Top

Published in:

01-08-2018 | Original Communication

Correlation among olfactory function, motors’ symptoms, cognitive impairment, apathy, and fatigue in patients with Parkinson’s disease

Authors: Carla Masala, Paolo Solla, A. Liscia, G. Defazio, L. Saba, A. Cannas, A. Cavazzana, T. Hummel, A. Haehner

Published in: Journal of Neurology | Issue 8/2018

Abstract

Although Parkinson’s disease (PD) is usually considered as a movement disorder, it is strongly associated with non-motor symptoms (NMS), including smell and taste dysfunctions, cognitive impairment, apathy, fatigue, and autonomic dysregulation. Olfactory deficit is considered the most common NMS in PD preceding the motor symptoms for years. The aim of this study was to investigate olfactory function, cognitive impairment, apathy, and fatigue in patients with PD in comparison with healthy controls, and subsequently to analyse the correlations between these NMS and motor symptoms severity in subjects with PD. One hundred and forty-seven participants were enrolled (96 PD patients, mean age in years 67.5, SD 7.2; 51 healthy controls; mean age 65.1, SD 11.8). Olfactory function was evaluated using the Sniffin’ Sticks test (odor detection threshold, discrimination and identification). The Montreal Cognitive Assessment (MoCA) was used to assess cognitive impairment. Apathy was examined by the self-report version of Starkstein Apathy Scale and fatigue was evaluated with the Parkinson’s Disease Fatigue Scale. PD patients showed severe impairment in odor detection threshold, discrimination, and identification compared to healthy controls. Moreover, in PD patients, apathy and fatigue scores were significantly increased, while MoCA scores were decreased in comparison with controls. Multivariate linear regression analyses showed that both apathy and Unified PD Rating Scale (UPDRS) were associated with odor identification, discrimination and Threshold–Discrimination–Identification (TDI) score. In conclusion, our results reported changes in apathy and motor disability as significant predictors in alterations of odor identification, discrimination and TDI score. Furthermore, these data suggest that olfactory dysfunction might progress in tight relation with motor impairment UPDRS but also with non-motor symptoms such as apathy.

Halliday GM, Stevens CH, Hons B (2011) Glia: initiators and progressors of pathology in Parkinson’ s disease. Mov Disord 26(1):6–17. https://doi.org/10.1002/23455 CrossRefPubMed

Poewe W (2008) Non-motor symptoms in Parkinson’s disease. Eur J Neurol 15(1):14–20. https://doi.org/10.1111/j.1468-1331.2008.02056.x CrossRefPubMed

Schapira AHV, Chaudhuri KR, Jenner P (2017) Non-motor features of Parkinson disease. Nat Rev Neurosci 18(7):435–450. https://doi.org/10.1038/nrn.2017.62 CrossRefPubMed

Ansari KA, Johnson A (1975) Olfactory function in patients with Parkinson’s disease. J Chronic Dis 28(9):493–497. https://doi.org/10.1016/0021-9681(75)90058-2 CrossRefPubMed

Berendse HW, Roos DS, Raijmakers P, Doty RL (2011) Motor and non-motor correlates of olfactory dysfunction in Parkinson’s disease. J Neurol Sci 310(1–2):21–24. https://doi.org/10.1016/j.jns.2011.06.020 CrossRefPubMed

Haehner A, Boesveldt S, Berendse HW, Mackay-Sim A, Fleischmann J, Silburn PA, Johnston AN, Mellick GD, Herting B, Reichmann H, Hummel T (2009) Prevalence of smell loss in Parkinson’s disease—a multicenter study. Parkinsonism Relat Disord 15(7):490–494. https://doi.org/10.1016/j.parkreldis.2008.12.005 CrossRefPubMed

Boesveldt S, Verbaan D, Knol DL, Visser M, van Rooden SM, van Hilten JJ, Berendse HW (2008) A comparative study of odor identification and odor discrimination deficits in Parkinson’s disease. Mov Disord 23(14):1984–1990. https://doi.org/10.1002/mds.22155 CrossRefPubMed

