Corticobasal degeneration with visual hallucination as an initial symptom: A case report.

Although the initial symptoms of corticobasal degeneration (CBD) are varied, psychiatric symptoms are uncommon. Here, we report the autopsy findings of a patient with early CBD who presented with hallucinations. A 68-year-old man developed memory loss and visions of bears and insects. Because of slow vertical eye movement, postural instability, and levodopa-unresponsive parkinsonism, the patient initially was clinically diagnosed with progressive supranuclear palsy. He died of a urinary tract infection 11 months after the onset of the disease. Histopathological examination revealed neuronal loss and gliosis, which were severe in the substantia nigra and moderate in the globus pallidus and subthalamic nucleus. Astrocytic plaques were scattered throughout the amygdala and premotor cortex. The superficial cortical layers lacked ballooned neurons and spongiosis, and tau deposition was greater in glia than in neurons. The amygdala contained a moderate number of argyrophilic grains and pretangles. Western blot analysis showed a 37-kDa band among the low-molecular-weight tau fragments. Because the CBD pathology was mild, we attributed the patient's visual hallucinations to the marked argyrophilic grain pathology. CBD can occur with psychiatric symptoms, including visual hallucinations, and argyrophilic grain pathology may be associated with psychiatric symptoms.

Atypical TDP-43 proteinopathy clinically presenting with progressive nonfluent aphasia: A case report.

Progressive nonfluent aphasia (PNFA) is a form of frontotemporal lobar degeneration (FTLD) caused by tau and transactive response DNA-binding protein of 43 kDa (TDP-43) accumulation. Here we report the autopsy findings of a 64-year-old right-handed man with an atypical TDP-43 proteinopathy who presented with difficulties with speech, verbal paraphasia, and dysphagia that progressed over the 36 months prior to his death. He did not show pyramidal tract signs until his death. At autopsy, macroscopic brain examination revealed atrophy of the left dominant precentral, superior, and middle frontal gyri and discoloration of the putamen. Spongiform change and neuronal loss were severe on the cortical surfaces of the precentral, superior frontal, and middle frontal gyri and the temporal tip. Immunostaining with anti-phosphorylated TDP-43 revealed neuronal cytoplasmic inclusions and long and short dystrophic neurites in the frontal cortex, predominantly in layers II, V, and VI of the temporal tip, amygdala, and transentorhinal cortex. Immunoblot analysis of the sarkosyl-insoluble fractions showed hyperphosphorylated TDP-43 bands at 45 kDa and phosphorylated C-terminal fragments at approximately 25 kDa. The pathological distribution and immunoblot band pattern differ from the major TDP-43 subtype and therefore may represent a new FTLD-TDP phenotype.

Clinical course of pathologically confirmed corticobasal degeneration and corticobasal syndrome.

The clinical presentation of corticobasal degeneration is diverse, while the background pathology of corticobasal syndrome is also heterogeneous. Therefore, predicting the pathological background of corticobasal syndrome is extremely difficult. Herein, we investigated the clinical findings and course in patients with pathologically, genetically and biochemically verified corticobasal degeneration and corticobasal syndrome with background pathology to determine findings suggestive of background disorder. Thirty-two patients were identified as having corticobasal degeneration. The median intervals from the initial symptoms to the onset of key milestones were as follows: gait disturbance, 0.0 year; behavioural changes, 1.0 year; falls, 2.0 years; cognitive impairment, 2.0 years; speech impairment, 2.5 years; supranuclear gaze palsy, 3.0 years; urinary incontinence, 3.0 years; and dysphagia, 5.0 years. The median survival time was 7.0 years; 50% of corticobasal degeneration was diagnosed as corticobasal degeneration/corticobasal syndrome at the final presentation. Background pathologies of corticobasal syndrome (n = 48) included corticobasal degeneration (33.3%), progressive supranuclear palsy (29.2%) and Alzheimer's disease (12.5%). The common course of corticobasal syndrome was initial gait disturbance and early fall. In addition, corticobasal degeneration-corticobasal syndrome manifested behavioural change (2.5 years) and cognitive impairment (3.0 years), as the patient with progressive supranuclear palsy-corticobasal syndrome developed speech impairment (1.0 years) and supranuclear gaze palsy (6.0 years). The Alzheimer's disease-corticobasal syndrome patients showed cognitive impairment (1.0 years). The frequency of frozen gait at onset was higher in the corticobasal degeneration-corticobasal syndrome group than in the progressive supranuclear palsy-corticobasal syndrome group [P = 0.005, odds ratio (95% confidence interval): 31.67 (1.46-685.34)]. Dysarthria at presentation was higher in progressive supranuclear palsy-corticobasal syndrome than in corticobasal degeneration-corticobasal syndrome [P = 0.047, 6.75 (1.16-39.20)]. Pyramidal sign at presentation and personality change during the entire course were higher in Alzheimer's disease-corticobasal syndrome than in progressive supranuclear palsy-corticobasal syndrome [P = 0.011, 27.44 (1.25-601.61), and P = 0.013, 40.00 (1.98-807.14), respectively]. In corticobasal syndrome, decision tree analysis revealed that 'freezing at onset' or 'no dysarthria at presentation and age at onset under 66 years in the case without freezing at onset' predicted corticobasal degeneration pathology with a sensitivity of 81.3% and specificity of 84.4%. 'Dysarthria at presentation and age at onset over 61 years' suggested progressive supranuclear palsy pathology, and 'pyramidal sign at presentation and personality change during the entire course' implied Alzheimer's disease pathology. In conclusion, frozen gait at onset, dysarthria, personality change and pyramidal signs may be useful clinical signs for predicting background pathologies in corticobasal syndrome.

