OLDER AGE AND PARKINSON’S DISEASE
Keywords:
Parkinson’s disease, aging, motor and non-motor symptoms
Abstract
The etiology of PD remains unclear, with aging identified as the primary risk factor. Epidemiological data show an increasing prevalence of PD with age, affecting 1-2% of persons over 65. The incidence of PD rises rapidly with age, peaking in the eighth decade of life. Motor symptoms in older PD patients are characterized by severe hypokinetic syndrome, axial features, and postural and gait difficulties. Non-motor symptoms, including cognitive impairment, sleep disorders, and dysautonomia, significantly impact quality of life. The prevalence of dementia and frailty increases with age and PD duration. This age group faces a higher risk of side effects from antiparkinsonian therapies, thus therapeutic adjustments are necessary to address the progression of both motor and non-motor symptoms.
The differential diagnosis of PD involves distinguishing it from other parkinsonian syndromes, which can be challenging due to overlapping symptoms and the absence of specific diagnostic tools.
The presence of mild parkinsonian signs in aged population predicts worse outcomes, including dementia, disability, and mortality.
This review provides a comprehensive overview of the clinical manifestations, therapeutic considerations, and differential diagnosis of PD in older adults, highlighting the importance of individualized treatment approaches.
References
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9. Ferreira JJ, Katzenschlager R, Bloem BR, Bonuccelli U, Burn D, Deuschl G, et al. Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson’s disease. Eur J Neurol. 2013;20(1):5–15.
10. Phokaewvarangkul O, Auffret M, Groppa S, Markovic V, Petrovic I, Bhidayasiri R. What was first and what is next in selecting device-aided therapy in Parkinson’s disease? Balancing evidence and experience. J Neural Transm (Vienna). 2024;Epub ahead.
11. de Rijk MC, Breteler MM, Graveland GA, Ott A, Grobbee DE, van der Meché FG, Hofman A. Prevalence of Parkinson’s disease in the elderly: the Rotterdam Study. Neurology. 1995;45:2143–46.
12. Alves G, Forsaa EB, Pedersen KF, Dreetz Gjerstad M, Larsen JP. Epidemiology of Parkinson’s disease. J Neurol. 2008;255(Suppl 5):18–32.
13. Dorsey ER, George BP, Leff B, Willis AW. The coming crisis: obtaining care for the growing burden of neurodegenerative conditions. Neurology. 2013;80(21):1989–96.
14. Zhang ZX, Roman GC. Worldwide occurrence of Parkinsons disease: an updated review. Neuroepidemiology. 1993;12:195–208.
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17. Bower JH, Maraganore DM, McDonnell SK, Rocca WA. Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976–1990. Neurology. 1999;52:1214–20.
18. Hirsch L, Jette N, Frolkis A, Steeves T, Pringsheim T. The Incidence of Parkinson’s Disease: A Systematic Review and Meta-Analysis. Neuroepidemiology. 2016;46(2):292-300.
19. Katzenschlager R, Head J, Schrag A, Ben-Shlomo Y, Evans A, Lees AJ. Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD. Neurology. 2008;71:474–80.
20. Herlofson K, Lie SA, Arsland D, Larsen JP. Mortality and Parkinson disease-A community based study. Neurology. 2004;62:937-945.
21. Morgante L, Salemi G, Meneghini F, Di Rosa AE, Epifanio A, Grigoletto F, et al. Parkinson’s disease survival: a population-based study. Arch Neurol. 2000;57:507-512.
22. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30(12):1591–601.
23. Hess CW, Hallett M. The Phenomenology of Parkinson’s Disease. Semin Neurol. 2017;37(2):109–17.
24. Banford A, Henderson E. Parkinson's disease in older people. Medicine, 2020; 49.1: 56-61.
25. Ebina J, Ebihara S, Kano O. Similarities, differences and overlaps between frailty and Parkinson’s disease. Geriatr Gerontol Int. 2022;22(4):259-270.
