Cerebral amyloid angiopathy (CAA) is characterized by amyloid-β aggregation in the media and adventitia of the leptomeningeal and cortical blood vessels. CAA is one of the strongest vascular contributors to Alzheimer’s disease (AD). It frequently co-occurs in AD patients, but the relationship between CAA and AD is incompletely understood. CAA may drive AD risk through damage to the neurovascular unit and accelerate parenchymal amyloid and tau deposition. Conversely, early AD may also drive CAA through cerebrovascular remodeling that impairs blood vessels from clearing amyloid-β. Sole reliance on autopsy examination to study CAA limits researchers’ ability to investigate CAA’s natural disease course and the effect of CAA on cognitive decline. Neuroimaging allows for in vivo assessment of brain function and structure and can be leveraged to investigate CAA staging and explore its associations with AD. In this review, we will discuss neuroimaging modalities that can be used to investigate markers associated with CAA that may impact AD vulnerability including hemorrhages and microbleeds, blood-brain barrier permeability disruption, reduced cerebral blood flow, amyloid and tau accumulation, white matter tract disruption, reduced cerebrovascular reactivity, and lowered brain glucose metabolism. We present possible areas for research inquiry to advance biomarker discovery and improve diagnostics.
Iturria-MedinaY, SoteroRC, ToussaintPJ, Mateos-PerezJM, EvansACAlzheimer’s Disease Neuroimaging Initiative (2016) Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis. Nat Commun7, 11934.
3.
NielsenRB, EgefjordL, AngleysH, MouridsenK, GejlM, MøllerA, BrockB, BrændgaardH, GottrupH, RungbyJ, EskildsenSF, ØstergaardL (2017) Capillary dysfunction is associated with symptom severity andneurodegeneration in Alzheimer’s disease. Alzheimers Dement13, 1143–1153.
4.
GovindpaniK, VinnakotaC, WaldvogelHJ, FaullRL, KwakowskyA (2020) Vascular dysfunction in Alzheimer’s disease: A biomarker of disease progression and a potential therapeutic target. Neural Regen Res15, 1030–1032.
5.
GrammasP (2011) Neurovascular dysfunction, inflammation and endothelial activation: Implications for the pathogenesis of Alzheimer’s disease. J Neuro inflammation8, 26.
6.
IadecolaC (2017) The neurovascular unit coming of age: A journey through neurovascular coupling in health and disease. Neuron96, 17–42.
CisternasP, TaylorX, Lasagna-ReevesCA (2019) The amyloid-tau-neuroinflammation axis in the context of cerebral amyloid angiopathy. Int J Mol Sci20, 6319.
9.
ArvanitakisZ, LeurgansSE, WangZ, WilsonRS, BennettDA, SchneiderJA (2011) Cerebral amyloid angiopathy pathology and cognitive domains in older persons. Ann Neurol2, 320–327.
10.
GoosJD, KesterMI, BarkhofF, KleinM, BlankensteinMA, ScheltensP, van der FlierWM (2009) Patients with Alzheimer disease with multiple microbleeds: Relation with cerebrospinal fluid biomarkers and cognition. Stroke40, 3455–3460.
11.
BoylePA, YuL, NagS, LeurgansS, WilsonRS, BennettDA, SchneiderJA (2015) Cerebral amyloid angiopathy and cognitive outcomes in community-based older persons. Neurology85, 1930–1936.
12.
SmithEE (2018) Cerebral amyloid angiopathy as a cause of neurodegeneration. J Neurochem144, 651–658.
13.
GreenbergSM, BacskaiBJ, Hernandez-GuillamonM, PruzinJ, SperlingR, van Veluw SJ (2020) Cerebral amyloid angiopathy and Alzheimer disease - one peptide, two pathways. Nat Rev Neurol16, 30–42.
14.
GreenbergSM, SalmanRA-S, BiesselsGJ, van BuchemM, CordonnierC, LeeJM, MontanerJ, SchneiderJA, SmithEE, VernooijM, WerringDJ (2014) Outcome markers for clinical trials in cerebral amyloid angiopathy. Lancet Neurol13, 419–428.
15.
SalatDH, SmithEE, TuchDS, BennerT, PappuV, SchwabKM, GurolME, RosasHD, RosandJ, GreenbergSM (2006) White matter alterations in cerebral amyloid angiopathy measured by diffusion tensor imaging. Stroke37, 1759–1764.
16.
FotiadisP, van Rooden S, van der Grond J, SchultzA, Martinez-RamirezS, AurielE, ReijmerY, van Opstal AM, AyresA, SchwabKMAlzheimer’s Disease Neuroimaging Initiative;HeddenT, RosandJ, ViswanathanA, WermerM, TerwindtG, SperlingRA, PolimeniJR, JohnsonKA, van Buchem MA, GreenbergSM, GurolME (2016) Cortical atrophy in patients with cerebral amyloid angiopathy: A case-control study. Lancet Neurol15, 811–819.
17.
GurolME, BeckerJA, FotiadisP, RileyG, SchwabK, JohnsonKA, GreenbergSM (2016) Florbetapir-PET to diagnose cerebral amyloid angiopathy: A prospective study. Neurology87, 2043–2049.
18.
SchoemakerD, CharidimouA, Zanon Zotin MC, RaposoN, JohnsonKA, SanchezJS, GreenbergSM, ViswanathanA (2021) Association of memory impairment with concomitant tau pathology in patients with cerebral amyloid angiopathy. Neurology96, e1975–e1986.
19.
GattiL, TinelliF, ScelzoE, ArioliF, Di Fede G, ObiciL, PantoniL, GiacconeG, CaroppoP, ParatiEA, BersanoA (2020) Understanding the pathophysiology of cerebral amyloid angiopathy. Int J Mol Sci21, 3435.
20.
KeableA, FennaK, YuenHM, JohnstonDA, SmythNR, SmithC, Al-Shahi Salman R, SamarasekeraN, NicollJA, AttemsJ, KalariaRN, WellerRO, CarareRO (2016) Deposition of amyloid beta in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy. Biochim Biophys Acta1862, 1037–1046.
21.
KressBT, IliffJJ, XiaM, WangM, WeiHS, ZeppenfeldD, XieL, KangH, XuQ, LiewJA, PlogBA, DingF, DeaneR, NedergaardM (2014) Impairment of paravascular clearance pathways in the aging brain. Ann Neurol76, 845–861.
AttemsJ, JellingerKA (2004) Only cerebral capillary amyloid angiopathy correlates with Alzheimer pathology–a pilot study. Acta Neuropathol107, 83–90.
27.
RoherAE, LowensonJD, ClarkeS, WoodsAS, CotterRJ, GowingE, BallMJ (1993) beta-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: Implications for the pathology of Alzheimer disease. Proc Natl Acad Sci U S A90, 10836–10840.
28.
ThalDR, GriffinWS, de VosRA, GhebremedhinE (2008) Cerebral amyloid angiopathy and its relationship to Alzheimer’s disease. Acta Neuropathol115, 599–609.
29.
ShinkaiY, YoshimuraM, ItoY, OdakaA, SuzukiN, YanagisawaK, IharaY (1995) Amyloid β-proteins 1— 40 and 1— 42(43) in the soluble fraction of extra- and intracranial blood vessel. Ann Neurol38, 421–428.
GkanatsiouE, PorteliusE, ToomeyCE, BlennowK, ZetterbergH, LashleyT, BrinkmalmG (2019) A distinct brain beta amyloid signature in cerebral amyloid angiopathy compared to Alzheimer’s disease. Neurosci Lett701, 125–131.
33.
Bonaterra-PastraA, BenítezS, PancorboO, Rodríguez-LunaD, VertC, RoviraA, FreijoMM, TurS, Martínez-ZabaletaM, Cardona PortelaP, VeraR, Lebrato-HernándezL, ArenillasJF, Pérez-SánchezS, Domínguez-MayoralA, FàbregasJM, MauriG, MontanerJ, Sánchez-QuesadaJL, Hernández-GuillamonM (2023) Association of candidate genetic variants and circulating levels of ApoE/ApoJwith common neuroimaging features of cerebral amyloid angiopathy. Front Aging Neurosci15, 1134399.
