Review
Clinical Neurology
Alejandra Gonzalez-Duarte, Aditi Varma-Doyle, Roy Freeman
Summary: PAF is a peripheral autonomic neurodegenerative disease caused by alpha-synuclein deposition, with chronic features of autonomic failure. Diagnostic biomarkers include skin immunohistochemistry for alpha-synuclein and measuring cerebrospinal fluid alpha-synuclein oligomers. A considerable number of PAF patients may convert to a central alpha-synucleinopathy.
CURRENT OPINION IN NEUROLOGY
(2021)
Article
Neurosciences
Jung Bin Kim, Hayom Kim, Chan-Nyung Lee, Kun-Woo Park, Byung-Jo Kim
Summary: Neurodegenerative changes in the central nervous system have been suggested as a mechanism for autonomic dysfunction in PD. The study found that PD patients with OH had more severe autonomic dysfunction and decreased volume in the right inferior temporal cortex. The association between changes in regional GM volume and visuospatial/visuoperceptual function and autonomic severity scores in PD patients with OH was also identified.
Article
Neurosciences
Martin Iniguez, Antonio Jimenez-Marin, Asier Erramuzpe, Marian Acera, Beatriz Tijero, Ane Murueta-Goyena, Rocio Del Pino, Tamara Fernandez, Mar Carmona-Abellan, Alberto Cabrera-Zubizarreta, Juan Carlos Gomez-Esteban, Jesus M. Cortes, Inigo Gabilondo
Summary: Heart rate variability (HRV) abnormalities are potential early biomarkers in Parkinson's disease (PD), and this study analyzed the synchronization between HRV and brain activity in PD patients using resting-state functional brain MRI. The findings suggest a desynchronization between heart and brain in PD, which has an impact on clinically relevant autonomic outcomes.
NPJ PARKINSONS DISEASE
(2022)
Article
Peripheral Vascular Disease
Andreea Slavescu, Lisa Byrne, Amanda Lavan, Robert Briggs
Summary: This case illustrates the contribution of orthostatic hypotension without typical symptoms to falls in Parkinson's disease. A significant proportion of individuals with severe orthostatic hypotension do not exhibit typical symptoms, and this is even more prevalent in patients with Parkinson's disease. Clinically, this is important as it complicates the attribution of falls to orthostatic hypotension, which can act as a prompt for fall prevention. Therefore, screening and management of orthostatic hypotension in Parkinson's disease patients, regardless of reported symptoms, is crucial to prevent falls.
JOURNAL OF HYPERTENSION
(2023)
Article
Neurosciences
Sang-Won Yoo, Joong-Seok Kim, Yoon-Sang Oh, Dong-Woo Ryu, Seunggyun Ha, Ji-Yeon Yoo, Kwang-Soo Lee
Summary: Reduced uptake of I-123-meta-iodobenzylguanidine (I-123-MIBG) and orthostatic hypotension (OH) are independently associated with worse clinical outcomes of Parkinson's disease (PD). The study also found that patients with OH had worse disease burden compared to those with normal I-123-MIBG uptake. The results suggest that extracranial cardiac markers may reflect disease burden regardless of labile blood pressure influence.
NPJ PARKINSONS DISEASE
(2021)
Article
Clinical Neurology
Sang-Won Yoo, Yoon-Sang Oh, Dong-Woo Ryu, Seunggyun Ha, Chul Hyoung Lyoo, Yuna Kim, Ji-Yeon Yoo, Joong-Seok Kim
Summary: This study aimed to explore subtypes of early Parkinson's disease (PD) patients with cardiac sympathetic denervation and their characteristics. The results showed an association between cardiac denervation subtypes and presynaptic dopamine transporter densities in PD patients. The study also observed an association between cardiac catecholamine capacity and cognition in PD patients.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Katherine Longardner, Aristide Merola, Irene Litvan, Alberto Maria De Stefano, Simona Maule, Fabrizio Vallelonga, Leonardo Lopiano, Alberto Romagnolo
Summary: Cardiovascular dysautonomia was associated with a sevenfold higher risk of developing dementia and a fivefold higher risk of falls in PD patients, as well as significantly higher impairment in ADLs and HRQoL. No relevant associations were found between the other autonomic domains and these outcomes.
