Hu rau: emily.li@wecisanche.com

Lub raum ua haujlwm tsis cuam tshuam rau lub hlwb Amyloid Burden ntawm PET duab hauv 90 ntxiv rau Kev Kawm Cohort

Wei Ling Lau, Mark Fisher et.al

Kev paub txog kev poob qis yog tshwm sim hauv cov kab mob raum ntev (CKD). Thaum cov pov thawj ntawm vascular Cognitive poob yog muaj nyob rau hauvtus me nyuam mobey kab(CKD). Thaum cov pov thawj ntawm vascular kev paub tsis meej nyob rau hauv cov pej xeem no muaj zog, lub luag hauj lwm ntawmAlzheimerLub pathology tsis paub. Peb tau soj ntsuam cov ntshav cystatin C-kwv yees glomerular filtration rate (eGFR), lub hlwb amyloid-positron emission tomography (PET) imaging, thiab kev paub txog kev ua haujlwm hauv 166 tus neeg koom los ntawm 90 ntxiv rau Kev Kawm. Lub hnub nyoog nruab nrab yog 93 xyoo (ntau 90-107) thiab 101 (61 feem pua) yog poj niam; 107 tus neeg koom tau muaj kev paub zoo li qub thaum 59 tus neeg koom nrog kev paub tsis meej tsis muaj dementia (CIND) lossis dementia. Qhov ntsuas ± tus qauv sib txawv cystatin C yog 1.59 ± 0.54 mg / L nrog eGFR 40.7 ± 18.7 ml / min / 1.73m2. Qhov siab dua amyloid-lub nra yog txuam nrog dementia, tab sis tsis yog hnub nyoog, ntshav qab zib, ntshav siab, lossis kab mob plawv. Peb pom tsis muaj kev sib raug zoo ntawm lub hlwb amyloid- lub nra thiab cystatin C eGFR. Peb yav dhau los tau tshaj tawm tias lub raum kev ua haujlwm tau cuam tshuam nrog kev paub thiab lub hlwb microbleeds hauv tib pawg ntawm cov neeg laus tshaj plaws (90 ntxiv rau xyoo). Sib sau ua ke, cov kev tshawb pom no qhia tias microvascular ntau dua li Alzheimer's pathology tsav CKD-kev paub txog kev txawj ntse.kev ua haujlwm tsis zoohauv cov pejxeem no.

Ntsiab lus:mob raum mob, cystatin C, amyloid PET, kev laus, kev txawj ntse poob, thiab dementia

Cistanche ntawm Kev Txhim Kho Raum Ua Haujlwm

Taw qhia

Mob raum mob(CKD) tau lees paub ntau ntxiv tias yog ib qho kev pheej hmoo ywj pheej rau cov kab mob cerebrovascular thiab kev paub tsis meej. Lub koom haum no zoo li muaj zog txawm tias muaj hnub nyoog siab tshaj: nyob rau hauv pawg neeg laus tshaj plaws ntawm cov neeg laus hauv zej zog hnub nyoog 90 ntxiv rau xyoo, peb pab pawg tsis ntev los no tau tshaj tawm txog kev koom tes tseem ceeb ntawm CKD (Mob raum mob) thiab xwm txheej dementia nrog rau infratentorial cerebral microbleeds. Kab mob Microvascular hauv CKD (Mob raum mob)suav nrog ntshav-hlwb barrierkev ua haujlwm tsis zoocerebral microbleeds, grey teeb meem atrophy, thiab arteriolar neuropathology; Nws yog tsav los ntawm yam xws li mob ntev, uremic toxins, thiab impaired cerebral ntshav txaus autoregulation.

Cystatin C, qhov hnyav qis molecular (13 kDa) protease inhibitor tsim los ntawm tag nrho cov nucleated hlwb hauv lub cev, yog lim dawb los ntawm glomeruli thiab degraded los ntawm proximal tubular cells. Cystatin C accumulates hauv CKD thiab yog qhov kev kwv yees siv tau ntau dualub raum ua haujlwm(kwv yees glomerular filtration rate, eGFR) dua li creatinine hauv cov neeg laus vim nws tsis cuam tshuam los ntawm kev noj zaub mov lossis cov leeg nqaij. Piv nrog creatinine-based eGFR, cystatin C-raws li eGFR yog qhov kev kwv yees muaj zog dua ntawm kev tuag thiab qhov tshwm sim tsis zoo hauv cov neeg laus.

