Age at onset and Parkinson disease phenotype

Gennaro Pagano, Nicola Ferrara, David J Brooks, Nicola Pavese, Gennaro Pagano, Nicola Ferrara, David J Brooks, Nicola Pavese

Abstract

Objective: To explore clinical phenotype and characteristics of Parkinson disease (PD) at different ages at onset in recently diagnosed patients with untreated PD.

Methods: We have analyzed baseline data from the Parkinson's Progression Markers Initiative database. Four hundred twenty-two patients with a diagnosis of PD confirmed by DaTSCAN imaging were divided into 4 groups according to age at onset (onset younger than 50 years, 50-59 years, 60-69 years, and 70 years or older) and investigated for differences in side, type and localization of symptoms, occurrence/severity of motor and nonmotor features, nigrostriatal function, and CSF biomarkers.

Results: Older age at onset was associated with a more severe motor and nonmotor phenotype, a greater dopaminergic dysfunction on DaTSCAN, and reduction of CSF α-synuclein and total tau. The most common presentation was the combination of 2 or 3 motor symptoms (bradykinesia, resting tremor, and rigidity) with rigidity being more common in the young-onset group. In about 80% of the patients with localized onset, the arm was the most affected part of the body, with no difference across subgroups.

Conclusions: Although the presentation of PD symptoms is similar across age subgroups, the severity of motor and nonmotor features, the impairment of striatal binding, and the levels of CSF biomarkers increase with age at onset. The variability of imaging and nonimaging biomarkers in patients with PD at different ages could hamper the results of future clinical trials.

© 2016 American Academy of Neurology.

References

    1. Lewis SJ, Foltynie T, Blackwell AD, Robbins TW, Owen AM, Barker RA. Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 2005;76:343–348.
    1. Eggers C, Pedrosa DJ, Kahraman D, et al. Parkinson subtypes progress differently in clinical course and imaging pattern. PLoS One 2012;7:e46813.
    1. Selikhova M, Williams DR, Kempster PA, Holton JL, Revesz T, Lees AJ. A clinico-pathological study of subtypes in Parkinson's disease. Brain 2009;132:2947–2957.
    1. Parkkinen L, O'Sullivan SS, Collins C, et al. Disentangling the relationship between Lewy bodies and nigral neuronal loss in Parkinson's disease. J Parkinsons Dis 2011;1:277–286.
    1. Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson's disease: a systematic review and meta-analysis. Mov Disord 2014;29:1583–1590.
    1. Kish SJ, Shannak K, Rajput A, Deck JH, Hornykiewicz O. Aging produces a specific pattern of striatal dopamine loss: implications for the etiology of idiopathic Parkinson's disease. J Neurochem 1992;58:642–648.
    1. de Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet Neurol 2006;5:525–535.
    1. Kempster PA, O'Sullivan SS, Holton JL, Revesz T, Lees AJ. Relationships between age and late progression of Parkinson's disease: a clinico-pathological study. Brain 2010;133:1755–1762.
    1. Critchley M. The neurology of old age. Lancet 1931;1:1221–1230.
    1. Wickremaratchi MM, Ben-Shlomo Y, Morris HR. The effect of onset age on the clinical features of Parkinson's disease. Eur J Neurol 2009;16:450–456.
    1. Quinn N, Critchley P, Marsden CD. Young onset Parkinson's disease. Mov Disord 1987;2:73–91.
    1. Gomez Arevalo G, Jorge R, Garcia S, Scipioni O, Gershanik O. Clinical and pharmacological differences in early- versus late-onset Parkinson's disease. Mov Disord 1997;12:277–284.
    1. Wickremaratchi MM, Perera D, O'Loghlen C, et al. Prevalence and age of onset of Parkinson's disease in Cardiff: a community based cross sectional study and meta-analysis. J Neurol Neurosurg Psychiatry 2009;80:805–807.
    1. Schrag A, Ben-Shlomo Y, Brown R, Marsden CD, Quinn N. Young-onset Parkinson's disease revisited clinical features, natural history, and mortality. Mov Disord 1998;13:885–894.
    1. Golbe LI. Young-onset Parkinson's disease: a clinical review. Neurology 1991;41:168–173.
    1. Wickremaratchi MM, Knipe MD, Sastry BS, et al. The motor phenotype of Parkinson's disease in relation to age at onset. Mov Disord 2011;26:457–463.
    1. Mehanna R, Moore S, Hou JG, Sarwar AI, Lai EC. Comparing clinical features of young onset, middle onset and late onset Parkinson's disease. Parkinsonism Relat Disord 2014;20:530–534.
    1. Szewczyk-Krolikowski K, Tomlinson P, Nithi K, et al. The influence of age and gender on motor and non-motor features of early Parkinson's disease: initial findings from the Oxford Parkinson Disease Center (OPDC) discovery cohort. Parkinsonism Relat Disord 2014;20:99–105.
    1. Parkinson Progression Marker Initiative. The Parkinson Progression Marker Initiative (PPMI). Prog Neurobiol 2011;95:629–635.
    1. Post B, Speelman JD, de Haan RJ; CARPA-study group. Clinical heterogeneity in newly diagnosed Parkinson's disease. J Neurol 2008;255:716–722.
    1. Kang JH, Irwin DJ, Chen-Plotkin AS, et al. ; Parkinson's Progression Markers Initiative. Association of cerebrospinal fluid β-amyloid 1-42, T-tau, P-tau181, and α-synuclein levels with clinical features of drug-naive patients with early Parkinson disease. JAMA Neurol 2013;70:1277–1287.
    1. Berg D, Postuma RB, Bloem B, et al. Time to redefine PD? Introductory statement of the MDS Task Force on the definition of Parkinson's disease. Mov Disord 2014;29:454–462.
    1. Marras C, Lang A. Parkinson's disease subtypes: lost in translation? J Neurol Neurosurg Psychiatry 2013;844:409–415.
    1. van der Hoorn A, Burger H, Leenders KL, de Jong BM. Handedness correlates with the dominant Parkinson side: a systematic review and meta-analysis. Mov Disord 2012;27:206–210.
    1. de la Fuente-Fernández R, Kishore A, Calne DB, Ruth TJ, Stoessl AJ. Nigrostriatal dopamine system and motor lateralization. Behav Brain Res 2000;112:63–68.
    1. Vidailhet M, Bonnet AM, Marconi R, Gouider-Khouja N, Agid Y. Do parkinsonian symptoms and levodopa-induced dyskinesias start in the foot? Neurology 1994;44:1613–1616.
    1. Dickson JM, Grunewald RA. Somatic symptom progression in idiopathic Parkinson's disease. Parkinsonism Relat Disord 2004;10:487–492.
    1. Rowland T, Chan HC, Brooks DJ, Pavese N. Progression of nigrostriatal projection functional loss through the striatum in Parkinson's disease: a clinico-PET correlation. MDS 17th International Congress of Parkinson's Disease and Movement Disorders, Volume 28; June 2013. Abstract Supplement.
    1. Yurkovich M, Avina-Zubieta JA, Thomas J, Gorenchtein M, Lacaille D. A systematic review identifies valid comorbidity indices derived from administrative health data. J Clin Epidemiol 2015;68:3–14.

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