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Dopamine dementia

Masayuki Nakamori, Eunsung Junn, Hideki Mochizuki, M Maral Mouradian
Parkinson's disease (PD) is a progressive neurodegenerative disorder that is diagnosed largely on clinical grounds due to characteristic motor manifestations that result from the loss of nigrostriatal dopaminergic neurons. While traditional pharmacological approaches to enhance dopamine levels, such as with L-dopa, can be very effective initially, the chronic use of this dopamine precursor is commonly plagued with motor response complications. Additionally, with advancing disease, non-motor manifestations emerge, including psychosis and dementia that compound patient disability...
February 12, 2019: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Ryuji Sakakibara, Fuyuki Tateno, Yosuke Aiba, Tsuyoshi Ogata, Masahiko Kishi, Hitoshi Terada, Tsutomu Inaoka, Tomoya Nakatsuka, Katsuyoshi Matsuoka
Objectives: Neuroimaging markers for Parkinson's disease (PD)/dementia with Lewy bodies (DLB) include dopamine transporter (DAT) scanning and metaiodobenzylguanidine (MIBG) myocardial scintigraphy. It is unknown which marker is useful to identify the premotor phase PD/DLB. We reported four patients who, during a negative DAT scan period, had a positive MIBG result that suggested premotor PD/DLB. Here we report 18 additional patients. Methods: This study was a prospective cohort study...
January 2019: Movement Disorders Clinical Practice
Dong-Hee Choi, In-Ae Choi, Cheol Soon Lee, Ji Hee Yun, Jongmin Lee
The neuropathology of Parkinson's disease with dementia (PDD) has been reported to involve heterogeneous and various disease mechanisms. Alpha-synuclein (α-syn) and amyloid beta (Aβ) pathology are associated with the cognitive status of PDD, and NADPH oxidase (NOX) is known to affect a variety of cognitive functions. We investigated the effects of NOX on cognitive impairment and on α-syn and Aβ expression and aggregation in PDD. In the 6-hydroxydopamine (6-OHDA)-injected mouse model, cognitive and motor function, and the levels of α-syn, Aβ, and oligomer A11 after inhibition of NOX4 expression in the hippocampal dentate gyrus (DG) were measured by the Morris water maze, novel object recognition, rotation, and rotarod tests, as well as immunoblotting and immunohistochemistry...
February 6, 2019: International Journal of Molecular Sciences
Pascale Baden, Cong Yu, Michela Deleidi
While the link between GBA and Parkinson's disease (PD) was initially unexpected, it is now well established that GBA mutations are the most frequent genetic risk for PD. GBA has also been linked to sporadic PD, dementia with Lewy bodies, and ageing. Thus, GBA represents a promising target to counteract brain disease and the age-related decline of lysosomal function. The exact mechanisms involved in the risk of developing PD in GBA mutation carriers are still unclear and research in this field has faced the major challenge of a lack of proper modeling systems...
January 31, 2019: Neurobiology of Disease
Jing Yang, Derek B Archer, Roxana G Burciu, Martijn L T M Müller, Arnab Roy, Edward Ofori, Nicolaas I Bohnen, Roger L Albin, David E Vaillancourt
INTRODUCTION: When using free-water diffusion imaging or positron emission tomography (PET), it is established that substania nigra microstructure and presynaptic dopamine activity are impaired in early PD. It is not well understood if these two forms of degeneration are redundant, or if they each provide a unique contribution to the clinical motor and cognitive symptoms. METHODS: A total of 129 PD and 75 control individuals underwent motor and cognitive evaluations, and in vivo [11C]dihydrotetrabenazine (DTBZ) monoaminergic brain PET imaging and diffusion imaging...
