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  1. Article ; Online: Association of Sleep Duration and Change Over Time With Imaging Biomarkers of Cerebrovascular, Amyloid, Tau, and Neurodegenerative Pathology.

    Baril, Andrée-Ann / Kojis, Daniel J / Himali, Jayandra J / Decarli, Charles S / Sanchez, Erlan / Johnson, Keith A / El Fakhri, Georges / Thibault, Emma / Yiallourou, Stephanie R / Himali, Dibya / Cavuoto, Marina G / Pase, Matthew P / Beiser, Alexa S / Seshadri, Sudha

    Neurology

    2023  Volume 102, Issue 1, Page(s) e207807

    Abstract: Background and objectives: Both short and long sleep duration were previously associated with incident dementia, but underlying mechanisms remain unclear. We evaluated how self-reported sleep duration and its change over time associate with (A)myloid, ( ... ...

    Abstract Background and objectives: Both short and long sleep duration were previously associated with incident dementia, but underlying mechanisms remain unclear. We evaluated how self-reported sleep duration and its change over time associate with (A)myloid, (T)au, (N)eurodegeneration, and (V)ascular neuroimaging markers of Alzheimer disease.
    Methods: Two Framingham Heart Study overlapping samples were studied: participants who underwent
    Results: The tested cohort was composed of 271 participants (age 53.6 ± 8.0 years; 51% male) in the PET imaging sample and 2,165 participants (age 61.3 ± 11.1 years; 45% male) in the MRI sample. No fully adjusted association was observed between cross-sectional sleep duration and neuroimaging metrics. In fully adjusted models compared with consistently sleeping 7-8 hours, groups transitioning to a longer sleep duration category over time had higher FW fraction (short to average β [SE] 0.0062 [0.0024],
    Discussion: Longer self-reported sleep duration over time was associated with neuroimaging biomarkers of cerebrovascular pathology as evidenced by higher WMH burden and FW fraction. A longer sleep duration extending over time may be an early change in the neurodegenerative trajectory.
    MeSH term(s) Male ; Humans ; Middle Aged ; Aged ; Female ; Sleep Duration ; Cross-Sectional Studies ; Amyloidogenic Proteins ; Neuroimaging ; Biomarkers
    Chemical Substances Amyloidogenic Proteins ; Biomarkers
    Language English
    Publishing date 2023-12-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/WNL.0000000000207807
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  2. Article ; Online: Association of Plasma YKL-40 With MRI, CSF, and Cognitive Markers of Brain Health and Dementia.

    Pase, Matthew P / Himali, Jayandra J / Puerta, Raquel / Beiser, Alexa S / Gonzales, Mitzi M / Satizabal, Claudia L / Yang, Qiong / Aparicio, Hugo J / Kojis, Daniel J / Decarli, Charles S / Lopez, Oscar L / Longstreth, Will / Gudnason, Vilmundur / Mosley, Thomas H / Bis, Joshua C / Fohner, Alison / Psaty, Bruce M / Boada, Mercè / García-González, Pablo /
    Valero, Sergi / Marquié, Marta / Tracy, Russell / Launer, Lenore J / Ruiz, Agustín / Fornage, Myriam / Seshadri, Sudha

    Neurology

    2024  Volume 102, Issue 4, Page(s) e208075

    Abstract: Background and objectives: Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk.: Methods: We performed cross-sectional and ... ...

    Abstract Background and objectives: Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk.
    Methods: We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total brain volume, hippocampal volume, and white matter hyperintensity volume (WMHV) as a percentage of intracranial volume, a general cognitive composite derived from neuropsychological testing (SD units [SDU]), and the risk of incident dementia. We sought to replicate associations with dementia in the clinic-based ACE csf cohort, which also had YKL-40 measured from the CSF.
    Results: Meta-analyses of MRI outcomes included 6,558 dementia-free participants, and for analysis of cognition, 6,670. The blood draw preceded MRI/cognitive assessment by up to 10.6 years across cohorts. The mean ages ranged from 50 to 76 years, with 39%-48% male individuals. In random-effects meta-analysis of study estimates, each SDU increase in log-transformed YKL-40 levels was associated with smaller total brain volume (β = -0.33; 95% CI -0.45 to -0.22;
    Discussion: Higher plasma YKL-40 levels were associated with lower brain volume, poorer cognition, and incident dementia. Plasma YKL-40 may be useful for studying the association of inflammation and its treatment on dementia risk.
    MeSH term(s) Aged ; Female ; Humans ; Male ; Middle Aged ; Alzheimer Disease ; Biomarkers ; Brain/diagnostic imaging ; Chitinase-3-Like Protein 1 ; Cognition ; Cognitive Dysfunction ; Cross-Sectional Studies ; Dementia/diagnostic imaging ; Magnetic Resonance Imaging ; Prospective Studies
    Chemical Substances Biomarkers ; Chitinase-3-Like Protein 1 ; CHI3L1 protein, human
    Language English
    Publishing date 2024-01-30
    Publishing country United States
    Document type Meta-Analysis ; Journal Article
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/WNL.0000000000208075
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  3. Article ; Online: Extrapyramidal signs by dementia severity in Alzheimer disease and dementia with Lewy bodies.

