Elevated Plasma Orexin-A Levels in Prodromal Dementia with Lewy Bodies

Gan, Jinghuan; Liu, Shuai; Chen, Zhichao; Yang, Yaqi; Ma, Lulin; Qing-bo, Meng; Wang, Xiaodan; Liu, Chunyan; Li, Xudong; Zhang, Wei; Ji, Yong

doi:10.3233/jad-220082

Cited by 7 publications

(6 citation statements)

References 32 publications

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“…Neuropsychiatric symptoms: rates of neuropsychiatric supportive symptoms in the MCI-LB criteria (hallucinations in non-visual modalities, systematized delusions, apathy, anxiety, and depression) were reported in up to seven studies. 23 – 29 When comparing MCI-LB with MCI-AD, our meta-analyses showed that the pooled prevalence of anxiety (31% vs. 18%), depression (37% vs. 22%), apathy (47% vs. 23%) and delusions (11% vs. 4%) was higher in MCI-LB ( Table 2 ). We found no difference for non-visual hallucinations (7% vs. 3%), though this feature was only recorded in three studies ( Table 2 ).…”

Section: Resultsmentioning

confidence: 95%

Research diagnostic criteria for mild cognitive impairment with Lewy bodies: A systematic review and meta‐analysis

Donaghy

Carrarini

Ferreira

et al. 2023

Alzheimer's & Dementia

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Introduction Operationalized research criteria for mild cognitive impairment with Lewy bodies (MCI‐LB) were published in 2020. The aim of this systematic review and meta‐analysis was to review the evidence for the diagnostic clinical features and biomarkers in MCI‐LB set out in the criteria. Methods MEDLINE, PubMed, and Embase were searched on 9/28/22 for relevant articles. Articles were included if they presented original data reporting the rates of diagnostic features in MCI‐LB. Results Fifty‐seven articles were included. The meta‐analysis supported the inclusion of the current clinical features in the diagnostic criteria. Evidence for striatal dopaminergic imaging and meta‐iodobenzylguanidine cardiac scintigraphy, though limited, supports their inclusion. Quantitative electroencephalogram (EEG) and fluorodeoxyglucose positron emission tomography (PET) show promise as diagnostic biomarkers. Discussion The available evidence largely supports the current diagnostic criteria for MCI‐LB. Further evidence will help refine the diagnostic criteria and understand how best to apply them in clinical practice and research. Highlights A meta‐analysis of the diagnostic features of MCI‐LB was carried out. The four core clinical features were more common in MCI‐LB than MCI‐AD/stable MCI. Neuropsychiatric and autonomic features were also more common in MCI‐LB. More evidence is needed for the proposed biomarkers. FDG‐PET and quantitative EEG show promise as diagnostic biomarkers in MCI‐LB.

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Section: Resultsmentioning

confidence: 95%

Research diagnostic criteria for mild cognitive impairment with Lewy bodies: A systematic review and meta‐analysis

Donaghy

Carrarini

Ferreira

et al. 2023

Alzheimer's & Dementia

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“…CSF cut-off values for Aβ-positive or Aβ-negative were Aβ1-42 < 550 pg/mL and/or Aβ1-42/Aβ1-40 ratio ≤ 0.05. CSF cut-off values for tau positive were p-tau181 > 50 pg/mL and/or t-tau > 399 pg/mL, all cut-off values were set based on the accumulation of previous experimental data of Kindstar Global Genetic Technology Co., LTD. APOE genotype was determined based on genomic DNA using polymerase chain reaction following the detailed protocol described in our previous study (Gan et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

“…Multiplanar oblique coronal (perpendicular to the axis of the hippocampus), transverse, and coronal position reconstructions were made of 3D T1-weighted images for diagnostic multisequence MRI; details of the protocol are provided in our previous study (Zhu et al, 2021 ; Gan et al, 2022 ). All MRI visual scales readings were reviewed by two experienced neuroradiologists in a double-blind manner and the final rating scores averaged.…”

Section: Methodsmentioning

confidence: 99%

Alzheimer's disease pathology: pathways between chronic vascular risk factors and blood-brain barrier dysfunction in a cohort of patients with different types of dementia

Gan

Yang

Zhang

et al. 2023

Front. Aging Neurosci.

