Aphasia, Primary Progressive/genetics* ; Humans ; Neuroimaging ; Neuropsychological Tests

BACKGROUND AND PURPOSE: There are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [¹⁸F]-THK5351 retention across all three subtypes and determine the topography of [¹⁸F]-THK5351 retention correlated with each neurolinguistic score. METHODS: We enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [¹⁸F]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [¹⁸F]-THK5351 retention. RESULTS: The nfvPPA patients exhibited higher [¹⁸F]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [¹⁸F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [¹⁸F]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [¹⁸F]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [¹⁸F]-THK5351 retention in the left temporal cortices. Repetition was associated with [¹⁸F]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices. CONCLUSIONS: The pattern of [¹⁸F]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.
Aphasia, Primary Progressive ; Cognition ; Comprehension ; Humans ; Magnetic Resonance Imaging ; Neurofibrillary Tangles ; Neuropsychological Tests ; Parietal Lobe ; Positron-Emission Tomography ; Prefrontal Cortex ; Rabeprazole ; Semantics ; Temporal Lobe

Primary progressive aphasia (PPA) is a heterogenous neurodegenerative disorder characterized by declining language and speech ability. Various underlying neuropathologies can induce PPA, and the disorder is divided into three subtypes—progressive non-fluent aphasia, semantic variant aphasia, and logopenic aphasia—according to clinical features. Accurate disease classification and prediction of underlying diseases are necessary for appropriate treatment, but proper use of imaging tests is important because clinical information alone often makes it difficult to make accurate decisions. Because there is a characteristic metabolic pattern according to the subtypes, F-18 fluorodeoxyglucose positron emission tomography (PET) can indicate subtype classification. In addition, PETstudies for imaging amyloid or dopamine transporters play an important role in demonstrating underlying disease. The present case showed that PET imaging studies are useful in diagnosis and could be used as a biomarker in PPA.
Amyloid ; Aphasia ; Aphasia, Primary Progressive ; Biomarkers ; Classification ; Diagnosis ; Dopamine ; Dopamine Plasma Membrane Transport Proteins ; Electrons ; Neurodegenerative Diseases ; Neuropathology ; Positron-Emission Tomography

No abstract available.
Alzheimer Disease* ; Aphasia, Primary Progressive*

BACKGROUND AND PURPOSE: To analyze 18F-THK5351 positron emission tomography (PET) scans of patients with clinically diagnosed nonfluent/agrammatic variant primary progressive aphasia (navPPA). METHODS: Thirty-one participants, including those with Alzheimer's disease (AD, n=13), navPPA (n=3), and those with normal control (NC, n=15) who completed 3 Tesla magnetic resonance imaging, 18F-THK5351 PET scans, and detailed neuropsychological tests, were included. Voxel-based and region of interest (ROI)-based analyses were performed to evaluate retention of 18F-THK5351 in navPPA patients. RESULTS: In ROI-based analysis, patients with navPPA had higher levels of THK retention in the Broca's area, bilateral inferior frontal lobes, bilateral precentral gyri, and bilateral basal ganglia. Patients with navPPA showed higher levels of THK retention in bilateral frontal lobes (mainly left side) compared than NC in voxel-wise analysis. CONCLUSIONS: In our study, THK retention in navPPA patients was mainly distributed at the frontal region which was well correlated with functional-radiological distribution of navPPA. Our results suggest that tau PET imaging could be a supportive tool for diagnosis of navPPA in combination with a clinical history.
Alzheimer Disease ; Aphasia, Primary Progressive* ; Basal Ganglia ; Broca Area ; Diagnosis ; Frontal Lobe ; Humans ; Magnetic Resonance Imaging ; Neurofibrillary Tangles ; Neuropsychological Tests ; Positron-Emission Tomography ; Primary Progressive Nonfluent Aphasia ; tau Proteins

