Alzheimer’s disease (AD) pathology impacts the response to treatment in patients with idiopathic normal pressure hydrocephalus (iNPH), possibly through changes in resting-state functional connectivity (rs-FC).
Objective:
To explore the relationship between cerebrospinal fluid biomarkers of AD and the default mode network (DMN)/hippocampal rs-FC in iNPH patients, based on their outcome after cerebrospinal fluid tap test (CSFTT), and in patients with AD.
Methods:
Twenty-six iNPH patients (mean age: 79.9±5.9 years; 12 females) underwent MRI and clinical assessment before and after CSFTT and were classified as responders (Resp) or not (NResp), based on the improvement at the timed up and go test and walking speed. Eleven AD patients (mean age: 70.91±5.2 years; 5 females), matched to iNPH for cognitive status, were also included. DMN and hippocampal rs-FC was related to amyloid-β42 and phosphorylated tau (pTau) levels.
Results:
Lower amyloid-β42 levels were associated with reduced inter- and intra-network rs-FC in NResp, and the interaction between amyloid-β42 and rs-FC was a predictor of outcome after CSFTT. The rs-FC between DMN and salience networks positively correlated to amyloid-β42 levels in both NResp and AD patients. The increase in the inter-network rs-FC after CSFTT was associated with higher pTau and lower amyloid-β42 levels in NResp, and to lower pTau levels in Resp.
Conclusion:
Amyloid-β42 and pTau impact on rs-FC and its changes after CSFTT in iNPH patients. The interaction between AD biomarkers and rs-FC might explain the responder status in iNPH.
HalperinJJ, KurlanR, SchwalbJM, CusimanoMD, GronsethG, GlossD (2015) Practice guideline: Idiopathic normal pressure hydrocephalus: Response to shunting and predictors of response. Neurology85, 2063–2071.
4.
MalmJ, Graff-RadfordNR, IshikawaM, KristensenB, LeinonenV, MoriE, OwlerBK, TullbergM, WilliamsMA, RelkinNR (2013) Influence of comorbidities in idiopathic normal pressure hydrocephalus - research and clinical care. A report of the ISHCSF task force on comorbidities in INPH. Fluids Barriers CNS10, 1–14.
5.
LeinonenV, KoivistoAM, AlafuzoffI, PyykköOT, RummukainenJ, von und zu FraunbergM, JääskeläinenJE, SoininenH, RinneJ, SavolainenS (2012) Cortical brain biopsy in long-term prognostication of 468 patients with possible normal pressure hydrocephalus. Neurodegener Dis10, 166–169.
6.
HamdehSA, VirhammarJ, SehlinD, AlafuzoffI, CesariniKG, MarklundN (2019) Brain tissue Aβ42 levels are linked to shunt response in idiopathic normal pressure hydrocephalus. J Neurosurg130, 121–129.
7.
HamiltonR, PatelS, LeeEB, JacksonEM, LopintoJ, ArnoldSE, ClarkCM, BasilA, ShawLM, XieSX, GradyMS, TrojanowskiJQ (2010) Lack of shunt response in suspected idiopathic normal pressure hydrocephalus with Alzheimer disease pathology. Ann Neurol68, 535–540.
8.
PomeraniecIJ, BondAE, LopesMB, JaneJA (2016) Concurrent Alzheimer’s pathology in patients with clinical normal pressure hydrocephalus: Correlation of high-volume lumbar puncture results, cortical brain biopsies, and outcomes. J Neurosurg124, 382–388.
9.
ElobeidA, LaurellK, CesariniKG, AlafuzoffI (2015) Correlations between Mini-Mental State Examination score, cerebrospinal fluid biomarkers, and pathology observed in brain biopsies of patients with normal-pressure hydrocephalus. J Neuropathol Exp Neurol74, 470–479.
10.
AllaliG, LaidetM, ArmandS, AssalF (2018) Brain comorbidities in normal pressure hydrocephalus. Eur J Neurol25, 542–548.
