Review
Clinical Neurology
Ito Kawakami, Jun-ichi Iga, Sho Takahashi, Yi-Ting Lin, Hiroshige Fujishiro
Summary: Senile depression is a heterogeneous syndrome that shows different clinical features compared to early-life depression. It may either be a risk factor for developing dementia or an early stage of dementia. The inconsistent findings regarding the association between senile depression and incident dementia may be due to the neuropathological heterogeneity underlying senile depression.
PSYCHIATRY AND CLINICAL NEUROSCIENCES
(2022)
Article
Multidisciplinary Sciences
Senthil T. Kumar, Anne-Laure Mahul-Mellier, Ramanath Narayana Hegde, Gwladys Riviere, Rani Moons, Alain Ibanez de Opakua, Pedro Magalhaes, Iman Rostami, Sonia Donzelli, Frank Sobott, Markus Zweckstetter, Hilal A. Lashuel
Summary: The E83Q mutation in alpha-synuclein accelerates fibrillization and leads to the formation of fibrils with distinct structural and dynamic properties. In cells, this mutation is associated with increased levels of aSyn, accumulation of p5129, and higher toxicity. In a neuronal seeding model, the E83Q mutation enhances fibril internalization, induces higher seeding activity, and results in the formation of diverse aSyn pathologies.
Article
Neurosciences
Young-Gun Lee, Seong Ho Jeong, Mincheol Park, Sung Woo Kang, Kyoungwon Baik, Seun Jeon, Phil Hyu Lee, Young Ho Sohn, Byoung Seok Ye
Summary: The coexistence of Alzheimer's disease pathology is common in Parkinson's disease. This study explores the implications of genetic risk scores for Alzheimer's disease (GRS-AD) in Parkinson's disease (PD). Higher GRS-AD and CSF p-tau/A beta are associated with cognitive decline in PD patients.
NPJ PARKINSONS DISEASE
(2022)
Article
Multidisciplinary Sciences
Pai-Yi Chiu, Fu-Chi Yang, Ming-Jang Chiu, Wei-Che Lin, Cheng-Hsien Lu, Shieh-Yueh Yang
Summary: This study investigated the combination of different biomarkers in AD, PD, and FTD and found that plasma biomarkers were consistent with pathology. This provides promise for the precise assessment of AD, PD, and FTD in clinical practice.
SCIENTIFIC REPORTS
(2022)
Article
Clinical Neurology
Masanori Kurihara, Hiroki Komatsu, Renpei Sengoku, Mari Shibukawa, Satoru Morimoto, Tomoyasu Matsubara, Akira Arakawa, Makoto Orita, Kenji Ishibashi, Akihiko Mitsutake, Shota Shibata, Hiroyuki Ishiura, Kaori Adachi, Kensuke Ohse, Keiko Hatano, Ryoko Ihara, Mana Higashihara, Yasushi Nishina, Aya Midori Tokumaru, Kenji Ishii, Yuko Saito, Shigeo Murayama, Kazutomi Kanemaru, Atsushi Iwata
Summary: This study aimed to investigate whether CSF biomarkers, including p-tau181, are altered in patients with Neuronal intranuclear inclusion disease (NIID). The results showed that CSF p-tau181 was significantly increased in NIID patients, and among those with elevated p-tau181, only a few patients had decreased CSF A beta 42. Additionally, CSF HVA and 5-HIAA concentrations were significantly higher in NIID patients.
Review
Clinical Neurology
Zina Hijazi, Nawaf Yassi, John T. O'Brien, Rosie Watson
Summary: This review examines cerebrovascular lesions in Lewy body dementia (LBD), finding that white matter changes and cerebral microbleeds are common pathological features. Compared to Parkinson's disease without dementia and age-matched controls, LBD patients have increased severity of white matter changes, which is not supported by neuropathological examination. The prevalence of cerebral microbleeds in LBD varies greatly, but is similar to Alzheimer's disease. Larger studies are needed to assess the impact of cerebrovascular lesions on clinical symptoms, disease progression, and outcomes.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
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
Clinical Neurology
Georges Naasan, Suzanne M. Shdo, Estrella Morenas Rodriguez, Salvatore Spina, Lea Grinberg, Lucia Lopez, Anna Karydas, William W. Seeley, Bruce L. Miller, Katherine P. Rankin
Summary: This study compared the rates and content of psychosis in patients with different neurodegenerative diseases. It found that patients with Lewy body disease/Alzheimer's disease pathology were more likely to have hallucinations, while patients with FTLD-TDP were more likely to have delusions. The data suggests that the nature and content of psychosis can provide valuable information about underlying neurodegenerative pathology.
Article
Clinical Neurology
Inigo Ruiz Barrio, Yasuo Miki, Zane T. Jaunmuktane, Thomas Warner, Eduardo De Pablo-Fernandez
Summary: This study aims to evaluate the association between orthostatic hypotension (OH) and dementia risk in patients with Parkinson disease (PD), as well as cognitive impairment risk in patients with multiple system atrophy (MSA). The study found that early OH increases the risk of cognitive impairment in patients with PD and MSA, but not its symptom severity. Further research is needed to determine if treating OH can modify the risk of dementia in these conditions.