January 6, 2019: Parkinsonism & related Disorders
Thomas J Biggans
When cognitive impairment is first evident it can be difficult to distinguish between different conditions such as idiopathic Parkinson's disease and Lewy body dementia. Imaging both cerebral perfusion and dopamine transporter function has been shown to provide accurate differentiation between the most common conditions. At present cerebral perfusion and dopamine transporter imaging is conducted on separate days. Carrying out both scans on the same day has the potential to benefit the patient through the social convenience of one visit to hospital and the earlier availability of results...
January 7, 2019: Medical Engineering & Physics
B Kumar, A Kuhad, A Kuhad
Lumateperone tosylate (ITI-007 tosylate, ITI-722) is a first-in-class investigational drug which acts syn-ergistically through multiple systems (serotonergic, dopaminergic and glutamatergic), thus representing a unique approach for the therapeutic management of a range of neuropsychiatric disorders. It possesses a potent antagonistic activity at 5-hydroxytryptamine (serotonin) 2A (5-HT2A) receptors and also binds to dopamine (D1, D2) receptors with partial agonism at presynaptic D2 receptors and postsynaptic antagonism...
December 2018: Drugs of Today
Lina Patterson, Steven P Rushton, Johannes Attems, Alan J Thomas, Christopher M Morris
AIMS: Depression is commonly observed even in prodromal stages of Lewy body disorders (LBD), and is associated with cognitive impairment and a faster rate of cognitive decline. Given the role of dopamine in the development of movement disorders, but also in motivation and reward, we investigated neurodegenerative pathology in dopaminergic circuitry in Parkinson's disease (PD), PD with dementia (PDD) and dementia with Lewy bodies (DLB) patients in relation to depressive symptoms. METHODS: α-synuclein, hyperphosphorylated tau and amyloid beta pathology was assessed in 17 DLB, 14 PDD and 8 PD cases within striatal and midbrain subregions, with neuronal cell density assessed in substantia nigra and ventral tegmental area...
December 24, 2018: Brain Pathology
Hanish Singh Jayasingh Chellammal, Alagarsamy Veerachamy, Dhani Ramachandran, Sridhar Babu Gummadi, Mohamed Mansor Manan, Narsimha Reddy Yellu
The progressive accumulation of amyloid beta (Aβ) peptide is neurotoxic and leads to Alzheimer's type dementia. Accumulation of Aβ has been associated with dysfunction of hypothalamic-pituitary-adrenal (HPA) axis and elevated pro-inflammatory cytokines. In this study, we investigated the effect of 1`δ-1`-acetoxyeugenol acetate (DAEA), isolated from Alpinia galanga (L.), on Aβ(25-35) induced neurodegeneration in mice. Mice were treated with three different doses of DAEA (12.5 mg/kg, 25 mg/kg and 50 mg/kg) for 28 days...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Nicolas Nicastro, Antoine F Eger, Frederic Assal, Valentina Garibotto
Feeling of presence (FOP) refers to the vivid sensation of a person's presence near oneself and is common in Dementia with Lewy Bodies (DLB). Based on previous observations on epileptic subjects, we hypothesized that DLB subjects with FOP would harbour 18 F-fluorodeoxyglucose PET hypometabolism in left parietal areas. 25 subjects (mean age 71.9 ± 6.7, disease duration at scan 1.7 ± 1.5 years) were included in the study, of whom nine (36%) experienced FOP. No significant between-group difference was observed regarding dopamine transporters striatal uptake (p = 0...
December 4, 2018: Brain Imaging and Behavior
Makoto Ohsawa, Yukiko Tanaka, Yoshito Ehara, Setsuko Makita, Kosuke Onaka
A recent classification analysis of neuropsychiatric symptoms in patients with Alzheimer's disease (AD) revealed a distinct cluster with apathy and eating problems including anorexia that exhibits frailty. The apathy and frailty are risk factors in the disease progresses. However, there is currently no effective drug for treating both anorexia and apathy in AD. Here, we conducted an open-label pilot study to determine whether ninjin'yoeito (NYT, TJ-108), a multicomponent drug, is effective for improving anorexia and apathy in patients with AD, and consequently their cognitive function...