Ferromagnetic Fluctuations in the Heavily Overdoped Regime of Single-Layer High-Tc Cuprate Superconductors.

To investigate proposed ferromagnetic fluctuations in the so-called single-layer Bi-2201 and La-214 high-Tc cuprates, we performed magnetization and electrical resistivity measurements using single-layer Tl-2201 cuprates Tl2Ba2CuO6+δ and La-214 La2-xSrxCuO4 in the heavily overdoped regime. Magnetization of Tl2Ba2CuO6+δ and La2-xSrxCuO4 exhibited the tendency to be saturated in high magnetic fields at low temperatures, suggesting the precursor behavior toward the formation of a ferromagnetic order. It was found that the power of temperature n obtained from the temperature dependence of the electrical resistivity is ~4/3 and ~5/3 for Bi-2201 and La2-xSrxCuO4, respectively, and is ~4/3 at high temperatures and ~5/3 at low temperatures in Tl2Ba2CuO6+δ. These results suggest that two- and three-dimensional ferromagnetic fluctuations exist in Bi-2201 and La2-xSrxCuO4, respectively. In Tl2Ba2CuO6+δ, it is suggested that the dimension of ferromagnetic fluctuations is two at high temperatures and three at low temperatures, respectively. The dimensionality of ferromagnetic fluctuations is understood in terms of the dimensionality of the crystal structure and the bonding of atoms in the blocking layer.

Important properties of anion exchange resins for efficient removal of PFOS and PFOA from groundwater.

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) present in various water sources have raised a serious concern on their health risk worldwide. Anion exchange is known to be one of the effective treatment methods but the resin properties suitable for theses contaminants have not been fully understood. We examined four commercially available anion exchange resins with different properties (DIAION™ PA312, HPA25M, UBA120, and WA30) and one polymer-based adsorbent (HP20), for their PFOA and PFOS removal in the batch experiment. All or a part of the selected resins were further characterized for their functional group, surface morphology and pore size distribution. The 72 h batch experiment with the 100 mg/L PFOA or PFOS in the laboratory pure water matrix showed a superior capacity of the strong base anion exchange resins, the porous-type HPA25M and PA312, and the gel-type UBA120, for PFOA removal (92.6-97.9%). Among those resins, the high porous HPA25M was suggested most effective due to its remarkably high reaction rate and effectiveness to PFOS (99.9%). In the groundwater matrix, however, the performance of the those anion exchange resins was generally suppressed, causing up to 71% decrease in their removal rates. The least matrix impact was observed for PFOS removal by HPA25M, which indicated the resin's high selectivity to the contaminant. The physiochemical analysis indicated that the presence of relatively large pores (1 nm-10 nm) over HPA25M played an important role in the PFAS removal.

Neuropathological analysis of cognitive impairment in progressive supranuclear palsy.

