Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
 
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2018, Vol. 9 Issue (1) : 51-65     DOI: 10.14336/AD.2017.0416
Orginal Article |
Trefoil Factor 3, Cholinesterase and Homocysteine: Potential Predictors for Parkinson’s Disease Dementia and Vascular Parkinsonism Dementia in Advanced Stage
Zou Jing1, Chen Zhigang1, Liang Caiqian2, Fu Yongmei2, Wei Xiaobo1, Lu Jianjun3, Pan Mengqiu3, Guo Yue4, Liao Xinxue4, Xie Huifang5, Wu Duobin5, Li Min6, Liang Lihui7,*, Wang Penghua8,*, Wang Qing1,*
1Department of Neurology, and
2Department of Emergency, The Third Affiliated Hospital of Sun Yat-Sen University, China.
3Department of Neurology, Guangdong 999 Brain Hospital, Guangzhou, China.
4Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, China.
5Department of Neurology, Zhujiang Hospital, Southern Medical University, China.
6School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
7Department of Geriatric Medicine, Hunan Provincial People’s Hospital, Changsha, Hunan, China.
8Department of Microbiology & Immunology, School of Medicine, New York Medical College, NY 10595, USA
Download: PDF(1680 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    
Abstract  

Trefoil factor 3 (TFF3), cholinesterase activity (ChE activity) and homocysteine (Hcy) play critical roles in modulating recognition, learning and memory in neurodegenerative diseases, such as Parkinson’s disease dementia (PDD) and vascular parkinsonism with dementia (VPD). However, whether they can be used as reliable predictors to evaluate the severity and progression of PDD and VPD remains largely unknown. Methods: We performed a cross-sectional study that included 92 patients with PDD, 82 patients with VPD and 80 healthy controls. Serum levels of TFF3, ChE activity and Hcy were measured. Several scales were used to rate the severity of PDD and VPD. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of PDD and VPD patients compared to healthy subjects. Results: Compared with healthy subjects, the serum levels of TFF3 and ChE activity were lower, while Hcy was higher in the PDD and VPD patients. These findings were especially prominent in male patients. The three biomarkers displayed differences between PDD and VPD sub-groups based on genders and UPDRS (III) scores’ distribution. Interestingly, these increased serum Hcy levels were significantly and inversely correlated with decreased TFF3/ChE activity levels. There were significant correlations between TFF3/ChE activity/Hcy levels and PDD/VPD severities, including motor dysfunction, declining cognition and mood/gastrointestinal symptoms. Additionally, ROC curves for the combination of TFF3, ChE activity and Hcy showed potential diagnostic value in discriminating PDD and VPD patients from healthy controls. Conclusions: Our findings suggest that serum TFF3, ChE activity and Hcy levels may underlie the pathophysiological mechanisms of PDD and VPD. As the race to find biomarkers or predictors for these diseases intensifies, a better understanding of the roles of TFF3, ChE activity and Hcy may yield insights into the pathogenesis of PDD and VPD.

Keywords TFF3      ChE activity      Hcy      Parkinson disease dementia      vascular parkinsonism dementia      pathogenesis     
Corresponding Authors: Liang Lihui,Wang Penghua,Wang Qing   
About author:

These authors contributed equally

Issue Date: 01 February 2018
Service
E-mail this article
E-mail Alert
RSS
Articles by authors
Zou Jing
Chen Zhigang
Liang Caiqian
Fu Yongmei
Wei Xiaobo
Lu Jianjun
Pan Mengqiu
Guo Yue
Liao Xinxue
Xie Huifang
Wu Duobin
Li Min
Liang Lihui
Wang Penghua
Wang Qing
Cite this article:   
Zou Jing,Chen Zhigang,Liang Caiqian, et al. Trefoil Factor 3, Cholinesterase and Homocysteine: Potential Predictors for Parkinson’s Disease Dementia and Vascular Parkinsonism Dementia in Advanced Stage[J]. Aging and disease, 2018, 9(1): 51-65.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2017.0416     OR     http://www.aginganddisease.org/EN/Y2018/V9/I1/51
Clinical parametersPDDHealthy subjectsVPD

