Article
Clinical Neurology
M. -Marsel Mesulam, Christina A. Coventry, Eileen H. Bigio, Jaiashre Sridhar, Nathan Gill, Angela J. Fought, Hui Zhang, Cynthia K. Thompson, Changiz Geula, Tamar Gefen, Margaret Flanagan, Qinwen Mao, Sandra Weintraub, Emily J. Rogalski
Summary: Primary progressive aphasia is a neurodegenerative disease that selectively impairs language function. Autopsies and longitudinal studies have shown that primary progressive aphasia has various neuropathological changes, with Alzheimer's disease being the most common. Different variants of primary progressive aphasia have distinct neuropathological correlates, and word comprehension impairments are strong predictors of underlying neuropathology. Different types of primary progressive aphasia have different patterns of cortical atrophy, but all show severe damage to the left hemisphere language network. This study is important for understanding the neuropathological and clinical differences in primary progressive aphasia.
Article
Geriatrics & Gerontology
Pan Li, Wei Quan, Zengguang Wang, Ying Liu, Hao Cai, Yuan Chen, Yan Wang, Miao Zhang, Zhiyan Tian, Huihong Zhang, Yuying Zhou
Summary: This study found that AD patients had a higher prevalence of vascular disease associated factors compared to FTLD group, and the first symptoms of AD were mainly cognitive impairment, while FTLD patients mainly exhibited behavioral abnormalities as early manifestations.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Neurosciences
Maxwell L. Eliott, Lindsay C. Hanford, Aya Hamadeh, Tom Hilbert, Tobias Kober, Bradford C. Dickerson, Ross W. Mair, Mark C. Eldaief, Randy L. Buckner
Summary: T1-weighted structural MRI is widely used for measuring brain morphometry, but it is uncertain if rapid scans are adequate for quantitative morphometry. Comparisons with an adopted 1.0 mm resolution scan showed that rapid scans can largely replace longer scans, but with lower reliability in midline regions and regions with susceptibility-induced artifacts.
Article
Clinical Neurology
John L. Robinson, Sharon X. Xie, Daniel R. Baer, EunRan Suh, Vivianna M. Van Deerlin, Nicholas J. Loh, David J. Irwin, Corey T. McMillan, David A. Wolk, Alice Chen-Plotkin, Daniel Weintraub, Theresa Schuck, Virginia M. Y. Lee, John Q. Trojanowski, Edward B. Lee
Summary: In this retrospective study, the incidence of 10 pathologies in neurodegenerative disease (ND) and normal aging was examined, with up to seven pathologies observed concurrently resulting in 161 different combinations. The presence of multiple additive pathologies was associated with factors such as longer disease duration, clinical dementia, older age, and APOE e4 status.
Article
Medicine, General & Internal
Chih-Yun Kuo, Hsin-Yi Tseng, Ivo Stachiv, Chon-Haw Tsai, Yi-Chun Lai, Tomas Nikolai
Summary: Neuropsychological tests are widely used for dementia assessment in clinical practice and are also important for differentiating between Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), especially in the initial clinical presentations of behavioral variants of frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA). However, the overlapping signs and cultural differences raise concerns about the validity and reliability of these tests. This case series combined NPTs with neuroimaging to examine their effectiveness in distinguishing between AD and FTLD, and the results showed that participants diagnosed with FTLD had lower scores in language and social cognition tests compared to AD participants, while PPA participants had lower scores in the Free and Cued Selective Reminding Test compared to bvFTD participants.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Xiao-Ming Wang, Peng Zeng, Ying-Yan Fang, Teng Zhang, Qing Tian
Summary: Research has found that deficiencies in PGRN and its hydrolytic products play important roles in the pathogenesis of neurodegenerative dementia, including various pathological changes. With therapeutic strategies targeting PGRN developed in various models, PGRN is highlighted as a potential target for anti-neurodegenerative treatment in dementia.