34.
BiffiA (2022) Main features of hereditary cerebral amyloid angiopathies: A systematic review. Cereb Circ Cogn Behav3, 100124.
35.
BrooksWS, KwokJB, HallidayGM, GodboltAK, RossorMN, CreaseyH, JonesAO, SchofieldPR (2004) Hemorrhage is uncommon in new Alzheimer family with Flemish amyloid precursor protein mutation. Neurology63, 1613–1617.
36.
van Etten ES, GurolME, van der Grond J, HaanJ, ViswanathanA, SchwabKM, AyresAM, AlgraA, RosandJ, van Buchem MA, TerwindtGM, GreenbergSM, WermerMJ (2016) Recurrent hemorrhage risk and mortality in hereditary and sporadic cerebral amyloid angiopathy. Neurology87, 1482–1487.
37.
ObiciL, DemarchiA, de Rosa G, BellottiV, MarcianoS, DonadeiS, ArbustiniE, PalladiniG, DiegoliM, GenoveseE, FerrariG, CoverlizzaS, MerliniG (2005) A novel AbetaPP mutation exclusively associated with cerebral amyloid angiopathy. Ann Neurol58, 639–644.
38.
PalsdottirA, SnorradottirAO, ThorsteinssonL (2006) Hereditary cystatin C amyloid angiopathy: Genetic, clinical, and pathological aspects. Brain Pathol16, 55–59.
39.
RossiG, GiacconeG, MalettaR, MorbinM, CapobiancoR, MangieriM, GiovagnoliAR, BizziA, TomainoC, PerriM, Di NataleM, TagliaviniF, BugianiO, BruniA (2004) A family with Alzheimer disease and strokes associated with A713T mutation of the APP gene. Neurology63, 910–912.
40.
IwanowskiP, KozubskiW, LosyJ (2015) Iowa-type hereditary cerebral amyloid angiopathy in a Polish family. J Neurol Sci356, 202–204.
41.
LevyE, CarmanMD, Fernandez-MadridIJ, PowerMD, LieberburgI, van Duinen SG, BotsGT, LuyendijkW, FrangioneB (1990) Mutation of the Alzheimer’s disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science248, 1124–1126.
42.
TagliaviniF, RossiG, PadovaniA, MagoniM, AndoraG, SgarziM, BizziA, SavoiardoM, CarellaF, MorbinM, GiacconeG, BugianiO (1999) A new βPP mutation related to hereditary cerebral haemorrhage. Alzheimers Rep2(S1), S28.
Kumar-SinghS, CrasP, WangR, KrosJM, van Swieten J, LübkeU, CeuterickC, SerneelsS, VennekensK, TimmermansJP, Van Marck E, MartinJJ, van Duijn CM, Van Broeckhoven C (2002) Dense-core senile plaques in the Flemish variant of Alzheimer’s disease are vasocentric. Am J Pathol161, 507–520.
47.
SleegersK, BrouwersN, GijselinckI, TheunsJ, GoossensD, WautersJ, Del-FaveroJ, CrutsM, van Duijn CM, Van Broeckhoven C (2006) APP duplication is sufficient to cause early onset Alzheimer’s dementia with cerebral amyloid angiopathy. Brain129, 2977–2983.
48.
ConidiME, BernardiL, PuccioG, SmirneN, MuracaMG, CurcioSA, ColaoR, PiscopoP, GalloM, AnfossiM, FrangipaneF, ClodomiroA, MirabelliM, VassoF, CupidiC, TorchiaG, Di Lorenzo R, MandichP, ConfaloniA, MalettaRG, BruniAC (2015) Homozygous carriers of APP A713T mutation in an autosomal dominant Alzheimer disease family. Neurology84, 2266–2273.
49.
KampJA, MourselLG, HaanJ, TerwindtGM, Lesnik Oberstein SA, van Duinen SG, van Roon-Mom WM (2014) Amyloid beta in hereditary cerebral hemorrhage with amyloidosis-Dutch type. Rev Neurosci25, 641–651.
50.
SellalF, WallonD, Martinez-AlmoynaL, MarelliC, DharA, OesterleH, Rovelet-LecruxA, RousseauS, KourkoulisCE, RosandJ, DiPucchioZY, FroschM, GombertC, AudoinB, MineM, RiantF, FrebourgT, HannequinD, CampionD, GreenbergSM, Tournier-LasserveE, NicolasG (2017) APP mutations in cerebral amyloid angiopathy with or without cortical calcifications: Report of three families and a literature review. J Alzheimers Dis56, 37–46.
WilcockDM, SchmittFA, HeadE (2016) Cerebrovascular contributions to aging and Alzheimer’s disease in Down syndrome. Biochim Biophys Acta1862, 909–914.
53.
Jastrzebski K, KacperskaMJ, MajosA, GrodzkaM, Głąbiński A (2015) Hemorrhagic stroke, cerebralamyloid angiopathy, Down syndrome and the Boston criteria. Neurol Neurochir Pol49, 193–196.
54.
GreenbergSM, CharidimouA (2018) Diagnosis of cerebral amyloid angiopathy: Evolution of the Boston criteria. Stroke49, 491–497.
55.
GreenbergSM, RebeckGW, VonsattelJP, Gomez-IslaT, HymanBT (1995) Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy. Ann Neurol38, 254–259.
56.
VintersHV (1987) Cerebral amyloid angiopathy. A critical review. Stroke18, 311–324.
57.
LinnJ, HalpinA, DemaerelP, RuhlandJ, GieseAD, DichgansM, van Buchem MA, BruckmannH, GreenbergSM (2010) Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology74, 1346–1350.
58.
BrenowitzWD, NelsonPT, BesserLM, HellerKB, KukullWA (2015) Cerebral amyloid angiopathy and its co-occurrence with Alzheimer’s disease and other cerebrovascular neuropathologic changes. Neurobiol Aging36, 2702–2708.
JakelL, De KortAM, KlijnCJM, SchreuderF, VerbeekMM (2022) Prevalence of cerebral amyloid angiopathy: A systematic review and meta-analysis. Alzheimers Dement18, 10–28.
61.
StewartPA, HayakawaK, AkersMA, VintersHV (1992) A morphometric study of the blood-brain barrier in Alzheimer’s disease. Lab Invest67, 734–742.
62.
FarkasE, De Jong GI, de Vos RA, Jansen Steur EN, LuitenPG (2000) Pathological features of cerebral cortical capillaries are doubled in Alzheimer’s disease and Parkinson’s disease. Acta Neuropathol100, 395–402.
63.
CanobbioI, AbubakerAA, VisconteC, TortiM, PulaG (2015) Role of amyloid peptides in vascular dysfunction and platelet dysregulation in Alzheimer’s disease. Front Cell Neurosci9, 65.
64.
BuéeL, HofPR, DelacourteA (1997) Brain microvascular changes in Alzheimer’s disease and other dementias. Ann N Y Acad Sci826, 7–24.
65.
VukicV, CallaghanD, WalkerD, LueLF, LiuQY, CouraudPO, RomeroIA, WekslerB, StanimirovicDB, ZhangW (2009) Expression of inflammatory genes induced by beta-amyloid peptides in human brain endothelial cells and in Alzheimer’s brain is mediated by the JNK-AP1 signaling pathway. Neurobiol Dis34, 95–106.
66.
AkiyamaH, IkedaK, KondoH, McGeerPL (1992) Thrombin accumulation in brains of patients with Alzheimer’s disease. Neurosci Lett146, 152–154.
67.
ParkL, AnratherJ, ZhouP, FrysK, PitstickR, YounkinS, CarlsonGA, IadecolaC (2005) NADPH-oxidase-derived reactive oxygen species mediate the cerebrovascular dysfunction induced by the amyloid beta peptide. J Neurosci25, 1769–1777.
68.
MerliniM, WannerD, NitschRM (2016) Tau pathology-dependent remodelling of cerebral arteries precedes Alzheimer’s disease-related microvascular cerebral amyloid angiopathy. Acta Neuropathol131, 737–752.