11.
Bech-AzeddineR, HøghP, JuhlerM, GjerrisF, WaldemarG (2007) Idiopathic normal-pressure hydrocephalus: Clinical comorbidity correlated with cerebral biopsy findings and outcome of cerebrospinal fluid shunting. J Neurol Neurosurg Psychiatry78, 157–161.
12.
YasarS, Jusue-TorresI, LuJ, RobisonJ, PatelMA, CrainB, CarsonKA, HoffbergerJ, BatraS, SankeyE, MoghekarA, RigamontiD (2017) Alzheimer’s disease pathology and shunt surgery outcome in normal pressure hydrocephalus. PLoS One12, e0182288.
13.
LuikkuAJ, HallA, NergO, KoivistoAM, HiltunenM, HelisalmiS, HerukkaSK, SutelaA, KojoukhovaM, MattilaJ, LötjönenJ, RummukainenJ, AlafuzoffI, JääskeläinenJE, RemesAM, SoininenH, LeinonenV (2016) Multimodal analysis to predict shunt surgery outcome of 284 patients with suspected idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien)158, 2311–2319.
HeddenT, Van DijkKRA, BeckerJA, MehtaA, SperlingRA, JohnsonKA, BucknerRL (2009) Disruption of functional connectivity in clinically normal older adults harboring amyloid burden. J Neurosci29, 12686–12694.
16.
BerronD, van WestenD, OssenkoppeleR, StrandbergO, HanssonO (2020) Medial temporal lobe connectivity and its associations with cognition in early Alzheimer’s disease. Brain143, 1233–1248.
17.
SchultzAP, ChhatwalJP, HeddenT, MorminoEC, HanseeuwBJ, SepulcreJ, HuijbersW, LaPointM, BuckleyRF, JohnsonKA, SperlingRA (2017) Phases of hyperconnectivity and hypoconnectivity in the default mode and salience networks track with amyloid and tau in clinically normal individuals. J Neurosci37, 4323–4331.
18.
PalmqvistS, SchöllM, StrandbergO, MattssonN, StomrudE, ZetterbergH, BlennowK, LandauS, JagustW, HanssonO (2017) Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity. Nat Commun8, 1214.
19.
SchultzAP, BuckleyRF, HamptonOL, ScottMR, ProperziMJ, Peña-GómezC, PruzinJJ, YangHS, JohnsonKA, SperlingRA, ChhatwalJP (2020) Longitudinal degradation of the default/salience network axis in symptomatic individuals with elevated amyloid burden. Neuroimage Clin26, 102052.
20.
GriffaA, BommaritoG, ArmandS, AssalF, HermannF, Van De VilleD, AllaliG (2020) Dynamic functional networks in idiopathic normal pressure hydrocephalus: Alterations and reversibility by CSF tap test. Hum Brain Mapp42, 1485–1502.
21.
KhooHM, KishimaH, TaniN, OshinoS, MaruoT, HosomiK, YanagisawaT, KazuiH, WatanabeY, ShimokawaT, AsoT, KawaguchiA, YamashitaF, SaitohY, YoshimineT (2016) Default mode network connectivity in patients with idiopathic normal pressure hydrocephalus. J Neurosurg124, 350–358.
MulderC, VerweyNA, Van Der FlierWM, BouwmanFH, KokA, Van ElkEJ, ScheltensP, BlankensteinMA (2010) Amyloid-β(1-42), total tau, and phosphorylated tau as cerebrospinal fluid biomarkers for the diagnosis of Alzheimer disease. Clin Chem56, 248–253.
24.
AllaliG, LaidetM, ArmandS, MomjianS, MarquesB, SajA, AssalF (2017) A combined cognitive and gait quantification to identify normal pressure hydrocephalus from its mimics: The Geneva’s protocol. Clin Neurol Neurosurg160, 5–11.
