We assessed whether carotid intima-media thickness (cIMT) is prospectively associated with amyloid-β (Aβ). 332 nondemented Atherosclerosis Risk in Communities Study participants with carotid ultrasounds (1990–1992) and PET scans (2012–2014) were studied. Participants in the highest (versus lowest) cIMT tertile had 2.17 times the odds of elevated Aβ (95% CI: 1.15–4.11), after demographic and APOE ɛ4 adjustments. An interaction with APOE ɛ4 was observed (p = 0.02). Greater cIMT was associated with elevated Aβ independent of vascular risk factors among those with ≥1 APOE ɛ4 allele, but not in noncarriers. In this cohort, higher cIMT was associated with Aβ deposition 22 years later, particularly among APOE ɛ4 carriers.
Alzheimer’s Association (2020) 2020 Alzheimer’s disease facts and figures. Alzheimers Dement16, 391–460.
2.
AisenPS, CummingsJ, JackCR, MorrisJC, SperlingR, FrölichL, JonesRW, DowsettSA, MatthewsBR, RaskinJ, ScheltensP, DuboisB (2017) On the path to 2025: Understanding the Alzheimer’s disease continuum . Alzheimers Res Ther9, 60.
3.
LazarRM, HowardVJ, KernanWN, AparicioHJ, LevineDA, VieraAJ, JordanLC, NyenhuisDL, PossinKL, SorondFA, WhiteCL, American Heart Association Stroke Council (2021) A primary care agenda for brain health: A scientific statement from the American Heart Association. Stroke52, e295–e308.
4.
GottesmanRF, SchneiderALC, ZhouY, CoreshJ, GreenE, GuptaN, KnopmanDS, MintzA, RahmimA, SharrettAR, WagenknechtLE, WongDF, MosleyTH (2017) Association between midlife vascular risk factors and estimated brain amyloid deposition. JAMA317, 1443–1450.
5.
RomeroJR, PreisSR, BeiserA, DeCarliC, D’AgostinoRB, WolfPA, VasanRS, PolakJF, SeshadriS (2016) Carotid atherosclerosis and cerebral microbleeds: The Framingham Heart Study . J Am Heart Assoc5, e002377.
6.
WangW, NorbyFL, GeorgeKM, AlonsoA, MosleyTH, GottesmanRF, MeyerML, LutseyPL (2021) Association of carotid intima-media thickness and other carotid ultrasound features with incident dementia in the ARIC-NCS. J Am Heart Assoc10, e020489.
7.
GustavssonA, van WestenD, StomrudE, EngströmG, NäggaK, HanssonO (2020) Midlife atherosclerosis and development of Alzheimer or vascular dementia. Ann Neurol87, 52–62.
8.
GuptaA, IadecolaC (2015) Impaired Aβ clearance: A potential link between atherosclerosis and Alzheimer’s disease. Front Aging Neurosci7, 115.
KangKM, LeeJH, YiD, ChoiHJ, LeeE, LeeY, LeeJ-Y, KimYK, SohnBK, SohnC-H, LeeDY, for the KBASE Research Group (2020) Association of carotid and intracranial stenosis with Alzheimer’s disease biomarkers. Alzheimers Res Therapy12, 106.
11.
WrightJD, FolsomAR, CoreshJ, SharrettAR, CouperD, WagenknechtLE, MosleyTH, BallantyneCM, BoerwinkleEA, RosamondWD, HeissG (2021) The ARIC (Atherosclerosis Risk In Communities) Study: JACC Focus Seminar 3/8. J Am Coll Cardiol77, 2939–2959.
12.
ChamblessLE, ZhongMM, ArnettD, FolsomAR, RileyWA, HeissG (1996) Variability in B-mode ultrasound measurements in the Atherosclerosis Risk in Communities (ARIC) study. . Ultrasound Med Biol22, 545–554.
13.
GottesmanRF, SchneiderALC, ZhouY, ChenX, GreenE, GuptaN, KnopmanDS, MintzA, RahmimA, SharrettAR, WagenknechtLE, WongDF, MosleyTHJr, (2016) The ARIC-PET amyloid imaging study: Brain amyloid differences by age, race, sex, and APOE. Neurology87, 473.
14.
