Abstract
Among patients with Parkinson’s disease (PD), a wide range of motor and non-motor symptoms (NMS) are evident. PD is often divided into tremor dominant (TD) and postural instability gait difficulty (PIGD) motor subtypes. We evaluated the effect of disease duration and aimed to characterize whether there are differences in the deterioration of cognitive function and other NMS between the PIGD and TD subtypes. Sixty-three subjects were re-evaluated at the follow-up visit about 5 years after baseline examination. Cognitive function and other NMS were assessed. At follow-up, the PIGD and TD groups were similar with respect to medications, comorbidities and disease-related symptoms. There was a significant time effect for all measures, indicating deterioration and worsening in both groups. However, cognitive scores, particularly those related to executive function, became significantly worse in the PIGD with a more moderate decrease in the TD group. For example, the computerized global cognitive score declined in the PIGD group from 94.21 ± 11.88 to 83.91 ± 13.76, p < 0.001. This decline was significantly larger (p = 0.03) than the decrease observed in the TD group (96.56 ± 10.29 to 92.21 ± 14.20, p = 0.047). A significant group × time interaction effect was found for the change in global cognitive score (p = 0.047), the executive function index (p = 0.002) and accuracy on a motor-cognitive catch game (p = 0.008). In contrast, several NMS including depression, health-related quality of life and fear of falling deteriorated in parallel in both subtypes, with no interaction effect. The present findings highlight the difference in the natural history of the disease between the two PD “motor” subtypes. While the PIGD group demonstrated a significant cognitive decline, especially in executive functions, a more favorable course was observed in the TD subtype. This behavior was not seen in regards to the other NMS.
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References
Jankovic J (2008) Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 79:368–376
Chaudhuri KR, Odin P, Antonini A, Martinez-Martin P (2011) Parkinson’s disease: the non-motor issues. Parkinsonism Relat Disord 17:717–723
Duncan GW, Khoo TK, Yarnall AJ, O’Brien JT, Coleman SY, Brooks DJ, Barker RA, Burn DJ (2014) Health-related quality of life in early Parkinson’s disease: the impact of nonmotor symptoms. Mov Disord 29:195–202
Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM, Chaudhuri KR (2011) The impact of non-motor symptoms on health-related quality of life of patients with Parkinson’s disease. Mov Disord 26:399–406
Swick TJ, Friedman JH, Chaudhuri KR, Surmann E, Boroojerdi B, Moran K, Ghys L, Trenkwalder C (2014) Associations between severity of motor function and nonmotor symptoms in Parkinson’s disease: a post hoc analysis of the RECOVER Study. Eur Neurol 71:140–147
Ray CK, Rojo JM, Schapira AH, Brooks DJ, Stocchi F, Odin P, Antonini A, Brown RJ, Martinez-Martin P (2013) A proposal for a comprehensive grading of Parkinson’s disease severity combining motor and non-motor assessments: meeting an unmet need. PLoS One 8:e57221
Zis P, Martinez-Martin P, Sauerbier A, Rizos A, Sharma JC, Worth PF, Sophia R, Silverdale M, Chaudhuri KR (2015) Non-motor symptoms burden in treated and untreated early Parkinson’s disease patients: argument for non-motor subtypes. Eur J Neurol 22:1145–1150
Dubois B, Pillon B (1997) Cognitive deficits in Parkinson’s disease. J Neurol 244:2–8
Herman T, Weiss A, Brozgol M, Wilf-Yarkoni A, Giladi N, Hausdorff JM (2015) Cognitive function and other non-motor features in non-demented Parkinson’s disease motor subtypes. J Neural Transm 122:1115–1124
Linder J, Birgander R, Olsson I, Riklund K, Larsson AK, Edstrom M, Stenlund H, Forsgren L (2009) Degenerative changes were common in brain magnetic resonance imaging in patients with newly diagnosed Parkinson’s disease in a population-based cohort. J Neurol 256:1671–1680
Muslimovic D, Post B, Speelman JD, Schmand B (2005) Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology 65:1239–1245
Verbaan D, Marinus J, Visser M, van Rooden SM, Stiggelbout AM, Middelkoop HA, van Hilten JJ (2007) Cognitive impairment in Parkinson’s disease. J Neurol Neurosurg Psychiatry 78:1182–1187
Dirnberger G, Jahanshahi M (2013) Executive dysfunction in Parkinson’s disease: a review. J Neuropsychol 7:193–224
Kudlicka A, Clare L, Hindle JV (2011) Executive functions in Parkinson’s disease: systematic review and meta-analysis. Mov Disord 26:2305–2315