JOURNAL OF NEUROCHEMISTRY
(2021)
Review
Neurosciences
Kevin Carvalho, Elodie Martin, Aurelia Ces, Nadege Sarrazin, Pauline Lagouge-Roussey, Caroline Nous, Leyna Boucherit, Ihsen Youssef, Annick Prigent, Emilie Faivre, Sabiha Eddarkaoui, Thibaut Gauvrit, Didier Vieau, Susana Boluda, Vincent Huin, Bertrand Fontaine, Luc Buee, Benoit Delatour, Patrick Dutar, Florian Sennlaub, Xavier Guillonneau, David Blum, Cecile Delarasse
Summary: The purinergic receptor P2X7 plays a crucial role in Alzheimer's disease and Tauopathies, with deletion of P2X7 having significant effects on inflammatory mediators and memory function in Tau pathology. P2X7 inhibitors may be ideal drugs for treating these neurodegenerative diseases.
PROGRESS IN NEUROBIOLOGY
(2021)
Review
Clinical Neurology
Michael J. J. Strong, Michael Swash
Summary: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two seemingly disparate syndromes, but they share common molecular vulnerabilities. The relationship between ALS and FTD is not based on unique neuroanatomic correlations, but rather on shared underlying mechanisms.
Article
Biochemistry & Molecular Biology
Giacomina Rossi, Erika Salvi, Luisa Benussi, Elkadia Mehmeti, Andrea Geviti, Sonia Bellini, Antonio Longobardi, Alessandro Facconi, Matteo Carrara, Cristian Bonvicini, Roland Nicsanu, Claudia Saraceno, Martina Ricci, Giorgio Giaccone, Giuliano Binetti, Roberta Ghidoni
Summary: This study investigated the role of variants in lysosomal genes in the age of onset of genetic FTLD. The researchers found that the p.Asn521Thr variant in the PINK1 gene was associated with earlier disease onset in GRN/C9orf72 pedigrees. Understanding the mechanisms behind this modulating effect could be critical for identifying biomarkers and designing drugs to modify the age of onset in FTLD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Tomohiro Umeda, Rumi Uekado, Keiko Shigemori, Hiroshi Eguchi, Takami Tomiyama
Summary: The cell-to-cell transmission of tau aggregates plays a crucial role in the spread of tau pathology in diseases like Alzheimer's. Recent research suggests that tau oligomers, rather than fibrils, are responsible for this process. A study in mice showed that intranasal rifampicin can inhibit the accumulation of tau oligomers and improve cognitive function in tauopathy. This suggests that intranasal rifampicin could be a potential treatment for halting the progression of tauopathy by inhibiting the propagation of tau oligomers.
Article
Clinical Neurology
Katherine P. Rankin, Gianina Toller, Lauren Gavron, Renaud La Joie, Teresa Wu, Tal Shany-Ur, Patrick Callahan, Maggie Krassner, Joel H. Kramer, Bruce L. Miller
Summary: The Social Behavior Observer Checklist (SBOCL) was developed as a 3-minute tool to help non-experts identify patients with neurodegenerative diseases based on patterns of interpersonal behavior. The checklist showed good reliability and predictive value, with specific subscale scores linked to different syndromes.