Thaum kab mob cerebral me me yog ib qho tshwm sim zoo hauv CKD, kev sib raug zoo ntawm CKD thiab lub hlwb amyloid- deposits tsis meej. Ntawm qhov kev ceeb toom, cystatin C tau raug tshaj tawm rau kev sib koom ua ke nrog amyloid-, uas sib sau ua ke hauv hippocampus thiab enterhinal cortex hauv cov tib neeg raug kev txom nyem.Alzheimer tus kab mob. Tsis tas li ntawd, ib qho polymorphism feem ntau ntawm cystatin C noob tau txuas rau qhov kev pheej hmoo ntawmAlzheimer tus kab mob. Peb, yog li ntawd, kev xav tias cov ntshav cystatin C siab dua (siab dua CKD) yuav cuam tshuam nrog kev nce hauv lub hlwb amyloid- lub nra.
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Kev yees duab ntawm amyloid-densities los ntawm positron emission tomography (PET) yog ib qho cuab yeej tshwm sim rau kev saib xyuas tsis muaj kev cuam tshuam ntawm amyloid deposition (17). Amyloid-PET tab tom tshawb nrhiav rau kev kuaj mob Alzheimer's pathology thiab tej zaum yuav muaj txiaj ntsig hauv kev taug qab cov lus teb (18, 19). Cov cuab yeej siv duab no yav dhau los tau tshawb pom hauv ib pawg me me ntawm 90 ntxiv rau cov hnub nyoog xyoo. Hauv txoj kev tshawb fawb tam sim no, peb tau tshuaj xyuas qhov kev sib koom ntawm amyloid-imaging nrog (a) kev txawj ntse thiab (b) cystatin C, nyob rau hauv ib pawg neeg laus tshaj plaws ntawm cov neeg laus hauv zej zog.

Cov khoom siv thiab cov txheej txheem

Peb tshaj tawm cov txiaj ntsig los ntawm ib pawg ntawm cov neeg koom nrog Kev Tshawb Fawb 90 ntxiv, kev kawm txuas ntxiv mus ntev ntawm kev laus thiab kev dementia hauv cov neeg muaj hnub nyoog 90 lossis laus dua. Cov neeg koom nrog Txoj Kev Kawm 90 ntxiv tau raug xaiv los ntawm ob pawg: cov neeg muaj txoj sia nyob ntawm Leisure World Cohort Study, kev tshawb fawb txog kev noj qab haus huv tau tsim nyob rau xyoo 1980s ntawm cov neeg nyob hauv Leisure World, cov neeg laus laus hauv Orange County, California, uas muaj hnub nyoog 90 xyoo lossis laus dua nyob rau lossis tom qab Lub Ib Hlis 1, 2003, thaum kev tso npe nkag rau hauv 90 ntxiv Kev Kawm tau pib, thiab 90 ntxiv rau cov neeg nyob hauv Orange County, California, uas nyob hauv 2-h tsav ntawm qhov chaw kawm, thiab koom nrog kawm los ntawm kev qhib nrhiav neeg ua haujlwm. Cov neeg koom nrog lawv tus kheej tshaj tawm lawv hnub yug, kev kawm, thiab keeb kwm kho mob. Lub Tsev Haujlwm Saib Xyuas Kev Ruaj Ntseg (IRB) ntawm University of California, Irvine (UC Irvine) tau pom zoo txoj kev tshawb no.

Amyloid PET Scan

Kev yees duab ntawm amyloid-densities los ntawm PET scan yog ib qho cuab yeej tawm tshiab rau kev saib xyuas tsis muaj kev cuam tshuam ntawm amyloid deposition. Nyob nruab nrab ntawm xyoo 2009 thiab 2020, 308 tus neeg koom tau txais 10-min PET scan ntawm ∼50 min tom qab txhaj tshuaj ntawm 370 MBq ntawm Florbetapir F18. Tom qab kev tswj xyuas zoo thiab kev ua kom zoo ntawm txhua haiv neeg PET cov duab rau qhov chaw template, tus qauv uptake value ratios (SUVR) tau suav nrog siv cov khoom siv cerebral dawb hauv cheeb tsam siv. Txhawm rau kom tau txais lub paj hlwb indices ntawm amyloid- deposition peb siv ib cheeb tsam statistically txhais cov paj hlwb (statROI) uas muaj cov precuneus thiab posterior cingulate cortices. Cov cheeb tsam no tau raug xaiv vim tias qhov kev faib tawm ntawm qhov txhais tau tias SUVR ua rau muaj kev sib cais ntau tshaj plaws ntawm cov neeg muaj kev paub tsis meej.

