Abstract
Non-motor symptoms (NMSs) are common in Parkinson’s disease (PD) and can precede, sometimes for several years. NMSs include, other than gastrointestinal symptoms like constipation and dysphagia, also hyposmia, weight loss and osteosarcopenia. These three NMSs seem to be inter-related and affect patients’ health and quality of life. Unfortunately, patients with these symptoms usually are not initially seen by a neurologist, and by the time they are consulted, nearly ~ 80% of the dopaminergic neurons in the substantia nigra have died. To date, no guidelines exist for screening, assessment and management of NMSs in general. A better understanding of these specific NMSs, likely in the context of others, will make it possible to approach and optimise the treatment of the motor symptoms thereby enhancing the welfare of PD patients. Identifying the NMSs could be very helpful, and among them, hyposmia, weight loss and osteosarcopenia may play an important role in solving the limitations in the diagnosis of PD. A strict collaboration between general practitioners, clinicians, geriatricians and neurologists can be one approach towards the diagnosis of pre-PD. Waiting until the motor symptoms develop and the patient is finally visited by the neurologist could be too late, considering the catastrophic prognosis of the disease.
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References
Perez-Pardo P, Kliest T, Dodiya HB et al (2017) The gut-brain axis in Parkinson's disease: possibilities for food-based therapies. Eur J Pharmacol 817:86–95
Shidfar F, Babaii Darabkhani P, Yazdanpanah L et al (2016) Assessment of nutritional status in patients with Parkinson's disease and its relationship with severity of the disease. Med J Islam Repub Iran 30:454
Mehta SH, Adler CH (2016) Advances in biomarker research in Parkinson's disease. Curr Neurol Neurosci 1:7. https://doi.org/10.1007/s11910-015-0607-4
Kalia LV, Lang AE (2015) Parkinson's disease. Lancet 386:896–912
Schapira AHV, Chaudhuri KR, Jenner P (2017) Non- motor features of Parkinson disease. Nat Rev Neurosci 18:435–450
Rodríguez-Violante M, Zerón-Martínez R, Cervantes-Arriaga A et al (2017) Who can diagnose Parkinson's disease first? Role of pre-motor symptoms. Arch Med Res 48:221–227
Crepaldi G, Maggi S (2005) Sarcopenia and osteoporosis: a hazardous duet. J Endocrinol Investig 28:66–68
Parkinson J (2002) An essay on the shaking palsy. J Neuropsychiatry Clin Neurosci 14:223–236
Klingelhoefer L, Reichmann H (2017) The gut and nonmotor symptoms in Parkinson's disease. Int Rev Neurobiol 134:787–809
Xiao Q, Chen S, Le W (2014) Hyposmia: a possible biomarker of Parkinson's disease. Neurosci Bull 30:134–140
Kashihara K (2006) Weight loss in Parkinson's disease. J Neurol 253:38–41
Chen H, Zhang SM, Hernán MA et al (2003) Weight loss in Parkinson's disease. Ann Neurol 53:676–679
Sheard JM, Ash S, Silburn PA et al (2011) Prevalence of malnutrition in Parkinson's disease: a systematic review. Nutr Rev 69:520–532. https://doi.org/10.1111/j.1753-4887.2011.00413.x
Prell T, Perner C (2018) Disease specific aspects of malnutrition in neurogeriatric patients. Front Aging Neurosci 10:80. https://doi.org/10.3389/fnagi.2018.00080
Torsney KM, Noyce AJ, Doherty KM et al (2014) Bone health in Parkinson’s disease: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 85:1159–1166
Drey M, Hasmann SE, Krenovsky JP et al (2017) Associations between early markers of Parkinson's disease and sarcopenia. Aging Neurosci Front. https://doi.org/10.3389/fnagi.2017.00053