FRONTIERS IN NEUROLOGY
(2021)
Article
Clinical Neurology
Ignacio Illan-Gala, Victor Montal, Sergi Borrego-Ecija, Maria Luisa Mandelli, Neus Falgas, Ariane E. Welch, Jordi Pegueroles, Miguel Santos-Santos, Alexandre Bejanin, Daniel Alcolea, Oriol Dols-Icardo, Olivia Belbin, M. Belen Sanchez-Saudinos, Nuria Bargallo, Sofia Gonzalez-Ortiz, Albert Llado, Rafael Blesa, Bradford C. Dickerson, Howard J. Rosen, Bruce L. Miller, Alberto Lleo, Maria Luisa Gorno-Tempini, Raquel Sanchez-Valle, Juan Fortea
Summary: Cortical mean diffusivity shows promise as a sensitive biomarker for the study of the neurodegeneration-related microstructural changes in primary progressive aphasia (PPA). Increases in cortical mean diffusivity are correlated with cortical thinning and disease severity in PPA patients.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Neuroimaging
M. Dylan Tisdall, Daniel T. Ohm, Rebecca Lobrovich, Sandhitsu R. Das, Gabor Mizsei, Karthik Prabhakaran, Ranjit Ittyerah, Sydney Lim, Corey T. McMillan, David A. Wolk, James Gee, John Q. Trojanowski, Edward B. Lee, John A. Detre, Paul Yushkevich, Murray Grossman, David J. Irwin
Summary: Frontotemporal lobar degeneration (FTLD) encompasses a range of neurodegenerative diseases characterized by proteinopathies, including Tau and TDP-43. Clinical differentiation between these subtypes is challenging, but integrated MRI and histopathology studies may help distinguish FTLD-Tau and FTLD-TDP.
NEUROIMAGE-CLINICAL
(2022)
Review
Biochemistry & Molecular Biology
Daniel W. Sirkis, Luke W. Bonham, Taylor P. Johnson, Renaud La Joie, Jennifer S. Yokoyama
Summary: This article reviews the clinical features, pathological changes, genetic variations, and research advances in early-onset Alzheimer's disease (EOAD). The research found that the integration of fluid biomarker research, multimodal imaging, and various 'omics techniques can improve the diagnostic accuracy of EOAD and enhance understanding of pathological changes. Additionally, genetic analysis of EOAD provides insights into the formation of AD tau pathology.
MOLECULAR PSYCHIATRY
(2022)
Article
Clinical Neurology
Takashi Kurashige, Hiroyuki Morino, Tomomi Murao, Yuishin Izumi, Tomohito Sugiura, Kazuya Kuraoka, Hideshi Kawakami, Tsuyoshi Torii, Hirofumi Maruyama
Summary: The study aims to identify and characterize the histopathology of peripheral axons in the skeletal muscle of patients with ALS. The results suggest that axonal pTDP-43 accumulations may be characteristic for patients with ALS, and it could be a potential novel diagnostic biomarker for ALS.
Review
Clinical Neurology
Barbara Borroni, Caroline Graff, Orla Hardiman, Albert C. Ludolph, Fermin Moreno, Markus Otto, Marco Piccininni, Anne M. Remes, James B. Rowe, Harro Seelaar, Elka Stefanova, Latchezar Traykov, Giancarlo Logroscino
Summary: FRONTIERS is a European research study aimed at improving the understanding of FTLD-related disorders and their epidemiology, with the goal of promoting appropriate public health service policies and treatment strategies.
ALZHEIMERS & DEMENTIA
(2022)
Article
Geriatrics & Gerontology
Minna Alenius, Tiia Ngandu, Sanna Koskinen, Ilona Hallikainen, Tuomo Haenninen, Mira Karrasch, Miia Kivipelto, Minna M. Raivio, Marja-Liisa Laakkonen, Johanna Krueger, Noora-Maria Suhonen, Laura Hokkanen
Summary: This study examined the impact of education, age, and gender on cognitive screening for early Alzheimer's disease and found that education was the strongest predictor of cognitive performance. Corrected cutoff scores based on education had better accuracy in differentiating between the control group and AD patients.
DEMENTIA AND GERIATRIC COGNITIVE DISORDERS
(2022)
Article
Geriatrics & Gerontology
Samuli Huttula, Henri Vayrynen, Seppo Helisalmi, Laura Kytovuori, Laura Luukkainen, Mikko Hiltunen, Anne M. Remes, Johanna Kruger
Summary: Early-onset dementia (EOD) has a strong genetic component. This study identified a variant in the NDUFA1 gene that may be associated with neurodegenerative dementia in EOD patients.