Mean (SD)MinMaxMean (SD)MinMaxMean (SD)MinMax
Gender (n)Male n (%)49(53.3)//44(55)//45(54.8)//
Female n (%)43(46.7)//36(45)//37(45.2)//
Age (years)65.73(11.18)568864.43(7.10)508270.29(9.87)6583
H&Y2.85(1.23)15///2.68(1.05)15
MMSE21.72(3.94)624///17.34(5.04)123
UPDRS50.92(23.13)1796///44.36(19.03)1683
UPRDRS(I)3.70(2.05)112///3.79(3.08)014
UPRDRS(II)18.17(9.64)345///16.57(8.79)340
UPRDRS(III)27.02(11.04)951///22.49(9.58)551
UPRDRS(Ⅵ)2.03(2.50)09///1.52(1.81)07
NMSS (total)86.77(53.47)20188///103.22(44.42)30235
Cardiovascular4.06 (2.90)012///4.96(3.95)018
Sleep/Fatigue17.50(9.58)036///19.64(8.90)246
Mood19.30(14.41)354///23.30(12.51)056
Perceptual problem2.87(4.48)018///3.47(5.92)026
Attention/memory11.27(7.79)030///14.51(7.11)030
Gastrointestina9.35(6.54)028///10.15(7.37)031
Urinar8.30(8.16)032///11.18(7.93)036
Sexual function5.45(6.23)018///8.41(7.69)024
Miscellaneous8.67(10.25)036///7.61(7.20)038
Daily dose of L-Dopa (mg)252.6(58.52)206.44291.14///275.06(65.77)223.35305.21
Disease Duration4.05(3.40)0.515///3.53(3.36)0.511
Table 1  Demographic, motor, and non-motor parameters.
VariablePDDVPDControlt Valuep ValueTukey’s
PDD/VPDPDD/ControlVPD/Control
Age65.73±11.1870.29±9.8764.43±7.102.9250.008**0.007**0.2950.005**
MMSE21.72±3.9417.34±5.04303.5230.001**0.008**0.000***0.000***
TFF315.21±11.8314.03±12.2518.20±6.21-2.6680.006*0.0890.007**0.005**
ChE activity7528±15737232±12547785±1962-1.8150.042*0.8820.0670.028*
Hcy16.18±4.9618.21±5.7210.45±3.193.4780.002**0.6250.008**0.006**
Table 2  Comparison of age, MMSE, TFF3, Hcy and ChE activity among PDD, VPD and normal healthy subjects.
VariablePDD (mean ± SD)Control (mean ± SD)PDD vs. ControlPDD(Male) vs. (Female)

ValuepValuep
TFF3Male15.03±11.2620.12±9.51-2.5580.009**b-2.9760.003**a
Female17.29±10.1720.43±7.10-2.9110.006**a
ChE activityMale7596±14337736±1648-2.0830.038*a-0.8630.520b
Female7680±12597839±1542-1.9150.026*b
HcyMale18.21±4.7211.39±2.803.9740.000***b3.2390.003*a
Female14.59±5.7310.74±2.253.0150.002*a
Table 3  Comparison of TFF3, Hcy and ChE activity between normal subjects and PDD patients according to genders.
VariableVPD (mean ± SD)Control (mean ± SD)VPD vs. ControlVPD(Male) vs. (Female)

ValuepValuep
TFF3Male14.67±11.5120.12±9.51-3.9560.000*a-3.2410.004**a
Female16.98±12.3620.43±7.10-3.5790.002*b
ChE activityMale7286±16267736±1648-2.0660.032*b-0.5710.739b
Female7351±18207839±1542-2.0170.041*a
HcyMale21.11±5.2411.39±2.803.9230.000***a2.9390.003**b
Female16.27±4.1910.74±2.253.3810.000***b
Table 4  Comparison of TFF3, Hcy and ChE activity between healthy subjects and VPD patients according to genders.
Figure 1.  Correlation analysis between TFF3/ChE activity and Hcy Levels in PDD and VPD patients