Article
Clinical Neurology
Johanna Nilsson, Katheryn A. Q. Cousins, Johan Gobom, Erik Portelius, Alice Chen-Plotkin, Leslie M. Shaw, Murray Grossman, David J. Irwin, John Q. Trojanowski, Henrik Zetterberg, Kaj Blennow, Ann Brinkmalm
Summary: This study quantified synaptic proteins in the cerebrospinal fluid of patients with neurodegenerative diseases and healthy controls, and identified potential biomarkers for synaptic dysfunction in these diseases. The study also found differential patterns of synaptic protein alterations across different neurodegenerative diseases.
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
David J. Koss, Daniel Erskine, Andrew Porter, Pawel Palmoski, Hariharan Menon, Olivia G. J. Todd, Marta Leite, Johannes Attems, Tiago F. Outeiro
Summary: Through a multidisciplinary approach, this study confirms the presence of nuclear alpha-synuclein in the brains of patients with dementia with Lewy bodies, which may undergo pathogenic modifications and contribute to the disease phenotype.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Neurosciences
Xiaoli Si, Tao Guo, Zhiyun Wang, Yi Fang, Luyan Gu, Lanxiao Cao, Wenyi Yang, Ting Gao, Zhe Song, Jun Tian, Xinzhen Yin, Xiaojun Guan, Cheng Zhou, Jingjing Wu, Xueqin Bai, Xiaocao Liu, Guohua Zhao, Minming Zhang, Jiali Pu, Baorong Zhang
Summary: This study used diffusion tensor image analysis to evaluate glymphatic system dysfunction in patients with iRBD and PD, and found correlations with disease severity and cognitive decline. However, further verification of the potential for assessing alpha-synucleinopathy progression using glymphatic system evaluation is needed, as well as the development of more imaging methods.
NPJ PARKINSONS DISEASE
(2022)
Article
Neurosciences
Xuan Yu, Marine Persillet, Ling Zhang, Yu Zhang, Sun Xiuping, Xianglei Li, Gao Ran, Ludivine S. Breger, Sandra Dovero, Gregory Porras, Benjamin Dehay, Erwan Bezard, Chuan Qin
Summary: The study demonstrated that disease is not transmitted through the bloodstream in a mouse model injected with patient-derived alpha-synuclein aggregates.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Geriatrics & Gerontology
Henika Patel, Pablo Martinez, Abigail Perkins, Xavier Taylor, Nur Jury, David McKinzie, Cristian A. Lasagna-Reeves
Summary: Pathological aggregation of tau and neuroinflammatory changes are crucial in the clinical course of Alzheimer's disease and related tauopathies. The PS19 mouse model study suggests that different pathological tau species may be associated with different functional deficits, and neuroinflammation may contribute to functional deficits independently of tau pathology.
NEUROBIOLOGY OF AGING
(2022)
Article
Clinical Neurology
Ece Bayram, David G. Coughlin, Irene Litvan
Summary: This study found that AD copathology is associated with worsened cognitive decline and reduced likelihood of LB clinical phenotype. Women with more severe AD copathology had worse cognitive decline and higher likelihood of AD clinical phenotype. Men with more severe AD copathology had lower likelihood of LB clinical phenotype.
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Thomas F. Tropea, Teresa Waligorska, Sharon X. Xie, Ilya M. Nasrallah, Katheryn A. Q. Cousins, John Q. Trojanowski, Murray Grossman, David J. Irwin, Daniel Weintraub, Edward B. Lee, David A. Wolk, Alice S. Chen-Plotkin, Leslie M. Shaw
Summary: The objective of this study was to determine if plasma tau phosphorylated at threonine 181 (p-tau181) can distinguish Alzheimer's disease (AD) from normal cognition (NC) in adults, predict cognitive and functional decline, and validate findings in an external cohort. The results showed that plasma p-tau181 can accurately differentiate AD pathology from NC, and higher levels of p-tau181 are associated with faster cognitive and functional decline.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Letter
Clinical Neurology
Thomas F. Tropea, Isabela Albuja, Katheryn A. Q. Cousins, David J. Irwin, Edward B. Lee, Alice S. Chen-Plotkin
ANNALS OF NEUROLOGY
(2023)
Article
Clinical Neurology
Alexandra L. Young, Jacob W. Vogel, John L. Robinson, Corey T. McMillan, Rik Ossenkoppele, David A. Wolk, David J. Irwin, Lauren Elman, Murray Grossman, Virginia M. Y. Lee, Edward B. Lee, Oskar Hansson
Summary: Through data-driven disease progression modelling, a fine-grained empirical staging system for TAR DNA-binding protein-43 (TDP-43) proteinopathies has been established, which can accurately classify frontotemporal lobar degeneration due to TDP-43 (FTLD-TDP), amyotrophic lateral sclerosis (ALS) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). The study reveals substantial heterogeneity in the progression patterns of ALS and FTLD-TDP, and highlights the need for further investigation in larger cross-cohort studies.