26. De Carolis L, Galli S, Bianchini E, Rinaldi D, Raju M, Caliò B, et al. Age at Onset Influences Progression of Motor and Non-Motor Symptoms during the Early Stage of Parkinson’s Disease: A Monocentric Retrospective Study. Brain Sci. 2023;13(2):157.
27. Hess CW, Okun MS. Diagnosing Parkinson Disease. Contin (Minneap Minn). 2016;22(4):1047–63.
28. Bologna M, Espay AJ, Fasano A, Paparella G, Hallett M, Berardelli A. Redefining Bradykinesia. Mov Disord. 2023;38(4):551–7.
29. Mendonça MD, Lampreia T, Miguel R, Caetano A, Barbosa R, Bugalho P. Motor and non-motor symptoms in old-age onset Parkinson’s disease patients. J Neural Transm (Vienna). 2017;124(7):863–7.
30. Bohnen NI, Müller ML, Zarzhevsky N, Koeppe RA, Bogan CW, Kilbourn MR, Frey KA, Albin RL. Leucoaraiosis, nigrostriatal denervation and motor symptoms in Parkinson’s disease. Brain. 2011;134(8):2358–2365.
31. Huang Y, Potter R, Sigurdson W, Santacruz A, Shih S, Ju YE, et al. Effects of age and amyloid deposition on Ab dynamics in the human central nervous system. Arch Neurol. 2012;69(1):51–8.
32. Legacy J, Herndon NE, Wheeler-hegland K, Okun MS, Patel B. A comprehensive review of the diagnosis and treatment of Parkinson’s disease dysphagia and aspiration. Expert Rev Gastroenterol Hepatol. 2020;14(6):411–424.
33. Srivanitchapoom P, Pandey S, Hallett M. Drooling in Parkinson’s Disease: a review. Park Relat Disord. 2014;20(11):1109–18.
34. Dashtipour K, Tafreshi A, Lee J, Crawley B. Speech disorders in Parkinson’s disease : pathophysiology, medical management and surgical approaches. Neurodegener Dis Manag. 2018;8(5):337–48.
35. Martens H, Van Nuffelen G, Wouters K, De Bodt M. Reception of Communicative Functions of Prosody in Hypokinetic Dysarthria due to Parkinson’s Disease. J Park Dis. 2916;6(1):219-29.
36. Doherty KM, van de Warrenburg BP, Peralta MC, Silveira-Moriyama L, Azulay JP, Gershanik OS, Bloem BR. Postural deformities in Parkinson's disease. Lancet Neurol. 2011;10(6):538-49.
37. Fabbri M, Campisi C, Ledda C, Rinaldi D, Tsukita K, Romagnolo A, et al. Incidence and predictors of postural abnormalities in Parkinson’s disease: a PPMI cohort study. J Neurol. 2024;May 25.
38. Stankovic Tutus I. Prospektivna studija napredovanja Parkinsonove bolesti u ranom motornom stadijumu- doktorska disertacija. Med Fak Univ u Beogradu 2021.
39. LeWitt PA, Kymes S, Hauser RA. Parkinson Disease and Orthostatic Hypotension in the Elderly: Recognition and Management of Risk Factors for Falls. Aging Dis. 2020;11(3):679–91.
40. De Pablo-Fernandez E, Tur C, Revesz T, Lees AJ, Holton JL, Warner TT. Association of autonomic dysfunction with disease progression and survival in Parkinson disease. JAMA. 2017;74(8):970-976.
41. Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG. The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord. 2008;23(6):837-44.
42. Ryden LE, Lewis SJG. Parkinson's Disease in the Era of Personalised Medicine: One Size Does Not Fit All. Drugs Aging. 2019 Feb;36(2):103-113.
43. Levy G, Louis ED, Cote L, Perez M, Mejia-Santana H, Andrews H, Harris J, Waters C, Ford B, Frucht S, Fahn S, Marder K. Contribution of aging to the severity of different motor signs in Parkinson disease. Arch Neurol. 2005;62(3):467-72.
