Abstract
Parkinson’s disease (PD) with mild cognitive impairment (PD-MCI) is currently diagnosed based on an arbitrarily predefined standard deviation of neuropsychological test scores, and more objective biomarkers for PD-MCI diagnosis are needed. The purpose of this study was to define possible brain perfusion-based biomarkers of not only mild cognitive impairment, but also risky gene carriers in PD using arterial spin labeling magnetic resonance imaging (ASL-MRI). Fifteen healthy controls (HC), 26 cognitively normal PD (PD-CN), and 27 PD-MCI subjects participated in this study. ASL-MRI data were acquired by signal targeting with alternating radio-frequency labeling with Look–Locker sequence at 3 T. Single nucleotide polymorphism genotyping for rs9468 [microtubule-associated protein tau (MAPT) H1/H1 versus H1/H2 haplotype] was performed using a Stratagene Mx3005p real-time polymerase chain-reaction system (Agilent Technologies, USA). There were 15 subjects with MAPT H1/H1 and 11 subjects with MAPT H1/H2 within PD-MCI, and 33 subjects with MAPT H1/H1 and 19 subjects with MAPT H1/H2 within all PD. Voxel-wise differences of cerebral blood flow (CBF) values between HC, PD-CN and PD-MCI were assessed by one-way analysis of variance followed by pairwise post hoc comparisons. Further, the subgroup of PD patients carrying the risky MAPT H1/H1 haplotype was compared with noncarriers (MAPT H1/H2 haplotype) in terms of CBF by a two-sample t test. A pattern that could be summarized as “posterior hypoperfusion” (PH) differentiated the PD-MCI group from the HC group with an accuracy of 92.6% (sensitivity = 93%, specificity = 93%). Additionally, the PD patients with MAPT H1/H1 haplotype had decreased perfusion than the ones with H1/H2 haplotype at the posterior areas of the visual network (VN), default mode network (DMN), and dorsal attention network (DAN). The PH-type pattern in ASL-MRI could be employed as a biomarker of both current cognitive impairment and future cognitive decline in PD.
Similar content being viewed by others
References
Abe Y et al (2003) Occipital hypoperfusion in Parkinson’s disease without dementia: correlation to impaired cortical visual processing. J Neurol Neurosurg Psychiatry 74:419–422. https://doi.org/10.1136/jnnp.74.4.419
Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–381. https://doi.org/10.1146/annurev.ne.09.030186.002041
Amboni M et al (2015) Resting-state functional connectivity associated with mild cognitive impairment in Parkinson’s disease. J Neurol 262:425–434. https://doi.org/10.1007/s00415-014-7591-5
Asllani I, Borogovac A, Brown TR (2008a) Regression algorithm correcting for partial volume effects in arterial spin labeling MRI. Magn Reson Med 60:1362–1371. https://doi.org/10.1002/mrm.21670
Asllani I, Habeck C, Scarmeas N, Borogovac A, Brown TR, Stern Y (2008b) Multivariate and univariate analysis of continuous arterial spin labeling perfusion MRI in Alzheimer’s disease. J Cereb Blood Flow Metab 28:725–736. https://doi.org/10.1038/sj.jcbfm.9600570
Benton AL, Hamsher KD, Varney NR, Spreen O (1983) Contributions to neuropsychological assessment: a clinical manual. Oxford University Press, New York
Bezdicek O, Ballarini T, Ruzicka F, Roth J, Mueller K, Jech R, Schroeter ML (2018) Mild cognitive impairment disrupts attention network connectivity in Parkinson's disease: a combined multimodal MRI and meta-analytical study. Neuropsychologia 112:105–115. https://doi.org/10.1016/j.neuropsychologia.2018.03.011
Blagus R, Lusa L (2013) SMOTE for high-dimensional class-imbalanced data. BMC Bioinform 14:106. https://doi.org/10.1186/1471-2105-14-106
Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 24:197–211
Buckner RL, Krienen FM, Castellanos A, Diaz JC, Yeo BT (2011) The organization of the human cerebellum estimated by intrinsic functional connectivity. J Neurophysiol 106:2322–2345. https://doi.org/10.1152/jn.00339.2011
Chawla NV, Bowyer KW, Hall LO, Kegelmeyer WP (2002) SMOTE: synthetic minority oversampling technique. J Artif Intell Res 16:321–357
Cox SR et al (2016) Associations between education and brain structure at age 73 years, adjusted for age 11 IQ. Neurology 87:1820–1826. https://doi.org/10.1212/Wnl.0000000000003247
Deshmane A, Gulani V, Griswold MA, Seiberlich N (2012) Parallel MR imaging. J Magn Reson Imaging 36:55–72. https://doi.org/10.1002/jmri.23639
