8,807 results match your criteria Frontotemporal Lobe Dementia


Effects of Palmitoylethanolamide Combined with Luteoline on Frontal Lobe Functions, High Frequency Oscillations, and GABAergic Transmission in Patients with Frontotemporal Dementia.

J Alzheimers Dis 2020 Jul 2. Epub 2020 Jul 2.

Santa Lucia Foundation, IRCCS, Rome, Italy.

Background: Frontotemporal dementia (FTD) is a presenile neurodegenerative disease for which there is no effective pharmacological treatment. Recently, a link has been proposed between neuroinflammation and FTD.

Objective: Here, we aim to investigate the effects of palmitoylethanolamide (PEA) combined with luteoline (PEA-LUT), an endocannabinoid with anti-inflammatory and neuroprotective effects, on behavior, cognition, and cortical activity in a sample of FTD patients. Read More

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http://dx.doi.org/10.3233/JAD-200426DOI Listing

Apathy and its impact on carer burden and psychological wellbeing in primary progressive aphasia.

J Neurol Sci 2020 Jun 30;416:117007. Epub 2020 Jun 30.

The University of Sydney, School of Psychology, Sydney, NSW, Australia; The University of Sydney, Brain & Mind Centre, Sydney, NSW, Australia. Electronic address:

Objective: While patients with primary progressive aphasia (PPA) typically present with predominant language impairment, behavioural symptoms, such as apathy, are often under-recognised. We aimed to systematically characterise apathy across the three recognised subtypes of PPA, plus atypical right-lateralised presentations of semantic dementia, and to evaluate the impact of apathy on carer burden and psychological wellbeing.

Methods: Baseline assessments from 114 PPA patients were included: 31 left semantic dementia (left SD) 16 right semantic dementia (right SD), 30 progressive nonfluent aphasia (PNFA) and 37 logopenic progressive aphasia (LPA). Read More

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http://dx.doi.org/10.1016/j.jns.2020.117007DOI Listing

C9orf72 arginine-rich dipeptide repeats inhibit UPF1-mediated RNA decay via translational repression.

Nat Commun 2020 Jul 3;11(1):3354. Epub 2020 Jul 3.

Department of Neuroscience, Yale University School of Medicine, New Haven, CT, 06520, USA.

Expansion of an intronic (GGGGCC) repeat region within the C9orf72 gene is a main cause of familial amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). A hallmark of c9ALS/FTD is the accumulation of misprocessed RNAs, which are often targets of cellular RNA surveillance. Here, we show that RNA decay mechanisms involving upstream frameshift 1 (UPF1), including nonsense-mediated decay (NMD), are inhibited in c9ALS/FTD brains and in cultured cells expressing either of two arginine-rich dipeptide repeats (R-DPRs), poly(GR) and poly(PR). Read More

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http://dx.doi.org/10.1038/s41467-020-17129-0DOI Listing

Frontotemporal dementia: Plasma metabolomic signature using gas chromatography-mass spectrometry.

J Pharm Biomed Anal 2020 Jun 16;189:113424. Epub 2020 Jun 16.

Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address:

Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by progressive impairment in behavior, executive function, and language. The behavioral variant (bvFTD) is the most clinical common form and requires differential diagnosis with atypical Alzheimer's disease (AD) cases. This study aimed to investigate the plasma metabolite profile of patients with bvFTD compared to AD patients and cognitively healthy individuals using gas chromatography coupled to mass spectrometry (GCMS). Read More

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http://dx.doi.org/10.1016/j.jpba.2020.113424DOI Listing

Interactions Between Decision-Making and Emotion in Behavioural-Variant Frontotemporal Dementia and Alzheimer's Disease.

Soc Cogn Affect Neurosci 2020 Jul 1. Epub 2020 Jul 1.

The University of Sydney, School of Psychology, Sydney, Australia.

Negative and positive emotions are known to shape decision-making towards more or less impulsive responses respectively. Decision-making and emotion processing are underpinned by shared brain regions including the ventromedio-prefrontal cortex (vmPFC) and the amygdala. How these processes interact at the behavioural and brain levels is still unclear. Read More

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http://dx.doi.org/10.1093/scan/nsaa085DOI Listing

Diagnostic and prognostic value of serum NfL and p-Tau in frontotemporal lobar degeneration.

J Neurol Neurosurg Psychiatry 2020 Jul 1. Epub 2020 Jul 1.

Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

Objective: To assess the diagnostic and prognostic value of serum neurofilament light (NfL) and serum phospho-Tau (p-Tau) in a large cohort of patients with frontotemporal lobar degeneration (FTLD).

