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 observa...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.展开更多
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. Ho...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.展开更多
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 resonan...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.展开更多
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 ...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.展开更多
文摘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.
文摘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.
文摘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.
基金Open access funding provided by Karolinska Institutesupported by Karin and Sten Mörtstedt CBD Solutions AB,the Swedish Parkinson fund,the ALF program of the Stockholm Stockholm City,Lexa/Nordstjernan,Knut and Alice Wallenberg Foundation,and Van Geest Foundation.PS is a Wallenberg Clinical Scholar.
文摘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.