JOURNAL OF NEUROLOGY
(2022)
Review
Geriatrics & Gerontology
Shuzhen Zhu, Hualing Li, Xiaoyan Xu, Yuqi Luo, Bin Deng, Xingfang Guo, Yang Guo, Wucheng Yang, Xiaobo Wei, Qing Wang
Summary: Cardiovascular autonomic dysfunctions are common in Parkinson's disease, leading to cognitive dysfunction, falls, and mortality. Both neurogenic and non-neurogenic mechanisms are involved, with baroreflex circulate failure being an important pathogenesis. Treatment options include both pharmacological and non-pharmacological approaches, although drugs that can enhance baroreflex sensitivity, especially by acting on central components, are urgently needed for improved outcomes in scientific research and clinical practice.
Article
Clinical Neurology
Lisanne J. Dommershuijsen, Alis Heshmatollah, Francesco U. S. Mattace Raso, Peter J. Koudstaal, M. Arfan Ikram, M. Kamran Ikram
Summary: Orthostatic hypotension is common in patients with Parkinson's disease (PD), but our study found that it is not significantly associated with an increased risk of PD in the general population.
MOVEMENT DISORDERS
(2021)
Article
Medicine, General & Internal
Hiroaki Fujita, Keitaro Ogaki, Tomohiko Shiina, Hiroki Onuma, Hirotaka Sakuramoto, Katsuya Satoh, Keisuke Suzuki
Summary: CJD with a V180I mutation is the most common form of genetic CJD in Japan. This case report highlights the importance of considering CJD in patients presenting with parkinsonism and cardiac sympathetic nerve denervation, even without a family history of CJD. The reduced uptake of cardiac MIBG scintigraphy in these patients cannot confirm a diagnosis of PD, and further evaluation for genetic CJD should be pursued.
Article
Behavioral Sciences
Jia-jing Wu, Hong Jin, Ying-qi Shao, Cheng-jie Mao, Jing Chen, Chun-feng Liu
Summary: Orthostatic hypotension is a common nonmotor symptom in patients with Parkinson's disease, with impacts on cognition and transcranial sonography findings. Older age is an independent risk factor for OH in PD patients, and there are differences in cognitive function and motor symptom scores between PD-OH and PD-NOH patients. The substantia nigra area may indicate different subtypes of PD or a tendency to develop parkinsonism syndrome.
BRAIN AND BEHAVIOR
(2021)
Article
Health Care Sciences & Services
Chathurini Fernando, Sarah Osborn, Malcolm Horne
Summary: Orthostatic hypotension is common but often unrecognized in Parkinson's Disease (PD). This study found that multiple home blood pressure measurements are more sensitive in detecting orthostatic hypotension, blood pressure variability, and hypertension than a single in clinic measurement.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Clinical Neurology
Yingqi Xing, Qing Li, Erhe Xu, Jingrong Zeng, Qiuping Li, Shanshan Mei, Yang Hua
Summary: This study investigated the changes in dynamic cerebral autoregulation in patients with Parkinson's disease and orthostatic hypotension. The results showed that the autoregulation ability of the brain was impaired in the orthostatic position in patients with symptomatic orthostatic hypotension, and tended to be impaired in the supine position in the orthostatic hypotension population.
FRONTIERS IN NEUROLOGY
(2022)
Article
Neurosciences
Tatiana Usnich, Henrike Hanssen, Katja Lohmann, Christina Lohse, Christine Klein, Meike Kasten, Norbert Bruggemann
Summary: This study found that PD patients carrying variants in the GBA gene are more likely to experience orthostatic symptoms compared to IPD patients. The drop in systolic blood pressure during posture changes suggests a close involvement of the autonomic nervous system in GBA-PD.