KnopmanDS, GriswoldME, LiretteST, GottesmanRF, KantarciK, SharrettAR, JackCR, Graff-RadfordJ, SchneiderALC, WindhamBG, CokerLH, AlbertMS, MosleyTH, ARIC Neurocognitive Investigators (2015) Vascular imaging abnormalities and cognition: Mediation by cortical volume in nondemented individuals: Atherosclerosis Risk in Communities-Neurocognitive Study. Stroke46, 433–440.
15.
GottesmanRF, MosleyTH, KnopmanDS, HaoQ, WongD, WagenknechtLE, HughesTM, QiaoY, DearbornJ, WassermanBA (2020) Association of intracranial atherosclerotic disease with brain β-amyloid deposition: Secondary analysis of the ARIC Study.JAMA Neurol77, 350.
16.
The ARIC investigators (1989) The Atherosclerosis Risk in Communities (ARIC) Study: Design and objectives. Am J Epidemiol129, 687–702.
17.
VolcikKA, BarkleyRA, HutchinsonRG, MosleyTH, HeissG, SharrettAR, BallantyneCM, BoerwinkleE (2006) Apolipoprotein E polymorphisms predict low density lipoprotein cholesterol levels and carotid artery wall thickness but not incident coronary heart disease in 12,491 ARIC study participants. Am J Epidemiol164, 342–8.
18.
WeuveJ, Tchetgen TchetgenEJ, GlymourMM, BeckTL, AggarwalNT, WilsonRS, EvansDA, Mendes de Leon CF (2012) Accounting for bias due to selective attrition: The example of smoking and cognitive decline. Epidemiology23, 119–128.
MoonSW, ByunMS, YiD, LeeJH, JeonSY, LeeY, KeeBS, LeeDY, KBASE Research Group (2019) The ankle-brachial index is associated with cerebral β-amyloid deposition in cognitively normal older adults. J Gerontol A Biol Sci Med Sci74, 1141–1148.
21.
BennettEE, GianattasioKZ, HughesTM, MosleyTH, WongDF, GottesmanRF, PowerMC (2020) The association between midlife lipid levels and late-life brain amyloid deposition. Neurobiol Aging92, 73–74.
22.
LiuC-C, KanekiyoT, XuH, BuG (2013) Apolipoprotein E and Alzheimer disease: Risk, mechanisms, and therapy. Nat Rev Neurol9, 106–118.
23.
WilleitP, TschidererL, AllaraE, ReuberK, SeekircherL, GaoL, LiaoX, LonnE, GersteinHC, YusufS, BrouwersFP, AsselbergsFW, van GilstW, AnderssenSA, GrobbeeDE, KasteleinJJP, VisserenFLJ, NtaiosG, HatzitoliosAI, SavopoulosC, NieuwkerkPT, StroesE, WaltersM, HigginsP, DawsonJ, GreseleP, GuglielminiG, MigliacciR, EzhovM, SafarovaM, BalakhonovaT, SatoE, AmahaM, NakamuraT, KapellasK, JamiesonLM, SkiltonM, BlumenthalJA, HinderliterA, SherwoodA, SmithPJ, van AgtmaelMA, ReissP, van VonderenMGA, KiechlS, KlingenschmidG, SitzerM, StehouwerCDA, UthoffH, ZouZ-Y, CunhaAR, NevesMF, WithamMD, ParkH-W, LeeM-S, BaeJ-H, BernalE, WachtellK, KjeldsenSE, OlsenMH, PreissD, SattarN, BeishuizenE, HuismanMV, EspelandMA, SchmidtC, AgewallS, OkE, Aşçi G, de GrootE, GrootemanMPC, BlankestijnPJ, BotsML, SweetingMJ, ThompsonSG, LorenzMW, For the PROG-IMT and theProof-ATHERO Study Groups (2020) Carotid intima-media thicknessprogression as surrogate marker for cardiovascular risk:Meta-analysis of 119 clinical trials involving 100 667 patients. . Circulation142, 621–642.
24.
BaradaranH, DemissieS, HimaliJJ, BeiserA, GuptaA, PolakJF, DeCarliC, SeshadriS, RomeroJR (2020) The progression of carotid atherosclerosis and imaging markers of dementia. Alzheimers Dement (N Y)6, e12015.
25.
WangJ-G, StaessenJA, LiY, Van BortelLM, NawrotT, FagardR, MesserliFH, SafarM (2006) Carotid intima-media thickness and antihypertensive treatment:Ameta-analysis of randomized controlled trials. Stroke37, 1933–1940.
