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Neurochem Res 2022 May 20. Epub 2022 May 20.

Department of Biomedical Engineering, School of Medicine, Vietnam National University Ho Chi Minh City (VNU-HCM), Ho Chi Minh City, 700000, Vietnam.

Parkinson's disease (PD) is a common central nervous system disorder (CNS) characterized by cell loss in the substantia nigra. Severe loss of dopaminergic neurons and Lewy body formation with α-synuclein inclusions are the main neuropathological features of PD. There's currently no cure for PD, but treatments are available to help relieve the symptoms and maintain quality of life. Read More

Cell Death Discov 2022 May 20;8(1):267. Epub 2022 May 20.

Department of Physiology, School of Medicine, Jinan University, 510632, Guangzhou, China.

Mounting evidence suggests the key role of brain-derived neurotrophic factor (BDNF) in the dopaminergic neurotoxicity of Parkinson's disease (PD). Activation of NF-E2-related factor-2 (Nrf2) and inhibition of methyl CpG-binding protein 2 (MeCP2) can regulate BDNF upregulation. However, the regulation of BDNF by Nrf2 and MeCP2 in the PD pathogenesis has not been reported. Read More

Brain 2022 May 20. Epub 2022 May 20.

The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal H3A 2B4, Canada.

Isolated REM sleep behaviour disorder (iRBD) is a synucleinopathy characterized by abnormal behaviours and vocalizations during REM sleep. Most iRBD patients develop dementia with Lewy bodies, Parkinson's disease, or multiple system atrophy over time. Patients with iRBD exhibit brain atrophy patterns that are reminiscent of those observed in overt synucleinopathies. Read More

Alzheimers Dement (N Y) 2022 11;8(1):e12294. Epub 2022 May 11.

Department of Neurology University of Pennsylvania Philadelphia Pennsylvania USA.

Introduction: Lewy body diseases are pathologically characterized by α-synuclein pathology. Alzheimer's disease (AD) co-pathology can influence phenotypes. In vivo AD biomarkers can suggest the presence of this co-pathology in unusual cases, but pathological validation remains essential. Read More

Neurochem Res 2022 May 19. Epub 2022 May 19.

Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-ku, Tokyo, 162-8480, Japan.

Potentially druggable mechanisms underlying synaptic deficits seen in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are under intense interrogations. In addition to defective synaptic vesicle trafficking, cytoskeletal disruption, autophagic perturbation, and neuroinflammation, hyperphosphorylation of microtubule-associated protein collapsin response mediator protein 2 (CRMP2, also known as DPYSL2) is newly determined to correlate with synaptic deficits in human DLB. The small molecule experimental therapeutic, lanthionine ketimine-5-ethyl ester (LKE), appears to interact with CRMP2 in a host of neurodegenerative mouse models, normalizing its phosphorylation level while promoting healthful autophagy in cell culture models and suppressing the proinflammatory phenotype of activated microglia. Read More

Brain Nerve 2022 May;74(5):692-699

Division of General Education (Neurology), Faculty of Health & Medical Care, Saitama Medical University.

Aged patients with dementia with Lewy body (DLB) present with delusional misidentification syndrome and occasionally Capgras' syndrome. It is difficult to treat the DLB patients presenting with these psychiatric symptoms, as well as dementia, parkinsonism, sleep disorders, and autonomic dysfunction. In advanced stage of DLB, it is necessary to pay careful attentions to the appropriate choice of drugs as well as to improve the environment surrounding the DLB patients. Read More

Brain Nerve 2022 May;74(5):685-691

Department of Neuropsychiatry, Ashikaga Red Cross Hospital.

The treatment and care for severe psychiatric symptoms associated with dementia with Lewy bodies is challenging. This is especially true for elderly patients because the use of antipsychotics is associated with an attendant mortality risk. In this article, dementia patients with Lewy bodies who presented with severe psychiatric symptoms such as Capgras syndrome (delusional misidentification syndrome), are described, and pharmacological and non-pharmacological strategies to address these symptoms are discussed. Read More

Parkinsons Dis 2022 9;2022:5535826. Epub 2022 May 9.

University of Maryland, School of Medicine, Department of Neurology, Baltimore, MD, USA.

Background: The American Academy of Neurology Parkinson Disease (PD) quality measures include an annual diagnostic review.