December 9, 2017: JAD Reports
Frederic Sampedro, Juan Marín-Lahoz, Saul Martínez-Horta, Javier Pagonabarraga, Jaime Kulisevsky
BACKGROUND: Cognitive decline in Parkinson's disease (PD) is a highly prevalent condition with no effective treatment. Cortical atrophy is thought to promote its development but to design optimal therapeutic approaches in this clinical setting we need to understand the physiopathological mechanisms leading to this disorder. OBJECTIVE: To characterize the impact of dopaminergic degeneration on cortical integrity in early PD. METHODS: We studied 87 recently-diagnosed PD patients and 38 healthy controls from the Parkinson's Progression Marker Initiative who underwent I123-ioflupane SPECT (DATSCAN) and T1-MRI imaging...
November 6, 2018: Neurobiology of Disease
Diana L Price, Maya A Koike, Asma Khan, Wolfgang Wrasidlo, Edward Rockenstein, Eliezer Masliah, Douglas Bonhaus
Accumulation of alpha-synuclein (ASYN) in neurons and other CNS cell types may contribute to the underlying pathology of synucleinopathies including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Multiple Systems Atrophy (MSA). In support of this hypothesis for PD, ASYN immunopositive aggregates are a prominent pathological feature of PD, and mutations and gene multiplications of human wild type (WT) ASYN cause rare familial autosomal-dominant forms of PD. Targeted therapeutics that reduce the accumulation of ASYN could prevent or slow the neurodegenerative processes in PD and other synucleinopathies...
November 1, 2018: Scientific Reports
Juan Marín-Lahoz, Javier Pagonabarraga, Saul Martinez-Horta, Ramón Fernandez de Bobadilla, Berta Pascual-Sedano, Jesús Pérez-Pérez, Alexandre Gironell, Jaime Kulisevsky
Introduction: Impulse control disorders (ICDs) are a common complication of Parkinson's disease (PD) receiving dopamine agonist (DAA) Impulsivity is considered an underlying mechanism but evidence of this relationship is scarce. To explore the relationship between impulsivity and the presence and severity of ICD in PD. Methods: Prospective cross-sectional study of consecutive PD outpatients. Patients with dementia or previously known ICDs were excluded. Two measures of impulsivity were assessed: Barratt Impulsiveness Scale (BIS-11) for impulsiveness trait (main exposure) and commission errors in the Continuous Performance Test (CE) for motor inhibition...
2018: Frontiers in Psychiatry
Nicolaas I Bohnen, Prabesh Kanel, Martijn L T M Müller
One of the first identified neurotransmitters in the brain, acetylcholine, is an important modulator that drives changes in neuronal and glial activity. For more than two decades, the main focus of molecular imaging of the cholinergic system in Parkinson's disease (PD) has been on cognitive changes. Imaging studies have confirmed that degeneration of the cholinergic system is a major determinant of dementia in PD. Within the last decade, the focus is expanding to studying cholinergic correlates of mobility impairments, dyskinesias, olfaction, sleep, visual hallucinations and risk taking behavior in this disorder...