Diez-Cirarda M, Strafella AP, Kim J, Pena J, Ojeda N, Cabrera-Zubizarreta A, Ibarretxe-Bilbao N (2018) Dynamic functional connectivity in Parkinson's disease patients with mild cognitive impairment and normal cognition. Neuroimage Clin 17:847–855. https://doi.org/10.1016/j.nicl.2017.12.013
Dosenbach NU, Fair DA, Cohen AL, Schlaggar BL, Petersen SE (2008) A dual-networks architecture of top-down control. Trends Cogn Sci 12:99–105. https://doi.org/10.1016/j.tics.2008.01.001
Fernandez-Seara MA et al (2012) Cortical hypoperfusion in Parkinson's disease assessed using arterial spin labeled perfusion MRI. Neuroimage 59:2743–2750. https://doi.org/10.1016/j.neuroimage.2011.10.033
Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198
Goetz CG et al (2008) Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 23:2129–2170. https://doi.org/10.1002/mds.22340
Gorges M et al (2019) Structural brain signature of cognitive decline in Parkinson's disease: DTI-based evidence from the LANDSCAPE study. Ther Adv Neurol Disord 12:1756286419843447. https://doi.org/10.1177/1756286419843447
Goris A et al (2007) Tau and alpha-synuclein in susceptibility to, and dementia in Parkinson’s disease. Ann Neurol 62:145–153. https://doi.org/10.1002/ana.21192
Gunther M, Bock M, Schad LR (2001) Arterial spin labeling in combination with a look-locker sampling strategy: inflow turbo-sampling EPI-FAIR (ITS-FAIR). Magn Reson Med 46:974–984
Hattori T et al (2012) Cognitive status correlates with white matter alteration in Parkinson's disease. Hum Brain Mapp 33:727–739. https://doi.org/10.1002/hbm.21245
Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442. https://doi.org/10.1212/wnl.17.5.427
Huang C, Mattis P, Tang C, Perrine K, Carbon M, Eidelberg D (2007) Metabolic brain networks associated with cognitive function in Parkinson's disease. Neuroimage 34:714–723. https://doi.org/10.1016/j.neuroimage.2006.09.003
Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184
Janvin CC, Larsen JP, Aarsland D, Hugdahl K (2006) Subtypes of mild cognitive impairment in Parkinson's disease: progression to dementia. Mov Disord 21:1343–1349. https://doi.org/10.1002/mds.20974
Jia X, Li Y, Li K, Liang P, Fu X (2018) Precuneus dysfunction in Parkinson's disease with mild cognitive impairment. Front Aging Neurosci 10:427. https://doi.org/10.3389/fnagi.2018.00427
Kamagata K et al (2011) Posterior hypoperfusion in Parkinson's disease with and without dementia measured with arterial spin labeling MRI. J Magn Reson Imaging 33:803–807. https://doi.org/10.1002/jmri.22515
Kehagia AA, Barker RA, Robbins TW (2013) Cognitive impairment in Parkinson's disease: the dual syndrome hypothesis. Neurodegener Dis 11:79–92. https://doi.org/10.1159/000341998
Le Heron CJ et al (2014) Comparing cerebral perfusion in Alzheimer's disease and Parkinson's disease dementia: an ASL-MRI study. J Cereb Blood Flow Metab 34:964–970. https://doi.org/10.1038/jcbfm.2014.40
Liepelt-Scarfone I et al (2011) Influence of different cut-off values on the diagnosis of mild cognitive impairment in Parkinson's disease. Parkinsons Dis. https://doi.org/10.4061/2011/540843
Litvan I et al (2011) MDS Task Force on mild cognitive impairment in Parkinson's disease: critical review of PD-MCI. Mov Disord 26:1814–1824. https://doi.org/10.1002/mds.23823
Litvan I et al (2012) Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines. Mov Disord 27:349–356. https://doi.org/10.1002/mds.24893
Ma Y, Huang C, Dyke JP, Pan H, Alsop D, Feigin A, Eidelberg D (2010) Parkinson's disease spatial covariance pattern: noninvasive quantification with perfusion MRI. J Cereb Blood Flow Metab 30:505–509. https://doi.org/10.1038/jcbfm.2009.256
Martinez-Horta S, Kulisevsky J (2011) Is all cognitive impairment in Parkinson's disease "mild cognitive impairment"? J Neural Transm (Vienna) 118:1185–1190. https://doi.org/10.1007/s00702-011-0675-9
Melzer TR et al (2011) Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson's disease. Brain 134:845–855. https://doi.org/10.1093/brain/awq377
Mioshi E, Dawson K, Mitchell J, Arnold R, Hodges JR (2006) The Addenbrooke's Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening. Int J Geriatr Psychiatry 21:1078–1085. https://doi.org/10.1002/gps.1610
Morley JF et al (2012) Genetic influences on cognitive decline in Parkinson's disease. Mov Disord 27:512–518. https://doi.org/10.1002/mds.24946