JOURNAL OF PARKINSONS DISEASE
(2022)
Article
Geriatrics & Gerontology
Kui Chen, Kangshuai Du, Yichen Zhao, Yongzhe Gu, Yanxin Zhao
Summary: This study identified distinct trajectories of orthostatic blood pressure changes in Parkinson's disease patients, including rapidly increasing, low-stable, and high-stable classes. Male sex, lower supine diastolic blood pressure, and lower total protein levels were significant predictors of a rapidly increasing Delta SBP trajectory.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Letter
Endocrinology & Metabolism
Masaaki Hirayama, Kinji Ohno
ANNALS OF NUTRITION AND METABOLISM
(2022)
Article
Clinical Neurology
Aya Ogura, Kazuya Kawabata, Hirohisa Watanabe, Shao Wei Choy, Epifanio Bagarinao, Toshiyasu Kato, Kazunori Imai, Michihito Masuda, Reiko Ohdake, Kazuhiro Hara, Ryoichi Nakamura, Naoki Atsuta, Tomohiko Nakamura, Masahisa Katsuno, Gen Sobue
Summary: In this study, a novel framework for diffusion-weighted imaging analysis called Fixel-based analysis (FBA) was used to investigate white matter changes in ALS patients. The findings showed reduced fiber density and morphology in the bilateral corticospinal tracts and corpus callosum of ALS patients. Clinical scores were negatively correlated with fiber density values in the corticospinal tracts.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Geriatrics & Gerontology
Genki Tohnai, Ryoichi Nakamura, Naoki Atsuta, Masahiro Nakatochi, Naoki Hayashi, Daisuke Ito, Hazuki Watanabe, Hirohisa Watanabe, Masahisa Katsuno, Yuishin Izumi, Akira Taniguchi, Kazuaki Kanai, Mitsuya Morita, Osamu Kano, Satoshi Kuwabara, Masaya Oda, Koji Abe, Masashi Aoki, Ikuko Aiba, Koichi Okamoto, Kouichi Mizoguchi, Tomohiko Ishihara, Akihiro Kawata, Takanori Yokota, Kazuko Hasegawa, Isao Nagano, Ichiro Yabe, Fumiaki Tanaka, Satoshi Kuru, Nobutaka Hattori, Kenji Nakashima, Ryuji Kaji, Gen Sobue
Summary: This study aimed to determine the frequencies and characteristics of DNAJC7 gene variants in a Japanese ALS cohort. Rare missense variants and one splice-site variant of DNAJC7 were detected in 807 Japanese patients with sporadic ALS. The variants were located around the TPR domain and the estimated frequency of DNAJC7 variants in Japanese ALS patients was 0.87%.
NEUROBIOLOGY OF AGING
(2022)
Article
Neurosciences
Epifanio Bagarinao, Hirohisa Watanabe, Satoshi Maesawa, Kazuya Kawabata, Kazuhiro Hara, Reiko Ohdake, Aya Ogura, Daisuke Mori, Noritaka Yoneyama, Kazunori Imai, Takamasa Yokoi, Toshiyasu Kato, Shuji Koyama, Masahisa Katsuno, Toshihiko Wakabayashi, Masafumi Kuzuya, Minoru Hoshiyama, Haruo Isoda, Shinji Naganawa, Norio Ozaki, Gen Sobue
Summary: The aging brain undergoes structural changes even in healthy individuals. Quantifying these changes can help distinguish between pathological changes and those associated with normal aging. Different brain regions are affected differently during the aging process, with some regions showing longitudinal decline and others mainly affected by cross-sectional changes.
Review
Biochemistry & Molecular Biology
Toshiharu Nagatsu, Akira Nakashima, Hirohisa Watanabe, Shosuke Ito, Kazumasa Wakamatsu
Summary: Parkinson's disease is an aging-related neurodegenerative disease characterized by movement disorders and deficiency of dopamine. Lewy bodies and abnormal accumulation of neuromelanin are the histopathological hallmarks of Parkinson's disease, leading to cell death of dopamine neurons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Kazuki Watanabe, Mitsuko Nakashima, Rie Wakatsuki, Tomoyasu Bunai, Yasuomi Ouchi, Tomohiko Nakamura, Hiroaki Miyajima, Hirotomo Saitsu
Summary: This study investigated the genetic basis and brain metabolism and blood flow of a Japanese family with spinocerebellar degeneration (SCD). Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were performed, but no likely pathogenic variants were identified. ExpansionHunter Denovo detected repeat expansions in the RFC1 gene, leading to the diagnosis of RFC1-related disorders. The patients showed a variety of clinical features, including motor neuropathy and cognitive impairment. Imaging studies revealed cortical damage in some patients, while others showed no apparent cerebral damage.