Methods: In this retrospective study, performed on 417 participants, we analysed serum NfL and p-Tau concentrations with an ultrasensitive single molecule array (Simoa) approach. We assessed the diagnostic values of serum biomarkers in the differential diagnosis between FTLD, Alzheimer's disease (AD) and healthy ageing; their role as markers of disease severity assessing the correlation with clinical variables, cross-sectional brain imaging and neurophysiological data; their role as prognostic markers, considering their ability to predict survival probability in FTLD. Read More

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http://dx.doi.org/10.1136/jnnp-2020-323487DOI Listing

Neuronal RNA-binding protein dysfunction in multiple sclerosis cortex.

Ann Clin Transl Neurol 2020 Jul 1. Epub 2020 Jul 1.

Department of Anatomy, Physiology and Pharmacology & Cameco MS Neuroscience Research Center, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.

Objective: Neurodegeneration is thought to be the primary cause of neurological disability in multiple sclerosis (MS). Dysfunctional RNA-binding proteins (RBPs) including their mislocalization from nucleus to cytoplasm, stress granule formation, and altered RNA metabolism have been found to underlie neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia. Yet, little is known about the role of dysfunctional RBPs in the pathogenesis of neurodegeneration in MS. Read More

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http://dx.doi.org/10.1002/acn3.51103DOI Listing

Longitudinal clinical, neuropsychological, and neuroimaging characterization of a kindred with a 12-octapeptide repeat insertion in : the next generation.

Neurocase 2020 Jun 30:1-9. Epub 2020 Jun 30.

Department of Neurology, Mayo Clinic , Rochester, MN, USA.

Background: Highly penetrant inherited mutations in the prion protein gene () offer a window to study the pathobiology of prion disorders.

Method: Clinical, neuropsychological, and neuroimaging characterization of a kindred.

Results: Three of four mutation carriers have progressed to a frontotemporal dementia phenotype. Read More

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http://dx.doi.org/10.1080/13554794.2020.1787458DOI Listing

de novo MAPT mutation G335A causes severe brain atrophy, 3R and 4R PHF-tau pathology and early onset frontotemporal dementia.

Acta Neuropathol Commun 2020 Jun 29;8(1):94. Epub 2020 Jun 29.

Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, 808 route de Lennik, Bldg GE, B-1070, Brussels, Belgium.

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http://dx.doi.org/10.1186/s40478-020-00977-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325098PMC

Brief cognitive tests validated in Peru for detection of cognitive impairment A systematic mapping of the scientific literature.

Dement Neuropsychol 2020 Apr-Jun;14(2):134-144

Servicio de Neurología, Instituto Peruano de Neurociencias, Lima, Perú.

Brief cognitive tests (BCTs) are necessary for early detection of cognitive impairment, particularly in primary care settings.

Objective: This report describes a systematic review of BCTs evaluated in Peruvian populations.

Methods: We used systematic mapping techniques to identify articles on screening tests for cognitive impairment involving Peruvian subjects. Read More

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http://dx.doi.org/10.1590/1980-57642020dn14-020006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304273PMC

The role of sequestosome 1/p62 protein in amyotrophic lateral sclerosis and frontotemporal dementia pathogenesis.

Neural Regen Res 2020 Dec;15(12):2186-2194

Harry Perkins Institute of Medical Research, University of Western Australia; Perron Institute for Neurological and Translational Science, Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Nedlands, Western Australia, Australia; Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, Western Australia, Australia.

Amyotrophic lateral sclerosis and frontotemporal lobar degeneration are multifaceted diseases with genotypic, pathological and clinical overlap. One such overlap is the presence of SQSTM1/p62 mutations. While traditionally mutations manifesting in the ubiquitin-associated domain of p62 were associated with Paget's disease of bone, mutations affecting all functional domains of p62 have now been identified in amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients. Read More

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http://dx.doi.org/10.4103/1673-5374.284977DOI Listing
December 2020

Longitudinal structural and metabolic changes in frontotemporal dementia.

Neurology 2020 Jun 26. Epub 2020 Jun 26.

From the Memory and Aging Center, Department of Neurology (A.B., G.T., G.M., Y.C., L.I., J.K., A.M.S., M.G.-T., B.L.M., A.L.B., H.J.R., G.D.R.), and Department of Radiology and Biomedical Imaging (G.D.R.), University of California San Francisco; Frontotemporal Disorders Unit (B.C.D.), Department of Neurology, Massachusetts General Hospital, Boston; and Harvard Medical School, Charleston; Department of Neurology (B.F.B., D.S.K.), Mayo Clinic, Rochester, MN; Molecular Biophysics and Integrated Bioimaging Division (W.J.J., G.D.R.), Lawrence Berkeley National Laboratory, CA; and Helen Wills Neuroscience Institute (G.D.R.), University of California Berkeley.

Objective: To compare the sensitivity of structural MRI and F-fludeoxyglucose PET (FDG-PET) to detect longitudinal changes in frontotemporal dementia (FTD).