Tan AH, Hew YC, Lim SY et al (2018) Altered body composition, sarcopenia, frailty, and their clinico-biological correlates, in Parkinson's disease. Parkinsonism Relat Disord 56:58–64. https://doi.org/10.1016/j.parkreldis.2018.06.020
Le W, Dong J, Li S et al (2017) Can biomarkers help the early diagnosis of Parkinson's disease? Neurosci Bull 33:535–542
Ansari KA, Johnson A (1975) Olfactory function in patients with Parkinson's disease. J Chronic Dis 28:493–497
Doty RL (2005) Clinical studies of olfaction. Chem Senses 30:i207–209
Ottaviano G, Frasson G, Nardello E et al (2016) Olfaction deterioration in cognitive disorders in the elderly. Aging Clin Exp Res 28:37–45. https://doi.org/10.1007/s40520-015-0380-x
Braak H, Rüb U, Gai WP et al (2003) Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 110:517–536
Witt M, Bormann K, Gudziol V et al (2009) Biopsies of olfactory epithelium in patients with Parkinson's disease. Mov Disord 24:906–914
Dall'Antonia I, Šonka K, Dušek P (2018) Olfaction and colour vision: what can they tell us about Parkinson's disease? Prague Med Rep 119:85–96
Oh YS, Kim JS, Hwang EJ et al (2018) Striatal dopamine uptake and olfactory dysfunction in patients with early Parkinson's disease. Parkinsonism Relat Disord 56:47–51
Hummel T, Sekinger B, Wolf SR et al (1997) ‘Sniffin’ sticks’: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses 22:39–52
Hawkes CH, Shephard BC, Daniel SE (1997) Olfactory dysfunction in Parkinson's disease. J Neurol Neurosurg Psychiatry 62:436–446
Tarakad A, Jankovic J (2017) Anosmia and Ageusia in Parkinson's disease. Int Rev Neurobiol 133:541–556
Iannilli E, Stephan L, Hummel T (2017) Olfactory impairment in Parkinson's disease is a consequence of central nervous system decline. J Neurol 264:1236–1246
Berendse HW, Roos DS, Raijmakers P et al (2011) Motor and non-motor correlates of olfactory dysfunction in Parkinson's disease. J Neurol Sci 310:21–24
St Louis EK, Boeve AR, Boeve BF (2017) REM sleep behavior disorder in Parkinson's disease and other synucleinopathies. Mov Disord 32:645–658
Haehner A, Hummel T, Reichmann H (2009) Olfactory dysfunction as a diagnostic marker for Parkinson's disease. Expert Rev Neurother 9:1773–1779
Sui X, Zhou C, Li J et al (2019) Hyposmia as a predictive marker of Parkinson's disease: a systematic review and meta-analysis. Biomed Res Int 19:3753786. https://doi.org/10.1155/2019/3753786
Gjerde KV, Müller B, Skeie GO et al (2018) Hyposmia in a simple smell test is associated with accelerated cognitive decline in early Parkinson's disease. Acta Neurol Scand 138:508–514
Welge-Lüssen A (2009) Ageing, neurodegeneration, and olfactory and gustatory loss. B-ENT 5:129–132
Mueller A, Reichman H, Livermore A et al (2002) Olfactory function in idiopathic Parkinson’s disease: results from cross-sectional studies in IPD patients and long-term follow-up of de-novo IPD patients. J Neural Transm 109:805–811
Wenning GK, Shephard B, Hawkes C et al (1995) Olfactory function in atypical parkinsonian syndromes. Acta Neurol Scand 91:247–250
Whitcroft KL, Cuevas M, Haehner A et al (2017) Patterns of olfactory impairment reflect underlying disease etiology. Laryngoscope 127:291–295
Leonhardt B, Tahmasebi R, Jagsch R et al (2019) Awareness of olfactory dysfunction in Parkinson's disease. Neuropsychology 33:633–641. https://doi.org/10.1037/neu0000544