Objective: To investigate the frequency and pattern of changes in diagnoses between PD and other causes of parkinsonism.

Methods: This prospective longitudinal cohort study included consented patients diagnosed with PD at least once and a minimum of two times at the Movement Disorders Center between 2002 and 2017. Read More

Transl Neurodegener 2022 May 17;11(1):29. Epub 2022 May 17.

ForeFront Parkinson's Disease Research Clinic, Brain and Mind Centre, School of Medical Sciences, University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia.

Front Aging Neurosci 2022 27;14:778093. Epub 2022 Apr 27.

Department of Psychiatry, School of Medicine, University of Cantabria, University Hospital Marqués de Valdecilla, Santander, Spain.

Background: Neurodegenerative diseases might affect social cognition in various ways depending on their components (theory of mind, emotional processing, attribution bias, and social perception) and the subtype of dementia they cause. This review aims to explore this difference in cognitive function among individuals with different aetiologies of dementia.

Methods: The following databases were explored: MEDLINE via PubMed, Cochrane Library, Lilacs, Web of Science, and PsycINFO. Read More

Front Aging Neurosci 2022 27;14:806000. Epub 2022 Apr 27.

Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, Italy.

Idiopathic Parkinson's disease (PD) is characterized by progressive loss of dopaminergic (DA) neurons during aging. The pathological hallmark of PD is the Lewy body detected in postmortem brain tissue, which is mainly composed of aggregated α-Synuclein (αSyn). However, it is estimated that 90% of PD cases have unknown pathogenetic triggers. Read More

Int J Mol Sci 2022 May 6;23(9). Epub 2022 May 6.

Brain Research Institute, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor 47500, Malaysia.

The neuropathological substrate of dementia with Lewy bodies (DLB) is defined by the inextricable cross-seeding accretion of amyloid-β (Aβ) and α-synuclein (α-syn)-laden deposits in cholinergic neurons. The recent revelation that neuropeptide kisspeptin-10 (KP-10) is able to mitigate Aβ toxicity via an extracellular binding mechanism may provide a new horizon for innovative drug design endeavors. Considering the sequence similarities between α-syn's non-amyloid-β component (NAC) and Aβ's C-terminus, we hypothesized that KP-10 would enhance cholinergic neuronal resistance against α-syn's deleterious consequences through preferential binding. Read More

Int J Mol Sci 2022 Apr 19;23(9). Epub 2022 Apr 19.

Experimental Neurology Laboratory, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.

The degeneration of nigral dopaminergic neurons is considered the hallmark of Parkinson's disease (PD), and it is triggered by different factors, including mitochondrial dysfunction, Lewy body accumulation, neuroinflammation, excitotoxicity and metal accumulation. Despite the extensive literature devoted to unravelling the signalling pathways involved in neuronal degeneration, little is known about the functional impairments occurring in these cells during illness progression. Of course, it is not possible to obtain direct information on the properties of the dopaminergic cells in patients. Read More

Brain 2022 May 12. Epub 2022 May 12.

IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Italy.

Multiple system atrophy (MSA) is characterized by accumulation of phosphorylated α-synuclein (p-syn) as glial cytoplasmic inclusions in the brain and a specific biomarker for this disorder is urgently needed. We aimed at investigating if p-syn can also be detected in skin Remak non-myelinating Schwann cells (RSCs) as Schwann cell cytoplasmic inclusions (SCCi) and may represent a reliable clinical biomarker for MSA. This cross-sectional diagnostic study evaluated skin p-syn in 96 patients: 46 with probable MSA (29 MSA-P and 17 MSA-C), 34 with Parkinson's disease (PD) and 16 with dementia with Lewy bodies (DLB). Read More

Acta Neuropathol 2022 May 12. Epub 2022 May 12.

Department of Biostatics and Bioinformatics, Duke University Medical Center, Durham, USA.

Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is most often seen in the oldest-old (≥ 90 years of age) but can also be present in the younger-old (< 90 years of age). In this study, we compared the neuropathological associations of LATE-NC and contribution of LATE-NC to cognitive impairment between the oldest-old and younger-old. We observed significant differences in the prevalence of LATE-NC and its association with other co-pathologies in these two age groups. Read More

Neurology 2022 May 12. Epub 2022 May 12.

Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China

Background And Objectives: Individuals with a history of recurrent dream-enactment behaviors, but with subthreshold REM sleep without atonia levels for REM sleep behavior disorder (RBD) diagnosis, are currently classified to have prodromal RBD (pRBD). However, the REM sleep elevated EMG diagnostic cut-off, progression trajectory, and long-term neurodegenerative outcome of pRBD are not well understood. This study aimed to delineate the evolution of REM sleep EMG levels, determine the EMG cut-off score for diagnosing pRBD, and examine the risk for neurodegenerative diseases of pRBD. Read More

NPJ Parkinsons Dis 2022 May 12;8(1):59. Epub 2022 May 12.

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

Focused ultrasound (FUS) thalamotomy is an emerging treatment for tremor-dominant Parkinson's disease (PD). We report the first postmortem neuropathologic study of FUS thalamotomy in a 68-year-old man with tremor-dominant PD, which was performed seven months before he died. Although the peak voxel temperature at the target was <54 °C, his tremor improved on intraoperative and postoperative assessments. Read More

Mov Disord 2022 May 9. Epub 2022 May 9.

Parkinson and Other Movement Disorders Center, Department of Neurosciences, University of California San Diego, La Jolla, California, USA.

Background: Lewy body (LB) dementias have limited clinical diagnostic accuracy because of frequent copathologies contributing to clinical heterogeneity. Although sex differences in clinical prevalence and frequency of pure LB pathology were shown, differences for clinicopathological correlations are less known.

Objective: The aim of this study was to determine sex differences for clinical associations of Alzheimer's disease (AD) copathology in those with LB pathology. Read More

Front Genet 2022 21;13:880997. Epub 2022 Apr 21.

School of Life Sciences, Shanghai University, Shanghai, China.

Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease, and many other disease types, cause cognitive dysfunctions such as dementia via the progressive loss of structure or function of the body's neurons. However, the etiology of these diseases remains unknown, and diagnosing less common cognitive disorders such as vascular dementia (VaD) remains a challenge. In this work, we developed a machine-leaning-based technique to distinguish between normal control (NC), AD, VaD, dementia with Lewy bodies, and mild cognitive impairment at the microRNA (miRNA) expression level. Read More

Neurobiol Aging 2022 Mar 19;116:12-15. Epub 2022 Mar 19.

Institute for Memory Impairments and Neurologic Disorders, University of California, Irvine, CA, USA; Department of Neurology, University of California, Irvine, CA, USA; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.

Cognitive resilience provides insights into maintaining good cognition despite dementia-related neuropathologic changes. It is of special interest in the oldest-old (age 90+) because age is the strongest risk factor for dementia. We describe the only participant of The 90+ Study, among 367 autopsies, who maintained normal cognition despite intermediate-high levels of 3 dementia-related neuropathologic changes, advanced age, and comorbidities associated with cognitive impairment. Read More

ACS Chem Neurosci 2022 May 6;13(10):1549-1557. Epub 2022 May 6.

Department of Medicinal Chemistry, The University of Minnesota, Minneapolis, Minnesota 55455, United States.

Synaptic and cognitive deficits mediated by a severe reduction in excitatory neurotransmission caused by a disproportionate accumulation of the neuronal protein tau in dendritic spines is a fundamental mechanism that has been found repeatedly in models of tauopathies, including Alzheimer's disease, Lewy body dementia, frontotemporal dementia, and traumatic brain injury. Synapses thus damaged may contribute to dementia, among the most feared cause of debilitation in the elderly, and currently there are no treatments to repair them. Caspase-2 (Casp2) is an essential component of this pathological cascade. Read More

Cell Mol Life Sci 2022 May 5;79(5):283. Epub 2022 May 5.

Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, Italy.

Mitochondria play important roles in the regulation of key cellular processes, including energy metabolism, oxidative stress response, and signaling towards cell death or survival, and are distinguished by carrying their own genome (mtDNA). Mitochondrial dysfunction has emerged as a prominent cellular mechanism involved in neurodegeneration, including Parkinson's disease (PD), a neurodegenerative movement disorder, characterized by progressive loss of dopaminergic neurons and the occurrence of proteinaceous Lewy body inclusions. The contribution of mtDNA variants to PD pathogenesis has long been debated and is still not clearly answered. Read More

Neurobiol Aging 2022 Jul 9;115:88-108. Epub 2022 Apr 9.

