Association of Cerebrospinal Fluid Adiponectin Levels With Cerebral Glucose Metabolism In Mild Cognitive Impairment: A Pilot Study

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Abstract

Background: Adiponectin has been implicated in the pathophysiology of dementia, especially Alzheimer’s disease. However, the association between cerebrospinal fluid (CSF) adiponectin levels and positron emission tomography (PET) imaging remains unclear.

Objective: To explore whether CSF adiponectin levels are associated with 11C-Pittsburgh compound B (PiB) or 18F-fluorodeoxyglucose (FDG) uptake in amnestic mild cognitive impairment (MCI) subjects.

Methods: Thirty-four amnestic MCI subjects underwent PiB-PET, FDG-PET, and CSF analysis. The CSF adiponectin levels were measured using the Bio-Plex 200 suspension array system. PET uptake was assessed for the frontal and temporoparietal lobes and posterior cingulate gyrus, referenced against the cerebellar cortex. The increased brain amyloid burden was defined as a mean uptake value ratio greater than 1.4. Spearman’s rank correlation analysis and a multiple regression model were used to examine the association between CSF adiponectin levels and PiB or FDG uptake.

Results: The mean age was 76.3 years; 38.2% were men, and 61.8% were women. A high amyloid burden was identified in 18 (52.9%) subjects. CSF adiponectin levels positively correlated with global FDG uptake (β = 0.45; 95% confidence interval (CI), 0.13 to 0.76, p < 0.01), especially in the parietotemporal lobe and posterior cingulate gyrus (β = 0.70; 95% CI, 0.41 to 0.99, p<0.01, β = 0.33; 95% CI, 0.03 to 0.63, p = 0.03, respectively) after adjusting for covariates, including age, sex, education years, body mass index, vascular risk factors, ApoEε4 status, and PiB status in all amnestic MCI subjects.

Conclusion: CSF adiponectin levels were associated with cortical glucose metabolism, particularly in the specific regions that connect with the medial temporal, but not brain amyloid burden in amnestic MCI subjects.

Keywords: Adiponectin, cerebrospinal fluid, 11C-Pittsburgh compound B positron emission tomography, 18Ffluorodeoxyglucose positron emission tomography, mild cognitive impairment, pilot study.