BACKGROUND: Cognitive impairment is an important symptom in progressive supranuclear palsy (PSP), but the pathological changes underlying the cognitive impairment are unclear. This study aimed to elucidate relationships between the severity of cognitive impairment and PSP-related pathology. METHODS: We investigated the clinicopathological characteristics of 10 autopsy cases of PSP, including neuronal loss/gliosis and the burden of PSP-related tau pathology by using a semiquantitative score in 17 brain regions. Other concurrent pathologies such as Braak neurofibrillary tangle stage, Thal amyloid phase, Lewy-related pathology, argyrophilic grains, and TDP-43-related pathology were also assessed. We retrospectively divided the patients into a normal cognition group (PSP-NC) and cognitive impairment group (PSP-CI) based on antemortem clinical information about cognitive impairment and compared the pathological changes between these groups. RESULTS: Seven patients were categorized into the PSP-CI group (men = 4) and three into the PSP-NC group (men = 3). The severity of neuronal loss/gliosis and concurrent pathologies were not different between the two groups. However, the total load of tau pretangles/neurofibrillary tangles was higher in the PSP-CI group than in the PSP-NC group. In addition, the burden of tufted astrocytes in the subthalamic nucleus and medial thalamus was higher in the PSP-CI group than in the PSP-NC group. CONCLUSION: Cognitive impairment in PSP may be associated with the amount of tufted astrocyte pathology in the subthalamic nucleus and medial thalamus.

[An autopsy case of polyarteritis nodosa accompanied with multiple immune-specific autoantibodies and rhabdomyolysis].

A 72-year-old male complained of fever lasting 1 month and developed muscle weakness and paresthesia in the legs. He presented with muscle weakness, grasping pain, decreased deep tendon reflexes in the extremities, and reduction of tactile sensation in the distal parts of the left leg muscles. Blood tests revealed leukocytosis and inflammatory reactions. Collagen-disease-specific autoantibodies including anti-double-stranded DNA and anti-Scl-70 antibodies were positive, but antineutrophil cytoplastic antibodies were negative. Nerve conduction studies revealed asymmetric axonal degeneration, indicating multiple mononeuropathy. We started intravenous methylprednisolone pulse and plasma exchange therapies. However, the patient developed intestinal necrosis and perforation, and he died 44 days after the onset of fever. An autopsy revealed vasculitis in small- to medium-sized vessels in multiple organs as well as myoglobin casts in the renal tubules, which were suggestive polyarteritis nodosa (PAN) accompanied with rhabdomyolysis. Positivity for collagen-disease-specific autoantibodies and accompanying rhabdomyolysis are atypical findings with PAN. This patient was not clinically diagnosed as PAN, and so promptly starting immunotherapies should be considered when a case presents with evidence of vasculitis.

First detailed case report of a pediatric patient with neuronal intranuclear inclusion disease diagnosed by NOTCH2NLC genetic testing.

INTRODUCTION: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease characterized clinically by eosinophilic hyaline intranuclear inclusions in neuronal and other somatic cells. Skin biopsies are reportedly useful in diagnosing NIID, and the genetic cause of NIID was identified as a GGC repeat expansion in NOTCH2NLC in recent years. The number of adult patients diagnosed via genetic testing has increased; however, there have been no detailed reports of pediatric NIID cases with GGC expansions in NOTCH2NLC. This is the first detailed report of a pediatric patient showing various neurological symptoms from the age of 10 and was ultimately diagnosed with NIID via skin biopsy and triplet repeat primed polymerase chain reaction analyses. CASE REPORT: This was an 18-year-old female who developed cyclic vomiting, distal dominant muscle weakness, and sustained miosis at 10 years. Nerve conduction studies revealed axonal degeneration, and her neuropathy had slowly progressed despite several rounds of high-dose methylprednisolone and intravenous immunoglobulin therapy. At 13 years, she had an acute encephalopathy-like episode. At 15 years, brain MRI revealed slightly high-intensity lesions on diffusion-weighted and T2-weighted imaging in the subcortical white matter of her frontal lobes that expanded over time. At 16 years, esophagography, upper gastrointestinal endoscopy, and esophageal manometry revealed esophageal achalasia, and per-oral endoscopic myotomy was performed. At 18 years, we diagnosed her with NIID based on the findings of skin specimen analyses and a GGC repeat expansion in NOTCH2NLC. CONCLUSION: NIID should be considered as a differential diagnosis in pediatric patients with various neurological symptoms.

Brain and spinal cord metastases with seminoma: A case report.