Duda JE (2010) Olfactory system pathology as a model of Lewy neurodegenerative disease. J Neurol Sci 289(1–2):49–54. https://doi.org/10.1016/j.jns.2009.08.042 CrossRefPubMed

Verbaan D, Boesveldt S, Van Rooden SM, Visser M, Marinus J, Macedo MG, Fang Y, Heutink P, Berendse HW, Van Hilten JJ (2008) Is olfactory impairment in Parkinson disease related to phenotypic or genotypic characteristics? Neurology 71(23):1877–1882. https://doi.org/10.1212/01.wnl.0000336651.48596.c7 CrossRefPubMed

10.

Braak H, Del Tredici K, Rüb U, De Vos RAI, Jansen Steur ENH, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24(2):197–211. https://doi.org/10.1016/S0197-4580(02)00065-9 CrossRefPubMed

11.

Croy I, Nordin S, Hummel T (2014) Olfactory disorders and quality of life-an updated review. Chem Senses 39(3):185–194. https://doi.org/10.1093/chemse/bjt072 CrossRefPubMed

12.

Deems DA, Doty RL, Settle RG, Moore-Gillon V, Shaman P, Mester AF, Kimmelman CP, Brightman VJ, Snow JB (1991) Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center. Arch Otolaryngol Head Neck Surg 117:519–528. https://doi.org/10.1001/archotol.1991.01870170065015 CrossRefPubMed

13.

Soudry Y, Lemogne C, Malinvaud D, Consoli SM, Bonfils P (2011) Olfactory system and emotion: common substrates. Eur Ann Otorhinolaryngol Head Neck Dis 128(1):18–23. https://doi.org/10.1016/j.anorl.2010.09.007 CrossRefPubMed

14.

Péron J, Dondaine T, Le Jeune F, Grandjean D, Vérin M (2012) Emotional processing in parkinson’s disease: a systematic review. Mov Disord 27(2):186–199. https://doi.org/10.1002/mds.24025 CrossRefPubMed

15.

Bohnen NI, Kaufer DI, Hendrickson R, Constantine GM, Mathis CA, Moore RY (2007) Cortical cholinergic denervation is associated with depressive symptoms in Parkinson’s disease and parkinsonian dementia. J Neurol Neurosurg Psychiatry 78(6):641–643. https://doi.org/10.1136/jnnp.2006.100073 CrossRefPubMedPubMedCentral

16.

Fullard ME, Tran B, Xie SX, Toledo JB, Scordia C, Linder C, Purri R, Weintraub D, Duda JE, Chahine LM, Morley JF (2016) Olfactory impairment predicts cognitive decline in early Parkinson’s disease. Parkinsonism Relat Disord 25:45–51. https://doi.org/10.1016/j.parkreldis.2016.02.013 CrossRefPubMedPubMedCentral

17.

Postuma R, Gagnon JF (2010) Cognition and olfaction in Parkinson’s disease. Brain 133(12):1–2. https://doi.org/10.1093/brain/awq225 CrossRef

18.

Stephenson R, Houghton D, Sundarararjan S, Doty RL, Stern M, Xie SX, Siderowf A (2010) Odor identification deficits are associated with increased risk of neuropsychiatric complications in patients with Parkinson’s disease. Mov Disord 25(13):2099–2104. https://doi.org/10.1002/mds.23234 CrossRefPubMedPubMedCentral

19.

Cramer CK, Friedman JH, Amick MM (2010) Olfaction and apathy in Parkinson’s disease. Parkinsonism Relat Disord 16(2):124–126. https://doi.org/10.1016/j.parkreldis.2009.09.004 CrossRefPubMed

20.

Hong JY, Sunwoo MK, Ham JH, Lee JJ, Lee PH, Sohn YH (2015) Apathy and olfactory dysfunction in early Parkinson’s disease. J Mov Disord 8(1):21–25. https://doi.org/10.14802/jmd.14029 CrossRefPubMedPubMedCentral

21.