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BackgroundBlood brain barrier (BBB) breakdown is considered a potential mechanism of dementia. The Alzheimer's disease (AD) biomarkers and vascular factors are also associated with BBB permeability.ObjectiveIn the present study, the combination effects of neuropathological biomarkers of AD and chronic vascular risk factors for BBB were investigated.MethodsThe cerebrospinal fluid (CSF)/serum albumin ratio (Qalb), an indicator of BBB permeability, was measured in a total of 95 hospitalized dementia patients. The demographics, clinical information, and laboratory tests were collected from the inpatient records. The CSF neuropathological biomarkers of AD and apolipoprotein E (APOE) genotype were also collected. The mediation analysis model was used to calculate the associations among neuropathological biomarkers of AD (mediator), the Qalb, and chronic vascular risk factors.ResultsThree types of dementia, AD (n = 52), Lewy body dementia (LBD, n = 19), and frontotemporal lobar degeneration (n = 24), were included with a mean Qalb of 7.18 (± 4.36). The Qalb was significantly higher in dementia patients with type 2 diabetes mellitus (T2DM, p = 0.004) but did not differ based on the presence of APOE ε4 allele, CMBs, or amyloid/tau/neurodegeneration (ATN) framework. The Qalb was negatively associated with the levels of Aβ1-42 (B = −20.775, p = 0.009) and Aβ1-40 (B = −305.417, p = 0.005) and positively associated with the presence of T2DM (B = 3.382, p < 0.001) and the levels of glycosylated hemoglobin (GHb, B = 1.163, p < 0.001) and fasting blood glucose (FBG, B = 1.443, p < 0.001). GHb is a direct chronic vascular risk factor for higher Qalb (total effect B = 1.135, 95% CI: 0.611–1.659, p < 0.001). Ratios of Aβ1-42/Aβ1-40 or t-tau/Aβ1-42 were mediators of the association between the Qalb and GHb; the direct effect of GHb on the Qalb was 1.178 (95% CI: 0.662–1.694, p < 0.001).ConclusionGlucose exposure can directly or indirectly affect BBB integrity through Aβ and tau, indicating glucose affects BBB breakdown and glucose stability plays an important role in dementia protection and management.

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“…We used peripheral blood to extract genomic DNA, and polymerase chain reaction was amplified to determine the APOE gene in this study. All the detailed method had been described at our previous study [ 27 ]. We were sure about all genotypes without knowledge of the patient status.…”

Section: Methodsmentioning

confidence: 99%

The presence and co-incidence of geriatric syndromes in older patients with mild-moderate Lewy body dementia

et al. 2022

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Introduction Geriatric symptoms are common in dementia cases, while few studies have focused on these symptoms in Lewy body dementia (LBD). The purpose of this study is to investigate the distributions of Apolipoprotein E (APOE) ε4 and geriatric symptoms, and explore their associaitons in Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). Methods A retrospective study with 185 mild-moderate probable DLB (n = 93) and PDD (n = 92) patients was assigned. Demographic and clinical characteristics, neuropsychological assessments, and APOE genotypes were recorded. Description, correlation and logistic regression models were used to analyze the presence of geriatric symptom complaints and their associations with APOE ε4. Results DLB patients displayed more frequency of fluctuating cognition, visual hallucination, rapid eye movement sleep behavior disorder, delusion, depression, anxiety, apathy, and loss of appetite, whereas the PDD cases had constipation, fear of falling, and insomnia more frequently. The APOE ε4 allele was more common in DLB than PDD (29.9% vs. 7.0%, p < 0.001), and the patients with DLB + APOE ε4 (+) were presented more delusions (p = 0.005) and apathy (p = 0.007) than patients with PDD + APOE ε4 (+). We also found that the APOE ε4 allele was significantly associated with hyperhidrosis (OR = 3.472, 95%CI: 1.082–11.144, p = 0.036) and depression (OR = 3.002, 95%CI: 1.079–8.353, p = 0.035) in DLB patients, while there were no significant associations between APOE ε4 allele and the age at visit, the age at onset, scores of MDS-UPDRS III, H&Y stage, ADL, MMSE, MOCA and NPI, as well as the presences of fluctuating cognition, VH, parkinsonism and RBD in both groups. Conclusion The presence and co-incidence of geriatric symptoms are common in patients with mild-moderate LBD. The presence of APOE ε4 allele is associated with hyperhidrosis and depression, but not global cognition, activitives of daily life, motor function and other neuropsychitric symptoms in DLB. These findings improve the awareness of geriatric symptoms, and contribute to the healthcare management of mild-moderate DLB and PDD.

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Elevated Plasma Orexin-A Levels in Prodromal Dementia with Lewy Bodies

Cited by 7 publications

References 32 publications

Research diagnostic criteria for mild cognitive impairment with Lewy bodies: A systematic review and meta‐analysis

Research diagnostic criteria for mild cognitive impairment with Lewy bodies: A systematic review and meta‐analysis

Alzheimer's disease pathology: pathways between chronic vascular risk factors and blood-brain barrier dysfunction in a cohort of patients with different types of dementia

The presence and co-incidence of geriatric syndromes in older patients with mild-moderate Lewy body dementia

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