NEUROLOGY-GENETICS
(2022)
Article
Clinical Neurology
Masashi Suzuki, Tomohiko Nakamura, Masaaki Hirayama, Masamichi Ueda, Mai Hatanaka, Yumiko Harada, Masahiro Nakatochi, Daisuke Nakatsubo, Satoshi Maesawa, Ryuta Saito, Koichi Fujiwara, Masahisa Katsuno
Summary: This study examined the HRV in Parkinson's disease patients using wearable sensors and found that the minimum values of SDNN and CVRR were significantly decreased in PD. Analyzing these minimum values in long-term recordings may be appropriate for detecting the decrease in HRV in PD.
JOURNAL OF NEURAL TRANSMISSION
(2022)
Article
Clinical Neurology
Aiko Okuma, Tomohiko Nakamura, Masahisa Katsuno, Tadashi Matsushita
Summary: This study examined the relationship between the immature development of the myelin sheath in children and the occurrence of bimodal waveforms in sensory nerve conduction studies. The findings showed that the frequency of bimodal waveforms and interpeak latency decreased with age, indicating that the bimodal waveform is present until the age of 15-16 years. This suggests that the underlying cause of the bimodal waveform is an immature myelin sheath.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Ryota Torii, Atsushi Hashizume, Shinichiro Yamada, Daisuke Ito, Yoshiyuki Kishimoto, Hideyuki Moriyoshi, Tomonori Inagaki, Ryoichi Nakamura, Tomohiko Nakamura, Tameto Naoi, Mitsuya Morita, Masahisa Katsuno
Summary: This study aimed to investigate the clinical and electrophysiologic features of female carriers and early-stage male patients with SBMA. The results showed that female carriers experienced mild muscle weakness in neck flexion and a slow walking speed, along with changes in neurogenic biomarkers.
Article
Clinical Neurology
Noriko Nishikawa, Miho Murata, Taku Hatano, Yohei Mukai, Yuji Saitoh, Takashi Sakamoto, Takashi Hanakawa, Yuichi Kamei, Hisateru Tachimori, Kenji Hatano, Hiroshi Matsuda, Yosuke Taruno, Nobukatsu Sawamoto, Yuta Kajiyama, Kensuke Ikenaka, Kazuya Kawabata, Tomohiko Nakamura, Hirotaka Iwaki, Hiroshi Kadotani, Yukiyoshi Sumi, Yuichi Inoue, Toshihiro Hayashi, Takeshi Ikeuchi, Yasushi Shimo, Hideki Mochizuki, Hirohisa Watanabe, Nobutaka Hattori, Yuji Takahashi, Ryosuke Takahashi
Summary: iRBD is a specific prodromal symptom of synucleinopathies, including PD. The J-PPMI study aimed to investigate biomarkers in Japanese iRBD patients. DaT and MIBG were found to be important biomarkers for confirming synucleinopathies, with a majority of patients meeting PD diagnostic criteria.
PARKINSONISM & RELATED DISORDERS
(2022)
Article
Environmental Sciences
Jun Ueyama, Mai Hayashi, Masaaki Hirayama, Hiroshi Nishiwaki, Mikako Ito, Isao Saito, Yoshio Tsuboi, Tomohiko Isobe, Kinji Ohno
Summary: Animal experiments suggest that pesticides may impact gut microbiota and the production of SCFAs and polyamines. This study investigated the relationship between pesticide exposure and fecal SCFAs and polyamines in Japanese adults. The findings indicate that OP exposure is independently associated with lower fecal acetate levels, possibly affecting the health of middle-aged and older adults. Further studies on a wider age range, including children, are needed to fully understand the long-term effects of pesticide exposure on gut health.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2023)
Article
Neurosciences
Hiroshi Nishiwaki, Jun Ueyama, Kenichi Kashihara, Mikako Ito, Tomonari Hamaguchi, Tetsuya Maeda, Yoshio Tsuboi, Masahisa Katsuno, Masaaki Hirayama, Kinji Ohno
Summary: Gut microbiota and fecal bile acids analysis in patients with alpha-synucleinopathies revealed decreased short-chain fatty acids-producing genera in dementia with Lewy bodies (DLB) and increased Ruminococcus torques and Collinsella. Random forest models showed that high Ruminococcus torques, high Collinsella, and low Bifidobacterium were predictive of DLB. In DLB, increased production of ursodeoxycholic acid (UDCA) may mitigate neuroinflammation at the substantia nigra.