69.
LiuJ, ZhuYS, KhanMA, BrunkE, Martin-CookK, WeinerMF, CullumCM, LuH, LevineBD, Diaz-ArrastiaR, ZhangR (2014) Global brain hypoperfusion and oxygenation in amnestic mild cognitive impairment. Alzheimers Dement10, 162–170.
70.
JangH, ChunMY, KimHJ, NaDL, SeoSW (2023) The effects of imaging markers on clinical trajectory in cerebral amyloid angiopathy: A longitudinal study in a memory clinic. Alzheimers Res Ther15, 14.
71.
DingJ, SigurðssonS, JónssonPV, EiriksdottirG, MeirellesO, KjartanssonO, LopezOL, van Buchem MA, GudnasonV, LaunerLJ (2017) Space and location of cerebral microbleeds, cognitive decline, and dementia in thecommunity. Neurology88, 2089–2097.
72.
AkoudadS, WoltersFJ, ViswanathanA, de Bruijn RF, van der LugtA, HofmanA, KoudstaalPJ, IkramMA, VernooijMW (2016) Association of cerebral microbleeds with cognitive decline and dementia. JAMA Neurol73, 934–943.
73.
PoelsMM, IkramMA, van der LugtA, HofmanA, NiessenWJ, KrestinGP, BretelerMM, VernooijMW (2012) Cerebral microbleeds are associated with worse cognitive function: The Rotterdam Scan Study. Neurology78, 326–333.
74.
InoueY, ShueF, BuG, KanekiyoT (2023) Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer’s disease. Mol Neurodegener18, 46.
CodjiaP, AyrignacX, MochelF, MouzatK, Carra-DalliereC, CastelnovoG, EllieE, Etcharry-BouyxF, VernyC, BelliardS, HannequinD, MarelliC, NadjarY, Le Ber I, DorbozI, SamaanS, Boespflug-TanguyO, LumbrosoS, LabaugeP (2018) Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: An MRI study of 16 french cases. AJNR Am J Neuroradiol39, 1657–1661.
77.
CharidimouA, BoulouisG, HaleyK, AurielE, van Etten ES, FotiadisP, ReijmerY, AyresA, VashkevichA, DipucchioZY, SchwabKM, Martinez-RamirezS, RosandJ, ViswanathanA, GreenbergSM, GurolME (2016) White matter hyperintensity patterns in cerebral amyloid angiopathy and hypertensive arteriopathy. Neurology86, 505–511.
78.
ThanprasertsukS, Martinez-RamirezS, Pontes-NetoOM, NiJ, AyresA, ReedA, SwordsK, GurolME, GreenbergSM, ViswanathanA (2014) Posterior white matter disease distribution as a predictor of amyloid angiopathy. Neurology83, 794–800.
79.
WardlawJM, SmithEE, BiesselsGJ, CordonnierC, FazekasF, FrayneR, LindleyRI, O’BrienJT, BarkhofF, BenaventeOR, BlackSE, BrayneC, BretelerM, ChabriatH, DecarliC, de Leeuw FE, DoubalF, DueringM, FoxNC, GreenbergS, HachinskiV, KilimannI, MokV, OostenbruggeR, PantoniL, SpeckO, StephanBC, TeipelS, ViswanathanA, WerringD, ChenC, SmithC, van Buchem M, NorrvingB, GorelickPB, DichgansM (2013) Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol12, 822–838.
80.
KimberlyWT, GilsonA, RostNS, RosandJ, ViswanathanA, SmithEE, GreenbergSM (2009) Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy. Neurology72, 1230–1235.
81.
VahediK, AlamowitchS (2011) Clinical spectrum of type IV collagen (COL4A1) mutations: A novel genetic multisystem disease. Curr Opin Neurol24, 63–68.
82.
NitkunanA, LanfranconiS, CharltonRA, BarrickTR, MarkusHS (2011) Brain atrophy and cerebral small vessel disease: A prospective follow-up study. Stroke42, 133–138.
83.
BeckC, KruetzelmannA, ForkertND, JuettlerE, SingerOC, KöhrmannM, KerstenJF, SobeskyJ, GerloffC, FiehlerJ, SchellingerPD, RötherJ, ThomallaG (2014) A simple brain atrophy measure improves the prediction of malignant middle cerebral artery infarction by acute DWI lesion volume. J Neurol261, 1097–1103.
84.
LabovitzDL, Boden-AlbalaB, HauserWA, SaccoRL (2007) Lacunar infarct or deep intracerebral hemorrhage: Who gets which? The Northern Manhattan study. Neurology68, 606–608.
85.
CaiZ, WangC, HeW, TuH, TangZ, XiaoM, YanLJ (2015) Cerebral small vessel disease and Alzheimer’s disease. Clin Interv Aging10, 1695–1704.
86.
KesterMI, GoosJD, TeunissenCE, BenedictusMR, BouwmanFH, WattjesMP, BarkhofF, ScheltensP, van der FlierWM (2014) Associations between cerebral small-vessel disease and Alzheimer disease pathology as measured by cerebrospinal fluid biomarkers. JAMA Neurol71, 855–862.
UhJ, YezhuvathU, ChengY, LuH (2010) In vivo vascular hallmarks of dif- fuse leukoaraiosis. J Magn Reson Imaging32, 184–190.
89.
MakedonovI, BlackSE, MacIntoshBJ (2013) Cerebral small vessel disease in aging and Alzheimer’s disease: A comparative study using MRI and SPECT. Eur J Neurol20, 243–250.
90.
LahnaD, SchwartzDL, WoltjerR, BlackSE, RoeseN, DodgeH, BoespflugEL, KeithJ, GaoF, RamirezJ, SilbertLC (2022) Venous collagenosis as pathogenesis of white matter hyperintensity. Ann Neurol92, 992–1000.
91.
NanD, ChengY, FengL, ZhaoM, MaD, FengJ (2019) Potential mechanism of venous system for leukoaraiosis: From post-mortem to in vivo research. Neurodegener Dis19, 101–108.
BarbosaJH, SantosAC, SalmonCE (2015) Susceptibility weighted imaging: Differentiating between calcification and hemosiderin. Radiol Bras48, 93–100.
101.
TongKA, AshwalS, HolshouserBA, ShutterL, HerigaultG, HaackeEM, KidoDK (2003) Improved detection of hemorrhagic shearing lesions in children with post-traumatic diffuse axonal injury: Initial results. Radiology227, 332–339.
102.
HaackeEM, DelPropostoZS, ChaturvediS, SehgalV, TenzerM, NeelavalliJ, KidoD (2007) Imaging cerebral amyloid angiopathy with susceptibility-weighted imaging. AJNR Am J Neuroradiol28, 316–317.
103.
AtlasSW, MarkAS, GrossmanRI, GomoriJM (1988) Intracranial hemorrhage: Gradient-echo MR imaging at 1.5 T. Comparison with spin-echo imaging and clinical applications. Radiology168, 803–807.
104.
WuZ, MittalS, KishK, YuY, HuJ, HaackeEM (2009) Identification of calcification with MRI using susceptibility-weighted imaging: A case study. J Magn Reson Imaging29, 177–182.
105.
IrimiaA, RostowskyKA, LawEM, ChuiHC (2022) Cerebral hemorrhages in traumatic brain injury. In Diagnosis and Treatment of Traumatic Brain Injury, 1st edition, Rajendram R, Preedy VR, Martin CR, eds. Academic Press, pp. 87-99.
106.
CharidimouA, LinnJ, VernooijMW, OpherkC, AkoudadS, BaronJC, GreenbergSM, JägerHR, WerringDJ (2015) Cortical superficial siderosis: Detection and clinical significance in cerebral amyloid angiopathy and related conditions. Brain138, 2126–2139.
107.
LinnJ, HermsJ, DichgansM, BrückmannH, FeslG, FreilingerT, WiesmannM (2008) Subarachnoid hemosiderosis and superficial cortical hemosiderosis in cerebral amyloid angiopathy. AJNR Am J Neuroradiol29, 184–186.
108.