Morley JF, Weintraub D, Mamikonyan E, Moberg PJ, Siderowf AD, Duda JE (2011) Olfactory dysfunction is associated with neuropsychiatric manifestations in Parkinson’s disease. Mov Disord 26(11):2051–2057. https://doi.org/10.1002/mds.23792 CrossRefPubMedPubMedCentral

22.

Doty RL, Deems DA, Stellar S (1988) Olfactory dysfunction in parkinsonism: a general deficit unrelated to neurologic signs, disease stage, or disease duration. Neurology 38(8):1237–1244. https://doi.org/10.1212/WNL.38.8.1237 CrossRefPubMed

23.

Gelb DJ, Oliver E, Gilman S (1999) Diagnostic criteria for Parkinson disease. Arch Neurol 56(1):33–39. https://doi.org/10.1001/archneur.56.1.33 CrossRefPubMed

24.

Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE, McKeith I, Quinn N, Sethi KD, Shults C, Wenning GK (2003) Movement disorders society scientific issues committee report: SIC task force appraisal of clinical diagnostic criteria for Parkinsonian disorders. Mov Disord 18(5):467–486. https://doi.org/10.1002/mds.10459 CrossRefPubMed

25.

Hoehn MM, Yahr MD (1998) Parkinsonism: onset, progression, and mortality. Neurology 50(2):318–318. https://doi.org/10.1212/WNL.50.2.318 CrossRefPubMed

26.

Fahn S, Elton R and Members of the UPDRS Development Committee (1987) The Unified Parkinson’s Disease Rating Scale. In: Fahn S, Marsden CD, Calne DB and Goldstein M (eds) Recent Developments in Parkinson’s Disease, vol. 2, McMellam Health Care Information, Florham Park, pp 153–163

27.

Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G (1997) “Sniffin” sticks’. Olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses 22(1):39–52. https://doi.org/10.1093/chemse/22.1.39 CrossRefPubMed

28.

Hummel T, Kobal G, Gudziol H, Mackay-Sim A (2007) Normative data for the “Sniffin’ Sticks” including tests of odor identification, odor discrimination, and olfactory thresholds: an upgrade based on a group of more than 3000 subjects. Eur Arch Otorhinolaryngol Suppl 264(3):237–243. https://doi.org/10.1007/s00405-006-0173-0 CrossRef

29.

Masala C, Saba L, Cecchini MP, Solla P, Loy F (2017) Olfactory function and age: a Sniffin’ Sticks extended test study performed in Sardinia. Chemosensory Percept. https://doi.org/10.1007/s12078-017-9233-7 CrossRef

30.

Conti S, Bonazzi S, Laiacona M, Masina M, Coralli MV (2015) Montreal Cognitive Assessment (MoCA)-Italian version: regression based norms and equivalent scores. Neurol Sci 36(2):209–214. https://doi.org/10.1007/s10072-014-1921-3 CrossRefPubMed

31.

Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53(4):695–699. https://doi.org/10.1111/j.1532-5415.2005.53221.x CrossRefPubMed

32.

Kluger BM, Pedersen KF, Tysnes OB, Ongre SO, Øygarden B, Herlofson K (2017) Is fatigue associated with cognitive dysfunction in early Parkinson’s disease? Parkinsonism Relat Disord 37:87–91. https://doi.org/10.1016/j.parkreldis.2017.02.005 CrossRefPubMed

33.

Brown RG, Dittner A, Findley L, Wessely SC (2005) The Parkinson Fatigue Scale. Parkinsonism Relat Disord 11(1):49–55. https://doi.org/10.1016/j.parkreldis.2004.07.007 CrossRefPubMed

34.

Haehner A, Hummel T, Reichmann H (2011) Olfactory loss in Parkinson’s disease. Parkinsons Dis 2011:450939. https://doi.org/10.4061/2011/450939 PubMedPubMedCentralCrossRef

35.