Imoscopi A, Inelmen EM, Sergi G et al (2012) Taste loss in the elderly: epidemiology, causes and consequences. Aging Clin Exp Res 24:570–579
Inelmen EM, Sergi G (2006) Biochemical parameters of nutrition—cachexia and wasting: a modern approach. Springer, New York, pp 59–72
Cecchini MP, Fasano A, Boschi F et al (2015) Taste in Parkinson's disease. J Neurol 262:806–813
Mischley LK (2017) Nutrition and nonmotor symptoms of Parkinson's disease. Int Rev Neurobiol 134:1143–1161
Fink HA, Kuskowski MA, Orwoll ES et al (2005) Association between Parkinson's disease and low bone density and falls in older men: the osteoporotic fractures in men study. J Am Geriatr Soc 53:1559–1564. https://doi.org/10.1111/j.1532-5415.2005.53464.x
Genever RW, Downes TW, Medcalf P (2005) Fracture rates in Parkinson's disease compared with age- and gender-matched controls: a retrospective cohort study. Age Ageing 34:21–24. https://doi.org/10.1093/ageing/afh203
Schneider JL, Fink HA, Ewing SK et al (2008) The association of Parkinson's disease with bone mineral density and fracture in older women. Osteoporos Int 19:1093–1097. https://doi.org/10.1007/s00198-008-0583-5
Wehren LE, Hawkes WG, Orwig DL et al (2003) Gender differences in mortality after hip fracture: the role of infection. J Bone Miner Res 18:2231–2237. https://doi.org/10.1359/jbmr.2003.18.12.2231
Wills AM, Pérez A, Wang J et al (2016) Association between change in body mass index, unified Parkinson's disease rating scale scores, and survival among persons with Parkinson disease: secondary analysis of longitudinal data from NINDS exploratory trials in parkinson disease long-term study 1. JAMA Neurol 73:321–328. https://doi.org/10.1001/jamaneurol.2015.426
Kim HJ, Oh ES, Lee JH et al (2012) Relationship between changes of body mass index (BMI) and cognitive decline in Parkinson's disease (PD). Arch Gerontol Geriatr 55:70–72. https://doi.org/10.1016/j.archger.2011.06.022
Nakamura T, Suzuki M, Ueda M et al (2017) Lower body mass index is associated with orthostatic hypotension in Parkinson's disease. J Neurol Sci 372:14–18. https://doi.org/10.1016/j.jns.2016.11.027
Cheshire WP Jr, Wszolek ZK (2005) Body mass index is reduced early in Parkinson's disease Park. Relat. Disord 11:35–38
Pak K, Shin HK, Kim EJ et al (2018) Weight loss is associated with rapid striatal dopaminergic degeneration in Parkinson's disease. Parkinsonism Relat Disord 51:67–72
Capecci M, Petrelli M, Emanuelli B et al (2013) Rest energy expenditure in Parkinson's disease: role of disease progression and dopaminergic therapy. Parkinsonism Relat Disord 19:238–241
Fiszer U, Michałowska M, Baranowska B et al (2010) Leptin and ghrelin concentrations and weight loss in Parkinson's disease. Acta Neurol Scand 121:230–236. https://doi.org/10.1111/j.1600-0404.2009.01185.x
Bayliss JA, Andrews ZB (2013) Ghrelin is neuroprotective in Parkinson's disease: molecular mechanisms of metabolic neuroprotection. Ther Adv Endocrinol Metab 4:25–36. https://doi.org/10.1177/2042018813479645]
Fasano A, Visanji NP, Liu LWC et al (2015) Pfeiffer gastrointestinal dysfunction in Parkinson's disease. Lancet Neurol 14:625–639
Johanson JF, Kralstein J (2007) Chronic constipation: a survey of the patient perspective. Aliment Pharmacol Ther 25:599–608. https://doi.org/10.1111/j.1365-2036.2006.03238.x
Potulska A, Friedman A, Królicki L et al (2003) Swallowing disorders in Parkinson’s disease. Parkinsonism Relat Disord 9:349–353. https://doi.org/10.1016/S1353-8020(03)00045-2