InoueY, NakajimaM, UetaniH, HiraiT, UedaM, KitajimaM, UtsunomiyaD, WatanabeM, HashimotoM, IkedaM, YamashitaY, AndoY (2016) Diagnostic significance of cortical superficial siderosis for Alzheimer Disease in patients with cognitive impairment. AJNR Am J Neuroradiol37, 223–227.
109.
CharidimouA, JägerRH, PeetersA, VandermeerenY, LalouxP, BaronJC, WerringDJ (2014) White matter perivascular spaces are related to cortical superficial siderosis in cerebral amyloid angiopathy. Stroke45, 2930–2935.
110.
CharidimouA, BoulouisG, GreenbergSM, ViswanathanA (2019) Cortical superficial siderosis and bleeding risk in cerebral amyloid angiopathy: A meta-analysis. Neurology93, e2192–e2202.
111.
KimJ, NaHK, ShinJH, KimHJ, SeoSW, SeongJK, NaDL (2018) Atrophy patterns in cerebral amyloid angiopathy with and without cortical superficial siderosis. Neurology90, e1751–e1758.
112.
ZhouC, LiuK, YanS, JinY (2019) Association between cortical superficial siderosis and dementia in patients with cognitive impairment: A meta-analysis. Front Neurol10, 8.
113.
ThalDR, GrinbergLT, AttemsJ (2012) Vascular dementia: Different forms of vessel disorders contribute to the development of dementia in the elderly brain. Exp Gerontol47, 816–824.
114.
PantoniL (2010) Cerebral small vessel disease: From pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol9, 689–701.
115.
ShamsS, MartolaJ, GranbergT, LiX, ShamsM, FereshtehnejadSM, CavallinL, AspelinP, Kristoffersen-WibergM, WahlundLO (2015) Cerebral microbleeds: Different prevalence, topography, and risk factors depending on dementiadiagnosis-the Karolinska Imaging Dementia Study. AJNR Am J Neuroradiol36, 661–666.
116.
PettersenJA, SathiyamoorthyG, GaoFQ, SzilagyiG, NadkarniNK, St George-Hyslop P, RogaevaE, BlackSE (2008) Microbleed topography, leukoaraiosis, and cognition in probable Alzheimer disease from the Sunnybrook dementia study. Arch Neurol65, 790–795.
117.
Vazquez-JustesD, AguirregoicoaI, FernandezL, Carnes-VendrellA, DakterzadaF, SanjuanL, MenaA, Pinol-RipollG (2022) Clinical impact of microbleeds in patients with Alzheimer’s disease. BMC Geriatr22, 774.
118.
SepehryAA, RauscherA, HsiungGY, LangDJ (2016) Microbleeds in Alzheimer’s Disease: A neuropsychological overview and meta-analysis. Can J Neurol Sci43, 753–759.
119.
CordonnierC, van der Flier WM (2011) Brain microbleeds and Alzheimer’s disease: Innocent observation or key player? Brain134, 335–344.
De Reuck J, AugerF, DurieuxN, DeramecourtV, CordonnierC, PasquierF, MaurageCA, LeysD, BordetR (2015) Topography of cortical microbleeds in Alzheimer’s disease with and without cerebral amyloid angiopathy: A post-mortem 7.0-Tesla MRI study. Aging Dis6, 437–443.
122.
SamarasekeraN, SmithC, Al-Shahi Salman R (2012) The association between cerebral amyloid angiopathy and intracerebral haemorrhage: Systematic review and meta-analysis. J Neurol Neurosurg Psychiatry83, 275–281.
123.
RosandJ, MuzikanskyA, KumarA, WiscoJJ, SmithEE, BetenskyRA, GreenbergSM (2005) Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy. Ann Neurol58, 459–462.
124.
RodriguesMA, SamarasekeraN, LerpiniereC, HumphreysC, McCarronMO, WhitePM, NicollJAR, SudlowCLM, CordonnierC, WardlawJM, SmithC, Al-Shahi Salman R (2018) The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy: Model development and diagnostic test accuracy study. Lancet Neurol17, 232–240.
125.
JakelL, KuiperijHB, GerdingLP, CustersEEM, van den BergE, JolinkWMT, SchreuderF, KustersB, KlijnCJM, VerbeekMM (2020) Disturbed balance in the expression of MMP9 and TIMP3 in cerebral amyloid angiopathy-related intracerebral haemorrhage. Acta Neuropathol Commun8, 99.
126.
AbbottNJ, RonnbackL, HanssonE (2006) Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci7, 41–53.
127.
ZlokovicBV (2008) The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron57, 178–201.
128.
HartzAM, BauerB, SoldnerEL, WolfA, BoyS, BackhausR, MihaljevicI, BogdahnU, KlunemannHH, SchuiererG, SchlachetzkiF (2012) Amyloid-beta contributes to blood-brain barrier leakage in transgenic human amyloid precursor protein mice and in humans with cerebral amyloid angiopathy. Stroke43, 514–523.
129.
MontagneA, ZhaoZ, ZlokovicBV (2017) Alzheimer’s disease: A matter of blood-brain barrier dysfunction? J Exp Med214, 3151–3169.
130.
NelsonAR, SweeneyMD, SagareAP, ZlokovicBV (2016) Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer’s disease. Biochim Biophys Acta1862, 887–900.
131.
KozbergMG, YiI, FreezeWM, AugerCA, ScherlekAA, GreenbergSM, van Veluw SJ (2022) Blood–brain barrier leakage and perivascular inflammation in cerebral amyloid angiopathy.. Brain Commun4, fcac245.
132.
HeyeAK, CullingRD, Valdes Hernandez Mdel C, ThrippletonMJ, WardlawJM (2014) Assessment of blood-brain barrier disruption using dynamic contrast-enhanced MRI. A systematic review. Neuroimage Clin6, 262–274.
133.
LiM, LiY, ZuoL, HuW, JiangT (2021) Increase of blood-brain barrier leakage is related to cognitive decline in vascular mild cognitive impairment. BMC Neurol21, 159.
134.
MontagneA, BarnesSR, SweeneyMD, HallidayMR, SagareAP, ZhaoZ, TogaAW, JacobsRE, LiuCY, AmezcuaL, HarringtonMG, ChuiHC, LawM, ZlokovicBV (2015) Blood-brain barrier breakdown in the aging human hippocampus. Neuron85, 296–302.
135.
NationDA, SweeneyMD, MontagneA, SagareAP, D’OrazioLM, PachicanoM, SepehrbandF, NelsonAR, BuennagelDP, HarringtonMG, BenzingerTLS, FaganAM, RingmanJM, SchneiderLS, MorrisJC, ChuiHC, LawM, TogaAW, ZlokovicBV (2019) Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nat Med25, 270–276.
van de Haar HJ, BurgmansS, JansenJFA, van Osch MJP, van Buchem MA, MullerM, HofmanPAM, VerheyFRJ, BackesWH (2016) Blood-brain barrier leakage in patients with early Alzheimer disease. Radiology281, 527–535.
138.
van de Haar HJ, JansenJFA, JeukensCRLPN, BurgmansS, van Buchem MA, MullerM, HofmanPAM, VerheyFRJ, van Osch MJP, BackesWH (2017) Subtle blood-brain barrier leakage rate and spatial extent: Considerations for dynamic contrast-enhanced MRI. Med Phys44, 4112–4125.
139.
AksoyD, BammerR, MlynashM, VenkatasubramanianC, EyngornI, SniderRW, GuptaSN, NarayanaR, FischbeinN, WijmanCA (2013) Magnetic resonance imaging profile of blood-brain barrier injury in patients with acute intracerebral hemorrhage. J Am Heart Assoc2, e000161.
BenvenisteH, LeeH, OzturkB, ChenX, KoundalS, VaskaP, TannenbaumA, VolkowND (2021) Glymphatic cerebrospinal fluid and solute transport quantified by MRI and PET imaging. Neuroscience474, 63–79.
142.
ChenX, LiuX, KoundalS, ElkinR, ZhuX, MonteB, XuF, DaiF, PedramM, LeeH, KipnisJ, TannenbaumA, Van Nostrand WE, BenvenisteH (2022) Cerebral amyloid angiopathy is associated with glymphatic transport reduction and time-delayed solute drainage along the neck arteries. Nat Aging2, 214–223.
