المؤلفون: Martirosian RA; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.)., Wiedner CD; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (C.D.W., R.B., J.J.H., S.S.), University of Texas Health Science Center at San Antonio., Sanchez J; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.)., Mun KT; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.)., Marla K; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.)., Teran C; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.)., Thirion M; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.)., Liebeskind DS; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.)., McGrath ER; Framingham Heart Study, MA (E.R.M.G., J.M.Z., A.S.B., C.D.C., J.J.H., S.S.).; HRB Clinical Research Facility, School of Medicine, University of Galway, Ireland (E.R.M.G.)., Zucker JM; Framingham Heart Study, MA (E.R.M.G., J.M.Z., A.S.B., C.D.C., J.J.H., S.S.)., Bernal R; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (C.D.W., R.B., J.J.H., S.S.), University of Texas Health Science Center at San Antonio., Beiser AS; Framingham Heart Study, MA (E.R.M.G., J.M.Z., A.S.B., C.D.C., J.J.H., S.S.).; Department of Neurology, Boston University School of Medicine, MA (A.S.B., J.J.H., S.S.).; Department of Biostatistics, Boston University School of Public Health, MA (A.S.B., J.J.H.)., DeCarli C; Framingham Heart Study, MA (E.R.M.G., J.M.Z., A.S.B., C.D.C., J.J.H., S.S.).; Department of Neurology, University of California Davis, Sacramento (C.D.C.)., Himali JJ; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (C.D.W., R.B., J.J.H., S.S.), University of Texas Health Science Center at San Antonio.; Department of Population Health Sciences (J.J.H.), University of Texas Health Science Center at San Antonio.; Framingham Heart Study, MA (E.R.M.G., J.M.Z., A.S.B., C.D.C., J.J.H., S.S.).; Department of Neurology, Boston University School of Medicine, MA (A.S.B., J.J.H., S.S.).; Department of Biostatistics, Boston University School of Public Health, MA (A.S.B., J.J.H.)., Seshadri S; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (C.D.W., R.B., J.J.H., S.S.), University of Texas Health Science Center at San Antonio.; Framingham Heart Study, MA (E.R.M.G., J.M.Z., A.S.B., C.D.C., J.J.H., S.S.).; Department of Neurology, Boston University School of Medicine, MA (A.S.B., J.J.H., S.S.)., Hinman JD; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.).

المصدر: Stroke [Stroke] 2024 Jun; Vol. 55 (6), pp. 1601-1608. Date of Electronic Publication: 2024 May 01.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0235266 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4628 (Electronic) Linking ISSN: 00392499 NLM ISO Abbreviation: Stroke Subsets: MEDLINE

مواضيع طبية MeSH: Biomarkers*/blood , Stroke*/blood , Stroke*/epidemiology , Stroke*/diagnostic imaging , Interleukin-18*/blood , Inflammation*/blood, Humans ; Male ; Female ; Middle Aged ; Aged ; Cohort Studies ; Incidence ; Risk Factors ; Magnetic Resonance Imaging ; Cognitive Dysfunction/blood ; Cognitive Dysfunction/epidemiology ; Cognitive Dysfunction/diagnostic imaging

مستخلص: Background: A coordinated network of circulating inflammatory molecules centered on the pleotropic pro-atherogenic cytokine interleukin-18 (IL-18) is linked to cerebral small vessel disease. We sought to validate the association of this inflammatory biomarker network with incident stroke risk, cognitive impairment, and imaging metrics in a sample of the Framingham Offspring Cohort.
Methods: Using available baseline measurements of serum levels of IL-18, GDF (growth and differentiation factor)-15, soluble form of receptor for advanced glycation end products, myeloperoxidase, and MCP-1 (monocyte chemoattractant protein-1) from Exam 7 of the Framingham Offspring Cohort (1998-2001), we constructed a population-normalized, equally weighted log-transformed mean Z -score value representing the average level of each serum analyte to create an inflammatory composite score (ICS5). Multivariable regression models were used to determine the association of ICS5 with incident stroke, brain magnetic resonance imaging features, and cognitive testing performance.
Results: We found a significant association between ICS5 score and increased risk for incident all-cause stroke (hazard ratio, 1.48 [95% CI, 1.05-2.08]; P =0.024) and ischemic stroke (hazard ratio, 1.51 [95% CI, 1.03-2.21]; P =0.033) in the Exam 7 cohort of 2201 subjects (mean age 62±9 years; 54% female) aged 45+ years with an all-cause incident stroke rate of 6.1% (135/2201) and ischemic stroke rate of 4.9% (108/2201). ICS5 and its component serum markers are all associated with the Framingham Stroke Risk Profile score (β±SE, 0.19±0.02; P <0.0001). In addition, we found a significant inverse association of ICS5 with a global cognitive score, derived from a principal components analysis of the neuropsychological battery used in the Framingham cohort (-0.08±0.03; P =0.019). No association of ICS5 with magnetic resonance imaging metrics of cerebral small vessel disease was observed.
Conclusions: Circulating serum levels of inflammatory biomarkers centered on IL-18 are associated with an increased risk of stroke and cognitive impairment in the Framingham Offspring Cohort. Linking specific inflammatory pathways to cerebral small vessel disease may enhance individualized quantitative risk assessment for future stroke and vascular cognitive impairment.
Competing Interests: Disclosures C. Teran is a former University of California Log Angeles Health employee supported by National Institutes of Health funding. Dr Liebeskind is scientific advisor and on the Board of Directors of Sage Cerebrovascular Diagnostics, Inc. Dr McGrath receives grant support from the Health Research Board. Dr DeCarli is a consultant to Eisai and Novo Nordisk. Dr Himali receives grant support from NIH, the Alzheimer’s Drug Discovery Foundation, and the Alzheimer’s Association. Dr Seshadri is a consultant for Biogen and Eisai. Dr Hinman is a listed inventor on the following patents held by the Regents of the University of California that include blood measurement of the molecules included in this study: Japan Patent No. 7211626; Korea Patent No. 10-2538752; US Application 62/461,161; Canada Application 3,054,083; EPO Application 18755090.0. Dr Hinman is also the founder of Sage Cerebrovascular Diagnostics, Inc. which has an exclusive license from the Regents to commercialize diagnostic tests using these markers. The other authors report no conflicts.

