The natural history of treated Parkinson's disease in an incident, community based cohort

被引:179
作者
Evans, Jonathan R. [1 ]
Mason, Sarah L. [1 ]
Williams-Gray, Caroline H. [1 ]
Foltynie, Thomas [2 ]
Brayne, Carol [3 ]
Robbins, Trevor W. [4 ]
Barker, Roger A. [1 ]
机构
[1] Univ Cambridge, Cambridge Ctr Brain Repair, Cambridge CB2 0SD, England
[2] UCL, Inst Neurol, London, England
[3] Univ Cambridge, Inst Publ Hlth, Cambridge CB2 0SD, England
[4] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 0SD, England
关键词
SYDNEY MULTICENTER; MOTOR IMPAIRMENT; PROGRESSION; DEMENTIA; LEVODOPA; PATHOGENESIS; SYNUCLEIN; ONSET; SIGNS; TAU;
D O I
10.1136/jnnp.2011.240366
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background Our understanding of the natural history of idiopathic Parkinson's disease (PD) remains limited. In the era of potential disease modifying therapies, there is an urgent need for studies assessing the natural evolution of treated PD from onset so that relevant outcome measures can be identified for clinical trials. No previous studies have charted progression in unselected patients followed from the point of diagnosis. Methods A representative cohort of 132 PD patients was followed from diagnosis for up to 7.9 years (mean 5.2 years). Comprehensive clinical and neuropsychological evaluations were performed every 18 months. Disease progression was evaluated using well validated clinical measures (motor progression and development of dyskinesia on the Unified PD Rating Scale and Hoehn-Yahr scale, dementia onset according to DSM-IV criteria). Multi-level linear modelling was used to chart the nature and rate of progression in parkinsonian symptoms and signs over time. The prognostic importance of baseline demographic, clinical and genetic variables was evaluated using survival analysis. Results Axial (gait and postural) symptoms evolve more rapidly than other motor features of PD and appear to be the best index of disease progression. Conversely, conventional outcome measures are relatively insensitive to change over time. Earlier onset of postural instability (Hoehn-Yahr stage 3) is strongly associated with increased age at disease onset and has a significant impact on quality of life. Conclusions Dementia risk is associated with increased age, impaired baseline semantic fluency and the MAPT H1/H1 genotype. The efficacy of disease modifying therapies may be more meaningfully assessed in terms of their effects in delaying the major milestones of PD, such as postural instability and dementia, since it is these that have the greatest impact on patients.
引用
收藏
页码:1112 / 1118
页数:7
相关论文
共 49 条
[1]   Neuropathology of dementia in Parkinson's disease: A prospective, community-based study [J].
Aarsland, D ;
Perry, R ;
Brown, A ;
Larsen, JP ;
Ballard, C .
ANNALS OF NEUROLOGY, 2005, 58 (05) :773-776
[2]   The epidemiology of dementia associated with Parkinson disease [J].
Aarsland, Dag ;
Kurz, Martin Wilhelm .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2010, 289 (1-2) :18-22
[3]   Rasagiline, Parkinson neuroprotection, and delayed-start trials Still no satisfaction? [J].
Ahlskog, J. Eric ;
Uitti, Ryan J. .
NEUROLOGY, 2010, 74 (14) :1143-1148
[4]   Pentagon copying is more impaired in dementia with Lewy bodies than in Alzheimer's disease [J].
Ala, TA ;
Hughes, LF ;
Kyrouac, GA ;
Ghobrial, MW ;
Elble, RJ .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2001, 70 (04) :483-488
[5]   Progression of motor impairment and disability in Parkinson disease - A population-based study [J].
Alves, G ;
Wentzel-Larsen, T ;
Aarsland, D ;
Larsen, JP .
NEUROLOGY, 2005, 65 (09) :1436-1441
[6]  
[Anonymous], N ENGL J MED
[7]  
[Anonymous], MULTILEVEL LINEAR MO
[8]  
[Anonymous], ANN NEUROL
[9]  
Bates D., 2009, Mixed-Effects Models in S and S-PLUS
[10]   DOES LONG-TERM AGGRAVATION OF PARKINSONS-DISEASE RESULT FROM NONDOPAMINERGIC LESIONS [J].
BONNET, AM ;
LORIA, Y ;
SAINTHILAIRE, MH ;
LHERMITTE, F ;
AGID, Y .
NEUROLOGY, 1987, 37 (09) :1539-1542