44. Lenka A, Padmakumar C, Pal PK. Treatment of Older Parkinson's Disease. Int Rev Neurobiol. 2017;132:381-405.
45. Goetz CG, Schwid SR, Eberly SW, Oakes D, Shoulson I. Parkinson Study Group TEMPO and PRESTO Investigators. Safety of rasagiline in elderly patients with Parkinson disease. Neurology. 2006;66(9):1427-9.
46. Sheu JJ, Tsai MT, Erickson SR, Wu CH. Association between Anticholinergic Medication Use and Risk of Dementia among Patients with Parkinson's Disease. Pharmacotherapy. 2019 Aug;39(8):798-808.
47. Joutsa J, Gardberg M, Röyttä M, Kaasinen V. Diagnostic accuracy of parkinsonism syndromes by general neurologists. Park Relat Disord. 2014;20(8):840–4.
48. Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ. The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain. 2002;125(4):861–70.
49. Meola G. Myotonic dystrophy type 2: the 2020 update. Acta Myol. 2020;39(4):222.
50. Scholz SW, Bras J. Genetics underlying atypical parkinsonism and related neurodegenerative disorders. Int J Mol Sci. 2015;16(10):24629–55.
51. Höglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, Lang AE, et al. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov Disord. 2017;32(6):853–64.
52. Wenning GK, Stankovic I, Vignatelli L, Fanciulli A, Calandra-Buonaura G, Seppi K, et al. The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy. Mov Disord. 2022 Jun;37(6):1131–48.
53. Gibb WR. Accuracy in the clinical diagnosis of parkinsonian syndromes. Postgrad Med J. 1988;64(751):345–51.
54. Köllensperger M, Geser F, Seppi K, Stampfer-Kountchev M, Sawires M, Scherfler C, et al. Red flags for multiple system atrophy. Mov Disord. 2008;23(8):1093–9.
55. Respondek G, Höglinger GU. The phenotypic spectrum of progressive supranuclear palsy. Parkinsonism Relat Disord. 2016;22 Suppl 1:S34-6.
56. Hussein M, Del Toro-Pérez C, Guevara-Sánchez E, Martínez-Sánchez P. Treatment of Vascular Parkinsonism: A Systematic Review. 2023;
57. Kalra S, Grosset DG, Benamer HTS. Differentiating vascular parkinsonism from idiopathic Parkinson’s disease: a systematic review. Mov Disord. 2010 Jan;25(2):149–56.
58. Anand R, Pandey S, Garg RK, Singh Malhotra H, Shrivastava S, Kar SK, et al. Phenomenology, quality of life, and predictors of reversibility in patients with drug-induced movement disorders: a prospective study. CNS Spectr. 2023 Oct;28(5):534–6.
59. Saeed U, Lang AE, Masellis M. Neuroimaging Advances in Parkinson’s Disease and Atypical Parkinsonian Syndromes. Front Neurol. 2020;11.
60. Bennett DA, Beckett LA, Murray AM, Shannon KM, Goetz CG, Pilgrim DM, Evans DA. Prevalence of parkinsonian signs and associated mortality in a community population of older people. N Engl J Med. 1996;334(2):71-6
61. Louis ED, Tang MX, Schupf N, Mayeux R. Functional correlates and prevalence of mild parkinsonian signs in a community population of older people. Arch Neurol. 2005;62(2):297-302
62. Yamanouchi H, Nagura H. Neurological Signs and Frontal White Matter Lesions in Vascular Parkinsonism. Stroke. 1997;28(5):965–969.
63. Lerche S, Hobert M, Brockmann K, Wurster I, Gaenslen A, Hasmann S, Eschweiler GW, Maetzler W, Berg D. Mild parkinsonian signs in the elderly-is there an association with PD? Crossectional findings in 992 individuals. PLoS One. 2014;9(3):e92878.
64. Mahoney JR, Verghese J, Holtzer R, Allali G. The evolution of mild parkinsonian signs in aging. J Neurol. 2014;261:1922–1928.
2. Collier TJ, Kanaan NM, Kordower JH. Aging and Parkinson’s disease: Different sides of the same coin? Mov Disord. 2017;32(7):983–90.