143.
HawkesCA, HartigW, KaczaJ, SchliebsR, WellerRO, NicollJA, CarareRO (2011) Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy. Acta Neuropathol121, 431–443.
144.
RutgersKS, van Remoortere A, van Buchem MA, VerripsCT, GreenbergSM, BacskaiBJ, FroschMP, van Duinen SG, Maat-SchiemanML, van der Maarel SM (2011) Differential recognition of vascular and parenchymal beta amyloid deposition. Neurobiol Aging32, 1774–1783.
145.
GurolME, DierksenG, BetenskyR, GidicsinC, HalpinA, BeckerA, CarmasinJ, AyresA, SchwabK, ViswanathanA, SalatD, RosandJ, JohnsonKA, GreenbergSM (2012) Predicting sites of new hemorrhage with amyloid imaging in cerebral amyloid angiopathy. Neurology79, 320–326.
146.
LyJV, DonnanGA, VillemagneVL, ZavalaJA, MaH, O’KeefeG, GongSJ, GunawanRM, SaunderT, AckermanU, Tochon-DanguyH, ChurilovL, PhanTG, RoweCC (2010) 11C-PIB binding is increased in patients with cerebral amyloid angiopathy-related hemorrhage. Neurology74, 487–493.
FaridK, CharidimouA, BaronJC (2017) Amyloid positron emission tomography in sporadic cerebral amyloid angiopathy: A systematic critical update. Neuroimage Clin15, 247–263.
149.
JohnsonKA, GregasM, BeckerJA, KinnecomC, SalatDH, MoranEK, SmithEE, RosandJ, RentzDM, KlunkWE, MathisCA, PriceJC, DekoskyST, FischmanAJ, GreenbergSM (2007) Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Ann Neurol62, 229–234.
150.
CharidimouA, FaridK, TsaiHH, TsaiLK, YenRF, BaronJC (2018) Amyloid-PET burden and regional distribution in cerebral amyloid angiopathy: A systematic review and meta-analysis of biomarker performance. J Neurol Neurosurg Psychiatry89, 410–417.
151.
PlantonM, Saint-AubertL, RaposoN, PayouxP, SalabertAS, AlbucherJF, OlivotJM, PeranP, ParienteJ (2020) Florbetapir regional distribution in cerebral amyloid angiopathy and Alzheimer’s disease: A PET study. J Alzheimers Dis73, 1607–1614.
152.
PfeilJ, HoenigMC, DoeringE, van Eimeren T, DrzezgaA, BischofGN (2021) Unique regional patterns of amyloid burden predict progression to prodromal and clinical stages of Alzheimer’s disease. Neurobiol Aging106, 119–129.
153.
BourassaP, TremblayC, SchneiderJA, BennettDA, CalonF (2019) Beta-amyloid pathology in human brain microvessel extracts from the parietal cortex: Relation with cerebral amyloid angiopathy and Alzheimer’s disease. Acta Neuropathol137, 801–823.
154.
SchultzAP, KloetRW, SohrabiHR, van der Weerd L, van Rooden S, WermerMJH, MourselLG, YaqubM, van Berckel BNM, ChatterjeeP, GardenerSL, TaddeiK, FaganAM, BenzingerTL, MorrisJC, SperlingR, JohnsonK, BatemanRJ, Dominantly Inherited Alzheimer N, GurolME, van Buchem MA, MartinsR, ChhatwalJP, GreenbergSM (2019) Amyloid imaging of dutch-type hereditary cerebral amyloid angiopathy carriers. Ann Neurol86, 616–625.
155.
KolbHC, AndresJI (2017) Tau positron emission tomography imaging.. Cold Spring Harb Perspect Biol9, a023721.
156.
YouY, PerkinsA, CisternasP, MunozB, TaylorX, YouY, GarringerHJ, OblakAL, AtwoodBK, VidalR, Lasagna-ReevesCA (2019) Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy. Acta Neuropathol Commun7, 26.
157.
OshimaK, UchikadoH, DicksonDW (2008) Perivascular neuritic dystrophy associated with cerebral amyloid angiopathy in Alzheimer’s disease. Int J Clin Exp Pathol1, 403–408.
158.
WilliamsS, ChalmersK, WilcockGK, LoveS (2005) Relationship of neurofibrillary pathology to cerebral amyloid angiopathy in Alzheimer’s disease. Neuropathol Appl Neurobiol31, 414–421.
159.
VidalR, BarbeitoAG, MiravalleL, GhettiB (2009) Cerebral amyloid angiopathy and parenchymal amyloid deposition in transgenic mice expressing the Danish mutant form of human BRI2. Brain Pathol19, 58–68.
160.
TracyTE, GanL (2018) Tau-mediated synaptic and neuronal dysfunction in neurodegenerative disease. Curr Opin Neurobiol51, 134–138.
161.
BraakH, ThalDR, GhebremedhinE, Del Tredici K (2011) Stages of the pathologic process in Alzheimer disease: Age categories from 1 to 100 years. J Neuropathol Exp Neurol70, 960–969.
162.
BraakH, Del Tredici K (2015) The preclinical phase of the pathological process underlying sporadic Alzheimer’s disease. Brain138, 2814–2833.
163.
SuL, SurendranathanA, HuangY, Bevan-JonesWR, PassamontiL, HongYT, ArnoldR, RodríguezPV, WangY, MakE, FryerTD, AigbirhioF, RoweJB, O’BrienJT (2021) Relationship between tau, neuroinflammation and atrophy inAlzheimer’s disease: The NIMROD study. Information Fusion67, 116–124.
164.
PereiraJB, HarrisonTM, La Joie R, BakerSL, JagustWJ (2020) Spatial patterns of tau deposition are associated with amyloid, ApoE, sex, and cognitive decline in older adults. Eur J Nucl Med Mol Imaging47, 2155–2164.
165.
BraakH, AlafuzoffI, ArzbergerT, KretzschmarH, TrediciK (2006) Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol112, 389–404.
RenardD, CastelnovoG, WacongneA, Le Floch A, ThouvenotE, MasJ, GabelleA, LabaugeP, LehmannS (2012) Interest of CSF biomarker analysis in possible cerebral amyloid angiopathy cases defined by the modified Boston criteria. J Neurol259, 2429–2433.
170.
BlennowK, WallinA, AgrenH, SpengerC, SiegfriedJ, VanmechelenE (1995) Tau protein in cerebrospinal fluid: A biochemical marker for axonal degeneration in Alzheimer disease? Mol Chem Neuropathol26, 231–245.
171.
KandimallaRJ, PrabhakarS, WaniWY, KaushalA, GuptaN, SharmaDR, GroverVK, BhardwajN, JainK, GillKD (2013) CSF p-tau levels in the prediction of Alzheimer’s disease. Biol Open2, 1119–1124.
172.
CharidimouA, FriedrichJO, GreenbergSM, ViswanathanA (2018) Core cerebrospinal fluid biomarker profile in cerebral amyloid angiopathy: A meta-analysis. Neurology90, e754–e762.
173.
Malek-AhmadiM, PerezSE, ChenK, MufsonEJ (2020) Braak stage, cerebral amyloid angiopathy, and cognitive decline in early Alzheimer’s disease. J Alzheimers Dis74, 189–197.
174.
RabinJS, NicholsE, La Joie R, CasalettoKB, PaltaP, Dams-O’ConnorK, KumarRG, GeorgeKM, SatizabalCL, SchneiderJA, PaJ, BrickmanAM (2022) Cerebral amyloid angiopathy interacts with neuritic amyloid plaques to promote tau and cognitive decline. Brain145, 2823–2833.
175.
PantoniL, GarciaJH (1997) Pathogenesis of leukoaraiosis: A review. Stroke28, 652–659.
176.
SimonJH, LiD, TraboulseeA, CoylePK, ArnoldDL, BarkhofF, FrankJA, GrossmanR, PatyDW, RadueEW, WolinskyJS (2006) Standardized MR imaging protocol for multiple sclerosis: Consortium of MS centers consensus guidelines. Am J Neuroradiol27, 455–461.
