginine vasopressin, the patient's vital signs returned to baseline values. Arginine vasopressin might be considered as a valuable alternative for treatment of severe refractory hypotension in autonomic dysfunction patients with FTD.
Administration, Intravenous ; Arginine Vasopressin ; Echocardiography, Transesophageal ; Frontotemporal Dementia* ; Gastrectomy ; Heart ; Humans ; Hypotension ; Male ; Middle Aged ; Resuscitation ; Stomach Neoplasms ; Syncope ; Vasopressins ; Vital Signs

BACKGROUND AND PURPOSE: Only a few studies have investigated the relationship between different subtypes and disease progression or prognosis in patients with behavioral variant frontotemporal dementia (bvFTD). Since a localized injury often produces more focal signs than a diffuse injury, we hypothesized that the clinical characteristics differ between patients with bvFTD who show diffuse frontal lobe atrophy (D-type) on axial magnetic resonance imaging (MRI) scans versus those with focal or circumscribed frontal lobe atrophy (F-type). METHODS: In total, 94 MRI scans (74 scans from bvFTD and 20 scans from age-matched normal controls) were classified into 35 D- and 39 F-type bvFTD cases based on an axial MRI visual rating scale. We compared baseline clinical characteristics, progression in motor and cognitive symptoms, and survival times between D- and F-types. Survival analyses were performed for 62 of the 74 patients. RESULTS: While D-type performed better on neuropsychological tests than F-type at baseline, D-type had higher baseline scores on the Unified Parkinson's Disease Rating Scale (UPDRS) Part III. Evaluations of motor progression showed that the disease duration with motor symptoms was shorter in D-type than F-type. Moreover, the survival time was shorter in D-type (6.9 years) than F-type (9.4 years). Cox regression analyses revealed that a high UPDRS Part III score at baseline contributed to an increased risk of mortality, regardless of the pattern of atrophy. CONCLUSIONS: The prognosis is worse for D-type than for those with F-type. Shorter survival in D-type may be associated with the earlier appearance of motor symptoms.
Atrophy* ; Disease Progression ; Frontal Lobe ; Frontotemporal Dementia* ; Frontotemporal Lobar Degeneration ; Humans ; Magnetic Resonance Imaging ; Mortality ; Neurobehavioral Manifestations ; Neuropsychological Tests ; Parkinson Disease ; Prognosis*

BACKGROUND AND PURPOSE: This study investigated the structural and functional changes in the motor system in amyotrophic lateral sclerosis (ALS; n=25) and behavioral-variant fronto-temporal dementia (bvFTD; n=17) relative to healthy controls (n=37). METHODS: Structural changes were examined using a region-of-interest approach, applying voxel-based morphometry for gray-matter changes and diffusion tensor imaging for white-matter changes. Functional changes in the motor system were elucidated using threshold-tracking transcranial magnetic stimulation (TMS) measurements of upper motor-neuron excitability. RESULTS: The structural analyses showed that in ALS there were more white-matter changes in the corticospinal and motor-cortex regions and more gray-matter changes in the cerebellum in comparison to controls. bvFTD showed substantial gray- and white-matter changes across virtually all motor-system regions compared to controls, although the brainstem was affected less than the other regions. Direct comparisons across patient groups showed that the gray- and white-matter motor-system changes inclusive of the motor cortex were greater in bvFTD than in ALS. By contrast, the functional integrity of the motor system was more adversely affected in ALS than in bvFTD, with both patient groups showing increased excitability of upper motor neurons compared to controls. CONCLUSIONS: Cross-correlation of structural and functional data further revealed a neural dissociation of different motor-system regions and tracts covarying with the TMS excitability across both patient groups. The structural and functional motor-system integrities appear to be dissociated between ALS and bvFTD, which represents useful information for the diagnosis of motor-system changes in these two disorders.
Amyotrophic Lateral Sclerosis* ; Brain Stem ; Cerebellum ; Dementia ; Diagnosis ; Diffusion Tensor Imaging ; Frontotemporal Dementia* ; Humans ; Motor Cortex ; Motor Neurons ; Transcranial Magnetic Stimulation