    Kaur, Berneet / Harvey, Danielle J / Decarli, Charles S / Zhang, Lin / Sabbagh, Marwan N / Olichney, John M

    Alzheimer disease and associated disorders

    2012  Volume 27, Issue 3, Page(s) 226–232

    Abstract: Alzheimer disease (AD) and dementia with Lewy bodies (DLB) are common etiologies of dementia with overlapping clinical features. Our objective was to determine which extrapyramidal signs (EPSs) are most helpful in identifying DLB. We analyzed data from ... ...

    Abstract Alzheimer disease (AD) and dementia with Lewy bodies (DLB) are common etiologies of dementia with overlapping clinical features. Our objective was to determine which extrapyramidal signs (EPSs) are most helpful in identifying DLB. We analyzed data from the National Alzheimer's Coordinating Center, including demographics, Unified Parkinson's Disease Rating Scale (UPDRS) scores, Mini-Mental State Examination (MMSE) scores, and clinical diagnosis. The subjects were divided into 3 groups: AD, DLB, or Lewy body variant (LBV). The UPDRS motor scores were totaled and analyzed within and across the MMSE strata using regression techniques. Further, we divided UPDRS subscores into 9 EPSs, dichotomized as either present or absent. Logistic regression analysis was used to compare each of the EPS in the AD and Lewy body (DLB+LBV) groups. DLB subjects (n=130) were more likely to be male individuals, younger, and have higher MMSE scores (P<0.001) compared with that in AD (n=1826) or LBV (n=105) subjects. Differences were found for total UPDRS score and number of EPSs (P<0.001), after controlling for age, sex, and MMSE. Logistic regression models demonstrated that masked facies best differentiated AD from Lewy body (odds ratio=6.5, P<0.001, 95% confidence interval, 3.8-11.1). If these findings are neuropathologically validated, then the presence of specific EPS may help clinicians better differentiate AD and DLB.
    MeSH term(s) Aged ; Aged, 80 and over ; Alzheimer Disease/complications ; Alzheimer Disease/diagnosis ; Cross-Sectional Studies ; Diagnosis, Differential ; Female ; Humans ; Lewy Body Disease/complications ; Lewy Body Disease/diagnosis ; Male ; Neuropsychological Tests ; Parkinsonian Disorders/etiology
    Language English
    Publishing date 2012-09-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1002700-2
    ISSN 1546-4156 ; 0893-0341
    ISSN (online) 1546-4156
    ISSN 0893-0341
    DOI 10.1097/WAD.0b013e31826f040d
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  4. Article ; Online: 3D comparison of low, intermediate, and advanced hippocampal atrophy in MCI.

    Apostolova, Liana G / Thompson, Paul M / Green, Amity E / Hwang, Kristy S / Zoumalan, Charleen / Jack, Clifford R / Harvey, Danielle J / Petersen, Ronald C / Thal, Leon J / Aisen, Paul S / Toga, Arthur W / Cummings, Jeffrey L / Decarli, Charles S

    Human brain mapping

    2010  Volume 31, Issue 5, Page(s) 786–797

    Abstract: We applied the hippocampal radial atrophy mapping technique to the baseline and follow-up magnetic resonance image data of 169 amnestic mild cognitive impairment (MCI) participants in the imaging arm of the Alzheimer's Disease Cooperative Study MCI ... ...