NEUROBIOLOGY OF AGING
(2022)
Article
Neurosciences
Laura Kytovuori, Jussi Sipila, Hiroshi Doi, Anri Hurme-Niiranen, Ari Siitonen, Eriko Koshimizu, Satoko Miyatake, Naomichi Matsumoto, Fumiaki Tanaka, Kari Majamaa
Summary: An intronic expansion in the RFC1 gene has been shown to cause cerebellar ataxia, neuropathy, and vestibular areflexia syndrome. This study found that the expansion is also present in some patients with Parkinson's disease.
NPJ PARKINSONS DISEASE
(2022)
Article
Clinical Neurology
Sami Heikkinen, Antti Cajanus, Kasper Katisko, Paivi Hartikainen, Ritva Vanninen, Annakaisa Haapasalo, Johanna Kruger, Anne M. Remes, Eino Solje
Summary: EP symptoms are associated with neuroimaging changes in PSP, CBD, and bvFTD patients, with significant pathological changes in the brain stem and SCP region in EP+ patients.
JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Helmi Soppela, Kasper Katisko, Yasmine Gadola, Johanna Kruger, Paivi Hartikainen, Antonella Alberici, Alberto Benussi, Anne Koivisto, Annakaisa Haapasalo, Anne M. Remes, Barbara Borroni, Eino Solje
Summary: The study highlights significant differences in modifiable factors such as education level and heart diseases in FTD patients, with Finnish FTD patients showing lower prevalence of hypertension compared to controls. Additionally, distinct profiles of modifiable factors were observed in different clinical phenotypes of FTD.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Psychology, Multidisciplinary
Minna Alenius, Laura Hokkanen, Sanna Koskinen, Ilona Hallikainen, Tuomo Haenninen, Mira Karrasch, Minna M. Raivio, Marja-Liisa Laakkonen, Johanna Krueger, Noora-Maria Suhonen, Miia Kivipelto, Tiia Ngandu
Summary: The study aimed to evaluate the feasibility of using real-world register data to identify persons with mild Alzheimer's disease (AD) and to describe their cognitive performance at the time of diagnosis. The results showed that patients with late-onset AD performed the worst in word list recognition, while patients with mixed cerebrovascular disease and AD performed the worst in constructional praxis and clock drawing tests.
FRONTIERS IN PSYCHOLOGY
(2022)
Article
Clinical Neurology
Anita Korpioja, Johanna Kruger, Anri Hurme-Niiranen, Eino Solje, Kasper Katisko, Joonas Lipponen, Maria Lehtilahti, Anne M. Remes, Kari Majamaa, Laura Kytovuori
Summary: The biallelic repeat expansion (AAGGG)(exp) in RFC1 is associated with neurodegeneration and cognitive impairment. This study found that patients with biallelic (AAGGG)(exp) exhibit cognitive symptoms, with some resembling frontotemporal dementia.