المؤلفون: Himali JJ; Framingham Heart Study, Framingham, Massachusetts.; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, Texas.; Department of Population Health Sciences, University of Texas Health Science Center, San Antonio.; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.; Boston University School of Medicine, Boston, Massachusetts., Baril AA; Framingham Heart Study, Framingham, Massachusetts.; Douglas Mental Health University Institute, Verdun, Quebec, Canada.; Department of Psychiatry, McGill University, Montreal, Quebec, Canada., Cavuoto MG; Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia., Yiallourou S; Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia., Wiedner CD; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, Texas., Himali D; Framingham Heart Study, Framingham, Massachusetts.; Boston University School of Medicine, Boston, Massachusetts., DeCarli C; Department of Neurology, University of California, Davis., Redline S; Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts., Beiser AS; Framingham Heart Study, Framingham, Massachusetts.; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.; Boston University School of Medicine, Boston, Massachusetts., Seshadri S; Framingham Heart Study, Framingham, Massachusetts.; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, Texas., Pase MP; Framingham Heart Study, Framingham, Massachusetts.; Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.; Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.

المصدر: JAMA neurology [JAMA Neurol] 2023 Dec 01; Vol. 80 (12), pp. 1326-1333.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: American Medical Association Country of Publication: United States NLM ID: 101589536 Publication Model: Print Cited Medium: Internet ISSN: 2168-6157 (Electronic) Linking ISSN: 21686149 NLM ISO Abbreviation: JAMA Neurol Subsets: MEDLINE

مواضيع طبية MeSH: Alzheimer Disease*/genetics , Sleep, Slow-Wave*, Humans ; Female ; Aged ; Middle Aged ; Male ; Cohort Studies ; Prospective Studies ; Apolipoprotein E4/genetics ; Sleep

مستخلص: Importance: Slow-wave sleep (SWS) supports the aging brain in many ways, including facilitating the glymphatic clearance of proteins that aggregate in Alzheimer disease. However, the role of SWS in the development of dementia remains equivocal.
Objective: To determine whether SWS loss with aging is associated with the risk of incident dementia and examine whether Alzheimer disease genetic risk or hippocampal volumes suggestive of early neurodegeneration were associated with SWS loss.
Design, Setting, and Participants: This prospective cohort study included participants in the Framingham Heart Study who completed 2 overnight polysomnography (PSG) studies in the time periods 1995 to 1998 and 2001 to 2003. Additional criteria for individuals in this study sample were an age of 60 years or older and no dementia at the time of the second overnight PSG. Data analysis was performed from January 2020 to August 2023.
Exposure: Changes in SWS percentage measured across repeated overnight sleep studies over a mean of 5.2 years apart (range, 4.8-7.1 years).
Main Outcome: Risk of incident all-cause dementia adjudicated over 17 years of follow-up from the second PSG.
Results: From the 868 Framingham Heart Study participants who returned for a second PSG, this cohort included 346 participants with a mean age of 69 years (range, 60-87 years); 179 (52%) were female. Aging was associated with SWS loss across repeated overnight sleep studies (mean [SD] change, -0.6 [1.5%] per year; P < .001). Over the next 17 years of follow-up, there were 52 cases of incident dementia. In Cox regression models adjusted for age, sex, cohort, positivity for at least 1 APOE ε4 allele, smoking status, sleeping medication use, antidepressant use, and anxiolytic use, each percentage decrease in SWS per year was associated with a 27% increase in the risk of dementia (hazard ratio, 1.27; 95% CI, 1.06-1.54; P = .01). SWS loss with aging was accelerated in the presence of Alzheimer disease genetic risk (ie, APOE ε4 allele) but not hippocampal volumes measured proximal to the first PSG.
Conclusions and Relevance: This cohort study found that slow-wave sleep percentage declined with aging and Alzheimer disease genetic risk, with greater reductions associated with the risk of incident dementia. These findings suggest that SWS loss may be a modifiable dementia risk factor.