Methods: Thirty patients with behavioral variant FTD (bvFTD), 7 with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA), 16 with semantic variant primary progressive aphasia (svPPA), and 43 cognitively normal controls underwent 2-4 MRI and FDG-PET scans (total scans/visit = 270) as part of the Frontotemporal Lobar Degeneration Neuroimaging Initiative study. Linear mixed-effects models were carried out voxel-wise and in regions of interest to identify areas showing decreased volume or metabolism over time in patients as compared to controls. Read More

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http://dx.doi.org/10.1212/WNL.0000000000009760DOI Listing

Decreased salivary lactoferrin levels are specific to Alzheimer's disease.

EBioMedicine 2020 Jun 19:102834. Epub 2020 Jun 19.

Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Spain; Group of Neurodegenerative Diseases, Hospital Universitario 12 de Octubre Research Institute (imas12), 28041 Madrid, Spain. Electronic address:

Background: Evidences of infectious pathogens in Alzheimer's disease (AD) brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary lactoferrin (Lf) levels, one of the major antimicrobial proteins, in AD patients.

Methods: To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-β (Aβ) load using amyloid-Positron-Emission Tomography (PET) neuroimaging, in two different cross-sectional cohorts including patients with different neurodegenerative disorders. Read More

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http://dx.doi.org/10.1016/j.ebiom.2020.102834DOI Listing

Altered levels of CSF proteins in patients with FTD, presymptomatic mutation carriers and non-carriers.

Transl Neurodegener 2020 Jun 23;9(1):27. Epub 2020 Jun 23.

Division of Affinity Proteomics, Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab, Tomtebodavägen 23 A, Alpha 2, 171 65 Solna, Stockholm, Sweden.

Background: The clinical presentations of frontotemporal dementia (FTD) are diverse and overlap with other neurological disorders. There are, as of today, no biomarkers in clinical practice for diagnosing the disorders. Here, we aimed to find protein markers in cerebrospinal fluid (CSF) from patients with FTD, presymptomatic mutation carriers and non-carriers. Read More

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http://dx.doi.org/10.1186/s40035-020-00198-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310563PMC

The effect of semantic memory degeneration on creative thinking: A voxel-based morphometry analysis.

Neuroimage 2020 Jun 20;220:117073. Epub 2020 Jun 20.

The University of Sydney, School of Psychology and Brain and Mind Centre, Camperdown, NSW, 2050, Australia. Electronic address:

Increasing attention is being directed towards explicating the neurocognitive mechanisms of divergent thinking. While neuroimaging studies have tended to dominate the contemporary creativity literature, lesion studies provide important converging evidence by revealing the regions that are not only implicated in, but essential for, task performance. Here we explored the capacity for divergent thinking in semantic dementia (SD), a neurodegenerative disorder characterised by the progressive degeneration of the conceptual knowledge base. Read More

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http://dx.doi.org/10.1016/j.neuroimage.2020.117073DOI Listing

The use of biotelemetry to explore disease progression markers in amyotrophic lateral sclerosis.

Amyotroph Lateral Scler Frontotemporal Degener 2020 Jun 23:1-11. Epub 2020 Jun 23.

Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.

To explore novel, real-world biotelemetry disease progression markers in patients with amyotrophic lateral sclerosis (ALS) and to compare with clinical gold-standard measures. This was an exploratory, non-controlled, non-drug 2-phase study comprising a variable length Pilot Phase (n = 5) and a 48-week Core study Phase (n = 25; NCT02447952). Patients with mild or moderate ALS wore biotelemetry sensors for ∼3 days/month at home, measuring physical activity, heart rate variability (HRV), and speech over 48 weeks. Read More

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http://dx.doi.org/10.1080/21678421.2020.1773501DOI Listing

Mutation Analysis of the Genes Associated with Parkinson's Disease in a Finnish Cohort of Early-Onset Dementia.

J Alzheimers Dis 2020 Jun 17. Epub 2020 Jun 17.

Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland.

Background: Alzheimer's disease, frontotemporal lobar degeneration, dementia with Lewy bodies, and Parkinson's disease (PD) overlap in clinical characteristics, neuropathology, and genetics.

Objective: The aim of this study was to evaluate the role of pathogenic mutations and rare variants in genes associated with PD among early-onset dementia (EOD) patients.

Methods: Rare non-synonymous variants (MAF < 0. Read More

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http://dx.doi.org/10.3233/JAD-200069DOI Listing

Variability of clinical syndromes and cerebral glucose metabolism in symptomatic frontotemporal lobar degeneration associated with progranulin mutations.

Amyotroph Lateral Scler Frontotemporal Degener 2020 Jun 22:1-7. Epub 2020 Jun 22.

Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Munich, Germany.

: The aims of our study were to describe the clinical phenotype and to characterize the cerebral glucose metabolism patterns as measured with fluordesoxyglucose-positron emission tomography (FDG-PET) in symptomatic FTLD-patients with different variants. : For this study, data were included from all patients ( = 10) of a single-center FTLD registry study who had a pathogenic GRN variant and who had undergone a cerebral FDG-PET scan. : An overt variability of clinical phenotypes was identified with half of the cases being not unambiguously classifiable into one of the clinical FTLD subtypes. Read More

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http://dx.doi.org/10.1080/21678421.2020.1779302DOI Listing

Potential for Treatment of Neurodegenerative Diseases with Natural Products or Synthetic Compounds that Stabilize Microtubules.

Curr Pharm Des 2020 Jun 21. Epub 2020 Jun 21.

Institute of Molecular and Translational Medicine, Faculty of Medicin U v H ěvo í á 5 77900 O omou . Czech Republic.

No effective therapeutics to treat neurodegenerative diseases exist, despite significant attempts to find drugs that can reduce or rescue the debilitating symptoms of tauopathies such as Alzheimer's disease, Parkinson's disease, frontotemporal dementia, amyotrophic lateral sclerosis, or Pick's disease. A number of in vitro and in vivo models exist for studying neurodegenerative diseases, including cell models employing induced-pluripotent stem cells, cerebral organoids, and animal models of disease. Recent research has focused on microtubule stabilizing agents, either natural products or synthetic compounds that can prevent the axonal destruction caused by tau protein pathologies. Read More

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http://dx.doi.org/10.2174/1381612826666200621171302DOI Listing

Congenic expression of poly-GA but not poly-PR in mice triggers selective neuron loss and interferon responses found in C9orf72 ALS.

Acta Neuropathol 2020 Jun 19. Epub 2020 Jun 19.

German Center for Neurodegenerative Diseases (DZNE), Munich, 81377, Munich, Germany.

Expansion of a (GC) repeat in C9orf72 causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the link of the five repeat-encoded dipeptide repeat (DPR) proteins to neuroinflammation, TDP-43 pathology, and neurodegeneration is unclear. Poly-PR is most toxic in vitro, but poly-GA is far more abundant in patients. To directly compare these in vivo, we created congenic poly-GA and poly-PR mice. Read More

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http://dx.doi.org/10.1007/s00401-020-02176-0DOI Listing

Psychiatric Manifestation of Anti-LGI1 Encephalitis.

Brain Sci 2020 Jun 16;10(6). Epub 2020 Jun 16.

Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.

Background: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is typically characterized by limbic encephalitis, faciobrachial dystonic seizures and hyponatremia. The frequency with which milder forms of anti-LGI1 encephalitis mimic isolated psychiatric syndromes, such as psychoses, or may lead to dementia if untreated, is largely unknown.

Case Presentation: Here, the authors present a 50-year-old patient who had suffered from neurocognitive deficits and predominant delusions for over one and a half years. Read More

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http://dx.doi.org/10.3390/brainsci10060375DOI Listing

A multi-center study of neurofilament assay reliability and inter-laboratory variability.

Amyotroph Lateral Scler Frontotemporal Degener 2020 Jun 19:1-7. Epub 2020 Jun 19.

Department of Neurology, University of Ulm, Ulm, Germany.

: Significantly elevated levels of neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) have been described in the blood and cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients. The aim of this study was to evaluate the analytical performance of different neurofilament assays in a round robin with 10 centers across Europe/U.S. Read More

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http://dx.doi.org/10.1080/21678421.2020.1779300DOI Listing
June 2020
2.591 Impact Factor

Frontotemporal dementia: a conference report from the 2nd FinFTD Symposium.

Neurodegener Dis Manag 2020 Jun 17. Epub 2020 Jun 17.

Molecular Neurodegeneration group, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.

The 2nd FinFTD Symposium was held on 13 September 2019, in Kuopio, Finland, and attracted 80 attendees from six different countries. The program, spanning from molecular mechanisms to biomarkers, prevention, diagnosis and treatment of frontotemporal lobar degeneration and related diseases, provided a great opportunity for researchers, clinicians, healthcare professionals and other participants to discuss about the current status and future directions of frontotemporal lobar degeneration research. Read More

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http://dx.doi.org/10.2217/nmt-2019-0039DOI Listing

Investigation of Factors Affecting Apathy in Three Major Types of Dementia.

Noro Psikiyatr Ars 2020 Jun 7;57(2):120-125. Epub 2019 Aug 7.

Department of Neurology, Dokuz Eylül University School of Medicine, İzmir, Turkey.