A significant negative correlation between (A) TFF3 and Hcy Levels in PDD patients (rs =-0.799, ***p<0.001); (B) ChE activity and Hcy Levels in PDD patients (rs =-0.732, ***p<0.001). (C) TFF3 and Hcy Levels in VPD patients (rs =-0.771, ***p<0.001). (D) ChE activity and Hcy Levels in VPD patients (rs =-0.713, ***p<0.001).

VariablePDD
Mean ± SD
VPD
Mean ± SD
PDD vs. VPD
Valuep
TFF3
GenderMale15.03±11.2614.67±11.510.1530.8786
Female17.29±10.1716.98±12.360.9020.123
UPDRS(III)UPDRS(III)≤3016.85±10.3315.37±10.162.6290.011a*
31<UPDRS(III)<5015.74±10.2914.16±10.033.1400.003 a**
UPDRS(III)≤3014.33±9.8113.85±9.271.2180.082
ChE activity
GenderMale7596±14337286±16260.9820.3285
Female7680±12597351±18200.9510.345
UPDRS(III)UPDRS(III)≤308027±10037829±15791.8830.075
31<UPDRS(III)<507829±12827320±10502.1450.037 a*
UPDRS(III)>507462±12917057±13312.3350.020 a*
Hcy
GenderMale18.21±4.7221.11±5.242.8320.006b**
Female14.59±5.7316.27±4.191.4760.144
UPDRS(III)UPDRS(III)≤3017.82±3.9419.33±4.910.2320.713
31<UPDRS(III)<5016.35±4.3118.56±4.430.5370.281
UPDRS(III)>5015.78±4.6017.41±3.890.8910.371
Table 5  Comparison of TFF3, Hcy and ChE activity between PDD and VPD patients according to genders and UPDRS-III scores.
Figure 2.  ROC curves to evaluate the utility of serum levels of TFF3, ChE activity and Hcy Levels for the discrimination of PDD/VPD patients from healthy controls

(A-D) The AUC of ROC curves for discrimination of PDD patients from healthy controls (A) TFF3, (B) ChE activity, and (C) Hcy were 0.778 (95%CI: 0.706-0.850, *p=0.037), 0.516 (95%CI: 0.423-0.609, p=0.737), and 0.690 (95%CI: 0.606-0.774, *p=0.043), respectively. The AUC of (D) TFF3+ChE activity+Hcy was 0.880 (95%CI: 0.828-0.932, *p=0.027). (E-H) The AUC of ROC curves for discrimination of VPD patients from healthy controls. (E) TFF3, (F) ChE activity, and (G) Hcy were 0.748 (95%CI: 0.671-0.826, *p=0.040), 0.567 (95%CI: 0.475-0.660, *p=0.047), and 0.623 (95%CI: 0.533-0.713, *p=0.046), respectively. The AUC of (H) TFF3+ChE activity+Hcy was 0.846 (95%CI:0.785-0.908, *p=0.031).

Figure 3.  MRI images in normal controls and PDD and VPD patients

(A) Normal subjects, (B) PDD patients, (C) VPD patients. The extent of white matter hyperintensities and multiple infarctions in the basal ganglia in the VPD patients are shown in T2-weighted and FLAIR images. Arrows indicate the infarction.