المؤلفون: Nichols E; Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA. Electronic address: eln1@uw.edu., Merrick R; Cambridge Public Health, University of Cambridge, Cambridge, UK., Hay SI; Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA., Himali D; Framingham Heart Study, Framingham, MA, USA., Himali JJ; Framingham Heart Study, Framingham, MA, USA; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA; Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA., Hunter S; Cambridge Public Health, University of Cambridge, Cambridge, UK., Keage HAD; Cognitive Ageing and Impairment Neurosciences Lab, Justice and Society, University of South Australia, Adelaide, SA, Australia., Latimer CS; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA., Scott MR; Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA., Steinmetz JD; Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA., Walker JM; Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mt Sinai, New York, NY, USA., Wharton SB; Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK., Wiedner CD; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA., Crane PK; Department of Medicine, University of Washington, Seattle, WA, USA., Keene CD; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA., Launer LJ; Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Baltimore, MD, USA., Matthews FE; Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK., Schneider J; Rush Alzheimer's Disease Center, Chicago, IL, USA; Rush University Medical Center, Chicago, IL, USA., Seshadri S; Framingham Heart Study, Framingham, MA, USA; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA; Department of Neurology, Boston University School of Medicine, Boston, MA, USA., White L; Pacific Health Research and Education Institute, Honolulu, HI, USA., Brayne C; Cambridge Public Health, University of Cambridge, Cambridge, UK., Vos T; Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.

المصدر: The lancet. Healthy longevity [Lancet Healthy Longev] 2023 Mar; Vol. 4 (3), pp. e115-e125.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, U.S. Gov't, Non-P.H.S.

بيانات الدورية: Publisher: Elsevier Ltd Country of Publication: England NLM ID: 101773309 Publication Model: Print Cited Medium: Internet ISSN: 2666-7568 (Electronic) Linking ISSN: 26667568 NLM ISO Abbreviation: Lancet Healthy Longev Subsets: MEDLINE

مواضيع طبية MeSH: Alzheimer Disease* , Cerebral Amyloid Angiopathy* , Atherosclerosis* , Limbic Encephalitis*, Male ; Female ; Humans ; Aged ; Aged, 80 and over ; Prevalence ; Autopsy ; Cross-Sectional Studies

مستخلص: Background: Population-based autopsy studies provide valuable insights into the causes of dementia but are limited by sample size and restriction to specific populations. Harmonisation across studies increases statistical power and allows meaningful comparisons between studies. We aimed to harmonise neuropathology measures across studies and assess the prevalence, correlation, and co-occurrence of neuropathologies in the ageing population.
Methods: We combined data from six community-based autopsy cohorts in the US and the UK in a coordinated cross-sectional analysis. Among all decedents aged 80 years or older, we assessed 12 neuropathologies known to be associated with dementia: arteriolosclerosis, atherosclerosis, macroinfarcts, microinfarcts, lacunes, cerebral amyloid angiopathy, Braak neurofibrillary tangle stage, Consortium to Establish a Registry for Alzheimer's disease (CERAD) diffuse plaque score, CERAD neuritic plaque score, hippocampal sclerosis, limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and Lewy body pathology. We divided measures into three groups describing level of confidence (low, moderate, and high) in harmonisation. We described the prevalence, correlations, and co-occurrence of neuropathologies.
Findings: The cohorts included 4354 decedents aged 80 years or older with autopsy data. All cohorts included more women than men, with the exception of one study that only included men, and all cohorts included decedents at older ages (range of mean age at death across cohorts 88·0-91·6 years). Measures of Alzheimer's disease neuropathological change, Braak stage and CERAD scores, were in the high confidence category, whereas measures of vascular neuropathologies were in the low (arterioloscerosis, atherosclerosis, cerebral amyloid angiopathy, and lacunes) or moderate (macroinfarcts and microinfarcts) categories. Neuropathology prevalence and co-occurrence was high (2443 [91%] of 2695 participants had more than one of six key neuropathologies and 1106 [41%] of 2695 had three or more). Co-occurrence was strongly but not deterministically associated with dementia status. Vascular and Alzheimer's disease features clustered separately in correlation analyses, and LATE-NC had moderate associations with Alzheimer's disease measures (eg, Braak stage ρ=0·31 [95% CI 0·20-0·42]).
Interpretation: Higher variability and more inconsistency in the measurement of vascular neuropathologies compared with the measurement of Alzheimer's disease neuropathological change suggests the development of new frameworks for the measurement of vascular neuropathologies might be helpful. Results highlight the complexity and multi-morbidity of the brain pathologies that underlie dementia in older adults and suggest that prevention efforts and treatments should be multifaceted.
Funding: Gates Ventures.
Competing Interests: Declaration of interests SS reports consulting fees from Biogen and Eisai. JS reports consulting fees from AVID, Alnylam Pharmaceuticals, and Cerveau Technologies. All other authors declare no competing interests.
(Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

SCR Disease Name: limbic-predominant age-related TDP-43 encephalopathy