Faculty of Medical Sciences, Translational and Clinical Research Institute, Newcastle University, Newcastle, UK.

Please modify the Abstract as follows:Here we tested if the reactivity of posterior resting-state electroencephalographic (rsEEG) alpha rhythms from the eye-closed to the eyes-open condition may differ in patients with dementia due to Lewy Bodies (DLB) and Alzheimer's disease (ADD) as a functional probe of the dominant neural synchronization mechanisms regulating the vigilance in posterior visual systems.We used clinical, demographical, and rsEEG datasets in 28 older adults (Healthy), 42 DLB, and 48 ADD participants. The eLORETA freeware was used to estimate cortical rsEEG sources. Read More

Alzheimers Dement (Amst) 2022 2;14(1):e12306. Epub 2022 May 2.

Division of Neurology, Department of Medicine University of Toronto Toronto Ontario Canada.

Introduction: Disability is common across Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). White matter hyperintensities (WMHs) are prevalent in both diagnoses and associated with disability; both diagnoses show neuropsychiatric symptoms (NPS) and impaired cognition.

Methods: In AD and DLB, we examined if WMHs, NPS, and cognition associate with basic and/or instrumental activities of daily living (BADLs and/or IADLs) cross-sectionally, and longitudinally over ≈1. Read More

Health Sci Rep 2022 May 2;5(3):e590. Epub 2022 May 2.

Centre for Age-Related Medicine (SESAM) Stavanger University Hospital Stavanger Norway.

Background And Aims: In older adults with dementia, low body mass index (BMI) is associated with higher mortality and other adverse health outcomes. BMI or nutritional status trajectories from diagnosis have not yet been well described in dementia, especially in people with Lewy body dementia (LBD); a group that has a poorer prognosis. With this study, we aimed to evaluate the BMI trajectory in people diagnosed with mild LBD and Alzheimer's disease (AD). Read More

EBioMedicine 2022 Apr 29;80:104021. Epub 2022 Apr 29.

MODAG GmbH, Wendelsheim, Germany; Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Germany. Electronic address:

Background: Synucleinopathies such as Parkinson ́s disease (PD), Dementia with Lewy bodies (DLB) and Multiple System Atrophy (MSA) are characterized by deposition of misfolded and aggregated α-synuclein. Small aggregates (oligomers) of α-synuclein have been shown to be the most relevant neurotoxic species and are targeted by anle138b, an orally bioavailable small molecule compound which shows strong disease-modifying effects in animal models of synucleinopathies.

Methods: Anle138b was studied in a single-centre, double-blind, randomised, placebo-controlled single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy subjects. Read More

Free Neuropathol 2022 Jan 23;3(9). Epub 2022 Mar 23.

Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA.

Background: Seeding of pathology related to Alzheimer's disease (AD) and Lewy body disease (LBD) by tissue homogenates or purified protein aggregates in various model systems has revealed prion-like properties of these disorders. Typically, these homogenates are injected into adult mice stereotaxically. Injection of brain lysates into newborn mice represents an alternative approach of delivering seeds that could direct the evolution of amyloid-β (Aβ) pathology co-mixed with either tau or α-synuclein (αSyn) pathology in susceptible mouse models. Read More

Front Neurol 2022 13;13:839539. Epub 2022 Apr 13.

Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, China.

Psychiatric-onset dementia with Lewy bodies (DLB) might include symptoms of depression, hallucinations, anxiety, and apathy. Here, we report a patient with DLB with recurrent panic attacks as her first symptom 5 years before a biological-based diagnosis of probable DLB. We provide an extended description of the clinical presentation and course from psychiatric-onset DLB to dementia in an 83-year-old woman. Read More

J Alzheimers Dis 2022 Apr 25. Epub 2022 Apr 25.

Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Department of Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.

Background: The majority of individuals with dementia will suffer from behavioral and psychological symptoms of dementia (BPSD). These symptoms contribute to functional impairment and caregiver burden.

Objective: To characterize BPSD in Alzheimer's disease (AD), vascular dementia (VaD), mixed (Mixed) dementia, Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and unspecified dementia in individuals residing in long-term care facilities. Read More

Transl Neurodegener 2022 05 2;11(1):24. Epub 2022 May 2.

ForeFront Parkinson's Disease Research Clinic, Brain and Mind Centre, School of Medical Sciences, University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia.

The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer's or Parkinson's disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. Read More