Cystatin C thiab eGFR

Ib qho ntshav kos rau cystatin C tau ntxiv rau IRB raws tu qauv thaum Lub Xya Hli 2014, tau sau thaum lub sijhawm kuaj PET kom txog rau lub Plaub Hlis 2017. Txij li lub Tsib Hlis 2017 cystatin C tau ntsuas thaum lub sijhawm teem sijhawm mus ntsib. Cystatin C noj thaum lossis ze lub sijhawm ntawm PET scan muaj rau 166 ntawm 308 tus neeg koom. Serum cystatin C tau ntsuas los ntawm Latex Enhanced Immunoturbidimetric Method los ntawm Pathology thiab Laboratory Services ntawm UC Irvine Medical Center. Qhov kwv yees glomerular filtration rate (eGFR) yog xam los ntawm cystatin C raws li qhovMob raum mob-Epidemiology Collaboration (CKD-EPI) sib npaug uas suav rau hnub nyoog thiab poj niam txiv neej (22). Cov ntshav coj mus ze tshaj plaws ntawm PET scan tau raug xaiv los tshuaj xyuas.

Neuropsychological Examination thiab Cognitive Status Evaluation

Cov neeg koom tau pom txhua txhua 6 lub hlis thiab muab cov qauv roj teeb ntawm 10 Cov Kev Ntsuam Xyuas neuropsychological indexing ntau yam kev txawj ntse thiab suav nrog Hloov Kho Mini-Mental State Examination (3MS), los ntawm kev cob qhia thiab ntawv pov thawj psychometrists. Cov neeg koom nrog kuj tau txais kev kuaj mob hlwb los ntawm cov kws kuaj mob neurological (cov kws kho mob tau kawm lossis cov kws kho mob) los txiav txim siab txog qhov kev paub zoo (ib txwm, kev paub tsis meej tsis muaj dementia [CIND], lossis dementia). Thaum mus ntsib no, cov keeb kwm kho mob kuj tau hloov kho. Kev mus ntsib ze tshaj plaws rau PET scan tau raug xaiv los tshuaj xyuas.

Kev txheeb xyuas cov ntaub ntawv

Txhais tau hais tias thiab tus qauv sib txawv (SD) ntawm PET statROI tau suav rau cov pej xeem, keeb kwm kev kho mob, thiab kev paub txog cov xwm txheej. Qhov sib txawv ntawm txhais tau tias tau sim siv t-tests thiab kev soj ntsuam ntawm qhov sib txawv (nrog rau kev soj ntsuam tom qab hoc rau ntau qhov kev sib piv ntawm cov ntsiab lus). Spearman rank correlation thiab ib nrab correlation coefficients raug xam rau hnub nyoog, eGFR thiab PET statROI. Spearman qib sib txheeb coefficient ntawm PET statROI thiab CKD(Mob raum mob) stage was also calculated. With 166 participants, the study was powered to detect a significant correlation of >0.22. Txhua qhov kev txheeb cais tau ua tiav siv SAS software version 9.4 rau Windows (SAS Institute Inc., Cary, NC).

TSEEM CEEB

Ntawm 3{{10}}8 tus neeg koom nrog amyloid PET scan, cystatin C ntsuas muaj nyob rau hauv 166 tus neeg koom. Ntawm 166, 101 (61 feem pua) yog poj niam thiab hnub nyoog nruab nrab yog 93 xyoo. Feem coob ntawm cov neeg koom (n=94) ua tiav cov ntshav kos rau cystatin C thiab amyloid PET scan tib hnub; tag nrho tab sis 10 tus neeg koom ua tiav amyloid PET scan hauv 90 hnub ntawm kev ntsuas cystatin C. Cystatin C ranged 0. Tus naj npawb ntawm cov neeg koom los ntawm CKD(Mob raum mob)theem yog: CKD theem 2, n=29 (17 feem pua ​​); CKD theem 3a, n=27 (16 feem pua ​​); CKD theem 3b, n=54 (33 feem pua ​​); CKD theem 4, n {{10}} (32 feem pua ​​); thiab CKD theem 5, n=3 (2 feem pua). PET statROI ranged 0.59-0.93 (txhais tau tias 0.76, SD=0.07).