Introduction: Brain and spinal cord metastases from testicular cancer occur rarely, and metastases with seminoma are extremely rare. Case presentation: A 42-year-old man who was diagnosed with seminoma and multiple metastases underwent first-line and salvage chemotherapy. Brain metastases were noted; consequently, surgery, third-line chemotherapy, and whole-brain irradiation were performed. Subsequently, paralysis developed, and spinal cord metastases were detected. He received fourth-line chemotherapy but died. Pathological autopsy revealed metastases only in the spinal cord. The cause of death was considered respiratory failure due to cervical spinal cord involvement from spinal metastases. Conclusion: Brain and spinal cord metastases from seminoma are rare. Thus, similar future cases should be treated appropriately.

An autopsy case of progressive supranuclear palsy. Pallido-nigro-luysian type with argyrophilic grains clinically presenting with personality and behavioral changes.

Pallido-nigro-luysian atrophy (PNLA) is a variant of progressive supranuclear palsy (PSP). Patients with PSP sometimes show psychiatric signs, but there are few reports about such signs being associated with PSP-PNLA. Here, we report a case of PSP-PNLA with argyrophilic grains (AGs) in a patient clinically diagnosed as having PSP-frontotemporal dementia (PSP-F). A 74-year-old man described as "kind" presented with impaired memory, irritability, and apathy. He showed levodopa-resistant parkinsonism and postural instability. Brain magnetic resonance imaging revealed mild atrophy of the midbrain and right-side-dominant atrophy of the hippocampus and temporal lobe. The patient was diagnosed as having PSP with frontal lobe cognitive or behavioral presentations (PSP-F). He died of aspiration pneumonia at age 81. At autopsy, macroscopic examination revealed depigmentation of the substantia nigra and grayish discoloration of the dentate nucleus, globus pallidus, and subthalamic nucleus. Severe gliosis was observed in the same regions. There were many phosphorylated tau-immunoreactive equivocal tufted astrocytes in the globus pallidus. Many neurofibrillary tangles and neuropil threads were observed in the substantia nigra and subthalamic nucleus, and few tau aggregates were observed in the frontal cortex. In contrast, AGs were abundant in the amygdala, entorhinal cortex, and anterior cingulate gyrus, with an asymmetric distribution. The pathological observations led us to change the diagnosis to PSP-PNLA with AGs. Although most cases of PSP-F derive from tau pathology in the frontal cortex, this patient did not have phosphorylated tau-immunoreactive aggregates in that location. Our observations suggest that the psychiatric signs of PSP-F should be considered as being due to the presence of limbic AGs, not frontal tau pathology.

Ultrastructural and biochemical classification of pathogenic tau, α-synuclein and TDP-43.

Intracellular accumulation of abnormal proteins with conformational changes is the defining neuropathological feature of neurodegenerative diseases. The pathogenic proteins that accumulate in patients' brains adopt an amyloid-like fibrous structure and exhibit various ultrastructural features. The biochemical analysis of pathogenic proteins in sarkosyl-insoluble fractions extracted from patients' brains also shows disease-specific features. Intriguingly, these ultrastructural and biochemical features are common within the same disease group. These differences among the pathogenic proteins extracted from patients' brains have important implications for definitive diagnosis of the disease, and also suggest the existence of pathogenic protein strains that contribute to the heterogeneity of pathogenesis in neurodegenerative diseases. Recent experimental evidence has shown that prion-like propagation of these pathogenic proteins from host cells to recipient cells underlies the onset and progression of neurodegenerative diseases. The reproduction of the pathological features that characterize each disease in cellular and animal models of prion-like propagation also implies that the structural differences in the pathogenic proteins are inherited in a prion-like manner. In this review, we summarize the ultrastructural and biochemical features of pathogenic proteins extracted from the brains of patients with neurodegenerative diseases that accumulate abnormal forms of tau, α-synuclein, and TDP-43, and we discuss how these disease-specific properties are maintained in the brain, based on recent experimental insights.

Observation of Cu Spin Fluctuations in High-Tc Cuprate Superconductor Nanoparticles Investigated by Muon Spin Relaxation.