VariableHcy in PDDHcy in VPD

rprp
TFF3-0.7990.000***-0.7710.000***
ChE activity-0.7320.000***-0.7130.000***
Table 6  Spearman’s rank correlation coefficient (rs) and p-values between TFF3/ChE activity and Hcy Levels in PDD and VPD patients.
VariableTFF3 (PDD)Hcy (PDD)ChE activity (PDD)TFF3 (VPD)Hcy (VPD)ChE activity (VPD)

rprprprprprp
Age0.4230.0910.1380.5500.1680.4330.4740.0870.2570.3750.1340.647
UPDRS-0.126**0.0070.1340.053-0.319*0.019-0.795**0.0010.1930.195-0.367*0.015
Up(Ⅰ)-0.0960.5210.1690.256-0.2700.237-0.1330.5350.0300.220-0.4630.096
Up(Ⅱ)-0.0910.5410.1730.247-0.1340.367-0.4580.0650.1430.289-0.1970.355
Up(Ⅲ)-0.327*0.0250.2830.213-0.397*0.015-0.578*0.0150.0730.274-0.298*0.017
Up(Ⅳ)-0.0520.6450.0420.712-0.0370.742-0.2660.1060.1850.079-0.0370.745
H&Y-0.315*0.0310.342*0.019-0.269*0.025-0.206*0.0470.306*0.026-0.379*0.022
MMSE0.378**0.009-0.364*0.0120.358*0.0140.249*0.026-0.339*0.0300.418**0.008
NMSS0.2410.1030.0060.9780.0650.6810.0860.0740.1270.0710.0490.462
Cardiovascular-0.2050.1680.359*0.015-0.2010.178-0.0940.1380.115*0.014-0.207*0.048
Sleep/Fatigue-0.4780.0840.4170.064-0.0570.755-0.0260.6160.0850.218-0.0410.526
Mood-0.351*0.0150.0670.681-0.391**0.001-0.343*0.0280.0700.601-0.393**0.001
Perceptual problem-0.0580.2180.0800.253-0.1850.105-0.0740.6460.0540.392-0.0350.831
Attention/
memory
-0.118*0.0140.0090.950-0.249*0.026-0.243*0.0290.362*0.013-0.341*0.034
Gastrointestina-0.668**0.009-0.1410.341-0.0690.645-0.769**0.0010.1130.103-0.1120.075
Urinar-0.0450.7630.0180.915-0.0210.894-0.0630.1900.0540.462-0.2050.198
Sexual function-0.2190.1400.0290.846-0.2270.164-0.0830.0710.0730.301-0.2500.115
Miscellaneous-0.0440.350-0.0070.919-0.2080.155-0.4100.0810.2300.119-0.1040.487
Daily dose of L-Dopa (mg)-0.0710.1300.1310.058-0.1000.497-0.0310.5020.0270.695-0.0020.972
Table 7  Spearman’s rank correlation coefficient (rs) and p-values between clinical variables and H&Y, MMSE, NMSS(total/domain) s in PDD and VPD patients.
[1] Delgado-Alvarado M, Gago B, Navalpotro-Gomez I, Jimenez-Urbieta H, Rodriguez-Oroz MC (2016). Biomarkers for dementia and mild cognitive impairment in Parkinson’s disease. Mov Disord, 31: 861-881
[2] Schrag A, Siddiqui UF, Anastasiou Z, Weintraub D, Schott JM (2017). Clinical variables and biomarkers in prediction of cognitive impairment in patients with newly diagnosed Parkinson’s disease: a cohort study. Lancet Neurol, 16: 66-75
[3] Yamanouchi H, Nagura H (1997). Neurological signs and frontal white matter lesions in vascular parkinsonism. A clinicopathologic study. Stroke, 28: 965-969
[4] Xu Y, Wei X, Liu X, Liao J, Lin J, Zhu C,et al. (2015). Low Cerebral Glucose Metabolism: A Potential Predictor for the Severity of Vascular Parkinsonism and Parkinson’s Disease. Aging Dis, 6: 426-436
[5] Zhang L, Yan J, Xu Y, Long L, Zhu C, Chen X,et al. (2011). The combination of homocysteine and C-reactive protein predicts the outcomes of Chinese patients with Parkinson’s disease and vascular parkinsonism. PLoS One, 6: e19333.
[6] Pan M, Gao H, Long L, Xu Y, Liu M, Zou J,et al. (2013). Serum uric acid in patients with Parkinson’s disease and vascular parkinsonism: a cross-sectional study. Neuroimmunomodulation, 20: 19-28