Haehner A, Hummel T, Reichmann H (2014) A clinical approach towards smell loss in Parkinson’s disease. J Parkinsons Dis 4(2):189–195. https://doi.org/10.3233/JPD-130278 PubMedCrossRef

36.

Doty RL (2012) Olfaction in Parkinson’s disease and related disorders. Neurobiol Dis 46(3):527–552. https://doi.org/10.1016/j.nbd.2011.10.026 CrossRefPubMed

37.

Hummel T, Nordin S (2005) Olfactory disorders and their consequences for quality of life. Acta Otolaryngol 125(2):116–121. https://doi.org/10.1080/00016480410022787 CrossRefPubMed

38.

Politis M, Wu K, Molloy S, Bain PG, Chaudhuri KR, Piccini P (2010) Parkinson’s disease symptoms: the patient’s perspective. Mov Disord 25(11):1646–1651. https://doi.org/10.1002/mds.23135 CrossRefPubMed

39.

Hurt CS, Alkufri F, Brown RG, Burn DJ, Hindle JV, Landau S, Wilson KC, Samuel M; PROMS-PD study group (2014) Cognition, coping, and outcome in Parkinson’s disease. J Parkinsons Dis 4(2):245–254. https://doi.org/10.3233/JPD-130314 PubMedCrossRef

40.

Opara JA, Brola W, Leonardi M, Błaszczyk B (2012) Quality of life in Parkinson’s disease. J Med Life 5(4):375–381PubMedPubMedCentral

41.

Hawkes CH, Del Tredici K, Braak H (2010) A timeline for Parkinson’s disease. Parkinsonism Relat Disord 16(2):79–84. https://doi.org/10.1016/j.parkreldis.2009.08.007 CrossRefPubMed

42.

Kalia LV, Lang AE (2015) Parkinson’s disease. Lancet 386(9996):896–912. https://doi.org/10.1016/S0140-6736(14)61393-3 CrossRefPubMed

43.

Pearce RKB, Hawkes CH, Daniel SE (1995) The anterior olfactory nucleus in Parkinson’ s disease. Mov Disord 10(3):283–287CrossRefPubMed

44.

Cheng W, Rolls ET, Gu H, Zhang J, Feng J (2015) Autism: reduced connectivity between cortical areas involved in face expression, theory of mind, and the sense of self. Brain 138(5):1382–1393. https://doi.org/10.1093/brain/awv051 CrossRefPubMedPubMedCentral

45.

Wang J, Eslinger PJ, Smith MB, Yang QX (2005) Functional magnetic resonance imaging study of human olfaction and normal aging. J Gerontol A Biol Sci Med Sci 60(4):510–514. https://doi.org/10.1093/gerona/60.4.510 CrossRefPubMed

46.

Wu X, Yu C, Fan F, Zhang K, Zhu C, Wu T, Li K, Chan P (2011) Correlation between progressive changes in piriform cortex and olfactory performance in early Parkinson’s disease. Eur Neurol 66(2):98–105. https://doi.org/10.1159/000329371 CrossRefPubMed

47.

Herting B, Schulze S, Reichmann H, Haehner A, Hummel T (2008) A longitudinal study of olfactory function in patients with idiopathic Parkinson’s disease. J Neurol 255(3):367–370. https://doi.org/10.1007/s00415-008-0665-5 CrossRefPubMed

48.

Müller NG, Machado L, Knight RT (2002) Contributions of Subregions of the prefrontal cortex to working memory: evidence from brain lesions in humans. J Cogn Neurosci 14(5):673–686. https://doi.org/10.1162/08989290260138582 CrossRefPubMed

49.

Altinayar S, Oner S, Can S, Kizilay A, Kamisli S, Sarac K (2014) Olfactory disfunction and its relation olfactory bulb volume in Parkinson’s disease. Eur Rev Med Pharmacol Sci 18(23):3659–3664PubMed

50.