    Abstract We applied the hippocampal radial atrophy mapping technique to the baseline and follow-up magnetic resonance image data of 169 amnestic mild cognitive impairment (MCI) participants in the imaging arm of the Alzheimer's Disease Cooperative Study MCI Donepezil/Vitamin E trial. Sixty percent of the subjects with none to mild hippocampal atrophy rated with the visual medial temporal atrophy rating scale (MTA score < 2) and 33.8% of the subjects with moderate to severe (MTA > or = 2) hippocampal atrophy converted to Alzheimer's disease (AD) during 3-year follow-up. MTA > or = 2 showed a trend for greater left sided hippocampal atrophy versus MTA < 2 groups at baseline (P(corrected) = 0.08). Higher MTA scores were associated with progressive atrophy of the subiculum and the CA1-3 subregions. The MTA < 2 group demonstrated significant bilateral atrophy progression at follow-up (left P(corrected) = 0.008; right P(corrected) = 0.05). Relative to MTA < 2 nonconverters, MTA < 2 converters showed further involvement of the subiculum and CA1 and additional involvement of CA2-3 at follow-up. Right CA1 atrophy was significantly associated with conversion to dementia (for 1 mm greater right CA1 radial distance subjects had 50% reduced hazard for conversion). Greater CA1 and subicular atrophy can be demonstrated early and is predictive of future conversion to AD, whereas CA2-3 involvement becomes more evident as the disease progresses.
    MeSH term(s) Aged ; Alzheimer Disease/drug therapy ; Alzheimer Disease/pathology ; Atrophy ; Cognition Disorders/drug therapy ; Cognition Disorders/pathology ; Disease Progression ; Female ; Follow-Up Studies ; Functional Laterality ; Hippocampus/pathology ; Humans ; Imaging, Three-Dimensional ; Longitudinal Studies ; Magnetic Resonance Imaging ; Male ; Nootropic Agents/therapeutic use ; Severity of Illness Index ; Vitamin E/therapeutic use
    Chemical Substances Nootropic Agents ; Vitamin E (1406-18-4)
    Language English
    Publishing date 2010-02-09
    Publishing country United States
    Document type Clinical Trial ; Comparative Study ; Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1197207-5
    ISSN 1097-0193 ; 1065-9471
    ISSN (online) 1097-0193
    ISSN 1065-9471
    DOI 10.1002/hbm.20905
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  5. Article ; Online: Distinctive RNA expression profiles in blood associated with white matter hyperintensities in brain.

    Xu, Huichun / Stamova, Boryana / Jickling, Glen / Tian, Yingfang / Zhan, Xinhua / Ander, Bradley P / Liu, Dazhi / Turner, Renée / Rosand, Jonathan / Goldstein, Larry B / Furie, Karen L / Verro, Piero / Johnston, S Claiborne / Sharp, Frank R / Decarli, Charles S

    Stroke

    2010  Volume 41, Issue 12, Page(s) 2744–2749

    Abstract: Background and purpose: White matter hyperintensities (WMH) are areas of high signal detected by T2 and fluid-attenuated inversion recovery sequences on brain MRI. Although associated with aging, cerebrovascular risk factors, and cognitive impairment, ... ...

    Abstract Background and purpose: White matter hyperintensities (WMH) are areas of high signal detected by T2 and fluid-attenuated inversion recovery sequences on brain MRI. Although associated with aging, cerebrovascular risk factors, and cognitive impairment, the pathogenesis of WMH remains unclear. Thus, RNA expression was assessed in the blood of individuals with and without extensive WMH to search for evidence of oxidative stress, inflammation, and other abnormalities described in WMH lesions in brain.
    Methods: Subjects included 20 with extensive WMH (WMH+), 45% of whom had Alzheimer disease, and 18 with minimal WMH (WMH-), 44% of whom had Alzheimer disease. All subjects were clinically evaluated and underwent quantitative MRI. Total RNA from whole blood was processed on human whole genome Affymetrix HU133 Plus 2.0 microarrays. RNA expression was analyzed using an analysis of covariance.
    Results: Two hundred forty-one genes were differentially regulated at ± 1.2-fold difference (P < 0.005) in subjects with WMH+ as compared to WMH-, regardless of cognitive status and 50 genes were differentially regulated with ± 1.5-fold difference (P < 0.005). Cluster and principal components analyses showed that the expression profiles for these genes distinguished WMH+ from WMH- subjects. Function analyses suggested that WMH-specific genes were associated with oxidative stress, inflammation, detoxification, and hormone signaling, and included genes associated with oligodendrocyte proliferation, axon repair, long-term potentiation, and neurotransmission.
    Conclusions: The unique RNA expression profile in blood associated with WMH is consistent with roles of systemic oxidative stress and inflammation, as well as other potential processes in the pathogenesis or consequences of WMH.
    MeSH term(s) Aged ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Brain/pathology ; Cluster Analysis ; Female ; Hormones/physiology ; Humans ; Inflammation/pathology ; Magnetic Resonance Imaging ; Male ; Microarray Analysis ; Oxidative Stress/genetics ; Oxidative Stress/physiology ; Principal Component Analysis ; RNA/biosynthesis ; RNA/blood ; RNA/genetics ; Signal Transduction/genetics ; Signal Transduction/physiology
    Chemical Substances Hormones ; RNA (63231-63-0)
    Language English
    Publishing date 2010-10-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80381-9
    ISSN 1524-4628 ; 0039-2499 ; 0749-7954
    ISSN (online) 1524-4628
    ISSN 0039-2499 ; 0749-7954
    DOI 10.1161/STROKEAHA.110.591875
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Update on the magnetic resonance imaging core of the Alzheimer's disease neuroimaging initiative.