[7] Benitez-Rivero S, Lama MJ, Huertas-Fernandez I, Alvarez de Toledo P, Caceres-Redondo MT, Martin-Rodriguez JF,et al. (2014). Clinical features and neuropsychological profile in vascular parkinsonism. J Neurol Sci, 345: 193-197
[8] Heller J, Dogan I, Schulz JB, Reetz K (2014). Evidence for gender differences in cognition, emotion and quality of life in Parkinson’s disease? Aging Dis, 5: 63-75
[9] Anang JB, Gagnon JF, Bertrand JA, Romenets SR, Latreille V, Panisset M,et al. (2014). Predictors of dementia in Parkinson disease: a prospective cohort study. Neurology, 83: 1253-1260
[10] Euser SM, Hofman A, Westendorp RG, Breteler MM (2009). Serum uric acid and cognitive function and dementia. Brain, 132: 377-382
[11] de Lau LM, Koudstaal PJ, Hofman A, Breteler MM (2005). Serum uric acid levels and the risk of Parkinson disease. Ann Neurol, 58: 797-800
[12] Gonzalez-Aramburu I, Sanchez-Juan P, Jesus S, Gorostidi A, Fernandez-Juan E, Carrillo F,et al. (2013). Genetic variability related to serum uric acid concentration and risk of Parkinson’s disease. Mov Disord, 28: 1737-1740
[13] Thim L, May FE (2005). Structure of mammalian trefoil factors and functional insights. Cell Mol Life Sci, 62: 2956-2973
[14] Jagla W, Wiede A, Dietzmann K, Rutkowski K, Hoffmann W (2000). Co-localization of TFF3 peptide and oxytocin in the human hypothalamus. FASEB J, 14: 1126-1131
[15] Probst JC, Zetzsche T, Weber M, Theilemann P, Skutella T, Landgraf R,et al. (1996). Human intestinal trefoil factor is expressed in human hypothalamus and pituitary: evidence for a novel neuropeptide. FASEB J, 10: 1518-1523
[16] Shi HS, Yin X, Song L, Guo QJ, Luo XH (2012). Neuropeptide Trefoil factor 3 improves learning and retention of novel object recognition memory in mice. Behav Brain Res, 227: 265-269
[17] Paterson RW, Bartlett JW, Blennow K, Fox NC, Shaw LM, Trojanowski JQ,et al. (2014). Cerebrospinal fluid markers including trefoil factor 3 are associated with neurodegeneration in amyloid-positive individuals. Transl Psychiatry, 4: e419.
[18] Rodrigues S, Van Aken E, Van Bocxlaer S, Attoub S, Nguyen QD, Bruyneel E,et al. (2003). Trefoil peptides as proangiogenic factors in vivo and in vitro: implication of cyclooxygenase-2 and EGF receptor signaling. FASEB J, 17: 7-16
[19] Tran CP, Cook GA, Yeomans ND, Thim L, Giraud AS (1999). Trefoil peptide TFF2 (spasmolytic polypeptide) potently accelerates healing and reduces inflammation in a rat model of colitis. Gut, 44: 636-642
[20] Rodriguez-Oroz MC, Lage PM, Sanchez-Mut J, Lamet I, Pagonabarraga J, Toledo JB,et al. (2009). Homocysteine and cognitive impairment in Parkinson’s disease: a biochemical, neuroimaging, and genetic study. Mov Disord, 24: 1437-1444
[21] Shimomura T, Anan F, Masaki T, Umeno Y, Eshima N, Saikawa T,et al. (2011). Homocysteine levels are associated with hippocampus volume in type 2 diabetic patients. Eur J Clin Invest, 41: 751-758
[22] Ray L, Khemka VK, Behera P, Bandyopadhyay K, Pal S, Pal K,et al. (2013). Serum Homocysteine, Dehydroepiandrosterone Sulphate and Lipoprotein (a) in Alzheimer’s Disease and Vascular Dementia. Aging Dis, 4: 57-64
[23] Xie Y, Feng H, Peng S, Xiao J, Zhang J (2017). Association of plasma homocysteine, vitamin B12 and folate levels with cognitive function in Parkinson’s disease: A meta-analysis. Neurosci Lett, 636: 190-195