Table 1 muab qhov nruab nrab ± SD ntawm PET statROI los ntawm cov neeg koom nrog cov yam ntxwv hauv 166 tus neeg koom nrog kev ntsuas cystatin C. Tsis yog poj niam txiv neej, kev kawm, kev haus luam yeeb lossis ib qho ntawm cov keeb kwm kho mob hloov pauv tau cuam tshuam nrog PET statROI. Kev tshuaj xyuas cov pawg loj dua ntawm 3{{10}}}8 cov neeg koom nrog PET imaging, cov neeg koom nrog vs. tsis muaj cystatin C ntsuas (166 vs. 142 cov neeg koom) sib txawv tsuas yog cov kab mob plawv (9 vs. 18 feem pua, p=0.02; cov ntaub ntawv tsis qhia). Ob pawg tsis sib txawv ntawm lub cev qhov ntsuas lub cev lossis cov thyroid-stimulating hormone, yam uas tuaj yeem hloov kho cystatin C qib. Peb tsis muaj ntaub ntawv qhia txog cov cim inflammatory xws li C reactive protein. Lub ntsiab lus statROI tau siab dua rau cov neeg uas muaj dementia (0.84) dua li cov neeg uas muaj kev paub zoo (0.75) lossis CIND (0.76), p=0.004. Nyob rau hauv ib pab pawg neeg soj ntsuam ntawm 94 tus neeg koom uas muaj tib-hnub cystatin C ntshav-kos thiab amyloid PET scan, kev koom tes nrog kev paub tsis meej nyob twj ywm thiab tseem ceeb (p=0.01). PET statROI tsis cuam tshuam nrog cystatin C (r=0.09), eGFR (−0.09) lossis hnub nyoog (r=0.12) (Table 2 thiab daim duab 1) lossis nrog CKD(Mob raum mob)theem (r=0.05) (Table 3)

SIJ HAWM/XEEM CEEB

Txoj kev tshawb fawb tam sim no qhia tau hais tias muaj kev koom tes tseem ceeb ntawm lub hlwb amyloid- lub nra ( ntsuas ntawm PET scan) thiab kev paub tsis meej hauv cov neeg laus tshaj plaws-laus pawg los ntawm 90 ntxiv Kev Kawm, tab sis tsis muaj kev koom tes ntawm cystatin C eGFR lossis CKD theem thiab lub hlwb amyloid- lub nra. Peb tau tshaj tawm yav dhau los txog kev koom tes tseem ceeb ntawm CKD(Mob raum mob), indices ntawm cerebral microvascular kab mob, thiab kev txawj ntse poob nyob rau hauv tib cohort. Ua ke, peb txoj haujlwm qhia tias txo qislub raum ua haujlwmthiab lub hlwb amyloid- lub nra cuam tshuam kev paub ntawm kev sib txawv ntawm pathophysiologic.

Txawm hais tias cov ntshav amyloid ntau dua tau tshaj tawm hauv CKD(Mob raum mob)Cov neeg mob, qhov no tej zaum yuav yog vim lub raum tshem tawm ntawm amyloid- . Peb txoj kev tshawb fawb tam sim no nyob rau hauv ib pawg neeg laus uas tsis yog lim ntshav ntshav yog ua raws li tsab ntawv ceeb toom los ntawm Reusche li al. kev soj ntsuam tom qab mortem los ntawm 50 cov neeg mob uas muaj qhov kawgraum tsis ua haujlwmnyob rau hauv mob hemodialysis. Tsis muaj kev nce ntxivAlzheimer tus kab mobmorphology, piv nrog cov hnub nyoog-matched tswj, tau pom. Hauv kev tshawb fawb tam sim no, peb pom tsis muaj kev sib raug zoo ntawm CKD(Mob raum mob) and brain amyloid-β burden, assessed non-invasively. Similarly, in a French cohort of community-dwellers >70 xyoo nyob qhov twg eGFR kuj tseem khaws cia (qhov nruab nrab eGFR 73 nrog interquartile ntau yam 60-84 ml/min/1.73 m2), CKD tau cuam tshuam nrog kev txawj ntse poob lub sijhawm tab sis tsis cuam tshuam nrog cov duab ntawmAlzheimer tus kab mob(cortical amyloid- thiab hippocampal atrophy). Lub zog ntawm txoj kev tshawb fawb tam sim no yog kev siv cystatin C eGFR kev ntsuas, uas tsis hloov pauv los ntawm kev noj zaub mov lossis cov leeg nqaij thiab yog li siv tau ntau dua li creatinine-based eGFR hauv cov neeg laus.