177.
ShimYS, YangDW, RoeCM, CoatsMA, BenzingerTL, XiongC, GalvinJE, CairnsNJ, MorrisJC (2015) Pathological correlates of white matter hyperintensities on magnetic resonance imaging. Dement Geriatr Cogn Disord39, 92–104.
178.
WardlawJM, Valdes Hernandez MC, Munoz-ManiegaS (2015) What are white matter hyperintensities made of? Relevance to vascular cognitive impairment. J Am Heart Assoc4, 001140.
179.
KallmesDF, HuiFK, MuglerJP 3rd (2001) Suppression of cerebrospinal fluid and blood flow artifacts in FLAIR MR imaging with a single-slab three-dimensional pulse sequence: Initial experience. Radiology221, 251–255.
180.
ChenYW, GurolME, RosandJ, ViswanathanA, RakichSM, GrooverTR, GreenbergSM, SmithEE (2006) Progression of white matter lesions and hemorrhages in cerebral amyloid angiopathy. Neurology67, 83–87.
181.
TostoG, ZimmermanME, CarmichaelOT, BrickmanAMAlzheimer’s Disease Neuroimaging Initiative (2014) Predicting aggressive decline in mild cognitive impairment: The importance of white matter hyperintensities. JAMA Neurol71, 872–877.
182.
SmithEE, NandigamKR, ChenYW, JengJ, SalatD, HalpinA, FroschM, WendellL, FazenL, RosandJ, ViswanathanA, GreenbergSM (2010) MRI markers of small vessel disease in lobar and deep hemispheric intracerebral hemorrhage. Stroke41, 1933–1938.
183.
ZhuYC, ChabriatH, GodinO, DufouilC, RosandJ, GreenbergSM, SmithEE, TzourioC, ViswanathanA (2012) Distribution of white matter hyperintensity in cerebral hemorrhage and healthy aging. J Neurol259, 530–536.
184.
HollandCM, SmithEE, CsapoI, GurolME, BrylkaDA, KillianyRJ, BlackerD, AlbertMS, GuttmannCR, GreenbergSM (2008) Spatial distribution of white-matter hyperintensities in Alzheimer disease, cerebral amyloid angiopathy, and healthy aging. Stroke39, 1127–1133.
185.
McAleeseKE, WalkerL, GrahamS, MoyaELJ, JohnsonM, ErskineD, CollobySJ, DeyM, Martin-RuizC, TaylorJP, ThomasAJ, McKeithIG, De Carli C, AttemsJ (2017) Parietal white matter lesions in Alzheimer’s disease are associated with cortical neurodegenerative pathology, but not with small vessel disease. Acta Neuropathol134, 459–473.
VilanovaA, ZhangS, KindlmannG, LaidlawD (2006) An introduction to visualization of diffusion tensor imaging and its applications. In Visualization and Processing of Tensor Fields. Mathematics and Visualization,Weickert J, Hagen H, eds. Springer, Berlin, Heidelberg, pp. 121-153.
LeeH, XuF, LiuX, KoundalS, ZhuX, DavisJ, YanezD, SchraderJ, StanisavljevicA, RothmanDL, WardlawJ, Van Nostrand WE, BenvenisteH (2021) Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy. J Cereb Blood Flow Metab41, 1103–1118.
190.
van Veluw SJ, ReijmerYD, van der Kouwe AJ, CharidimouA, RileyGA, LeemansA, BacskaiBJ, FroschMP, ViswanathanA, GreenbergSM (2019) Histopathology of diffusion imaging abnormalities in cerebral amyloid angiopathy. Neurology92, e933–e943.
191.
IrimiaA, NgoV, ChaudhariNN, ZhangF, JoshiSH, PenkovaAN, O’DonnellLJ, Sheikh-BahaeiN, ZhengX, ChuiHC (2022) White matter degradation near cerebral microbleeds is associated with cognitive change after mild traumatic brain injury. Neurobiol Aging120, 68–80.
ReijmerYD, FotiadisP, CharidimouA, van Veluw SJ, XiongL, RileyGA, Martinez-RamirezS, SchwabK, ViswanathanA, GurolME, GreenbergSM (2017) Relationship between white matter connectivity loss and cortical thinning in cerebral amyloid angiopathy. Hum Brain Mapp38, 3723–3731.
194.
FreezeWM, Zanon Zotin MC, ScherlekAA, PerosaV, AugerCA, WarrenAD, van der WeerdL, SchoemakerD, HornMJ, GurolME, GokcalE, BacskaiBJ, ViswanathanA, GreenbergSM, ReijmerYD, van Veluw SJ (2022) Corpus callosum lesions are associated with worse cognitive performance in cerebral amyloid angiopathy.. Brain Commun4, fcac105.
195.
Lo Buono V, PalmeriR, CoralloF, AlloneC, PriaD, BramantiP, MarinoS (2020) Diffusion tensor imaging of white matter degeneration in early stage of Alzheimer’s disease: A review. Int J Neurosci130, 243–250.
196.
ShaikhI, BeaulieuC, GeeM, McCrearyCR, BeaudinAE, Valdes-CabreraD, SmithEE, CamicioliR (2022) Diffusion tensor tractography of the fornix in cerebral amyloid angiopathy, mild cognitive impairment and Alzheimer’s disease. Neuroimage Clin34, 103002.
197.
TonioloS, SerraL, OlivitoG, CaltagironeC, MercuriNB, MarraC, CercignaniM, BozzaliM (2020) Cerebellar white matter disruption in Alzheimer’s disease patients: A diffusion tensor imaging study. J Alzheimers Dis74, 615–624.
198.
ShuN, WangZ, QiZ, LiK, HeY (2011) Multiple diffusion indices reveals white matter degeneration inAlzheimer’s disease and mild cognitive impairment: A tract-based spatial statistics study. J Alzheimers Dis26 Suppl 3, 275–285.
199.
LiuJ, LiangP, YinL, ShuN, ZhaoT, XingY, LiF, ZhaoZ, LiK, HanY (2017) White matter abnormalities in two different subtypes of amnestic mild cognitive impairment. PLoS One12, e0170185.
200.
LiuY, SpulberG, LehtimakiKK, KononenM, HallikainenI, GrohnH, KivipeltoM, HallikainenM, VanninenR, SoininenH (2011) Diffusion tensor imaging and tract-based spatial statistics in Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging32, 1558–1571.
201.
DouaudG, JbabdiS, BehrensTE, MenkeRA, GassA, MonschAU, RaoA, WhitcherB, KindlmannG, MatthewsPM, SmithS (2011) DTI measures in crossing-fibre areas: Increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer’s disease. Neuroimage55, 880–890.
202.
PievaniM, AgostaF, PaganiE, CanuE, SalaS, AbsintaM, GeroldiC, GanzolaR, FrisoniGB, FilippiM (2010) Assessment of white matter tract damage in mild cognitive impairment and Alzheimer’s disease. Hum Brain Mapp31, 1862–1875.
203.
HuangH, FanX, WeinerM, Martin-CookK, XiaoG, DavisJ, DevousM, RosenbergR, Diaz-ArrastiaR (2012) Distinctive disruption patterns of white matter tracts in Alzheimer’s disease with full diffusion tensor characterization. Neurobiol Aging33, 2029–2045.
204.
Delli Pizzi S, FranciottiR, TaylorJP, ThomasA, TartaroA, OnofrjM, BonanniL (2015) Thalamic involvement in fluctuating cognition in dementia with Lewy bodies: Magnetic resonance evidences. Cereb Cortex25, 3682–3689.
205.
MadhavanA, SchwarzCG, DuffyJR, StrandEA, MachuldaMM, DrubachDA, KantarciK, PrzybelskiSA, ReidRI, SenjemML, GunterJL, ApostolovaLG, LoweVJ, PetersenRC, JackCR, JosephsKA, WhitwellJL (2016) Characterizing white matter tract degeneration in syndromic variants of Alzheimer’s disease: A diffusion tensor imaging study. J Alzheimers Dis49, 633–643.
