Connections Between Insomnia and Cognitive Aging

Insomnia is a common sleep disorder among older adults,and a risk factor for poor physical and mental health.However,the relationship between insomnia and cognitive health is not well understood.Here,we review observational studies that have investigated whether insomnia is associated with deficits in objective cognitive performance and an increased risk of dementia,magnetic resonance imaging studies that have assessed grey matter volumes and white matter microstructure,and interventional studies that have explored whether the treatment of insomnia can improve cognitive outcomes.There are inconsistent findings regarding impaired performance in objective cognitive tests and reduced grey matter volumes,and limited,emerging,evidence that suggests that insomnia is associated with an increased risk of dementia and reduced white matter integrity.Although the interventional literature is still in its infancy,there is some indication that treatment may have an impact on vigilance.Well-powered studies examining sources of heterogeneity are warranted.

职业特点与阿尔茨海默病

Objective: To investigate the association between Alzheimer disease (AD) and worker functions and traits associated with occupations. Background: Studies have reported that occupational attainment is related to AD. However, most have not identified specific worker functions and traits (i.e., occupational demands) of occupations that may explain the association, nor have they accounted for changing occupational demands over time. Methods: Within and between group differences in mental, motor, physical, and social occupational demands of 122 AD cases and 235 control subjects were compared across four decades of life (20s, 30s, 40s, and 50s) using repeatedmeasures analyses of covariance adjusted for race, gender, year of birth, and education. Results: Overall, mental occupational demands were significantly lower and physical occupational demands were significantly higher for cases than for control subjects. Case/control differences in mental demand scores were not found in their 20s but only in later decades. Differences in physical demands were found in all decades but their 30s. Social and motor demands did not differ between cases and control subjects. Among cases only, there were no signifi cant occupational demand score differences across decades. In contrast, mental and social demand scores of control subjects increased in later decades, and motor demand scores declined. Like cases, physical demand scores of control subjects remained stable across the decades. Conclusions: The authors’ results may indicate a relatively early influence of Alzheimer disease neuropathology on capacity to pursue mentally demanding occupations. However, results also are consistent with the notion that mentally demanding occupations have a direct influence on Alzheimer disease neuropathology.

影像表现异常的人生长激素相关医源性克罗伊茨费尔特-雅各布病

Background: Although more than 160 cases of iatrogenic Creutzfeldt-Jakob disease (iCJD) from human growth hormone (hGH) treatment have been documented, to our knowledge abnormal cerebellar findings on magnetic resonance imaging (MRI) have not been reported. Objective: To report a case of hGH-related iCJD with abnormal cerebellar MRI findings on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted MRI (DWI). Design: Case report. Setting: Outpatient neurology clinic at a university medical center. Patient: A 33-year old man who had sub acute gait ataxia and blurred vision. Results: Beginning 19 years prior, this pa tient had received cadaveric pituitary-derived hGH treatment for at least 5 yea rs. Magnetic resonance imaging revealed FLAIR and DWI abnormalities, particularl y in the cerebellum. He died 7 months after disease onset of autopsyconfirmed iC JD. Pathological changes corresponded largely to MRI findings. Conclusions: To o ur knowledge, this is the first case of hGH-related iCJD with FLAIR and DWI abn ormalities within the cerebellum. As symptoms referable to the cerebellum occur early in iCJD, it suggests that these MRI sequences may allow earlier diagnosis of this form of prion disease.

Large-scale proximity extension assay reveals CSF midkine and DOPA decarboxylase as supportive diagnostic biomarkers for Parkinson’s disease

Background There is a need for biomarkers to support an accurate diagnosis of Parkinson’s disease(PD).Cerebrospinal fluid(CSF)has been a successful biofluid for finding neurodegenerative biomarkers,and modern highly sensitive multiplexing methods offer the possibility to perform discovery studies.Using a large-scale multiplex proximity extension assay(PEA)approach,we aimed to discover novel diagnostic protein biomarkers allowing accurate discrimination of PD from both controls and atypical Parkinsonian disorders(APD).Methods CSF from patients with PD,corticobasal syndrome(CBS),progressive supranuclear palsy(PSP),multiple system atrophy and controls,were analysed with Olink PEA panels.Three cohorts were used in this study,comprising 192,88 and 36 cases,respectively.All samples were run on the Cardiovascular II,Oncology II and Metabolism PEA panels.Results Our analysis revealed that 26 and 39 proteins were differentially expressed in the CSF of test and validation PD cohorts,respectively,compared to controls.Among them,6 proteins were changed in both cohorts.Midkine(MK)was increased in PD with the strongest effect size and results were validated with ELISA.Another most increased protein in PD,DOPA decarboxylase(DDC),which catalyses the decarboxylation of DOPA(L-3,4-dihydroxyphenylalanine)to dopamine,was strongly correlated with dopaminergic treatment.Moreover,Kallikrein 10 was specifically changed in APD compared with both PD and controls,but unchanged between PD and controls.Wnt inhibitory factor 1 was consistently downregulated in CBS and PSP patients in two independent cohorts.Conclusions Using the large-scale PEA approach,we have identified potential novel PD diagnostic biomarkers,most notably MK and DDC,in the CSF of PD patients.

皮质下小血管病诊断的共识声明

血管性认知损害是用于描述一组涉及大血管和小血管的散发性和遗传性异质性疾病的诊断术语。皮质下小血管病可导致腔隙性梗死和进行性白质损害。被称为宾斯旺格病（Binswanger＇s disease, BD）的进行性白质损害患者构成了从单纯血管性疾病到合并神经变性病变的疾病谱。BD患者是一个相对同质性的亚组，存在缺氧缺血、腔隙性梗死和炎症，它们协同作用破坏血脑屏障和髓鞘。通过临床、脑脊液、神经心理学和影像学检查获得的多模式疾病标记物能促进该亚组患者的鉴别。本共识声明确定了一系列基于基础病理学改变的潜在生物学标记物，这将有助于诊断以及将来协作性治疗试验的患者选择。