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
Clinical Neurology
Danielle S. Abraham, Thanh Phuong Pham Nguyen, Leah J. Blank, Dylan Thibault, Shelly L. Gray, Sean Hennessy, Charles E. Leonard, Daniel Weintraub, Allison W. Willis
Summary: This study examined the differential prescribing patterns between new and established treatments for common neurological conditions. Using data from a national sample of US commercially insured adults from 2005-2019, the study compared new users of recently approved medications for three conditions: diabetic peripheral neuropathy, Parkinson disease psychosis, and epilepsy. The results showed that newer medications were more frequently prescribed to individuals with prior treatment, suggesting potential bias in comparative effectiveness and safety studies. The study emphasizes the importance of reporting propensity score non-overlap in comparative studies involving newer medications and suggests methodological approaches to address channeling bias.
Review
Clinical Neurology
David G. Coughlin, David J. Irwin
Summary: Several advances have been made in fluid and tissue-based biomarkers for Parkinson's disease (PD) and other synucleinopathies in the last few years. Immunohistochemistry, immunofluorescence, and alpha-synuclein seeding amplification assays now offer a crucial advancement in identifying different species of alpha-synuclein in PD patients. Co-pathology of Alzheimer's disease (AD) is commonly found in PD and dementia with Lewy bodies (DLB), and biofluid biomarkers for tau and amyloid beta species can detect this co-pathology.
Article
Clinical Neurology
Daniel Weintraub, Marina Picillo, Hyunkeun Ryan Cho, Chelsea Caspell-Garcia, Cornelis Blauwendraat, Ethan G. Brown, Lana M. Chahine, Christopher S. Coffey, Roseanne D. Dobkin, Tatiana Foroud, Doug Galasko, Karl Kieburtz, Kenneth Marek, Kalpana Merchant, Brit Mollenhauer, Kathleen L. Poston, Tanya Simuni, Andrew Siderowf, Andrew Singleton, John Seibyl, Caroline M. Tanner
Summary: This study used data from a multi-site, international, prospective cohort study to investigate the impact of dopamine system-related biomarkers on cognitive impairment in Parkinson's disease. The results showed that alterations in the dopamine system were associated with the development of cognitive impairment in Parkinson's disease. If confirmed causative, these findings suggest that the dopamine system is instrumental to cognitive health status throughout the disease course.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Review
Medical Laboratory Technology
Ju Hee Kang, Magdalena Korecka, Edward B. Lee, Katheryn A. Q. Cousins, Thomas F. Tropea, Alice A. Chen-Plotkin, David J. Irwin, David Wolk, Magdalena Brylska, Yang Wan, Leslie M. Shaw
Summary: Development of validated biomarkers for early detection of Alzheimer's disease neuropathology is crucial for therapeutic trials. Although CSF and neuroimaging biomarkers have limitations, there is a growing focus on accelerating the development of blood-based AD biomarkers. The use of the AT(N) classification by CSF and imaging biomarkers provides a more objective diagnosis of AD. Blood-based AD biomarkers can be utilized as screening tools in therapeutic trials and clinical care.
CLINICAL CHEMISTRY
(2023)
Article
Clinical Neurology
Daniel Weintraub
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Min Chen, Sarah Burke, Christopher A. Olm, David J. Irwin, Lauren Massimo, Edward B. Lee, John Q. Trojanowski, James C. Gee, Murray Grossman
Summary: Chen et al. used graph-theoretic analyses of antemortem, multimodal MRIs to examine spreading pathology in structural networks of those with autopsy-confirmed frontotemporal lobar degeneration with either tau or transactional DNA binding protein of similar to 43 kDa inclusions. They report distinct patterns of long-range and short-range network degradation between the two pathologies, suggesting different mechanisms for their spread.
BRAIN COMMUNICATIONS
(2023)
Article
Clinical Neurology
Sanjana Shellikeri, Sunghye Cho, Sharon Ash, Carmen Gonzalez-Recober, Corey T. Mcmillan, Lauren Elman, Colin Quinn, Defne A. Amado, Michael Baer, David J. Irwin, Lauren Massimo, Christopher A. Olm, Mark Y. Liberman, Murray Grossman, Naomi Nevler
Summary: This study evaluated the effectiveness of automated digital speech measures in assessing bulbar motor impairments in patients with ALS-FTD spectrum disorders. The results showed that vowel measures derived from spontaneous speech were able to effectively assess bulbar dysfunction, with greater sensitivity and specificity compared to traditional assessments such as speaking rate.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Clinical Neurology
Vindhya Koneru, Alberto J. Espay, Allan J. Cole, Daniel Weintraub, Kathleen Crist, Maria B. Pascual, William G. Ondo
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Daniel Weintraub
MOVEMENT DISORDERS
(2023)