NPJ PARKINSONS DISEASE
(2022)
Review
Clinical Neurology
Hirohisa Watanabe, Sayuri Shima, Yasuaki Mizutani, Akihiro Ueda, Mizuki Ito
Summary: This review summarizes the improvements in understanding the pathophysiology and early clinical symptoms of multiple system atrophy (MSA), as well as advancements in diagnostic methods and disease-modifying therapies for the condition. The introduction of new diagnostic criteria in 2022 and the use of artificial intelligence and machine learning in neuroimaging have significantly improved diagnostic accuracy. Treatment advancements, including immunotherapy against alpha-synuclein and stem cell therapies, show promise in targeting different aspects of the disease.
JOURNAL OF MOVEMENT DISORDERS
(2023)
Review
Clinical Neurology
Toshiharu Nagatsu, Akira Nakashima, Hirohisa Watanabe, Shosuke Ito, Kazumasa Wakamatsu, Fabio A. Zucca, Luigi Zecca, Moussa Youdim, Maximilian Wulf, Peter Riederer, Johannes M. Dijkstra
Summary: The dark pigment neuromelanin (NM) is abundant in dopamine (DA) neurons in the substantia nigra (SN) and norepinephrine (NE) neurons in the locus coeruleus (LC) in the human brain. During the progression of Parkinson's disease (PD), NM levels in these neurons decrease. The synthesis pathway involves conversion of tyrosine to L-DOPA, then to DA or NE, followed by autoxidation and conversion to eumelanic or pheomelanic NM.
JOURNAL OF NEURAL TRANSMISSION
(2023)
Review
Neurosciences
Masaaki Hirayama, Hiroshi Nishiwaki, Tomonari Hamaguchi, Kinji Ohno
Summary: Parkinson's disease (PD) is characterized by the accumulation of alpha-synuclein fibrils (Lewy bodies) in the brain, starting from the intestinal neural plexus. The gut microbiota plays a role in intestinal and brain pathologies, with increased Akkermansia degrading the intestinal mucus layer and reducing regulatory T cells, while decreased short-chain fatty acids (SCFAs) contribute to microglial activation. In dementia with Lewy bodies (DLB), specific genera may mitigate neuroinflammation. Modulating the gut microbiota and its metabolites may have potential therapeutic effects for PD and Lewy body diseases.
NPJ PARKINSONS DISEASE
(2023)
Article
Clinical Neurology
Jun-Pyo Hong, Hanim Kwon, Euyhyun Park, Sun-Uk Lee, Chan-Nyoung Lee, Byung-Jo Kim, Ji-Soo Kim, Kun-Woo Park
Summary: In patients with mild-to-moderate PD, vestibular function assessed by video head-impulse tests appears relatively preserved and has minimal impact on the risk of falls. Risk of postural instability is associated with the severity of clinical symptoms in PD.
PARKINSONISM & RELATED DISORDERS
(2024)
Article
Clinical Neurology
Yaqin Xiang, XiuRong Huang, Qian Xu, Zhenhua Liu, Yase Chen, Qiying Sun, Junling Wang, Hong Jiang, Lu Shen, Xinxiang Yan, Beisha Tang, Jifeng Guo
Summary: Using the novel data-driven method DEBM, this study determined the sequence of several common biomarker changes in Parkinson's disease (PD). The left putamen was found to be the earliest biomarker to become abnormal, followed by the right putamen, CSF alpha-synuclein, right caudate, left caudate, and serum NfL. The estimated disease stages showed significant differences between PD and healthy controls, and achieved a high accuracy for distinguishing PD from HC.
PARKINSONISM & RELATED DISORDERS
(2024)
Article
Clinical Neurology
Yan Li, David J. McLernon, Carl E. Counsell, Angus D. Macleod
Summary: This study aimed to investigate the incidence and risk factors for institutionalisation in Parkinson's disease (PD) and atypical parkinsonism (AP). The study found that institutionalisation was more frequent in AP compared to PD and controls. Age, poorer cognition, and more-severe parkinsonian impairment were independent predictors of institutionalisation.
PARKINSONISM & RELATED DISORDERS
(2024)