Hauv kev sib piv rau qhov tsis muaj kev koom tes nrog Alzheimer's-sociated pathology, ua ntej ua haujlwm los ntawm peb thiab lwm tus tau qhia txog kev koom tes ntawm CKD(Mob raum mob) thiab kab mob cerebral microvascular. CKD-txo cov kab mob cerebral me me muaj xws li microbleeds, microinfacts, lacunes, teeb meem dawb lossis thoob ntiaj teb atrophy, thiab arteriolosclerosis. Hauv kev txheeb xyuas ua ntej ntawm The 90 plus Study cohort, qis dualub raum ua haujlwmcuam ​​tshuam nrog kev puas tsuaj thoob ntiaj teb kev paub, kev ua haujlwm ntawm kev ua haujlwm, thiab kev muaj peev xwm pom-spatial; infratentorial microbleeds; thiab qis grey teeb meem ntim (4). Qhov kev pheej hmoo ntawm qhov tshwm sim dementia nyob rau hauv siab tshaj plaws cystatin C tertile yog 3.81 (hloov rau lub hnub nyoog, poj niam txiv neej, kev kawm, thiab comorbid tej yam kev mob) thiab tau attenuated thaum microbleeds tau suav nrog hauv cov qauv kev pheej hmoo, qhia tias qhov cuam tshuam ntawm CKD ntawm kev txawj ntse.kev ua haujlwm tsis zooyog ib nrab kho los ntawm microbleeds. Hauv 2,526 tus neeg koom los ntawm cov pej xeem-raws li Rotterdam Txoj Kev Kawm, qis cystatin C-raws li eGFR tau cuam tshuam nrog ntau dua ntawm lacunes thiab loj dua cov teeb meem dawb qhov mob. Nws yog ib qho tseem ceeb kom nco ntsoov tias qee yam kev pheej hmoo rauAlzheimer tus kab mobyog qhov tseem ceeb hauv CKD, suav nrog vascularkev ua haujlwm tsis zoothiab nce serum homocysteine ​​​​. Muab cov kev pheej hmoo sib koom no, cov kev tshawb fawb uas cuam tshuam CKD nrog kev pheej hmoo ntawmAlzheimer tus kab mobyuav tsum tau ua tib zoo txhais. Nyob rau hauv txoj kev tshawb no tam sim no, kev ntsuam xyuas ntawm amyloid- uas yog ib tug pathological substrate rau Alzheimer's tsis correlated nrog.lub raum ua haujlwm. 

Peb lees paub ntau yam kev txwv kev kawm. Txoj Kev Kawm 90 ntxiv muab cov ntaub ntawv ntev ntev rau cov tib neeg muaj hnub nyoog 90 xyoo thiab laus dua, tab sis vim tias feem coob ntawm cov neeg tuaj koom yog neeg dawb, muaj kev kawm siab, thiab muaj txiaj ntsig zoo cov txiaj ntsig yuav tsis tuaj yeem ua rau lwm pawg neeg. Peb tsis tuaj yeem txiav txim siab txog kev muaj sia nyob, vim tias cov neeg nyob hauv zej zog hauv 90 ntxiv Kev Tshawb Fawb tau muaj kev noj qab haus huv ntawm cov hlab plawv thiab tsis muaj CKD siab heev. Peb txoj kev tshawb fawb tej zaum yuav tsis muaj zog los txheeb xyuas kev sib koom tes ntawm CKD(Mob raum mob)thiab lub hlwb amyloid- lub nra. Thaum kawg, txawm hais tias feem ntau cov neeg koom (n=94) tau ntsuas cystatin C thiab amyloid PET imaging nyob rau tib hnub, lub sijhawm nruab nrab ntawm PET imaging thiab sau ntshav rau cystatin C tau sib txawv. Txawm li cas los xij, kev tsom xam pab pawg txwv txwv rau cov neeg koom nrog uas tau ntsuas tib hnub ntawm cystatin C thiab amyloid-PET imaging pom tau tias muaj kev sib raug zoo ntawm cov statROI siab dua nrog kev paub tsis meej, qhia tias tag nrho pab pawg neeg soj ntsuam tseem sawv cev.

Hauv cov ntsiab lus, cystatin C-kwv yeeslub raum ua haujlwmtsis cuam tshuam nrog lub hlwb amyloid- lub nra rau cov neeg laus > 90 xyoo. Kev ua haujlwm ua ntej los ntawm peb thiab lwm tus tau pom tias muaj kev sib koom tes ywj pheej ntawm CKD nrog kev paub thiab kab mob hauv hlwb. Cov kev tshawb pom no qhia tias kev paub tsis meej hauv CKD(Mob raum mob)Cov pejxeem feem ntau qhia txog vascular ntau dua li amyloid-pathology.

Los ntawm: ' Lub raum Ua Haujlwm Tsis Muaj Teeb Meem Rau Lub Ncauj Amyloid Burden ntawm PET Imaging hauv 90 ntxiv rau Kev Kawm Cohort ' los ntawm Wei Ling Lau , Mark Fisher et.al

Frontiers hauv Tshuaj |www.frontiersin.org. 6 Cuaj hlis 2021|Nqe 8|ib 671945