Muslimovic D, Post B, Speelman JD, Schmand B (2005) Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology 65:1239–1245. https://doi.org/10.1212/01.wnl.0000180516.69442.95
Nasreddine ZS et al (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695–699. https://doi.org/10.1111/j.1532-5415.2005.53221.x
Nombela C et al (2014) Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease: ICICLE-PD study. Brain 137:2743–2758. https://doi.org/10.1093/brain/awu201
Petcharunpaisan S, Ramalho J, Castillo M (2010) Arterial spin labeling in neuroimaging World. J Radiol 2:384–398. https://doi.org/10.4329/wjr.v2.i10.384
Petrou M, Kotagal V, Bohnen NI (2012) An update on brain imaging in parkinsonian dementia. Imaging Med 4:201–213. https://doi.org/10.2217/iim.12.10
Pievani M, de Haan W, Wu T, Seeley WW, Frisoni GB (2011) Functional network disruption in the degenerative dementias. Lancet Neurol 10:829–843. https://doi.org/10.1016/S1474-4422(11)70158-2
Pollock JM, Tan H, Kraft RA, Whitlow CT, Burdette JH, Maldjian JA (2009) Arterial spin-labeled MR perfusion imaging: clinical applications. Magn Reson Imaging Clin N Am 17:315–338. https://doi.org/10.1016/j.mric.2009.01.008
Robinson AL, Heaton RK, Lehman RA, Stilson DW (1980) The utility of the Wisconsin Card Sorting Test in detecting and localizing frontal lobe lesions. J Consult Clin Psychol 48:605–614. https://doi.org/10.1037//0022-006x.48.5.605
Schaefer A et al (2018) Local-global parcellation of the human cerebral cortex from intrinsic functional connectivity MRI. Cereb Cortex 28:3095–3114. https://doi.org/10.1093/cercor/bhx179
Smith A, Helmuth J (1968) The symbol-digit modalities test: a neuropsychologic test of learning and other cerebral disorders. Learn Disord Spec Child Publ Seattle 83:91
Stroop JR (1992) Studies of interference in serial verbal reactions. J Exp Psychol Gen 121:15–23 (Reprinted from Journal Experimental-Psychology, Vol 18, Pg 643-662, 1935)
Syrimi ZJ, Vojtisek L, Eliasova I, Viskova J, Svatkova A, Vanicek J, Rektorova I (2017) Arterial spin labelling detects posterior cortical hypoperfusion in non-demented patients with Parkinson's disease. J Neural Transm (Vienna) 124:551–557. https://doi.org/10.1007/s00702-017-1703-1
Uysal-Canturk P, Hanagasi HA, Bilgic B, Gurvit H, Emre M (2018) An assessment of Movement Disorder Society Task Force diagnostic criteria for mild cognitive impairment in Parkinson's disease. Eur J Neurol 25:148–153. https://doi.org/10.1111/ene.13467
van Eimeren T, Monchi O, Ballanger B, Strafella AP (2009) Dysfunction of the default mode network in Parkinson disease: a functional magnetic resonance imaging study. Arch Neurol 66:877–883. https://doi.org/10.1001/archneurol.2009.97
Wei X et al (2016) Combined diffusion tensor imaging and arterial spin labeling as markers of early Parkinson’s disease. Sci Rep-Uk 6:33762. https://doi.org/10.1038/srep33762
Williams-Gray CH et al (2009) The distinct cognitive syndromes of Parkinson's disease: 5 year follow-up of the CamPaIGN cohort. Brain 132:2958–2969. https://doi.org/10.1093/brain/awp245
Wirth M, Pichet Binette A, Brunecker P, Kobe T, Witte AV, Floel A (2017) Divergent regional patterns of cerebral hypoperfusion and gray matter atrophy in mild cognitive impairment patients. J Cereb Blood Flow Metab 37:814–824. https://doi.org/10.1177/0271678X16641128
Wolpert D (ed) (1995) The relationship between PAC, the statistical physics framework, the Bayesian framework, and the VC framework. In: The mathematics of generalization. Addison-Wesley
Yamashita K et al (2017) Cerebral blood flow laterality derived from arterial spin labeling as a biomarker for assessing the disease severity of parkinson's disease. J Magn Reson Imaging 45:1821–1826. https://doi.org/10.1002/jmri.25489
Yeo BT et al (2011) The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol 106:1125–1165. https://doi.org/10.1152/jn.00338.2011
Funding
This study was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) 1001 Grant #115S219 and Istanbul University Scientific Research Projects Unit Project #1567/42362.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Arslan, D.B., Gurvit, H., Genc, O. et al. The cerebral blood flow deficits in Parkinson’s disease with mild cognitive impairment using arterial spin labeling MRI. J Neural Transm 127, 1285–1294 (2020). https://doi.org/10.1007/s00702-020-02227-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-020-02227-6