2018: International Review of Neurobiology
Claudio Babiloni, Claudio Del Percio, Roberta Lizio, Giuseppe Noce, Susanna Lopez, Andrea Soricelli, Raffaele Ferri, Maria Teresa Pascarelli, Valentina Catania, Flavio Nobili, Dario Arnaldi, Francesco Famà, Francesco Orzi, Carla Buttinelli, Franco Giubilei, Laura Bonanni, Raffaella Franciotti, Marco Onofrj, Paola Stirpe, Peter Fuhr, Ute Gschwandtner, Gerhard Ransmayr, Lucia Fraioli, Lucilla Parnetti, Lucia Farotti, Michela Pievani, Fabrizia D'Antonio, Carlo De Lena, Bahar Güntekin, Lutfu Hanoğlu, Görsev Yener, Derya Durusu Emek-Savaş, Antonio Ivano Triggiani, John Paul Taylor, Ian McKeith, Fabrizio Stocchi, Laura Vacca, Giovanni B Frisoni, Maria Francesca De Pandis
We hypothesized that dopamine neuromodulation might affect cortical excitability in Parkinson's disease (PD) patients set in quiet wakefulness, as revealed by resting state eyes-closed electroencephalographic (rsEEG) rhythms at alpha frequencies (8-12 Hz). Clinical and rsEEG rhythms in PD with dementia (N = 35), PD with mild cognitive impairment (N = 50), PD with normal cognition (N = 35), and normal (N = 50) older adults were available from an international archive. Cortical rsEEG sources were estimated by exact low-resolution brain electromagnetic tomography...
August 30, 2018: Neurobiology of Aging
Li Guo, Eduardo M Normando, Parth Arvind Shah, Lies De Groef, M Francesca Cordeiro
Parkinson's disease (PD) is one of the most common neurodegenerative disorders and the second leading cause of dementia worldwide. With an aging population, the prevalence of the disease has dramatically increased. Clinical management has advanced through recent developments in dopaminergic imaging and genetic risk profiling. However, early and accurate diagnosis of the disorder remains a challenge, largely because of the lack of noninvasive and inexpensive reliable diagnostic tests. Besides the well-studied cerebral neurodegeneration that underlies the cardinal symptoms of PD (ie, bradykinesia, tremor, rigidity, and postural instability), ocular changes have also been described in PD, including visual dysfunction, pupil abnormality, lens opacity, and retinal neuronal loss and dysfunction...
September 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Mahmudur G M Rahman, Muhammad M Islam, Tetsuya Tsujikawa, Yasushi Kiyono, Hidehiko Okazawa
OBJECTIVE: To calculate the specific binding ratio (SBR) appropriately in dopamine transporter (DAT) imaging, a method for extracting the striatal volume of interest (VOI) was developed. METHODS: This study included 200 patients (72 ± 10 years) who were suspected of parkinsonian syndromes (PS) or dementia with Lewy body (DLB). The patients were divided into three groups of PS with dopaminergic degeneration, DLB and non-PS after [123 I]ioflupane (FP-CIT) SPECT and clinical follow-up...
October 1, 2018: Annals of Nuclear Medicine
Toshihide Ogawa, Shinya Fujii, Keita Kuya, Shin-Ichiro Kitao, Yuki Shinohara, Mana Ishibashi, Yoshio Tanabe
An accurate diagnosis of Parkinson's disease (PD) is a prerequisite for therapeutic management. In spite of recent advances in the diagnosis of parkinsonian disorders, PD is misdiagnosed in between 6 and 25% of patients, even in specialized movement disorder centers. Although the gold standard for the diagnosis of PD is a neuropathological assessment, neuroimaging has been playing an important role in the differential diagnosis of PD and is used for clinical diagnostic criteria. In clinical practice, differential diagnoses of PD include atypical parkinsonian syndromes such as dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, caused by a striatal dopamine deficiency following nigrostrial degeneration...
September 2018: Yonago Acta Medica
Shoichi Sasaki
INTRODUCTION: The objective of this study was to examine the prevalence of the coexistence of parkinsonism in patients with mild cognitive impairment (MCI) or mild Alzheimer's disease (AD). METHODS: Outpatients were evaluated with Mini-Mental State Examination, Clinical Dementia Rating Scale, NIA-AA criteria, MRI, and 123 I-IMP SPECT (3D-SSP). Parkinsonism in patients diagnosed with MCI (Mini-Mental State Examination ≥24, n = 63) or mild AD (Mini-Mental State Examination 20-23, n = 43) was examined using the Unified Parkinson's Disease Rating Scale-III and 123 I-FP-CIT dopamine transporter SPECT...
September 14, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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