3. Buchman AS, Shulman JM, Nag S, Leurgans SE, Arnold SE, Morris MC, Schneider JA, Bennett DA. Nigral pathology and Parkinsonian signs in elders without Parkinson’s disease. Ann Neurol. 2012;71(2):258–266.
4. Koller W, O’Hara R, Weiner W, Lang A, Nutt J, Agid Y, Bonnet AM, Jankovic J. Relationship of aging to Parkinson’s disease. Adv Neurol. 1987;45:317–21.
5. Aevarsson O, Svanborg A, Skoog I. Seven-year survival rate after age 85 years: relation to Alzheimer disease and vascular dementia. Arch Neurol. 1988;55(9):1226–32.
6. Buchanan SM, Richards M, Schott JM, Schrag A. Mild Parkinsonian Signs: A Systematic Review of Clinical, Imaging, and Pathological Associations. Mov Disord. 2021;36(11):2481-2493.
7. Pagano G, Ferrara N, Brooks DJ, Pavese N. Age at onset and Parkinson disease phenotype. Neurology. 2016;86(15):1400–7.
8. Diederich NJ, Moore CG, Leurgans SE, Chmura TA, Goetz CG. Parkinson disease with old-age onset: a comparative study with subjects with middle-age onset. Arch Neurol. 2003;60(4):529-33.
9. Ferreira JJ, Katzenschlager R, Bloem BR, Bonuccelli U, Burn D, Deuschl G, et al. Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson’s disease. Eur J Neurol. 2013;20(1):5–15.
10. Phokaewvarangkul O, Auffret M, Groppa S, Markovic V, Petrovic I, Bhidayasiri R. What was first and what is next in selecting device-aided therapy in Parkinson’s disease? Balancing evidence and experience. J Neural Transm (Vienna). 2024;Epub ahead.
11. de Rijk MC, Breteler MM, Graveland GA, Ott A, Grobbee DE, van der Meché FG, Hofman A. Prevalence of Parkinson’s disease in the elderly: the Rotterdam Study. Neurology. 1995;45:2143–46.
12. Alves G, Forsaa EB, Pedersen KF, Dreetz Gjerstad M, Larsen JP. Epidemiology of Parkinson’s disease. J Neurol. 2008;255(Suppl 5):18–32.
13. Dorsey ER, George BP, Leff B, Willis AW. The coming crisis: obtaining care for the growing burden of neurodegenerative conditions. Neurology. 2013;80(21):1989–96.
14. Zhang ZX, Roman GC. Worldwide occurrence of Parkinsons disease: an updated review. Neuroepidemiology. 1993;12:195–208.
15. de Rijk MC, Launer LJ, Berger K, Breteler MM, Dartigues JF, Baldereschi M, et al. Prevalence of Parkinson’s disease in Europe: a collaborative study of population-based cohorts-Neuroloic Diseases in Elderly Research Group. Neurology. 2000;54:s21-23.
16. Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2014;29(13):1583–90.
17. Bower JH, Maraganore DM, McDonnell SK, Rocca WA. Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976–1990. Neurology. 1999;52:1214–20.
18. Hirsch L, Jette N, Frolkis A, Steeves T, Pringsheim T. The Incidence of Parkinson’s Disease: A Systematic Review and Meta-Analysis. Neuroepidemiology. 2016;46(2):292-300.
19. Katzenschlager R, Head J, Schrag A, Ben-Shlomo Y, Evans A, Lees AJ. Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD. Neurology. 2008;71:474–80.
20. Herlofson K, Lie SA, Arsland D, Larsen JP. Mortality and Parkinson disease-A community based study. Neurology. 2004;62:937-945.
21. Morgante L, Salemi G, Meneghini F, Di Rosa AE, Epifanio A, Grigoletto F, et al. Parkinson’s disease survival: a population-based study. Arch Neurol. 2000;57:507-512.
22. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30(12):1591–601.
23. Hess CW, Hallett M. The Phenomenology of Parkinson’s Disease. Semin Neurol. 2017;37(2):109–17.
24. Banford A, Henderson E. Parkinson's disease in older people. Medicine, 2020; 49.1: 56-61.
25. Ebina J, Ebihara S, Kano O. Similarities, differences and overlaps between frailty and Parkinson’s disease. Geriatr Gerontol Int. 2022;22(4):259-270.