Taylor JP, Rowan EN, Lett D, O’Brien JT, McKeith IG, Burn DJ (2008) Poor attentional function predicts cognitive decline in patients with non-demented Parkinson’s disease independent of motor phenotype. J Neurol Neurosurg Psychiatry 79:1318–1323
Hoops S, Nazem S, Siderowf AD, Duda JE, Xie SX, Stern MB, Weintraub D (2009) Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease. Neurology 73:1738–1745
Jankovic J, McDermott M, Carter J, Gauthier S, Goetz C, Golbe L, Huber S, Koller W, Olanow C, Shoulson I (1990) Variable expression of Parkinson’s disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. Neurology 40:1529–1534
Fahn S, Elton R, Members of the UPDRS development committee (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Calne D, Goldstein M (eds) Recent developments in Parkinson’s disease. Macmillan Health Care Information, Florham Park, pp 153–163
Selikhova M, Kempster PA, Revesz T, Holton JL, Lees AJ (2013) Neuropathological findings in benign tremulous parkinsonism. Mov Disord 28:145–152
Stebbins GT, Goetz CG, Burn DJ, Jankovic J, Khoo TK, Tilley BC (2013) How to identify tremor dominant and postural instability/gait difficulty groups with the movement disorder society unified Parkinson’s disease rating scale: comparison with the unified Parkinson’s disease rating scale. Mov Disord 28:668–670
Allcock LM, Kenny RA, Burn DJ (2006) Clinical phenotype of subjects with Parkinson’s disease and orthostatic hypotension: autonomic symptom and demographic comparison. Mov Disord 21:1851–1855
Ba F, Obaid M, Wieler M, Camicioli R, Martin WR (2016) Parkinson disease: the relationship between non-motor symptoms and motor phenotype. Can J Neurol Sci 43:261–267
Burn DJ, Landau S, Hindle JV, Samuel M, Wilson KC, Hurt CS, Brown RG (2012) Parkinson’s disease motor subtypes and mood. Mov Disord 27:379–386
Reijnders JS, Ehrt U, Lousberg R, Aarsland D, Leentjens AF (2009) The association between motor subtypes and psychopathology in Parkinson’s disease. Parkinsonism Relat Disord 15:379–382
Tremblay C, Achim AM, Macoir J, Monetta L (2013) The heterogeneity of cognitive symptoms in Parkinson’s disease: a meta-analysis. J Neurol Neurosurg Psychiatry 84:1265–1272
van der Hoek TC, Bus BA, Matui P, van der Marck MA, Esselink RA, Tendolkar I (2011) Prevalence of depression in Parkinson’s disease: effects of disease stage, motor subtype and gender. J Neurol Sci 310:220–224
Khoo TK, Yarnall AJ, Duncan GW, Coleman S, O’Brien JT, Brooks DJ, Barker RA, Burn DJ (2013) The spectrum of nonmotor symptoms in early Parkinson disease. Neurology 80:276–281
Wu Y, Guo XY, Wei QQ, Ou RW, Song W, Cao B, Zhao B, Shang HF (2016) Non-motor symptoms and quality of life in tremor dominant vs postural instability gait disorder Parkinson’s disease patients. Acta Neurol Scand 133:330–337
Rajput AH, Voll A, Rajput ML, Robinson CA, Rajput A (2009) Course in Parkinson disease subtypes: a 39-year clinicopathologic study. Neurology 73:206–212
Burn DJ, Rowan EN, Allan LM, Molloy S, O’Brien JT, McKeith IG (2006) Motor subtype and cognitive decline in Parkinson’s disease, Parkinson’s disease with dementia, and dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 77:585–589
Domellof ME, Elgh E, Forsgren L (2011) The relation between cognition and motor dysfunction in drug-naive newly diagnosed patients with Parkinson’s disease. Mov Disord 26:2183–2189
Lyros E, Messinis L, Papathanasopoulos P (2008) Does motor subtype influence neurocognitive performance in Parkinson’s disease without dementia? Eur J Neurol 15:262–267
Herman T, Weiss A, Brozgol M, Giladi N, Hausdorff JM (2014) Gait and balance in Parkinson’s disease subtypes: objective measures and classification considerations. J Neurol 261:2401–2410
Rosenberg-Katz K, Herman T, Jacob Y, Giladi N, Hendler T, Hausdorff JM (2013) Gray matter atrophy distinguishes between Parkinson disease motor subtypes. Neurology 80:1476–1484
Goetz CG, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stebbins GT, Stern MB, Tilley BC, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, Van Hilten JJ, LaPelle N (2007) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): process, format, and clinimetric testing plan. Mov Disord 22:41–47
Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N (2008) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 23:2129–2170
Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE (2010) Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord 25:2649–2653
Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198
Nasreddine ZS, Phillips NA, Bedirian 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 53:695–699
