scholarly journals Genetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Myung Jun Lee ◽  
Kyoungjune Pak ◽  
Han-Kyeol Kim ◽  
Kelly N. Nudelman ◽  
Jong Hun Kim ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Genetic Factors ◽  
Late Onset ◽  
Single Photon ◽  
Age At Onset ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Dopaminergic Dysfunction ◽  
Tomography Data ◽  
Motor Onset

AbstractTo estimate dopaminergic dysfunction in patients with Parkinson disease (PD) during the premotor stage and to investigate the effect of genetic factors on the trajectories. Using longitudinal dopamine transporter single-photon emission computed tomography data from 367 sporadic PD (sPD), 72 LRRK2 (G2019S), and 39 GBA (N370S) PD patients in the Parkinson’s Progression Markers Initiative (PPMI) study, we estimated the temporal trajectories of putaminal-specific binding ratios using an integrating function between baseline values and their annual change rates. In order to test reproducibility, we computed another trajectory for sPD using positron emission tomography data of 38 sPD patients at Gangnam Severance Hospital (GSH). Temporal trajectories of sPD were compared between the groups separated by age at onset (AAO) and polygenic load for common PD risk variants, and also compared with genetic PD. sPD patients in both the PPMI and GSH cohorts showed similar onset of dopaminergic degeneration around 10 years before motor onset. Early-onset PD patients exhibited later onset of degeneration and a faster decline in dopaminergic activity during the premotor period than late-onset patients. sPD patients with high polygenic load were associated with earlier onset and slower progression of dopaminergic dysfunction. Compared to the sPD and LRRK2 PD groups, GBA PD patients exhibited faster deterioration of dopaminergic function during the premotor stage. Dopaminergic dysfunction in PD appears to start about 10 years before motor onset. Genetic factors may be contributing to the heterogeneity of dopaminergic deterioration during the premotor stage.

scholarly journals Radioiodination and Purification of [131I]β-CIT and [131I]FP-CIT with an Automated Radiosynthesizer

2022 ◽  
Vol 15 (1) ◽  
pp. 96
Author(s):  
Elisabeth Plhak ◽  
Edith Gößnitzer ◽  
Reingard M. Aigner ◽  
Herbert Kvaternik
Keyword(s):  
Solid Phase ◽  
Single Photon ◽  
Photon Emission ◽  
Tropane Alkaloids ◽  
Radiochemical Yield ◽  
Emission Computed Tomography ◽  
Dopaminergic Dysfunction ◽  
Free Iodine ◽  
Iodine 131 ◽  
Photon Emission Computed Tomography

Dopaminergic transporter (DAT) imaging with single photon emission computed tomography (SPECT) is used to diagnose Parkinson’s disease and to differentiate it from other neurodegenerative disorders without presynaptic dopaminergic dysfunction. The radioiodinated tropane alkaloids [123I]FP-CIT and [123I]β-CIT enable the evaluation of the integrity of DATs. Commonly, the labeling of these compounds is performed by electrophilic substitution of the alkylstannylated precursors with radioactive iodine and following purification by HPLC or solid phase extraction (SPE). This work presents the first radioiodination of β-CIT and FP-CIT with no carrier added [131I]NaI on a Scintomics GRP synthesis module. Free iodine-131 and impurities were removed by SPE over a C-18 Sep-Pak cartridge. We achieved a radiochemical yield of >75% and a radiochemical purity of >98% with both compounds. Our development of an automated synthesis on a commercially available synthesizer ensures robust and efficient labeling of [131I]FP-CIT and [131I]β-CIT starting with low concentrated radioiodine.

scholarly journals Case Report: Usefulness of Biomarkers for Alzheimer's Disease in Two Cases With Very-Late-Onset Schizophrenia-Like Psychosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuto Satake ◽  
Hideki Kanemoto ◽  
Kenji Yoshiyama ◽  
Ryoko Nakahama ◽  
Keiko Matsunaga ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Psychotic Disorders ◽  
Late Onset ◽  
Single Photon ◽  
Photon Emission ◽  
Brain Magnetic Resonance Imaging ◽  
Later Life ◽  
Emission Computed Tomography ◽  
Amyloid Pet