25.
KangK, KoPW, JinM, SukK, LeeHW (2014) Idiopathic normal-pressure hydrocephalus, cerebrospinal fluid biomarkers, and the cerebrospinal fluid tap test. J Clin Neurosci21, 1398–1403.
26.
IshikawaM, HashimotoM, MoriE, KuwanaN, KazuiH (2012) The value of the cerebrospinal fluid tap test for predicting shunt effectiveness in idiopathic normal pressure hydrocephalus. Fluids Barriers CNS9, 1.
27.
JingamiN, Asada-UtsugiM, UemuraK, NotoR, TakahashiM, OzakiA, KiharaT, KageyamaT, TakahashiR, ShimohamaS, KinoshitaA (2015) Idiopathic normal pressure hydrocephalus has a different cerebrospinal fluid biomarker profile from Alzheimer’s disease. J Alzheimers Dis45, 109–115.
28.
YeoBTT, KrienenFM, SepulcreJ, SabuncuMR, LashkariD, HollinsheadM, RoffmanJL, SmollerJW, ZölleiL, PolimeniJR, FischlB, LiuH, BucknerRL (2011) The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol106, 1125–1165.
29.
SchaeferA, KongR, GordonEM, LaumannTO, ZuoX-N, HolmesAJ, EickhoffSB, YeoBTT (2018) Local-global parcellation of the human cerebral cortex from intrinsic functional connectivity MRI. Cereb Cortex28, 3095–3114.
30.
FischlB, SalatDH, BusaE, AlbertM, DieterichM, HaselgroveC, van der KouweA, KillianyR, KennedyD, KlavenessS, MontilloA, MakrisN, RosenB, DaleAM (2002) Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain. Neuron33, 341–355.
31.
PowerJD, BarnesKA, SnyderAZ, SchlaggarBL, PetersenSE (2012) Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage59, 2142–2154.
32.
WahlundLO, BarkhofF, FazekasF, BrongeL, AugustinM, SjögrenM, WallinA, AderH, LeysD, PantoniL, PasquierF, ErkinjunttiT, ScheltensP (2001) A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke32, 1318–1322.
33.
BenjaminiY, YekutieliD (2001) The control of the false discovery rate in multiple testing under dependency. Ann Stat29, 1165–1188.
34.
KrishnanA, WilliamsLJ, McIntoshAR, AbdiH (2011) Partial least squares (PLS) methods for neuroimaging: A tutorial and review. Neuroimage56, 455–475.
35.
ZöllerD, SandiniC, KarahanoğluFI, PadulaMC, SchaerM, EliezS, Van De VilleD (2019) Large-scale brain network dynamics provide a measure of psychosis and anxiety in 22q11.2 deletion syndrome. Biol Psychiatry Cogn Neurosci Neuroimaging4, 881–892.
36.
Müller-SchmitzK, Krasavina-LokaN, YardimciT, LipkaT, KolmanAGJ, RobbersS, MengeT, KujovicM, SeitzRJ (2020) Normal pressure hydrocephalus associated with Alzheimer’s disease. Ann Neurol88, 703–711.
37.
JeppssonA, HölttaM, ZetterbergH, BlennowK, WikkelsøC, TullbergM (2016) Amyloid mis-metabolism in idiopathic normal pressure hydrocephalus. Fluids Barriers CNS13, 13.
38.
ReevesBC, KarimyJK, KundishoraAJ, MestreH, CerciHM, MatoukC, AlperSL, LundgaardI, NedergaardM, KahleKT (2020) Glymphatic system impairment in Alzheimer’s disease and idiopathic normal pressure hydrocephalus. Trends Mol Med26, 285–295.
39.
LeinonenV, MenonLG, CarrollRS, Dello IaconoD, GrevetJ, JääskeläinenJE, BlackPM (2011) Cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus. Int J Alzheimers Dis2011, 312526.
