History of falls in Parkinson disease is associated with reduced cholinergic activity

被引:293
作者
Bohnen, N. I. [1 ,2 ,3 ,4 ]
Mueller, M. L. T. M.
Koeppe, R. A.
Studenski, S. A. [5 ,6 ]
Kilbourn, M. A.
Frey, K. A. [2 ]
Albin, R. L. [2 ,3 ,4 ]
机构
[1] Univ Michigan, Funct Neuroimaging Cognit & Mobil Lab, Dept Radiol, Div Nucl Med, Ann Arbor, MI 48105 USA
[2] Univ Michigan, Dept Neurol, Ann Arbor, MI 48105 USA
[3] VAAAHS, Neurol Serv, Ann Arbor, MI USA
[4] VAAAHS, GRECC, Ann Arbor, MI USA
[5] VAPHS, Geriatr Serv, Pittsburgh, PA USA
[6] VAPHS, GRECC, Pittsburgh, PA USA
关键词
CEREBRAL ACETYLCHOLINESTERASE ACTIVITY; PROGRESSIVE SUPRANUCLEAR PALSY; POSITRON-EMISSION-TOMOGRAPHY; PEDUNCULOPONTINE NUCLEUS; MOVEMENT-DISORDERS; DEMENTIA; GAIT; INNERVATION; ATTENTION; BRAIN;
D O I
10.1212/WNL.0b013e3181c1ded6
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: To investigate the relationships between history of falls and cholinergic vs dopaminergic denervation in patients with Parkinson disease (PD). Background: There is a need to explore nondopaminergic mechanisms of gait control as the majority of motor impairments associated with falls in PD are resistant to dopaminergic treatment. Alterations in cholinergic neurotransmission in PD may be implicated because of evidence that gait control depends on cholinergic system-mediated higher-level cortical and subcortical processing, including pedunculopontine nucleus (PPN) function. Methods: In this cross-sectional study, 44 patients with PD (Hoehn & Yahr stages I-III) without dementia and 15 control subjects underwent a clinical assessment and [(11)C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) and [(11)C] dihydrotetrabenazine (DTBZ) vesicular monoamine transporter type 2 (VMAT2) brain PET imaging. Results: Seventeen patients (38.6%) reported a history of falls and 27 patients had no falls. Analysis of covariance of the cortical AChE hydrolysis rates demonstrated reduced cortical AChE in the PD fallers group (-12.3%) followed by the PD nonfallers (-6.6%) compared to control subjects (F = 7.22, p = 0.0004). Thalamic AChE activity was lower only in the PD fallers group (-11.8%; F = 4.36, p = 0.008). There was no significant difference in nigrostriatal dopaminergic activity between PD fallers and nonfallers. Conclusions: Unlike nigrostriatal dopaminergic denervation, cholinergic hypofunction is associated with fall status in Parkinson disease (PD). Thalamic AChE activity in part represents cholinergic output of the pedunculopontine nucleus (PPN), a key node for gait control. Our results are consistent with other data indicating that PPN degeneration is a major factor leading to impaired postural control and gait dysfunction in PD. Neurology (R) 2009; 73: 1670-1676
引用
收藏
页码:1670 / 1676
页数:7
相关论文
共 31 条
[1]   Changes in motor subtype and risk for incident dementia in Parkinson's disease [J].
Alves, Guido ;
Petter Larsen, Jan ;
Emre, Murat ;
Wentzel-Larsen, Tore ;
Aarsland, Dag .
MOVEMENT DISORDERS, 2006, 21 (08) :1123-1130
[2]   An update on falls [J].
Bloem, BR ;
Steijns, JAG ;
Smits-Engelsman, BC .
CURRENT OPINION IN NEUROLOGY, 2003, 16 (01) :15-26
[3]   Degree of inhibition of cortical acetylcholinesterase activity and cognitive effects by donepezil treatment in Alzheimer's disease [J].
Bohnen, NI ;
Kaufer, DI ;
Hendrickson, R ;
Ivanco, LS ;
Lopresti, BJ ;
Koeppe, RA ;
Meltzer, CC ;
Constantine, G ;
Davis, JG ;
Mathis, CA ;
DeKosky, ST ;
Moore, RY .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2005, 76 (03) :315-319
[4]   Cognitive correlates of cortical cholinergic denervation in Parkinson's disease and parkinsonian dementia [J].
Bohnen, NI ;
Kaufer, DI ;
Hendrickson, R ;
Ivanco, LS ;
Lopresti, BJ ;
Constantine, GM ;
Mathis, CA ;
Davis, JG ;
Moore, RY ;
DeKosky, ST .
JOURNAL OF NEUROLOGY, 2006, 253 (02) :242-247
[5]   Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease - An in vivo positron emission tomographic study [J].
Bohnen, NI ;
Kaufer, DI ;
Ivanco, LS ;
Lopresti, B ;
Koeppe, RA ;
Davis, JG ;
Mathis, CA ;
Moore, RY ;
DeKosky, ST .
ARCHIVES OF NEUROLOGY, 2003, 60 (12) :1745-1748
[6]   Postural control, gait, and dopamine functions in parkinsonian movement disorders [J].
Bohnen, Nicolaas I. ;
Cham, Rakie .
CLINICS IN GERIATRIC MEDICINE, 2006, 22 (04) :797-+
[7]  
Fahn S., 1987, RECENT DEV PARKINSON, V2, P293, DOI DOI 10.2490/JJRMC.47.791
[8]   MINI-MENTAL STATE - PRACTICAL METHOD FOR GRADING COGNITIVE STATE OF PATIENTS FOR CLINICIAN [J].
FOLSTEIN, MF ;
FOLSTEIN, SE ;
MCHUGH, PR .
JOURNAL OF PSYCHIATRIC RESEARCH, 1975, 12 (03) :189-198
[9]   A home diary to assess functional status in patients with Parkinson's disease with motor fluctuations and dyskinesia [J].
Hauser, RA ;
Friedlander, J ;
Zesiewicz, TA ;
Adler, CH ;
Seeberger, LC ;
O'Brien, CF ;
Molho, ES ;
Factor, SA .
CLINICAL NEUROPHARMACOLOGY, 2000, 23 (02) :75-81
[10]   CHOLINERGIC INNERVATION OF THE HUMAN THALAMUS - DUAL ORIGIN AND DIFFERENTIAL NUCLEAR-DISTRIBUTION [J].
HECKERS, S ;
GEULA, C ;
MESULAM, MM .
JOURNAL OF COMPARATIVE NEUROLOGY, 1992, 325 (01) :68-82