The association between primary psychotic disorders emerging in later life and neurodegenerative diseases, including Alzheimer's disease (AD), is controversial. We present two female non-demented cases of psychosis with onset above the age of 60 years. Cases 1 and 2 were aged was 68 and 81 years, respectively. They suffered from persecutory delusions and scored 28 on the Mini-Mental State Examination (MMSE) at the first examination. Although detailed neuropsychological tests detected amnesia, they had preserved daily life function. Brain magnetic resonance imaging, N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) single-photon emission computed tomography, and cardiac [123I]-metaiodobenzylguanidine (123I-MIBG) scintigraphy showed no specific abnormalities in either case. We diagnosed them with very-late-onset schizophrenia-like psychosis (VLOSLP) because there was no evidence that their psychoses were derived from organic diseases or affective disorders. Upon close inspection, the AD biomarkers, cerebrospinal fluid (CSF) testing and Florbetapir F 18 positron emission tomography (PET), were positive in Case 1 and negative in Case 2. Case 1 scored 25 1 year later and 23 2 years later on the MMSE and was finally diagnosed as AD dementia. These two cases suggest that some clinically diagnosed VLOSLPs may be a prodromal AD. Although VLOSLP is a disease entity supposed to be a primary psychotic disorder, some are probably secondary psychosis with insidious neurodegeneration. Advanced biomarkers such as amyloid PET and CSF may contribute to the detection of secondary psychosis from clinically diagnosed VLOSLP.

Vascular risk factors and the relationships between cognitive impairment and hypoperfusion in late-onset Alzheimer’s disease

2018 ◽  
Vol 30 (6) ◽  
pp. 350-358 ◽  
Author(s):  
Michio Takahashi ◽  
Yasunori Oda ◽  
Koichi Sato ◽  
Yukihiko Shirayama
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Single Photon ◽  
Photon Emission ◽  
Disease Assessment ◽  
Emission Computed Tomography ◽  
Vascular Risk ◽  
Risk Patients

AbstractObjectiveOur recent single-photon emission computed tomography (SPECT) study of patients with late-onset Alzheimer’s disease (AD) revealed that regional cerebral blood flow (rCBF) was reduced in the frontal, temporal, and limbic lobes, and to a lesser degree in the parietal and occipital lobes. Moreover, these patients’ scores on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) were significantly correlated with rCBF in some gyri of the frontal, parietal, and limbic lobes. Our present study aimed to understand how vascular factors and metabolic disease influenced the relationship between rCBF and ADAS-cog scores.MethodsWe divided late-onset AD patients into two groups according to their Hachinski Ischemic Score (HIS), low vascular risk patients had values of ≤4 (n=25) and high vascular risk patients had scores ≥5 (n=15). We examined rCBF using brain perfusion SPECT data.ResultsThe degrees and patterns of reduced rCBF were largely similar between late-onset AD patients in both groups, regardless of HIS values. Cognitive function was significantly associated with rCBF among late-onset AD patients with low vascular risk (HIS≤4), but not among those with high vascular risk (HIS≥5). Furthermore, metabolic diseases, such as hypertension and diabetes mellitus, disrupted the relationships between hypoperfusion and cognitive impairments in late-onset AD patients.ConclusionFactors other than hypoperfusion, such as hypertension and diabetes mellitus, could be involved in the cognitive dysfunction of late-onset AD patients with high vascular risk.

Clinical overlap between behavioral variant of frontotemporal dementia and bipolar disorder: A case report

2016 ◽  
Vol 33 (S1) ◽  
pp. S335-S336 ◽  
Author(s):  
P. Oliveira ◽  
C. Roque ◽  
V. Santos ◽  
N. Madeira
Keyword(s):  
Bipolar Disorder ◽  
Frontotemporal Dementia ◽  
Psychiatric Symptoms ◽  
Late Onset ◽  
Single Photon ◽  
Photon Emission ◽  
Interpersonal Behavior ◽  
Psychotic Symptoms ◽  
Emission Computed Tomography ◽  
Global Pattern

The behavioral variant of frontotemporal dementia (FTD) often begins with psychiatric symptoms, including changes in personal conduct and/or interpersonal behavior. Prior to developing cognitive impairment, differentiating FTD from primary psychiatric disorders might be challenging.This work presents a case of a manic episode with psychotic features in a 61-year-old man, whom personality changes and daily life difficulties arouse and persist after optimal management of the active manic and psychotic symptoms. Neuropsychological assessment detailed severe deficits among visuospatial and planning performances. Structural neuroimaging (CT-scan) primary revealed a global pattern of brain volume reduction. Severe perfusion deficits on frontal and both parietal lobes were shown on 99mTc-HMPAO single-photon emission computed tomography (SPECT). The hypothesis of probable FTD (behavioral variant) was established.The present case highlights how putative atypical and late-onset forms of bipolar disorder (BD) might instead progress to FTD. Several links are being advanced between the BD and FTD, for instance the close involvement of the C9ORF72 gene in a group of BD patients which progresses to dementia. These relations have actually been on focus recently. The field is however still relatively unexplored.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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