[1]
Gauthier S, Reisberg B, Zaudig M, et al. International psychogeriatric association expert conference on mild cognitive impairment. Mild cognitive impairment. Lancet 2006; 367(9518): 1262-70.
[http://dx.doi.org/10.1016/S0140-6736(06)68542-5] [PMID: 16631882]
[2]
Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999; 56(3): 303-8.
[http://dx.doi.org/10.1001/archneur.56.3.303] [PMID: 10190820]
[3]
Daviglus ML, Plassman BL, Pirzada A, et al. Risk factors and preventive interventions for Alzheimer disease: state of the science. Arch Neurol 2011; 68(9): 1185-90.
[http://dx.doi.org/10.1001/archneurol.2011.100] [PMID: 21555601]
[4]
Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C. Potential for primary prevention of Alzheimer’s disease: An analysis of population-based data. Lancet Neurol 2014; 13(8): 788-94.
[http://dx.doi.org/10.1016/S1474-4422(14)70136-X] [PMID: 25030513]
[5]
Whitmer RA. Type 2 diabetes and risk of cognitive impairment and dementia. Curr Neurol Neurosci Rep 2007; 7(5): 373-80.
[http://dx.doi.org/10.1007/s11910-007-0058-7] [PMID: 17764626]
[6]
van Himbergen TM, Beiser AS, Ai M, et al. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease: Results from the Framingham Heart Study. Arch Neurol 2012; 69(5): 594-600.
[http://dx.doi.org/10.1001/archneurol.2011.670] [PMID: 22213409]
[7]
Song J, Lee JE. Adiponectin as a new paradigm for approaching Alzheimer’s disease. Anat Cell Biol 2013; 46(4): 229-34.
[http://dx.doi.org/10.5115/acb.2013.46.4.229] [PMID: 24386594]
[8]
Bloemer J, Pinky PD, Govindarajulu M, et al. Role of adiponectin in central nervous system disorders. Neural Plast 2018; 20184593530
[http://dx.doi.org/10.1155/2018/4593530] [PMID: 30150999]
[9]
Forny-Germano L, De Felice FG, Vieira MNDN. The role of leptin and adiponectin in obesity-associated cognitive decline and Alzheimer’s disease. Front Neurosci 2019; 12: 1027.
[http://dx.doi.org/10.3389/fnins.2018.01027] [PMID: 30692905]
[10]
Kiliaan AJ, Arnoldussen IA, Gustafson DR. Adipokines: A link between obesity and dementia? Lancet Neurol 2014; 13(9): 913-23.
[http://dx.doi.org/10.1016/S1474-4422(14)70085-7] [PMID: 25142458]
[11]
Spranger J, Verma S, Göhring I, et al. Adiponectin does not cross the blood-brain barrier but modifies cytokine expression of brain endothelial cells. Diabetes 2006; 55(1): 141-7.
[http://dx.doi.org/10.2337/diabetes.55.01.06.db05-1077] [PMID: 16380487]
[12]
Letra L, Rodrigues T, Matafome P, Santana I, Seiça R. Adiponectin and sporadic Alzheimer’s disease: Clinical and molecular links. Front Neuroendocrinol 2019; 52: 1-11.
[http://dx.doi.org/10.1016/j.yfrne.2017.10.002] [PMID: 29038028]
[13]
Ng RC, Chan KH. Potential neuroprotective effects of adiponectin in Alzheimer’s disease. Int J Mol Sci 2017; 18(3): 592.
[http://dx.doi.org/10.3390/ijms18030592] [PMID: 28282917]
[14]
Yau SY, Li A, Hoo RL, et al. Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin. Proc Natl Acad Sci USA 2014; 111(44): 15810-5.
[http://dx.doi.org/10.1073/pnas.1415219111] [PMID: 25331877]
[15]
Zhang D, Wang X, Wang B, et al. Adiponectin regulates contextual fear extinction and intrinsic excitability of dentate gyrus granule neurons through AdipoR2 receptors. Mol Psychiatry 2017; 22(7): 1044-55.
[http://dx.doi.org/10.1038/mp.2016.58] [PMID: 27137743]
[16]
Une K, Takei YA, Tomita N, et al. Adiponectin in plasma and cerebrospinal fluid in MCI and Alzheimer’s disease. Eur J Neurol 2011; 18(7): 1006-9.
[http://dx.doi.org/10.1111/j.1468-1331.2010.03194.x] [PMID: 20727007]
[17]
Waragai M, Adame A, Trinh I, et al. Possible involvement of adiponectin, the anti-diabetes molecule, in the pathogenesis of Alzheimer’s disease. J Alzheimers Dis 2016; 52(4): 1453-9.
[http://dx.doi.org/10.3233/JAD-151116] [PMID: 27079710]
[18]
Khemka VK, Bagchi D, Bandyopadhyay K, et al. Altered serum levels of adipokines and insulin in probable Alzheimer’s disease. J Alzheimers Dis 2014; 41(2): 525-33.
[http://dx.doi.org/10.3233/JAD-140006] [PMID: 24625795]
[19]
Teixeira AL, Diniz BS, Campos AC, et al. Decreased levels of circulating adiponectin in mild cognitive impairment and Alzheimer’s disease. Neuromolecular Med 2013; 15(1): 115-21.
[http://dx.doi.org/10.1007/s12017-012-8201-2] [PMID: 23055000]
[20]
Ma J, Zhang W, Wang HF, et al. Peripheral blood adipokines and insulin levels in patients with Alzheimer’s disease: A replication study and meta-analysis. Curr Alzheimer Res 2016; 13(3): 223-33.
[http://dx.doi.org/10.2174/156720501303160217111434] [PMID: 26906354]
[21]
Wennberg AM, Gustafson D, Hagen CE, et al. Serum adiponectin levels, neuroimaging, and cognition in the Mayo Clinic study of aging. J Alzheimers Dis 2016; 53(2): 573-81.