[24] Kamat PK, Kalani A, Givvimani S, Sathnur PB, Tyagi SC, Tyagi N (2013). Hydrogen sulfide attenuates neurodegeneration and neurovascular dysfunction induced by intracerebral-administered homocysteine in mice. Neuroscience, 252: 302-319
[25] Atack JR, Perry EK, Bonham JR, Candy JM, Perry RH (1986). Molecular forms of acetylcholinesterase and butyrylcholinesterase in the aged human central nervous system. J Neurochem, 47: 263-277
[26] Perry EK, Perry RH, Blessed G, Tomlinson BE (1978). Changes in brain cholinesterases in senile dementia of Alzheimer type. Neuropathol Appl Neurobiol, 4: 273-277
[27] Chipperfield B, Newman PM, Moyes IC (1981). Decreased erythrocyte cholinesterase activity in dementia. Lancet. 1981 Jul 25;2(8239):199.
[28] Bonelli RM, Aschoff A, Niederwieser G, Heuberger C, Jirikowski G (2002). Cerebrospinal fluid tissue transglutaminase as a biochemical marker for Alzheimer’s disease. Neurobiol Dis, 11: 106-110
[29] Carelli-Alinovi C, Dinarelli S, Girasole M, Misiti F (2016). Vascular dysfunction-associated with Alzheimer’s disease. Clin Hemorheol Microcirc. 2016;64(4):679-687.
[30] Ben Assayag E, Shenhar-Tsarfaty S, Ofek K, Soreq L, Bova I, Shopin L,et al. (2010). Serum cholinesterase activities distinguish between stroke patients and controls and predict 12-month mortality. Mol Med, 16: 278-286
[31] Dunet V, Deverdun J, Charroud C, Le Bars E, Molino F, Menjot de Champfleur S,et al. (2016). Cognitive Impairment and Basal Ganglia Functional Connectivity in Vascular Parkinsonism. AJNR Am J Neuroradiol. 37(12):2310-2316.
[32] Firbank MJ, Colloby SJ, Burn DJ, McKeith IG, O’Brien JT (2003). Regional cerebral blood flow in Parkinson’s disease with and without dementia. Neuroimage, 20: 1309-1319
[33] Janelidze S, Lindqvist D, Francardo V, Hall S, Zetterberg H, Blennow K,et al. (2015). Increased CSF biomarkers of angiogenesis in Parkinson disease. Neurology, 85: 1834-1842
[34] Gemma C (2010). Neuroimmunomodulation and Aging. Aging Dis, 1: 169-172
[35] Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y,et al. (2007). Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord, 22: 1689-1707
[36] Zijlmans JC, Daniel SE, Hughes AJ, Revesz T, Lees AJ (2004). Clinicopathological investigation of vascular parkinsonism, including clinical criteria for diagnosis. Mov Disord, 19: 630-640
[37] Fahn S (1987). Drug treatment of hyperkinetic movement disorders. Semin Neurol, 7: 192-208
[38] Hoehn MM, Yahr MD (2001). Parkinsonism: onset, progression, and mortality. 1967. Neurology, 57: S11-26
[39] Li H, Zhang M, Chen L, Zhang J, Pei Z, Hu A,et al. (2010). Nonmotor symptoms are independently associated with impaired health-related quality of life in Chinese patients with Parkinson’s disease. Mov Disord, 25: 2740-2746
[40] Chaudhuri KR, Martinez-Martin P, Brown RG, Sethi K, Stocchi F, Odin P,et al. (2007). The metric properties of a novel non-motor symptoms scale for Parkinson’s disease: Results from an international pilot study. Mov Disord, 22: 1901-1911
[41] 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
[42] Reinoso G, Allen JC, Jr., Au WL, Seah SH, Tay KY, Tan LC (2015). Clinical evolution of Parkinson’s disease and prognostic factors affecting motor progression: 9-year follow-up study. Eur J Neurol, 22: 457-463