Mueller A, Abolmaali ND, Hakimi AR, Gloeckler T, Herting B, Reichmann H, Hummel T (2005) Olfactory bulb volumes in patients with idiopathic Parkinson’s disease a pilot study. J Neural Transm (Vienna) 112(10):1363–1370. https://doi.org/10.1007/s00702-005-0280-x CrossRef

51.

Paschen L, Schmidt N, Wolff S, Cnyrim C, van Eimeren T, Zeuner KE, Deuschl G, Witt K (2015) The olfactory bulb volume in patients with idiopathic Parkinson’s disease. Eur J Neurol 22(7):1068–1073. https://doi.org/10.1111/ene.12709 CrossRefPubMed

52.

Huisman E, Uylings HBM, Hoogland PV (2004) A 100% increase of dopaminergic cells in the olfactory bulb may explain hyposmia in Parkinson’s Disease. Mov Disord 19:687–692. https://doi.org/10.1002/mds.10713 CrossRefPubMed

53.

Iannilli E (2017) Olfactory impairment in Parkinson’ s disease is a consequence of central nervous system decline. J Neurol 264(6):1236–1246. https://doi.org/10.1007/s00415-017-8521-0 CrossRefPubMed

54.

Morley J, Weintraub D, Mamikonyan E, Moberg PJ, Siderowf AD, Duda JE (2011) Olfactory dysfunction is associated with neuropsychiatric manifestations in Parkinson’s disease. Mov Disord 26(11):2051–2057CrossRefPubMedPubMedCentral

55.

Blonder LX, Slevin JT (2011) Emotional dysfunction in Parkinson’s disease. Behav Neurol 24(3):201–217. https://doi.org/10.3233/BEN-2011-0329 CrossRefPubMedPubMedCentral

56.

Pont-Sunyer C, Hotter A, Gaig C, Seppi K, Compta Y, Katzenschlager R et al, Tolosa E (2015) The onset of nonmotor symptoms in parkinson’s disease (the onset pd study). Mov Disord 30(2):229–237. https://doi.org/10.1002/mds.26077 CrossRefPubMed

57.

Tolosa E, Gaig C, Santamaría J, Compta Y (2009) Diagnosis and the premotor phase of Parkinson disease. Neurology 17(7):S12-20. https://doi.org/10.1212/WNL.0b013e318198db11 72) .CrossRef

58.

Schrag A (2006) Quality of life and depression in Parkinson’s disease. J Neurol Sci 248(1–2):151–157. https://doi.org/10.1016/j.jns.2006.05.030 CrossRefPubMed

59.

Rickards H (2005) Depression in neurological disorders: Parkinson’s disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry 76(1):i48–i52. https://doi.org/10.1136/jnnp.2004.060426 CrossRefPubMedPubMedCentral

Title: Correlation among olfactory function, motors’ symptoms, cognitive impairment, apathy, and fatigue in patients with Parkinson’s disease
Authors: Carla Masala
Paolo Solla
A. Liscia
G. Defazio
L. Saba
A. Cannas
A. Cavazzana
T. Hummel
A. Haehner
Publication date: 01-08-2018
Publisher: Springer Berlin Heidelberg
Published in: Journal of Neurology / Issue 8/2018
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-018-8913-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Correlation among olfactory function, motors’ symptoms, cognitive impairment, apathy, and fatigue in patients with Parkinson’s disease

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 8/2018

Characterisation of tissue-type metabolic content in secondary progressive multiple sclerosis: a magnetic resonance spectroscopic imaging study

Primary lateral sclerosis and the amyotrophic lateral sclerosis–frontotemporal dementia spectrum

Application value of serum biomarkers for choosing memantine therapy for moderate AD

Isolated acute vestibular syndrome due to presumed primary central nervous system lymphoma involving the dorsal medulla

A strategy for managing flu-like symptoms after botulinum toxin injections

Comparison of CT black hole sign and other CT features in predicting hematoma expansion in patients with ICH