Introducion: Apathy is an important factor in the clinical management of dementia, as it has been associated with poor disease outcome, reduced daily functioning and caregiver distress. Considering apathy as a problem that needs to be managed and knowing the factors affecting apathy will enable appropriate initiatives to be planned. This study was conducted to compare apathy across three types of dementia and determine the factors affecting apathy for each of the three types of dementia. Read More

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http://dx.doi.org/10.29399/npa.22964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285638PMC

Depressive Symptom Profiles Predict Specific Neurodegenerative Disease Syndromes in Early Stages.

Front Neurol 2020 29;11:446. Epub 2020 May 29.

Memory and Aging Center, University of California, San Francisco, San Francisco, CA, United States.

During early stages, patients with neurodegenerative diseases (NDG) often present with depressive symptoms. However, because depression is a heterogeneous disorder, more precise delineation of the specific depressive symptom profiles that arise early in distinct NDG syndromes is necessary to enhance patient diagnosis and care. Five-hundred and sixty four participants self-reported their depressive symptoms using the Geriatric Depression Scale (GDS), including 111 healthy older control subjects (NC) and 453 patients diagnosed with one of six NDGs who were at the mild stage of disease (CDR® Dementia Staging Instrument ≤ 1) [186 Alzheimer's disease (AD), 76 behavioral variant frontotemporal dementia (bvFTD), 52 semantic variant primary progressive aphasia (svPPA), 46 non-fluent variant PPA (nfvPPA), 49 progressive supranuclear palsy syndrome (PSPS), 44 corticobasal syndrome (CBS)]. Read More

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http://dx.doi.org/10.3389/fneur.2020.00446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273507PMC

DSC Brain Perfusion Using Advanced Deconvolution Models in the Diagnostic Work-up of Dementia and Mild Cognitive Impairment: A Semiquantitative Comparison with HMPAO-SPECT-Brain Perfusion.

J Clin Med 2020 Jun 9;9(6). Epub 2020 Jun 9.

Departments of Neuroradiology, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany.

Background: SPECT (single-photon emission-computed tomography) is used for the detection of hypoperfusion in cognitive impairment and dementia but is not widely available and related to radiation dose exposure. We compared the performance of DSC (dynamic susceptibility contrast) perfusion using semi- and fully adaptive deconvolution models to HMPAO-SPECT (99mTc-hexamethylpropyleneamine oxime-SPECT).

Material And Methods: Twenty-seven patients with dementia of different subtypes including frontotemporal dementia (FTD) and mild cognitive impairment (MCI) received a multimodal diagnostic work-up including DSC perfusion at a clinical 3T high-field scanner and HMPAO-SPECT. Read More

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http://dx.doi.org/10.3390/jcm9061800DOI Listing

Amyotrophic lateral sclerosis: a clinical review.

Eur J Neurol 2020 Jun 11. Epub 2020 Jun 11.

KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), Leuven, Belgium.

ALS is a neurodegenerative disorder affecting primarily the motor system, but in which extra-motor manifestations are increasingly recognized. The loss of upper and lower motor neurons in the motor cortex, the brain stem nuclei and the anterior horn of the spinal cord, gives rise to progressive muscle weakness and wasting. ALS often has a focal onset, but subsequently spreads to different body regions, where failure of respiratory muscles typically limits survival to 2-5 years after disease onset. Read More

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http://dx.doi.org/10.1111/ene.14393DOI Listing

Therapeutic Targeting of Proteostasis in Amyotrophic Lateral Sclerosis-a Systematic Review and Meta-Analysis of Preclinical Research.

Front Neurosci 2020 25;14:511. Epub 2020 May 25.

UK Dementia Research Institute, The University of Edinburgh, Edinburgh, United Kingdom.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive fatal neurodegenerative condition. There are no effective treatments. The only globally licensed medication, that prolongs life by 2-3 months, was approved by the FDA in 1995. Read More

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http://dx.doi.org/10.3389/fnins.2020.00511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261930PMC

Clinical and pathologic features of cognitive-predominant corticobasal degeneration.

Neurology 2020 Jun 9. Epub 2020 Jun 9.

From the Departments of Neuroscience (N.S., M.E.M., D.W.D.), Psychiatry and Psychology (O.A.S., O.P.), and Neurology (R.J.U., Z.K.W., N.R.G.-R.), Mayo Clinic, Jacksonville, FL; Department of Neurology (I.L.), University of California San Diego, La Jolla; Department of Neurology (R.D.), Mount Sinai Medical Center, Miami Beach, FL; and Department of Neurology (K.A.J.), Mayo Clinic, Rochester, MN.

Objective: To describe clinical and pathologic characteristics of corticobasal degeneration (CBD) with cognitive predominant problems during the disease course.