[43] Oosterveld LP, Allen JC, Jr., Ng EY, Seah SH, Tay KY, Au WL,et al. (2015). Greater motor progression in patients with Parkinson disease who carry LRRK2 risk variants. Neurology, 85: 1039-1042
[44] Ellman GL, Courtney KD, Andres V, Jr., Feather-Stone RM (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol, 7: 88-95
[45] Winikates J, Jankovic J (1999). Clinical correlates of vascular parkinsonism. Arch Neurol, 56: 98-102
[46] Zijlmans J, Evans A, Fontes F, Katzenschlager R, Gacinovic S, Lees AJ,et al. (2007). [123I] FP-CIT spect study in vascular parkinsonism and Parkinson’s disease. Mov Disord, 22: 1278-1285
[47] Kalra S, Grosset DG, Benamer HT (2010). Differentiating vascular parkinsonism from idiopathic Parkinson’s disease: a systematic review. Mov Disord, 25: 149-156
[48] Saracchi E, Fermi S, Brighina L (2014). Emerging candidate biomarkers for Parkinson’s disease: a review. Aging Dis, 5: 27-34
[49] Sterling NW, Lichtenstein M, Lee EY, Lewis MM, Evans A, Eslinger PJ,et al. (2016). Higher Plasma LDL-Cholesterol is Associated with Preserved Executive and Fine Motor Functions in Parkinson’s Disease. Aging Dis, 7: 237-245
[50] von Bernhardi R, Alarcon R, Mezzano D, Fuentes P, Inestrosa NC (2005). Blood cells cholinesterase activity in early stage Alzheimer’s disease and vascular dementia. Dement Geriatr Cogn Disord, 19: 204-212
[51] Szilagyi AK, Nemeth A, Martini E, Lendvai B, Venter V (1987). Serum and CSF cholinesterase activity in various kinds of dementia. Eur Arch Psychiatry Neurol Sci, 236: 309-311
[52] Bohnen NI, Muller ML, Koeppe RA, Studenski SA, Kilbourn MA, Frey KA,et al. (2009). History of falls in Parkinson disease is associated with reduced cholinergic activity. Neurology, 73: 1670-1676
[53] Prins ND, Den Heijer T, Hofman A, Koudstaal PJ, Jolles J, Clarke R,et al. (2002). Homocysteine and cognitive function in the elderly: the Rotterdam Scan Study. Neurology, 59: 1375-1380
[54] Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB,et al. (2002). Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med, 346: 476-483
[55] Zoccolella S, dell’Aquila C, Specchio LM, Logroscino G, Lamberti P (2010). Elevated homocysteine levels in Parkinson’s Disease: is there anything besides L-dopa treatment? Curr Med Chem, 17: 213-221
[56] Xie Y, Feng H, Peng S, Xiao J, Zhang J (2017). Association of plasma homocysteine, vitamin B12 and folate levels with cognitive function in Parkinson’s disease: A meta-analysis. Neurosci Lett. 636:190-195.
[57] Baccarelli A, Zanobetti A, Martinelli I, Grillo P, Hou L, Lanzani G,et al. (2007). Air pollution, smoking, and plasma homocysteine. Environ Health Perspect, 115: 176-181
[58] Ramsey JM, Cooper JD, Bot M, Guest PC, Lamers F, Weickert CS,et al. (2016). Sex Differences in Serum Markers of Major Depressive Disorder in the Netherlands Study of Depression and Anxiety (NESDA). PLoS One, 11: e0156624.
[59] Liu SQ, Roberts D, Zhang B, Ren Y, Zhang LQ, Wu YH (2013). Trefoil factor 3 as an endocrine neuroprotective factor from the liver in experimental cerebral ischemia/reperfusion injury. PLoS One, 8(10):e77732.