PARKINSONISM & RELATED DISORDERS
(2022)
Article
Clinical Neurology
Kasper Katisko, Nadine Huber, Tarja Kokkola, Paivi Hartikainen, Johanna Kruger, Anna-Leena Heikkinen, Veera Paananen, Ville Leinonen, Ville E. Korhonen, Seppo Helisalmi, Sanna-Kaisa Herukka, Valentina Cantoni, Yasmine Gadola, Silvana Archetti, Anne M. Remes, Annakaisa Haapasalo, Barbara Borroni, Eino Solje
Summary: This study found that total levels of TDP-43 in the serum are decreased in patients with frontotemporal dementia (FTD), especially in those with C9orf72 repeat expansion or concomitant motoneuron disease (FTD-MND) phenotype. Serum-based measurement of TDP-43 may serve as a useful tool for predicting TDP-43 neuropathology associated with C9orf72 repeat expansion and FTD-MND in future diagnostics and intervention studies.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Neurosciences
Helmi Soppela, Johanna Krueger, Paivi Hartikainen, Anne Koivisto, Annakaisa Haapasalo, Barbara Borroni, Anne M. Remes, Kasper Katisko, Eino Solje
Summary: In this retrospective case-control study, the relationship between traumatic brain injury (TBI) and frontotemporal dementia (FTD) was evaluated. The results showed a higher prevalence of TBI in FTD patients and an association with earlier onset of symptoms. These findings suggest that TBI may be a triggering factor for FTD.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Clinical Neurology
Giancarlo Logroscino, Marco Piccininni, Caroline Graff, Orla Hardiman, Albert C. Ludolph, Fermin Moreno, Markus Otto, Anne M. Remes, James B. Rowe, Harro Seelaar, Eino Solje, Elka Stefanova, Latchezar Traykov, Vesna Jelic, Melissa Taheri Rydell, Niall Pender, Sarah Anderl-Straub, Myriam Barandiaran, Alazne Gabilondo, Johanna Kruger, Alexander G. Murley, Timothy Rittman, Emma L. van der Ende, John C. van Swieten, Paeivi Hartikainen, Gorana Mandic Stojmenovic, Shima Mehrabian, Luisa Benussi, Antonella Alberici, Maria Teresa Dell'Abate, Chiara Zecca, Barbara Borroni
Summary: This study examined the incidence of frontotemporal lobar degeneration (FTLD)-associated syndromes in Europe and found that they are more common than previously recognized, warranting diagnosis at any age. The findings have important implications for health and social care planning, as well as the design of future clinical trials.
Article
Neurosciences
Jussi O. T. Sipila, Laura Kytovuori, Tuomas Rauramaa, Hugo Rauhamaa, Valtteri Kaasinen, Kari Majamaa
Summary: Several heterozygous variants of the GBA1 gene have been linked to increased risk of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). GBA1-associated PD is more severe than idiopathic PD, and more severe variants are associated with worse clinical phenotypes. A family with a heterozygous p.Pro454Leu variant in GBA1 is reported, which is associated with a diverse range of severe and rapidly progressive neurodegenerative diseases with Lewy bodies. Pathogenicity prediction algorithms and evolutionary analyses suggest that p.Pro454Leu is deleterious.
NPJ PARKINSONS DISEASE
(2023)
Article
Neurosciences
Kasper Katisko, Johanna Kruger, Helmi Soppela, Paivi Hartikainen, Aivi Hartikainen, Annakaisa Haapasalo, Anne M. Remes, Eino Solje
Summary: Patients with frontotemporal dementia (FTD) often receive psychiatric misdiagnoses and are treated with off-label psychopharmacological medications prior to diagnosis. Female gender and behavioral variant of FTD phenotype alongside with depressive and psychotic symptoms are associated with the use of these medications.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Clinical Neurology
Anna-Leena Heikkinen, Veera Tikkanen, Tuomo Hanninen, Christer Hublin, Anne M. Koivisto, Toni T. Saari, Anne M. Remes, Teemu I. Paajanen, Johanna Kruger
Summary: This study examined the suitability of two screening tools (IFS and FAB) in assessing early-onset dementia and cognitive impairment patients. The results suggest that the IFS may be more reliable than the FAB in detecting executive dysfunction.
JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
(2023)
Article
Clinical Neurology
Henrik Ahvenjarvi, Marja Niiranen, Sakari Simula, Paivi Hamalainen, Helja-Marja Surcel, Anne M. Remes, Mervi Ryytty, Johanna Kruger
Summary: This study aimed to investigate the effects of demographic and clinical characteristics, as well as lifestyle risk factors on experienced fatigue and health-related quality of life (HRQoL) among different types of relapsing remitting multiple sclerosis (RRMS) patients. The study found that fatigue and HRQoL were negatively correlated, with more severe disease types associated with higher levels of fatigue and lower HRQoL. Age, disease course, and changes in treatment were also associated with worsened fatigue and HRQoL.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2023)