[http://dx.doi.org/10.3233/JAD-151201] [PMID: 27163809]
[22]
Molgaard CA. Multivariate analysis of Hachinski’s Scale for discriminating senile dementia of the Alzheimer’s Type from multiinfarct dementia. Neuroepidemiology 1987; 6(3): 153-60.
[http://dx.doi.org/10.1159/000110111] [PMID: 3658084]
[23]
Di Domenico F, Pupo G, Giraldo E, et al. Oxidative signature of cerebrospinal fluid from mild cognitive impairment and Alzheimer disease patients. Free Radic Biol Med 2016; 91: 1-9.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.12.004] [PMID: 26675344]
[24]
Taddei K, Clarnette R, Gandy SE, Martins RN. Increased plasma apolipoprotein E (apoE) levels in Alzheimer’s disease. Neurosci Lett 1997; 223(1): 29-32.
[http://dx.doi.org/10.1016/S0304-3940(97)13394-8] [PMID: 9058415]
[25]
Gupta VB, Laws SM, Villemagne VL, et al. AIBL Research Group. Plasma apolipoprotein E and Alzheimer disease risk: The AIBL study of aging. Neurology 2011; 76(12): 1091-8.
[http://dx.doi.org/10.1212/WNL.0b013e318211c352] [PMID: 21422459]
[26]
Eguchi A, Kimura N, Aso Y, et al. Relationship between the Japanese version of the Montreal cognitive assessment and PET imaging in subjects with mild cognitive impairment. Curr Alzheimer Res 2019; 16(9): 852-60.
[http://dx.doi.org/10.2174/1567205016666190805155230] [PMID: 31385770]
[27]
Herholz K, Salmon E, Perani D, et al. Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. Neuroimage 2002; 17(1): 302-16.
[http://dx.doi.org/10.1006/nimg.2002.1208] [PMID: 12482085]
[28]
Jack CR Jr, Lowe VJ, Senjem ML, et al. 11C PiB and structural MRI provide complementary information in imaging of Alzheimer’s disease and amnestic mild cognitive impairment. Brain 2008; 131(Pt 3): 665-80.
[http://dx.doi.org/10.1093/brain/awm336] [PMID: 18263627]
[29]
Kimura N, Aso Y, Yabuuchi K, et al. Association of modifiable lifestyle factors with cortical amyloid burden and cerebral glucose metabolism in older adults with mild cognitive impairment. JAMA Netw Open 2020; 3(6)e205719
[http://dx.doi.org/10.1001/jamanetworkopen.2020.5719] [PMID: 32515796]
[30]
Jicha GA, Parisi JE, Dickson DW, et al. Neuropathologic outcome of mild cognitive impairment following progression to clinical dementia. Arch Neurol 2006; 63(5): 674-81.
[http://dx.doi.org/10.1001/archneur.63.5.674] [PMID: 16682537]
[31]
Waragai M, Ho G, Takamatsu Y, et al. Importance of adiponectin activity in the pathogenesis of Alzheimer’s disease. Ann Clin Transl Neurol 2017; 4(8): 591-600.
[http://dx.doi.org/10.1002/acn3.436] [PMID: 28812049]
[32]
Ng RCL, Cheng OY, Jian M, et al. Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice. Mol Neurodegener 2016; 11(1): 71.
[http://dx.doi.org/10.1186/s13024-016-0136-x] [PMID: 27884163]
[33]
Mullins RJ, Diehl TC, Chia CW, Kapogiannis D. Insulin resistance as a link between amyloid-beta and tau pathologies in Alzheimer’s disease. Front Aging Neurosci 2017; 9: 118.
[http://dx.doi.org/10.3389/fnagi.2017.00118]
[34]
Toda N, Ayajiki K, Okamura T. Obesity-induced cerebral hypoperfusion derived from endothelial dysfunction: One of the risk factors for Alzheimer’s disease. Curr Alzheimer Res 2014; 11(8): 733-44.
[http://dx.doi.org/10.2174/156720501108140910120456] [PMID: 25212912]
[35]
Nishimura M, Izumiya Y, Higuchi A, et al. Adiponectin prevents cerebral ischemic injury through endothelial nitric oxide synthase dependent mechanisms. Circulation 2008; 117(2): 216-23.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.725044] [PMID: 18158361]
[36]
Ali T, Yoon GH, Shah SA, Lee HY, Kim MO. Osmotin attenuates amyloid beta-induced memory impairment, tau phosphorylation and neurodegeneration in the mouse hippocampus. Sci Rep 2015; 5: 11708.
[http://dx.doi.org/10.1038/srep11708]
[37]
Desgranges B, Baron JC, de la Sayette V, et al. The neural substrates of memory systems impairment in Alzheimer’s disease. A PET study of resting brain glucose utilization. Brain 1998; 121(Pt 4): 611-31.
[http://dx.doi.org/10.1093/brain/121.4.611] [PMID: 9577389]
[38]
Pousti F, Ahmadi R, Mirahmadi F, Hosseinmardi N, Rohampour K. Adiponectin modulates synaptic plasticity in hippocampal dentate gyrus. Neurosci Lett 2018; 662: 227-32.
[PMID: 29079430]
[39]
Cisternas P, Martinez M, Ahima RS, William Wong G, Inestrosa NC. Modulation of glucose metabolism in hippocampal neurons by adiponectin and resistin. Mol Neurobiol 56(4): 3024-37.
[http://dx.doi.org/10.1007/s12035-018-1271-x]
[40]
Mosconi L, Sorbi S, de Leon MJ, et al. Hypometabolism exceeds atrophy in presymptomatic early-onset familial Alzheimer’s disease. J Nucl Med 2006; 47(11): 1778-86.
[PMID: 17079810]