The nano-size effects of high-Tc cuprate superconductor La2-xSrxCuO4 with x = 0.20 are investigated using X-ray diffractometry, Transmission electron microscopy, and muon-spin relaxation (µSR). It is investigated whether an increase in the bond distance of Cu and O atoms in the conducting layer compared to those of the bulk state might affect its physical and magnetic properties. The µSR measurements revealed the slowing down of Cu spin fluctuations in La2-xSrxCuO4 nanoparticles, indicating the development of a magnetic correlation at low temperatures. The magnetic correlation strengthens as the particle size reduces. This significantly differs from those observed in the bulk form, which show a superconducting state below Tc. It is indicated that reducing the particle size of La2-xSrxCuO4 down to nanometer size causes the appearance of magnetism. The magnetism enhances with decreasing particle size.

First Japanese autopsy case showing LRRK2 mutation G2019S and TDP-43 proteinopathy.

This is the first Japanese autopsy case of Leucine-rich repeat kinase 2 (LRRK2) G2019S mutation with atypical TDP43 proteinopathy. Our case is important that presented clinically dysphagia and pathologically TDP-43 proteinopathy. TDP43 may play an important role of clinical presentation with LRRK2 G2019S mutation carriers.

An autopsy case of PARK2 due to a homozygous exon 2 deletion of parkin and associated with α-synucleinopathy.

Lewy bodies (LBs) are usually detected in patients with idiopathic Parkinson's disease (PD), but there have been few reports of LBs in a familial form of early-onset PD associated with several mutations in parkin, a gene that encodes a ubiquitin E3 ligase involved in mitochondrial homeostasis, being also known as PARK2. Here, we report a case of PD with a PARK2 mutation characterized by a homozygous deletion of exon 2 and incidental LB pathology. A 60-year-old man developed tremor in the upper limbs. Although levodopa was initially effective, his symptoms slowly progressed. His cardiac uptake of 123 I-metaiodobenzylguanidine, as assessed by myocardial scintigraphy, decreased from an early stage after the onset. At the age of 81 years, he developed Legionella pneumonia and died of respiratory failure. Histopathological examination revealed a moderate loss of pigmented neurons, as well as gliosis in the substantia nigra and the locus coeruleus. Little LB-related pathology was found in the locus coeruleus, dorsal nucleus of vagal nerve, and basal nucleus of Meynert. The cardiac sympathetic nerve in the epicardium showed a reduction in the numbers of fibers immunoreactive for tyrosine hydroxylase and phosphorylated neurofilament protein. Genetic analysis of frozen brain materials revealed a homozygous deletion of exon 2 of parkin. To our knowledge, this is the first autopsy case with a homozygous deletion of exon 2 of parkin. The number of LBs was small, the age of disease onset was later than that in typical PARK2-associated PD patients, and cardiac sympathetic denervation was also present. Thus, we considered the LBs in our case as incidental and preclinical α-synucleinopathy.

Dravet syndrome with parkinsonian symptoms and intact dopaminergic neurons: A case report.

INTRODUCTION: Dravet syndrome (DS) is severe myoclonic epilepsy in infancy and associated with a heterozygous mutation of the gene for the sodium channel alpha 1 subunit (SCN1A). Recently, adult patients with DS have been reported to show parkinsonism, but no corresponding neuroimaging data are available. Here, we present neuroimaging data in 2 adult patients with DS showing parkinsonian symptoms. CASE REPORT: Case 1: A man who had intractable seizures from the age of 1 year and 2 months was diagnosed with DS at 7 with a mutation in the SCN1A gene. At 18, he had parkinsonian symptoms such as masked face and bradykinesia. At 20, he was admitted to our department. Dopamine transporter single-photon emission computed tomography (DAT SPECT) showed no decrease in striatal binding of 123I-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane (123I-FP-CIT), and myocardial scintigraphy showed no decrease in cardiac uptake of 123I-metaiodobenzylguanidine (123I-MIBG). Levodopa showed no significant improvement in his symptoms. Case 2: A woman who had febrile seizures at 4 months of age and myoclonic seizures at 1 year and 5 months was diagnosed with DS at 31. She had myoclonus, resting tremor, hypertonia, antecollis, crouch gait, and bradykinesia. DAT SPECT imaging showed no decrease in striatal FP-CIT binding, and levodopa did not improve her symptoms. DISCUSSION: The normal DAT SPECT and 123I-MIBG results suggest that dopaminergic neurons projecting onto striatal neurons were not impaired in our patients, explaining the lack of response to levodopa. Thus, dopamine imaging can help to guide treatment decisions in patients with DS and parkinsonism.

[A case of sporadic late-onset nemaline myopathy associated with myasthenia gravis positive for anti-titin antibody and anti-Kv1.4 antibody].