    Jack, Clifford R / Bernstein, Matt A / Borowski, Bret J / Gunter, Jeffrey L / Fox, Nick C / Thompson, Paul M / Schuff, Norbert / Krueger, Gunnar / Killiany, Ronald J / Decarli, Charles S / Dale, Anders M / Carmichael, Owen W / Tosun, Duygu / Weiner, Michael W

    Alzheimer's & dementia : the journal of the Alzheimer's Association

    2010  Volume 6, Issue 3, Page(s) 212–220

    Abstract: Functions of the Alzheimer's Disease Neuroimaging Initiative (ADNI) magnetic resonance imaging (MRI) core fall into three categories: (1) those of the central MRI core laboratory at Mayo Clinic, Rochester, Minnesota, needed to generate high quality MRI ... ...

    Abstract Functions of the Alzheimer's Disease Neuroimaging Initiative (ADNI) magnetic resonance imaging (MRI) core fall into three categories: (1) those of the central MRI core laboratory at Mayo Clinic, Rochester, Minnesota, needed to generate high quality MRI data in all subjects at each time point; (2) those of the funded ADNI MRI core imaging analysis groups responsible for analyzing the MRI data; and (3) the joint function of the entire MRI core in designing and problem solving MR image acquisition, pre-processing, and analyses methods. The primary objective of ADNI was and continues to be improving methods for clinical trials in Alzheimer's disease. Our approach to the present ("ADNI-GO") and future ("ADNI-2," if funded) MRI protocol will be to maintain MRI methodological consistency in the previously enrolled "ADNI-1" subjects who are followed up longitudinally in ADNI-GO and ADNI-2. We will modernize and expand the MRI protocol for all newly enrolled ADNI-GO and ADNI-2 subjects. All newly enrolled subjects will be scanned at 3T with a core set of three sequence types: 3D T1-weighted volume, FLAIR, and a long TE gradient echo volumetric acquisition for micro hemorrhage detection. In addition to this core ADNI-GO and ADNI-2 protocol, we will perform vendor-specific pilot sub-studies of arterial spin-labeling perfusion, resting state functional connectivity, and diffusion tensor imaging. One of these sequences will be added to the core protocol on systems from each MRI vendor. These experimental sub-studies are designed to demonstrate the feasibility of acquiring useful data in a multicenter (but single vendor) setting for these three emerging MRI applications.
    MeSH term(s) Alzheimer Disease/cerebrospinal fluid ; Alzheimer Disease/complications ; Alzheimer Disease/diagnosis ; Amyloid beta-Peptides/cerebrospinal fluid ; Brain/diagnostic imaging ; Brain/pathology ; Brain Mapping ; Cognition Disorders/cerebrospinal fluid ; Cognition Disorders/diagnostic imaging ; Cognition Disorders/etiology ; Genome-Wide Association Study ; Humans ; Magnetic Resonance Imaging/methods ; Magnetic Resonance Imaging/trends ; Peptide Fragments/cerebrospinal fluid ; Positron-Emission Tomography/methods
    Chemical Substances Amyloid beta-Peptides ; Peptide Fragments ; amyloid beta-protein (1-42)
    Language English
    Publishing date 2010-04-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2211627-8
    ISSN 1552-5279 ; 1552-5260
    ISSN (online) 1552-5279
    ISSN 1552-5260
    DOI 10.1016/j.jalz.2010.03.004
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  7. Article ; Online: Evidence for a role of the rare p.A152T variant in MAPT in increasing the risk for FTD-spectrum and Alzheimer's diseases.