26. De Carolis L, Galli S, Bianchini E, Rinaldi D, Raju M, Caliò B, et al. Age at Onset Influences Progression of Motor and Non-Motor Symptoms during the Early Stage of Parkinson’s Disease: A Monocentric Retrospective Study. Brain Sci. 2023;13(2):157.
27. Hess CW, Okun MS. Diagnosing Parkinson Disease. Contin (Minneap Minn). 2016;22(4):1047–63.
28. Bologna M, Espay AJ, Fasano A, Paparella G, Hallett M, Berardelli A. Redefining Bradykinesia. Mov Disord. 2023;38(4):551–7.
29. Mendonça MD, Lampreia T, Miguel R, Caetano A, Barbosa R, Bugalho P. Motor and non-motor symptoms in old-age onset Parkinson’s disease patients. J Neural Transm (Vienna). 2017;124(7):863–7.
30. Bohnen NI, Müller ML, Zarzhevsky N, Koeppe RA, Bogan CW, Kilbourn MR, Frey KA, Albin RL. Leucoaraiosis, nigrostriatal denervation and motor symptoms in Parkinson’s disease. Brain. 2011;134(8):2358–2365.
31. Huang Y, Potter R, Sigurdson W, Santacruz A, Shih S, Ju YE, et al. Effects of age and amyloid deposition on Ab dynamics in the human central nervous system. Arch Neurol. 2012;69(1):51–8.
32. Legacy J, Herndon NE, Wheeler-hegland K, Okun MS, Patel B. A comprehensive review of the diagnosis and treatment of Parkinson’s disease dysphagia and aspiration. Expert Rev Gastroenterol Hepatol. 2020;14(6):411–424.
33. Srivanitchapoom P, Pandey S, Hallett M. Drooling in Parkinson’s Disease: a review. Park Relat Disord. 2014;20(11):1109–18.
34. Dashtipour K, Tafreshi A, Lee J, Crawley B. Speech disorders in Parkinson’s disease : pathophysiology, medical management and surgical approaches. Neurodegener Dis Manag. 2018;8(5):337–48.
35. Martens H, Van Nuffelen G, Wouters K, De Bodt M. Reception of Communicative Functions of Prosody in Hypokinetic Dysarthria due to Parkinson’s Disease. J Park Dis. 2916;6(1):219-29.
36. Doherty KM, van de Warrenburg BP, Peralta MC, Silveira-Moriyama L, Azulay JP, Gershanik OS, Bloem BR. Postural deformities in Parkinson's disease. Lancet Neurol. 2011;10(6):538-49.
37. Fabbri M, Campisi C, Ledda C, Rinaldi D, Tsukita K, Romagnolo A, et al. Incidence and predictors of postural abnormalities in Parkinson’s disease: a PPMI cohort study. J Neurol. 2024;May 25.
38. Stankovic Tutus I. Prospektivna studija napredovanja Parkinsonove bolesti u ranom motornom stadijumu- doktorska disertacija. Med Fak Univ u Beogradu 2021.
39. LeWitt PA, Kymes S, Hauser RA. Parkinson Disease and Orthostatic Hypotension in the Elderly: Recognition and Management of Risk Factors for Falls. Aging Dis. 2020;11(3):679–91.
40. De Pablo-Fernandez E, Tur C, Revesz T, Lees AJ, Holton JL, Warner TT. Association of autonomic dysfunction with disease progression and survival in Parkinson disease. JAMA. 2017;74(8):970-976.
41. Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG. The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord. 2008;23(6):837-44.
42. Ryden LE, Lewis SJG. Parkinson's Disease in the Era of Personalised Medicine: One Size Does Not Fit All. Drugs Aging. 2019 Feb;36(2):103-113.
43. Levy G, Louis ED, Cote L, Perez M, Mejia-Santana H, Andrews H, Harris J, Waters C, Ford B, Frucht S, Fahn S, Marder K. Contribution of aging to the severity of different motor signs in Parkinson disease. Arch Neurol. 2005;62(3):467-72.