Roos DS, Oranje OJM, Freriksen AFD et al (2018) Flavor perception and the risk of malnutrition in patients with Parkinson's disease. J Neural Transm 125:925–930
Aarsland D, Beyer MK, Kurz MW (2008) Dementia in Parkinson’s disease. Curr Opin Neurol 21:676–682. https://doi.org/10.1097/WCO.0b013e3283168df0
Dennison EM, Compston JE, Flahive J et al (2012) Effect of co-morbidities on fracture risk: findings from the Global Longitudinal Study of Osteoporosis in Women (GLOW). Bone 50:1288–1293
van den Bos F, Speelman AD, Samson M et al (2013) Parkinson's disease and osteoporosis. Age Ageing 42:156–162
Kamanli A, Ardicoglu O, Ozgocmen S et al (2008) Bone mineral density in patients with Parkinson’s disease. Aging Clin Exp Res 20:277–279
Vaserman N (2005) Parkinson's disease and osteoporosis. Jt Bone Spine 72:282–288
Invernizzi M, Carda S, Viscontini GS et al (2009) Osteoporosis in Parkinson's disease. Parkinsonism Relat Disord 15:339–346
Dargent-Molina P, Poitiers F, Bréart G et al (2000) In elderly women weight is the best predictor of a very low bone mineral density: evidence from the EPIDOS study. Osteoporos Int 11:881–888
Bezza A, Bezza Z, Ouzzif H et al (2008) Prevalence and risk factors of osteoporosis in patients with Parkinson's disease. Rheumatol Int 28:1205–1209
Vetrano DL, Pisciotta MS, Laudisio A et al (2018) Sarcopenia in Parkinson disease: comparison of different criteria and association with disease severity. J Am Med Dir Assoc 19:523–527
Yazar T, Yazar HO, Zayimoğlu E et al (2018) Incidence of sarcopenia and dynapenia according to stage in patients with idiopathic Parkinson's disease. Neurol Sci 39:1415–1421
Scalzo P, Kümmer A, Cardoso F et al (2010) Serum levels of interleukin-6 are elevated in patients with Parkinson’s disease and correlate with physical performance. Neurosci Lett 468:56–58. https://doi.org/10.1016/j.neulet.2009.10.062
Cesari M, Penninx BWJH, Pahor M et al (2004) Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 59:242–248. https://doi.org/10.1093/gerona/59.3.M242
Caviness JN, Smith BE, Stevens JC et al (2002) Motor unit number estimates in idiopathic Parkinson’s disease. Parkinsonism Relat Disord 8:161–164. https://doi.org/10.1016/S1353-8020(01)00007-4
Drey M, Krieger B, Sieber CC et al (2014) Motoneuron loss is associated with sarcopenia. J Am Med Dir Assoc 15:435–439. https://doi.org/10.1016/j.jamda.2014.02.002
Guigoz Y, Vellas B, Garry PJ (1996) Assessing the nutritional status of the elderly: the mini nutritional assessment as part of the geriatric evaluation. Nutr Rev 54:S59–65
Sergi G, Trevisan C, Veronese N et al (2016) Imaging of sarcopenia. Eur J Radiol 85:1519–1524
https://www.sheffield.ac.uk/FRAX/index.aspx. Accessed 18 Jan 2020
Cruz-Jentoft AJ, Baeyens JP, Bauer JM et al (2010) Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing 39:412–423
Sergi G, De Rui M, Stubbs B et al (2017) Measurement of lean body mass using bioelectrical impedance analysis: a consideration of the pros and cons. Aging Clin Exp Res 29:591–597
Pigozzo S, Inelmen EM, Paola Lucato P et al (2017) Vitamina D: aspetti clinici e di laboratorio. Biochim Clin 41:12–22
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De Rui, M., Inelmen, E.M., Trevisan, C. et al. Parkinson’s disease and the non-motor symptoms: hyposmia, weight loss, osteosarcopenia. Aging Clin Exp Res 32, 1211–1218 (2020). https://doi.org/10.1007/s40520-020-01470-x
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DOI: https://doi.org/10.1007/s40520-020-01470-x