[60] Shinotoh H, Namba H, Yamaguchi M, Fukushi K, Nagatsuka S, Iyo M,et al. (1999). Positron emission tomographic measurement of acetylcholinesterase activity reveals differential loss of ascending cholinergic systems in Parkinson’s disease and progressive supranuclear palsy. Ann Neurol, 46: 62-69
[61] Bjelland I, Tell GS, Vollset SE, Refsum H, Ueland PM (2003). Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study. Arch Gen Psychiatry, 60: 618-626
[62] O’Suilleabhain PE, Sung V, Hernandez C, Lacritz L, Dewey RB, Jr., Bottiglieri T,et al. (2004). Elevated plasma homocysteine level in patients with Parkinson disease: motor, affective, and cognitive associations. Arch Neurol, 61: 865-868
[63] Chen D, Wei X, Zou J, Wang R, Liu X, Xu X,et al. (2015). Contra-Directional Expression of Serum Homocysteine and Uric Acid as Important Biomarkers of Multiple System Atrophy Severity: A Cross-Sectional Study. Front Cell Neurosci, 9:247.
[64] Hooshmand B, Polvikoski T, Kivipelto M, Tanskanen M, Myllykangas L, Erkinjuntti T,et al. (2013). Plasma homocysteine, Alzheimer and cerebrovascular pathology: a population-based autopsy study. Brain, 136: 2707-2716
[65] Obeid R, Herrmann W (2006). Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett, 580: 2994-3005
[66] Seshadri S (2006). Elevated plasma homocysteine levels: risk factor or risk marker for the development of dementia and Alzheimer’s disease? J Alzheimers Dis, 9: 393-398
[67] Hemanth Kumar B, Arun Reddy R, Mahesh Kumar J, Dinesh Kumar B, Diwan PV (2016). Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia. Can J Physiol Pharmacol: 1-11
[68] Choe YM, Sohn BK, Choi HJ, Byun MS, Seo EH, Han JY,et al. (2014). Association of homocysteine with hippocampal volume independent of cerebral amyloid and vascular burden. Neurobiol Aging, 35: 1519-1525
[69] Boldyrev A, Bryushkova E, Mashkina A, Vladychenskaya E (2013). Why is homocysteine toxic for the nervous and immune systems? Curr Aging Sci, 6: 29-36
[70] Streck EL, Vieira PS, Wannmacher CM, Dutra-Filho CS, Wajner M, Wyse AT (2003). In vitro effect of homocysteine on some parameters of oxidative stress in rat hippocampus. Metab Brain Dis, 18: 147-154
[71] Stefanello FM, Franzon R, Tagliari B, Wannmacher C, Wajner M, Wyse AT (2005). Reduction of butyrylcholinesterase activity in rat serum subjected to hyperhomocysteinemia. Metab Brain Dis, 20: 97-103
[72] Streck EL, Delwing D, Tagliari B, Matte C, Wannmacher CM, Wajner M,et al. (2003). Brain energy metabolism is compromised by the metabolites accumulating in homocystinuria. Neurochem Int, 43: 597-602
[73] Scherer EB, Stefanello FM, Mattos C, Netto CA, Wyse AT (2007). Homocysteine reduces cholinesterase activity in rat and human serum. Int J Dev Neurosci, 25: 201-205
[1] Sasanka Chakrabarti,Vineet Kumar Khemka,Anindita Banerjee,Gargi Chatterjee,Anirban Ganguly,Atanu Biswas. Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment[J]. A&D, 2015, 6(4): 282-299.
[2] Tetsuro Hida,Atsushi Harada,Shiro Imagama,Naoki Ishiguro. Managing Sarcopenia and Its Related-Fractures to Improve Quality of Life in Geriatric Populations[J]. Aging and Disease, 2014, 5(4): 226-237.
Viewed
Full text


Abstract

Cited

  Shared   
Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail: editorial@aginganddisease.org
Powered by Beijing Magtech Co. Ltd