44. Lenka A, Padmakumar C, Pal PK. Treatment of Older Parkinson's Disease. Int Rev Neurobiol. 2017;132:381-405.
45. Goetz CG, Schwid SR, Eberly SW, Oakes D, Shoulson I. Parkinson Study Group TEMPO and PRESTO Investigators. Safety of rasagiline in elderly patients with Parkinson disease. Neurology. 2006;66(9):1427-9.
46. Sheu JJ, Tsai MT, Erickson SR, Wu CH. Association between Anticholinergic Medication Use and Risk of Dementia among Patients with Parkinson's Disease. Pharmacotherapy. 2019 Aug;39(8):798-808.
47. Joutsa J, Gardberg M, Röyttä M, Kaasinen V. Diagnostic accuracy of parkinsonism syndromes by general neurologists. Park Relat Disord. 2014;20(8):840–4.
48. Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ. The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain. 2002;125(4):861–70.
49. Meola G. Myotonic dystrophy type 2: the 2020 update. Acta Myol. 2020;39(4):222.
50. Scholz SW, Bras J. Genetics underlying atypical parkinsonism and related neurodegenerative disorders. Int J Mol Sci. 2015;16(10):24629–55.
51. Höglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, Lang AE, et al. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov Disord. 2017;32(6):853–64.
52. Wenning GK, Stankovic I, Vignatelli L, Fanciulli A, Calandra-Buonaura G, Seppi K, et al. The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy. Mov Disord. 2022 Jun;37(6):1131–48.
53. Gibb WR. Accuracy in the clinical diagnosis of parkinsonian syndromes. Postgrad Med J. 1988;64(751):345–51.
54. Köllensperger M, Geser F, Seppi K, Stampfer-Kountchev M, Sawires M, Scherfler C, et al. Red flags for multiple system atrophy. Mov Disord. 2008;23(8):1093–9.
55. Respondek G, Höglinger GU. The phenotypic spectrum of progressive supranuclear palsy. Parkinsonism Relat Disord. 2016;22 Suppl 1:S34-6.
56. Hussein M, Del Toro-Pérez C, Guevara-Sánchez E, Martínez-Sánchez P. Treatment of Vascular Parkinsonism: A Systematic Review. 2023;
57. Kalra S, Grosset DG, Benamer HTS. Differentiating vascular parkinsonism from idiopathic Parkinson’s disease: a systematic review. Mov Disord. 2010 Jan;25(2):149–56.
58. Anand R, Pandey S, Garg RK, Singh Malhotra H, Shrivastava S, Kar SK, et al. Phenomenology, quality of life, and predictors of reversibility in patients with drug-induced movement disorders: a prospective study. CNS Spectr. 2023 Oct;28(5):534–6.
59. Saeed U, Lang AE, Masellis M. Neuroimaging Advances in Parkinson’s Disease and Atypical Parkinsonian Syndromes. Front Neurol. 2020;11.
60. Bennett DA, Beckett LA, Murray AM, Shannon KM, Goetz CG, Pilgrim DM, Evans DA. Prevalence of parkinsonian signs and associated mortality in a community population of older people. N Engl J Med. 1996;334(2):71-6
61. Louis ED, Tang MX, Schupf N, Mayeux R. Functional correlates and prevalence of mild parkinsonian signs in a community population of older people. Arch Neurol. 2005;62(2):297-302
62. Yamanouchi H, Nagura H. Neurological Signs and Frontal White Matter Lesions in Vascular Parkinsonism. Stroke. 1997;28(5):965–969.
63. Lerche S, Hobert M, Brockmann K, Wurster I, Gaenslen A, Hasmann S, Eschweiler GW, Maetzler W, Berg D. Mild parkinsonian signs in the elderly-is there an association with PD? Crossectional findings in 992 individuals. PLoS One. 2014;9(3):e92878.
64. Mahoney JR, Verghese J, Holtzer R, Allali G. The evolution of mild parkinsonian signs in aging. J Neurol. 2014;261:1922–1928.