Methods: In a series of autopsy-confirmed cases of CBD, we identified patients with cognitive rather than motor predominant features (CBD-Cog), including 5 patients thought to have Alzheimer disease (AD) and 10 patients thought to have behavioral variant frontotemporal dementia (FTD). We compared clinical and pathologic features of CBD-Cog with those from a series of 31 patients with corticobasal syndrome (CBD-CBS). Read More

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http://dx.doi.org/10.1212/WNL.0000000000009734DOI Listing

The behavioral pattern of patients with frontotemporal dementia during the COVID-19 pandemic.

Int Psychogeriatr 2020 Jun 10:1-6. Epub 2020 Jun 10.

Department of psychiatry, Course of Integrated Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

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http://dx.doi.org/10.1017/S104161022000109XDOI Listing

Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders.

Sci Rep 2020 Jun 8;10(1):9161. Epub 2020 Jun 8.

Department of Neurology, Sant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau - IIB Sant Pau, Barcelona, Spain.

Cerebrospinal fluid (CSF) biomarkers are useful in the diagnosis and the prediction of progression of several neurodegenerative diseases. Among them, CSF neurofilament light (NfL) protein has particular interest, as its levels reflect neuroaxonal degeneration, a common feature in various neurodegenerative diseases. In the present study, we analyzed NfL levels in the CSF of 535 participants of the SPIN (Sant Pau Initiative on Neurodegeneration) cohort including cognitively normal participants, patients with Alzheimer disease (AD), Down syndrome (DS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Read More

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http://dx.doi.org/10.1038/s41598-020-66090-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280194PMC

ALS/FTD mutations in UBQLN2 impede autophagy by reducing autophagosome acidification through loss of function.

Proc Natl Acad Sci U S A 2020 Jun 8;117(26):15230-15241. Epub 2020 Jun 8.

Center for Biomedical Engineering and Technology, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201;

Mutations in cause amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerations. However, the mechanism by which the UBQLN2 mutations cause disease remains unclear. Alterations in proteins involved in autophagy are prominent in neuronal tissue of human ALS patients and in a transgenic P497S UBQLN2 mouse model of ALS/FTD, suggesting a pathogenic link. Read More

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http://dx.doi.org/10.1073/pnas.1917371117DOI Listing
June 2020
9.809 Impact Factor

Divergence, Convergence, and Therapeutic Implications: A Cell Biology Perspective of C9ORF72-ALS/FTD.

Mol Neurodegener 2020 Jun 8;15(1):34. Epub 2020 Jun 8.

Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.

Ever since a GGGGCC hexanucleotide repeat expansion mutation in C9ORF72 was identified as the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), three competing but nonexclusive hypotheses to explain how this mutation causes diseases have been proposed and are still under debate. Recent studies in the field have tried to understand how the repeat expansion disrupts cellular physiology, which has suggested interesting convergence of these hypotheses on downstream, functional defects in cells, such as nucleocytoplasmic transport disruption, membrane-less organelle defects, and DNA damage. These studies have not only provided an integrated view of the disease mechanism but also revealed novel cell biology implicated in neurodegeneration. Read More

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http://dx.doi.org/10.1186/s13024-020-00383-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282082PMC

Glia in neurodegeneration: Drivers of disease or along for the ride?

Neurobiol Dis 2020 Jun 6;142:104957. Epub 2020 Jun 6.

Department of Neurology, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA 90095, United States.

While much of the research on neurodegenerative diseases has focused on neurons, non-neuronal cells are also affected. The extent to which glia and other non-neuronal cells are causally involved in disease pathogenesis versus more passively responding to disease is an area of active research. This is complicated by the fact that there is rarely one known cause of neurodegenerative diseases; rather, these disorders likely involve feedback loops that perpetuate dysfunction. Read More

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http://dx.doi.org/10.1016/j.nbd.2020.104957DOI Listing

[Coping and Supporting Patients and Families of Frontotemporal Lobar Degeneration].

Brain Nerve 2020 Jun;72(6):623-632

Department of Psychiatry, Osaka University Graduate School of Medicine.

Frontotemporal lobar degeneration (FTLD) is a comprehensive term encompassing a group of clinically overlapping but heterogeneous conditions with selective frontal and temporal lobar neurodegeneration. Among the three clinical subtypes of FTLD, behavioral variant frontotemporal dementia (bvFTD) and semantic dementia (SD) were specified as "designated intractable diseases" by the Japanese Ministry of Health, Labor and Welfare in 2015. Under this designation system, relatively young patient with bvFTD or SD of certain severities can receive partial financial support from the Japanese local government. Read More

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http://dx.doi.org/10.11477/mf.1416201572DOI Listing

[Evaluation of Semantic Dementia Patient].

Authors:
Kenjiro Komori

Brain Nerve 2020 Jun;72(6):593-610

Room of Psychology, Juzen-Yurinoki Hospital.