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

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

BACKGROUND: Non-fluent agrammatic primary progressive aphasia (naPPA) is characterized by progressive non-fluent speech disorder and might be associated with taupathy such as corticobasal degeneration (CBD) and progressive supranuclear palsy. We report a case of overlap syndrome presented with language impairment, and diagnosed as naPPA with possible CBD. CASE REPORT: A 58-year-old woman visited a memory and dementia clinic, with a 10-month history of progressive language disturbance. She was diagnosed as naPPA and overlapping CBD, based on the clinical features and neuroimaging findings including florbetaben PET. CONCLUSIONS: naPPA is pathologically caused by taupathy, and might progress to asymmetrical parkinsonism and apraxia, suggestive of CBD. Overlapping clinical features in our case represent various phenotypes of taupathy.
Aphasia, Primary Progressive* ; Apraxias ; Dementia ; Female ; Humans ; Memory ; Middle Aged ; Neuroimaging ; Parkinsonian Disorders ; Phenotype ; Supranuclear Palsy, Progressive

Primary progressive aphasia (PPA) is a clinical syndrome diagnosed when three core criteria are met. First, there should be a language impairment (i.e., aphasia) that interferes with the usage or comprehension of words. Second, the neurological work-up should determine that the disease is neurodegenerative, and therefore progressive. Third, the aphasia should arise in relative isolation, without equivalent deficits of comportment or episodic memory. The language impairment can be fluent or non-fluent and may or may not interfere with word comprehension. Memory for recent events is preserved although memory scores obtained in verbally mediated tests may be abnormal. This distinctive clinical pattern is most conspicuous in the initial stages of the disease, and reflects a relatively selective atrophy of the language network, usually located in the left hemisphere. There are different clinical variants of PPA, each with a characteristic pattern of atrophy. Clinicoanatomical correlations in patient with these variants have led to new insights on the organization of the large-scale language network in the human brain. For example, the left anterior temporal lobe, which was not part of the classic language network, has been shown to play a critical role in word comprehension and object naming. Furthermore, patients with PPA have shown that fluency can be dissociated from grammaticality. The underlying neuropathological diseases are heterogeneous and can include Alzheimer's disease as well as frontotemporal lobar degeneration. The clinician's task is to recognize PPA and differentiate it from other neurodegenerative phenotypes, use biomarkers to surmise the nature of the underlying neuropathology, and institute the most fitting multimodal interventions.
Alzheimer Disease ; Aphasia ; Aphasia, Primary Progressive* ; Atrophy ; Biomarkers ; Brain ; Comprehension ; Dementia ; Frontotemporal Lobar Degeneration ; Humans ; Memory ; Memory, Episodic ; Neuropathology ; Phenotype ; Temporal Lobe

Frontotemporal dementia (FTD) is a degenerative disease characterized by the selective frontal and temporal lobe atrophy, and progressive deficits in behavior, executive function, or language. The prevalence and incidence of FTD are 15-22/100000 and 2.7-4.1/100000, respectively, in midlife. Hereditary is an important risk factor for FTD. Although there is some controversy regarding the further syndromatic subdivision of the different types of FTD, FTD is clinically classified into behavioral variant of frontotemporal dementia, semantic dementia and progressive nonfluent aphasia. FTD can be misdiagnosed as many psychiatric disorders because of similarity of the prominent behavioral features. Advances in clinical, imaging, and molecular characterization have increased the accuracy of FTD diagnosis, thus developing for the accurate differentiation of these syndromes from psychiatric disorders. We also discuss about therapeutic strategies for symptom management of FTD. Medications such as serotonin reuptake inhibitors, antipsychotics, and other novel treatments have been used in FTD with various rates of success. Further advanced research should be directed at understanding and developing new diagnostic and therapeutic modalities to improve the FTD patients' prognosis and quality of life.
Antipsychotic Agents ; Atrophy ; Diagnosis ; Drug Therapy ; Executive Function ; Frontotemporal Dementia* ; Genetics ; Incidence ; Prevalence ; Primary Progressive Nonfluent Aphasia ; Prognosis ; Quality of Life ; Risk Factors ; Serotonin Uptake Inhibitors ; Temporal Lobe