A 66-year-old woman who had myasthenia gravis (MG) admitted for type II respiratory failure and right heart failure. Although she had neither ptosis, eye movement disorder, nor diplopia, she had orbital muscles weakness, reduction of gag reflex, dysarthria, dysphagia, and mild proximal muscle weakness. Blood tests showed anti-striated muscle antibodies (anti-titin antibody and anti-Kv1.4 antibody). A muscle biopsy of the left biceps showed a marked variation in fiber size, mild mononuclear cell infiltration was seen surrounding blood vessels in perimysium and nemaline bodies in some fibers. Immunohistochemical stains showed many muscle fibers express HLA-ABC. The patient was diagnosed as sporadic late-onset nemaline myopathy (SLONM) with MG, and treated by tacrolimus. After treatment, her respiratory function gradually improved and she discharged. In the case of atypical MG, measurement of anti-striated muscle antibody or muscle biopsy should be considered.

A Single-institution Study on Predictors of Short-term Progression from Mild Cognitive Impairment in Parkinson's Disease to Parkinson's Disease with Dementia.

BACKGROUND: Patients with non-demented Parkinson's disease (PD) sometime have mild cognitive impairment (MCI), and mild cognitive impairment in Parkinson's disease (PD-MCI) may convert to Parkinson's disease with dementia (PDD) within several years. Cognitive impairment also occurs in the early stages of the disease, gradually progressing to lower quality of life and instrumental activities of daily living. It is important to elucidate the predictors of progression from PD-MCI to PDD via longitudinal studies. METHODS: This was a single center, case-control study. We analysed data from 49 patients with PD-MCI diagnosed as level I using the Movement Disorder Society PD-MCI criteria at baseline who had completed 1.5 years of follow-up. We defined patients who progressed to PDD as patients with progressive PD-MCI and patients who did not progress to PDD as patients with non-progressive PD-MCI. Depression, apathy, sleep disorders, constipation, light-headedness, hallucinations, impulse control disorders (ICDs) and impulsive-compulsive behaviors (ICBs) at baseline were statistically analysed as predictors of progression. RESULTS: Of the 49 PD-MCI patients, 33 did not convert to PDD (non-progressive PD-MCI), and 16 converted to PDD (progressive PD-MCI). The Mini-Mental State Examination (MMSE) score, light-headedness and ICDs were elucidated as predictors of progressive PD-MCI via a multivariate logistic regression model. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each item were MMSE score, OR 0.324, 95% CI 0.119-0.882, P = 0.027; light-headedness, OR 27.665, 95% CI 2.263-338.185, P= 0.009; and ICDs, OR 53.451, 95% CI 2.298-291.085, P = 0.010. CONCLUSION: Cognitive function, ICDs and light-headedness may be risk factors for the development of PDD in PD-MCI patients.

Cognitive and behavioral status in Japanese ALS patients: a multicenter study.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) patients may present with cognitive and behavioral abnormalities similar to frontotemporal dementia (FTD). In this multicenter study we examined Japanese ALS patients with and without FTD in order to characterize the full extent of cognitive and behavioral abnormalities, including associations with functional motor status, anxiety and depression. METHODS: Patients were evaluated using the Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), Hospital Anxiety and Depression Scale, ALS Functional Rating Scale-Revised, spirometry, and verbal fluency tests. Caregivers were asked to complete the ALS-FTD-Questionnaire (ALS-FTD-Q), a behavioral screen. We defined severe cognitive impairment (MoCA < 21 or FAB < 11), mild impairment (11 ≤ MoCA ≤ 25 or 11 ≤ FAB ≤ 15), and normal cognition (MoCA > 25 or FAB > 15). Severe and mild behavioral impairments and normal behavior were defined by the ALS-FTD-Q scores. RESULTS: In 145 ALS patients, better cognitive scores were correlated with earlier age at onset, whereas a worse behavioral score was associated with a longer disease duration and higher level of anxiety and depression. Around seventy percent of all ALS patients showed mild (40-45%) or severe cognitive impairment with cognitive impairment outnumbering behavioral impairment fivefold. Cognitive functions were more impaired in patients with age of onset over 65 years, while behavioral scores were not related to age. CONCLUSIONS: Considering the high prevalence of in particular cognitive impairment, and the diversity of impairments, the cognitive and behavioral aspects of Japanese ALS patients should be given more attention clinically.