Semantic dementia (SD) is a clinical syndrome characterized by selective and progressive semantic memory impairment due to frontotemporal lobar degeneration (FTLD). Semantic memory disorders appear in every cognitive fields, be it language or recognition of familiar people and objects. Left-right asymmetry produces a distinctive clinical symptom of anterior temporal lobe atrophy. Read More

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http://dx.doi.org/10.11477/mf.1416201570DOI Listing

[Symptomatology of Behavioral Variant of Frontotemporal Dementia].

Brain Nerve 2020 Jun;72(6):585-592

Department of Psychiatry, The Jikei University School of Medicine.

In patients with the behavioral variant of frontotemporal dementia, the core clinical phenotype of frontotemporal lobar degeneration, various social behaviors such as disinhibition, apathy, lack of empathy, stereotypy, and changes in eating behavior occur from the onset of the disease, and progresses slowly with frontal lobe damage. Because there are no disease-specific biomarkers, the diagnosis of frontotemporal dementia is based on the evaluation of behavioral symptoms, with neuroimaging methods and cognitive tests as assisting methods. Although diagnostic criteria are useful, frontotemporal dementia may be difficult to differentiate from other conditions, including mental illnesses. Read More

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http://dx.doi.org/10.11477/mf.1416201569DOI Listing

[Frontotemporal Lobar Degeneration: A Historical Overview of the Concept].

Brain Nerve 2020 Jun;72(6):561-573

Department of Neuropsychiatry, Aizu Medical Center, Fukushima Medical School.

Arnold Pick described a focal cortical syndrome caused by focal temporal and/or frontal cortical atrophy, later reffered to as Pick's disease (PiD), a prototype of frontotemporal lobar degeneration (FTLD). In contrast to the current concept of PiD, the presence of Pick bodies (tau-positive inclusions) was not thought to be necessary for the diagnosis of PiD. Four out of the seven patients in his original paper had predominant left temporal atrophy and language related symptoms corresponding to semantic dementia. Read More

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http://dx.doi.org/10.11477/mf.1416201567DOI Listing

Characterization of novel progranulin gene variants in Italian patients with neurodegenerative diseases.

Neurobiol Aging 2020 May 13. Epub 2020 May 13.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bellaria Hospital, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy. Electronic address:

Loss-of-function mutations in the gene encoding for the protein progranulin (PGRN), GRN, are one of the major genetic abnormalities involved in frontotemporal lobar degeneration. However, genetic variations, mainly missense, in GRN have also been linked to other neurodegenerative diseases. We found 12 different pathogenic/likely pathogenic variants in 21 patients identified in a cohort of Italian patients affected by various neurodegenerative disorders. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2020.05.004DOI Listing

Loss of TMEM106B leads to myelination deficits: implications for frontotemporal dementia treatment strategies.

Brain 2020 Jun;143(6):1905-1919

Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.

Genetic variants that define two distinct haplotypes at the TMEM106B locus have been implicated in multiple neurodegenerative diseases and in healthy brain ageing. In frontotemporal dementia (FTD), the high expressing TMEM106B risk haplotype was shown to increase susceptibility for FTD with TDP-43 inclusions (FTD-TDP) and to modify disease penetrance in progranulin mutation carriers (FTD-GRN). To elucidate the biological function of TMEM106B and determine whether lowering TMEM106B may be a viable therapeutic strategy, we performed brain transcriptomic analyses in 8-month-old animals from our recently developed Tmem106b-/- mouse model. Read More

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http://dx.doi.org/10.1093/brain/awaa141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296855PMC

Salience Network Atrophy Links Neuron Type-Specific Pathobiology to Loss of Empathy in Frontotemporal Dementia.

Cereb Cortex 2020 Jun 5. Epub 2020 Jun 5.

Department of Neurology, Memory and Aging Center, University of California San Francisco, 675 Nelson Rising Lane, San Francisco, California 94158, USA.

Each neurodegenerative syndrome reflects a stereotyped pattern of cellular, regional, and large-scale brain network degeneration. In behavioral variant of frontotemporal dementia (bvFTD), a disorder of social-emotional function, von Economo neurons (VENs), and fork cells are among the initial neuronal targets. These large layer 5 projection neurons are concentrated in the anterior cingulate and frontoinsular (FI) cortices, regions that anchor the salience network, a large-scale system linked to social-emotional function. Read More

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http://dx.doi.org/10.1093/cercor/bhaa119DOI Listing

Bipolar Disorder Among Patients Diagnosed With Frontotemporal Dementia.

J Neuropsychiatry Clin Neurosci 2020 Jun 5:appineuropsych20010003. Epub 2020 Jun 5.