Doniger GM, Simon ES, Schweiger A (2008) Adjustment of cognitive scores with a co-normed estimate of premorbid intelligence: implementation using mindstreams computerized testing. Appl Neuropsychol 15:250–263
Hausdorff JM, Doniger GM, Springer S, Yogev G, Giladi N, Simon ES (2006) A common cognitive profile in elderly fallers and in patients with Parkinson’s disease: the prominence of impaired executive function and attention. Exp Aging Res 32:411–429
Powell LE, Myers AM (1995) The Activities-specific Balance Confidence (ABC) Scale. J Gerontol A Biol Sci Med Sci 50A:M28–M34
Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO (1982) Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 17:37–49
Chaudhuri KR, Martinez-Martin P (2008) Quantitation of non-motor symptoms in Parkinson’s disease. Eur J Neurol 15(Suppl 2):2–7
Peto V, Jenkinson C, Fitzpatrick R, Greenhall R (1995) The development and validation of a short measure of functioning and well being for individuals with Parkinson’s disease. Qual Life Res 4:241–248
Alves G, Larsen JP, Emre M, Wentzel-Larsen T, Aarsland D (2006) Changes in motor subtype and risk for incident dementia in Parkinson’s disease. Mov Disord 21:1123–1130
Williams-Gray CH, Foltynie T, Brayne CE, Robbins TW, Barker RA (2007) Evolution of cognitive dysfunction in an incident Parkinson’s disease cohort. Brain 130:1787–1798
Maidan I, Nieuwhof F, Bernad-Elazari H, Reelick MF, Bloem BR, Giladi N, Deutsch JE, Hausdorff JM, Claassen JA, Mirelman A (2016) The role of the frontal lobe in complex walking among patients with Parkinson’s disease and healthy older adults: an fNIRS study. Neurorehabil Neural Repair 30:963–971
Stuss DT, Levine B (2002) Adult clinical neuropsychology: lessons from studies of the frontal lobes. Annu Rev Psychol 53:401–433
Maidan I, Rosenberg-Katz K, Jacob Y, Giladi N, Deutsch JE, Hausdorff JM, Mirelman A (2016) Altered brain activation in complex walking conditions in patients with Parkinson’s disease. Parkinsonism Relat Disord 25:91–96
Factor SA, Steenland NK, Higgins DS, Molho ES, Kay DM, Montimurro J, Rosen AR, Zabetian CP, Payami H (2011) Postural instability/gait disturbance in Parkinson’s disease has distinct subtypes: an exploratory analysis. J Neurol Neurosurg Psychiatry 82:564–568
Selikhova M, Williams DR, Kempster PA, Holton JL, Revesz T, Lees AJ (2009) A clinico-pathological study of subtypes in Parkinson’s disease. Brain 132:2947–2957
Nutt JG (2016) Motor subtype in Parkinson’s disease: different disorders or different stages of disease? Mov Disord 31:957–961
Antonini A, Barone P, Marconi R, Morgante L, Zappulla S, Pontieri FE, Ramat S, Ceravolo MG, Meco G, Cicarelli G, Pederzoli M, Manfredi M, Ceravolo R, Mucchiut M, Volpe G, Abbruzzese G, Bottacchi E, Bartolomei L, Ciacci G, Cannas A, Randisi MG, Petrone A, Baratti M, Toni V, Cossu G, Del DP, Bentivoglio AR, Abrignani M, Scala R, Pennisi F, Quatrale R, Gaglio RM, Nicoletti A, Perini M, Avarello T, Pisani A, Scaglioni A, Martinelli PE, Iemolo F, Ferigo L, Simone P, Soliveri P, Troianiello B, Consoli D, Mauro A, Lopiano L, Nastasi G, Colosimo C (2012) The progression of non-motor symptoms in Parkinson’s disease and their contribution to motor disability and quality of life. J Neurol 259:2621–2631
Erro R, Picillo M, Vitale C, Amboni M, Moccia M, Santangelo G, Pellecchia MT, Barone P (2016) The non-motor side of the honeymoon period of Parkinson’s disease and its relationship with quality of life: a 4-year longitudinal study. Eur J Neurol 23:1673–1679
Muller B, Assmus J, Herlofson K, Larsen JP, Tysnes OB (2013) Importance of motor vs. non-motor symptoms for health-related quality of life in early Parkinson’s disease. Parkinsonism Relat Disord 19:1027–1032
Prakash KM, Nadkarni NV, Lye WK, Yong MH, Tan EK (2016) The impact of non-motor symptoms on the quality of life of Parkinson’s disease patients: a longitudinal study. Eur J Neurol 23:854–860
Zis P, Rizos A, Martinez-Martin P, Pal S, Silverdale M, Sharma JC, Sauerbier A, Chaudhuri KR (2014) Non-motor symptoms profile and burden in drug naive versus long-term Parkinson’s disease patients. J Parkinson’s Dis 4:541–547
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Arie, L., Herman, T., Shema-Shiratzky, S. et al. Do cognition and other non-motor symptoms decline similarly among patients with Parkinson’s disease motor subtypes? Findings from a 5-year prospective study. J Neurol 264, 2149–2157 (2017). https://doi.org/10.1007/s00415-017-8605-x
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DOI: https://doi.org/10.1007/s00415-017-8605-x