206.
BaykaraE, GesierichB, AdamR, TuladharAM, BiesbroekJM, KoekHL, RopeleS, JouventE ,
Alzheimer’s Disease Neuroimaging InitiativeChabriatH, Ertl-WagnerB, EwersM, SchmidtR, de Leeuw FE, BiesselsGJ, DichgansM, DueringM (2016) A novel imaging marker for small vessel disease based on skeletonization of white matter tracts and diffusion histograms. Ann Neurol80, 581–592.
SchoutenTM, de Vos F, van Rooden S, BoutsM, van Opstal AM, FeisRA, TerwindtGM, WermerMJH, van Buchem MA, GreenbergSM, de Rooij M, RomboutsS, van der Grond J (2019) Multiple approaches to diffusion magnetic resonance imaging in hereditary cerebral amyloid angiopathy mutation carriers. J Am Heart Assoc8, e011288.
209.
McCrearyCR, BeaudinAE, SuboticA, ZwiersAM, AlvarezA, CharltonA, GoodyearBG, FrayneR, SmithEE (2020) Cross-sectional and longitudinal differences in peak skeletonized white matter mean diffusivity in cerebralamyloid angiopathy. Neuroimage Clin27, 102280.
210.
HornMJ, GokcalE, BeckerJA, DasAS, SchwabK, Zanon Zotin MC, GoldsteinJN, RosandJ, ViswanathanA, PolimeniJR, DueringM, GreenbergSM, GurolME (2023) Peak width of skeletonized mean diffusivity and cognitive performance in cerebral amyloid angiopathy. Front Neurosci17, 1141007.
211.
Zanon Zotin MC, YilmazP, SveikataL, SchoemakerD, van Veluw SJ, EthertonMR, CharidimouA, GreenbergSM, DueringM, ViswanathanA (2023) Peak width of skeletonized mean diffusivity: A neuroimaging marker for white matter injury. Radiology306, e212780.
212.
RaposoN, Zanon Zotin MC, SchoemakerD, XiongL, FotiadisP, CharidimouA, PasiM, BoulouisG, SchwabK, SchirmerMD, EthertonMR, GurolME, GreenbergSM, DueringM, ViswanathanA (2021) Peak width of skeletonized mean diffusivity as neuroimaging biomarker in cerebral amyloid angiopathy. AJNR Am J Neuroradiol42, 875–881.
213.
FanAP, GuoJ, KhalighiMM, GulakaPK, ShenB, ParkJH, GandhiH, HolleyD, RutledgeO, SinghP, HaywoodT, SteinbergGK, ChinFT, ZaharchukG (2017) Long-delay arterial spin labeling provides more accurate cerebral blood flow measurements in Moyamoya patients: A simultaneous positron emission tomography/MRI study. Stroke48, 2441–2449.
214.
ThalDR, Capetillo-ZarateE, LarionovS, StaufenbielM, ZurbrueggS, BeckmannN (2009) Capillary cerebral amyloid angiopathy is associated with vessel occlusion and cerebral blood flow disturbances. Neurobiol Aging30, 1936–1948.
215.
ChenH, ZhangJH (2011) Cerebral amyloid angiopathy-related microhemorrhages in Alzheimer’s disease: A review of investigative animal models. Acta Neurochir Suppl111, 15–7.
216.
WierengaCE, HaysCC, ZlatarZZ (2014) Cerebral blood flow measured by arterial spin labeling MRI as a preclinical marker of Alzheimer’s disease. J Alzheimers Dis42 Suppl 4, S411–S419.
217.
ParkesLM, RashidW, ChardDT, ToftsPS (2004) Normal cerebral perfusion measurements using arterial spin labeling: Reproducibility, stability, and age and gender effects. Magn Reson Med51, 736–743.
218.
LiuTT, BrownGG (2007) Measurement of cerebral perfusion with arterial spin labeling: Part 1. Methods. J Int Neuropsychol Soc13, 517–525.
219.
van Opstal AM, van Rooden S, van Harten T, GhariqE, LabadieG, FotiadisP, GurolME, TerwindtGM, WermerMJH, van Buchem MA, GreenbergSM, van der Grond J (2017) Cerebrovascular function in presymptomatic and symptomaticindividuals with hereditary cerebral amyloid angiopathy: A case-control study. Lancet Neurol16, 115–122.
220.
DumasA, DierksenGA, GurolME, HalpinA, Martinez-RamirezS, SchwabK, RosandJ, ViswanathanA, SalatDH, PolimeniJR, GreenbergSM (2012) Functional magnetic resonance imaging detection of vascular reactivity incerebral amyloid angiopathy. Ann Neurol72, 76–81.
221.
WeijsRWJ, ShkredovaDA, BrekelmansACM, ThijssenDHJ, ClaassenJAHR (2022) Longitudinal changes in cerebral blood flow and their relation with cognitive decline in patients with dementia: Current knowledge and future directions. Alzheimers Dement19, 532–548.
222.
DuanW, ZhouGD, BalachandrasekaranA, BhumkarAB, BorastePB, BeckerJT, KullerLH, LopezOL, GachHM, DaiW (2021) Cerebral blood flow predicts conversion of mild cognitive impairment into Alzheimer’s disease and cognitive decline: An arterial spin labeling follow-up study. J Alzheimers Dis82, 293–305.
223.
BinnewijzendMA, KuijerJP, BenedictusMR, van der Flier WM, WinkAM, WattjesMP, van Berckel BN, ScheltensP, BarkhofF (2013) Cerebral blood flow measured with 3D pseudocontinuous arterial spin-labeling MR imaging in Alzheimer disease and mild cognitive impairment: A marker for disease severity. Radiology267, 221–230.
ZhangH, WangY, LyuD, LiY, LiW, WangQ, LiY, QinQ, WangX, GongM, JiaoH, LiuW, JiaJ (2021) Cerebral blood flow in mild cognitive impairment and Alzheimer’s disease: A systematic review and meta-analysis. Ageing Res Rev71, 101450.
226.
CamargoA, WangZAlzheimer’s Disease Neuroimaging Initiative (2021) Longitudinal cerebral blood flow changes in normal aging and the Alzheimer’s disease continuum identified by arterial spin labeling MRI. J Alzheimers Dis81, 1727–1735.
227.
HechtM, KramerLM, von Arnim CAF, OttoM, ThalDR (2018) Capillary cerebral amyloid angiopathy in Alzheimer’s disease: Association with allocortical/hippocampal microinfarcts and cognitive decline. Acta Neuropathol135, 681–694.
228.
BeaudinAE, McCrearyCR, MazerolleEL, GeeM, SharmaB, SuboticA, ZwiersAM, CoxE, NellesK, CharltonA, FrayneR, IsmailZ, BeaulieuC, JicklingGC, CamicioliRM, PikeGB, SmithEE (2022) Cerebrovascular reactivity across the entire brain in cerebral amyloid angiopathy. Neurology98, e1716–e1728.
229.
WillieCK, TzengYC, FisherJA, AinsliePN (2014) Integrative regulation of human brain blood flow. J Physiol592, 841–859.
230.
TyagiSK, MahapatraAK, MishraNK (2000) Transcranial doppler evaluation of blood flow velocity changes in basal cerebral arteries in cerebral AVMs following embolisation and surgery. Neurol India48, 112–115.
231.
AliMFA (2021) Transcranial Doppler ultrasonography (uses, limitations, and potentials): A review article. Egypt J Neurosurg36, 20.
232.
HillmanEM (2014) Coupling mechanism and significance of the BOLD signal: A status report. Annu Rev Neurosci37, 161–181.
233.
OgawaS, LeeTM, KayAR, TankDW (1990) Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A87, 9868–9872.
234.
DrewPJ (2019) Vascular and neural basis of the BOLD signal. Curr Opin Neurobiol58, 61–69.
235.
Menendez-GonzalezM, Garcia-GarciaJ, CallejaS, RojoJ, RibacobaR (2011) Vasomotor reactivity is similarly impaired in patients with Alzheimer’s disease and patients with amyloid hemorrhage. J Neuroimaging21, e83–e85.