    Coppola, Giovanni / Chinnathambi, Subashchandrabose / Lee, Jason JiYong / Dombroski, Beth A / Baker, Matt C / Soto-Ortolaza, Alexandra I / Lee, Suzee E / Klein, Eric / Huang, Alden Y / Sears, Renee / Lane, Jessica R / Karydas, Anna M / Kenet, Robert O / Biernat, Jacek / Wang, Li-San / Cotman, Carl W / Decarli, Charles S / Levey, Allan I / Ringman, John M /
    Mendez, Mario F / Chui, Helena C / Le Ber, Isabelle / Brice, Alexis / Lupton, Michelle K / Preza, Elisavet / Lovestone, Simon / Powell, John / Graff-Radford, Neill / Petersen, Ronald C / Boeve, Bradley F / Lippa, Carol F / Bigio, Eileen H / Mackenzie, Ian / Finger, Elizabeth / Kertesz, Andrew / Caselli, Richard J / Gearing, Marla / Juncos, Jorge L / Ghetti, Bernardino / Spina, Salvatore / Bordelon, Yvette M / Tourtellotte, Wallace W / Frosch, Matthew P / Vonsattel, Jean Paul G / Zarow, Chris / Beach, Thomas G / Albin, Roger L / Lieberman, Andrew P / Lee, Virginia M / Trojanowski, John Q / Van Deerlin, Vivianna M / Bird, Thomas D / Galasko, Douglas R / Masliah, Eliezer / White, Charles L / Troncoso, Juan C / Hannequin, Didier / Boxer, Adam L / Geschwind, Michael D / Kumar, Satish / Mandelkow, Eva-Maria / Wszolek, Zbigniew K / Uitti, Ryan J / Dickson, Dennis W / Haines, Jonathan L / Mayeux, Richard / Pericak-Vance, Margaret A / Farrer, Lindsay A / Ross, Owen A / Rademakers, Rosa / Schellenberg, Gerard D / Miller, Bruce L / Mandelkow, Eckhard / Geschwind, Daniel H

    Human molecular genetics

    2012  Volume 21, Issue 15, Page(s) 3500–3512

    Abstract: Rare mutations in the gene encoding for tau (MAPT, microtubule-associated protein tau) cause frontotemporal dementia-spectrum (FTD-s) disorders, including FTD, progressive supranuclear palsy (PSP) and corticobasal syndrome, and a common extended ... ...

    Abstract Rare mutations in the gene encoding for tau (MAPT, microtubule-associated protein tau) cause frontotemporal dementia-spectrum (FTD-s) disorders, including FTD, progressive supranuclear palsy (PSP) and corticobasal syndrome, and a common extended haplotype spanning across the MAPT locus is associated with increased risk of PSP and Parkinson's disease. We identified a rare tau variant (p.A152T) in a patient with a clinical diagnosis of PSP and assessed its frequency in multiple independent series of patients with neurodegenerative conditions and controls, in a total of 15 369 subjects. Tau p.A152T significantly increases the risk for both FTD-s (n = 2139, OR = 3.0, CI: 1.6-5.6, P = 0.0005) and Alzheimer's disease (AD) (n = 3345, OR = 2.3, CI: 1.3-4.2, P = 0.004) compared with 9047 controls. Functionally, p.A152T (i) decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently; and (ii) reduces the tendency to form abnormal fibers. However, there is a pronounced increase in the formation of tau oligomers. Importantly, these findings suggest that other regions of the tau protein may be crucial in regulating normal function, as the p.A152 residue is distal to the domains considered responsible for microtubule interactions or aggregation. These data provide both the first genetic evidence and functional studies supporting the role of MAPT p.A152T as a rare risk factor for both FTD-s and AD and the concept that rare variants can increase the risk for relatively common, complex neurodegenerative diseases, but since no clear significance threshold for rare genetic variation has been established, some caution is warranted until the findings are further replicated.
    MeSH term(s) Aged ; Alzheimer Disease/epidemiology ; Alzheimer Disease/genetics ; Frontotemporal Dementia/epidemiology ; Frontotemporal Dementia/genetics ; Genetic Predisposition to Disease ; Genetic Variation ; Genotype ; Haplotypes ; Humans ; Middle Aged ; Risk ; tau Proteins/genetics
    Chemical Substances MAPT protein, human ; tau Proteins
    Language English
    Publishing date 2012-05-03
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108742-0
    ISSN 1460-2083 ; 0964-6906
    ISSN (online) 1460-2083
    ISSN 0964-6906
    DOI 10.1093/hmg/dds161
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