Departments of Neurology (Mendez, Parand, Akhlaghipour) and Psychiatry and Biobehavioral Sciences (Mendez), David Geffen School of Medicine, University of California at Los Angeles; and VA Greater Los Angeles Healthcare System (Mendez, Parand).

Objective: Previous studies have documented manic and hypomanic symptoms in behavioral variant frontotemporal dementia (bvFTD), suggesting a relationship between bipolar disorder and bvFTD.

Methods: The investigators conducted a literature review as well as a review of the psychiatric histories of 137 patients with bvFTD, and patients with a prior diagnosis of bipolar disorder were identified. The clinical characteristics of patients' bipolar disorder diagnosis, family history, features of bvFTD, and results from fluorodeoxyglucose positron emission tomography (FDG-PET), as well as autopsy findings, were evaluated. Read More

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http://dx.doi.org/10.1176/appi.neuropsych.20010003DOI Listing

Transcranial stimulation in frontotemporal dementia: A randomized, double-blind, sham-controlled trial.

Alzheimers Dement (N Y) 2020 27;6(1):e12033. Epub 2020 May 27.

Neurology Unit Department of Clinical and Experimental Sciences University of Brescia Brescia Italy.

Introduction: Frontotemporal dementia (FTD) is a progressive disease for which no curative treatment is currently available. We aimed to determine whether transcranial direct current stimulation (tDCS) can modulate intracortical connectivity and improve cognition in symptomatic FTD patients and presymptomatic FTD subjects.

Methods: We performed a double-blind, randomized, sham-controlled trial with anodal tDCS or sham stimulation over the left prefrontal cortex in 70 participants (15 presymptomatic and 55 symptomatic FTD). Read More

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http://dx.doi.org/10.1002/trc2.12033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253155PMC

From basic research to the clinic: innovative therapies for ALS and FTD in the pipeline.

Mol Neurodegener 2020 Jun 1;15(1):31. Epub 2020 Jun 1.

International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, 34149, Trieste, Italy.

Amyotrophic lateral sclerosis (ALS) and Frontotemporal Degeneration (FTD) are neurodegenerative disorders, related by deterioration of motor and cognitive functions and short survival. Aside from cases with an inherited pathogenic mutation, the causes of the disorders are still largely unknown and no effective treatment currently exists. It has been shown that FTD may coexist with ALS and this overlap occurs at clinical, genetic, and molecular levels. Read More

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http://dx.doi.org/10.1186/s13024-020-00373-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268618PMC

Comparison of Prodromal Symptoms of Patients with Behavioral Variant Frontotemporal Dementia and Alzheimer Disease.

Dement Geriatr Cogn Disord 2020 Jun 2:1-9. Epub 2020 Jun 2.

Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland,

Introduction: Behavioral variant frontotemporal dementia (bvFTD) is the most common clinical subtype of frontotemporal lobar degeneration. bvFTD is often characterized by changes in behavior and personality, frequently leading to psychiatric misdiagnoses. On the other hand, substantial clinical overlap with other neurodegenerative diseases, such as Alzheimer disease (AD), further complicates the diagnostics. Read More

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http://dx.doi.org/10.1159/000507544DOI Listing

Decline of cognitive and behavioral functions in amyotrophic lateral sclerosis: a longitudinal study.

Amyotroph Lateral Scler Frontotemporal Degener 2020 Jun 2:1-7. Epub 2020 Jun 2.

ALS Center, Department of Neurology, Azienda Ospedaliera Universitaria Maggiore della Carità, Novara, Italy.

: A cognitive impairment, ranging from frontotemporal dementia (FTD) to milder forms of dysexecutive or behavioral dysfunction, is detected in 30-50% of patients affected by amyotrophic lateral sclerosis (ALS) at diagnosis. Such condition considerably influences the prognosis, and possibly impacts on the decision-making process with regards to end-of-life choices. The aim of our study is to examine the changes of cognitive and behavioral impairment in a large population of ALS from the time of diagnosis to a 6-month follow-up (IQR 5. Read More

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http://dx.doi.org/10.1080/21678421.2020.1771732DOI Listing

Expanding the Phenotype of Frontotemporal Lobar Degeneration With FUS-Positive Pathology (FTLD-FUS).

J Neuropathol Exp Neurol 2020 Jul;79(7):809-812

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Atypical frontotemporal lobar degeneration with ubiquitin-positive inclusions (aFTLD-U) is an uncommon cause of frontotemporal dementia characterized by fused in sarcoma-positive inclusions. It is classified as a subtype of frontotemporal lobar degeneration with FUS pathology. Cases with aFTLD-U pathology typically display an early onset of symptoms and severe psychobehavioral changes in the absence of significant aphasia, cognitive-intellectual dysfunction or motor features. Read More

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http://dx.doi.org/10.1093/jnen/nlaa045DOI Listing