PecaS, McCrearyCR, DonaldsonE, KumarpillaiG, ShobhaN, SanchezK, CharltonA, SteinbackCD, BeaudinAE, FlückD, PillayN, FickGH, PoulinMJ, FrayneR, GoodyearBG, SmithEE (2013) Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy. Neurology81, 1659–1665.
239.
RichiardiJ, MonschAU, HaasT, BarkhofF, Van de Ville D, RaduEW, KressigRW, HallerS (2015) Altered cerebrovascular reactivity velocity in mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging36, 33–41.
240.
CantinS, VillienM, MoreaudO, TropresI, KeignartS, ChiponE, Le Bas JF, WarnkingJ, KrainikA (2011) Impaired cerebral vasoreactivity to CO2 in Alzheimer’s disease using BOLD fMRI. Neuroimage58, 579–587.
241.
SurS, LinZ, LiY, YasarS, RosenbergP, MoghekarA, HouX, KalyaniR, HazelK, PottanatG, XuC, van Zijl P, PillaiJ, LiuP, AlbertM, LuH (2020) Association of cerebrovascular reactivity and Alzheimer pathologic markers with cognitive performance. Neurology95, e962–e972.
242.
HolmesKR, Tang-WaiD, SamK, McKettonL, PoublancJ, CrawleyAP, SobczykO, CohnM, DuffinJ, TartagliaMC, BlackSE, FisherJA, WassermanB, MikulisDJ (2020) Slowed temporal and parietal cerebrovascular response in patients with Alzheimer’s disease. Can J Neurol Sci47, 366–373.
243.
YezhuvathUS, UhJ, ChengY, Martin-CookK, WeinerM, Diaz-ArrastiaR, van Osch M, LuH (2012) Forebrain-dominant deficit in cerebrovascular reactivity in Alzheimer’s disease. Neurobiol Aging33, 75–82.
244.
FoxMD, GreiciusM (2010) Clinical applications of resting state functional connectivity. Front Syst Neurosci4, 19.
245.
FoxMD, RaichleME (2007) Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci8, 700–711.
246.
DrenthN, van der Grond J, RomboutsS, van Buchem MA, TerwindtGM, WermerMJH, ChhatwalJP, GurolME, GreenbergSM, van Rooden S (2021) Cerebral amyloid angiopathy is associated with decreased functional brain connectivity. Neuroimage Clin29, 102546.
MerliniM, MeyerEP, Ulmann-SchulerA, NitschRM (2011) Vascular β-amyloid and early astrocyte alterations impair cerebrovascular function and cerebral metabolism in transgenic arcAβ mice. Acta Neuropathol122, 293–311.
255.
SegobinS, La Joie R, RitzL, BeaunieuxH, DesgrangesB, ChetelatG, PitelAL, EustacheF (2015) FDG-PET contributions to the pathophysiology of memory impairment. Neuropsychol Rev25, 326–355.
256.
YuS (2006) Review of F-FDG synthesis and quality control. Biomed Imaging Interv J2, e57.
257.
BergeretSQM, RodallecM, CurisE, DumurgierJ, HugonJ, PaquetC, FaridK, BaronJC (2021) [18 F]FDG PET may differentiate cerebral amyloid angiopathy from Alzheimer’s disease. Eur J Neurol28, 1511–1519.
258.
HanX, RenH, NandiA, FanX, KoehlerRC (2021) Analysis of glucose metabolism by (18)F-FDG-PET imaging and glucose transporter expression in a mouse model of intracerebral hemorrhage. Sci Rep11, 10885.
259.
SamurakiM, MatsunariI, YoshitaM, ShimaK, Noguchi-ShinoharaM, HamaguchiT, OnoK, YamadaM (2015) Cerebralamyloid angiopathy-related microbleeds correlate with glucose metabolism and brain volume in Alzheimer’s disease. J Alzheimers Dis48, 517–528.
260.
ChoiEJ, SonYD, NohY, LeeH, KimYB, ParkKH (2018) Glucose hypometabolism in hippocampal subdivisions in Alzheimer’s disease: A pilot study using high-resolution (1)(8)F-FDG PET and 7.0-T MRI. J Clin Neurol14, 158–164.
261.
LiTR, DongQY, JiangXY, KangGX, LiX, XieYY, JiangJH, HanYAlzheimer’s Disease Neuroimaging Initiative (2022) Exploring brain glucose metabolic patterns in cognitively normal adults at risk of Alzheimer’s disease: A cross-validation study with Chinese and ADNI cohorts. Neuroimage Clin33, 102900.
262.
HerholzK (2010) Cerebral glucose metabolism in preclinical and prodromal Alzheimer’s disease. Expert Rev Neurother10, 1667–1673.
263.
TondoG, IaccarinoL, CaminitiSP, PresottoL, SantangeloR, IannacconeS, MagnaniG, PeraniD (2020) The combined effects of microglia activation and brain glucose hypometabolism in early-onset Alzheimer’s disease. Alzheimers Res Ther12, 50.
264.
CroteauE, CastellanoCA, FortierM, BoctiC, FulopT, PaquetN, CunnaneSC (2018) A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer’s disease. Exp Gerontol107, 18–26.
265.
GeurtsLJ, ZwanenburgJJM, KlijnCJM, LuijtenPR, BiesselsGJ (2018) Higher pulsatility in cerebral perforating arteries in patients with small vessel disease related stroke, a 7T MRI study. Stroke50, 62–68.
266.
BouvyWH, GeurtsLJ, KuijfHJ, LuijtenPR, KappelleLJ, BiesselsGJ, ZwanenburgJJ (2016) Assessment of blood flow velocity and pulsatility in cerebral perforating arteries with 7-T quantitative flow MRI. NMR Biomed29, 1295–1304.
267.
GeurtsL, BiesselsGJ, LuijtenP, ZwanenburgJ (2018) Better and faster velocity pulsatility assessment in cerebral white matter perforating arteries with 7T quantitative flow MRI through improved slice profile, acquisition scheme, and postprocessing. Magn Reson Med79, 1473–1482.
268.
NiJ, AurielE, Martinez-RamirezS, KeilB, ReedAK, FotiadisP, GurolEM, GreenbergSM, ViswanathanA (2015) Cortical localization of microbleeds in cerebral amyloid angiopathy: An ultra high-field 7T MRI study. J Alzheimers Dis43, 1325–1330.
269.
BulkM, MourselLG, van der Graaf LM, van Veluw SJ, GreenbergSM, van Duinen SG, van Buchem MA, van Rooden S, van der Weerd L (2018) Cerebral amyloid angiopathy with vascular iron accumulation and calcification. Stroke49, 2081–2087.
270.
LiuS, UtriainenD, ChaiC, ChenY, WangL, SethiSK, XiaS, HaackeEM (2019) Cerebral microbleed detection using susceptibility weighted imaging and deep learning. Neuroimage198, 271–282.
271.
SudarshanVK, RaghavendraU, GudigarA, CiaccioEJ, VijayananthanA, SahathevanR, AcharyaUR (2022) Assessment of CT for the categorization of hemorrhagic stroke (HS) and cerebral amyloid angiopathy hemorrhage (CAAH): A review. Biocybern Biomed Eng42, 888–901.
272.
JungYH, LeeH, KimHJ, NaDL, HanHJ, JangH, SeoSW (2020) Prediction of amyloid beta PET positivity using machine learning in patients with suspected cerebral amyloid angiopathy markers. Sci Rep10, 18806.
273.
JangH, JangYK, KimHJ, WerringDJ, LeeJS, ChoeYS, ParkS, LeeJ, KimKW, KimY, ChoSH, KimSE, KimSJ, CharidimouA, NaDL, SeoSW (2019) Clinical significance of amyloid beta positivity in patients with probable cerebral amyloid angiopathy markers. Eur J Nucl Med Mol Imaging46, 1287–1298.
274.
SaitoS, TanakaM, Satoh-AsaharaN, CarareRO, IharaM (2021) Taxifolin:Apotential therapeutic agent for cerebral amyloid angiopathy. Front Pharmacol12, 643357.
