References

nnp

Neurology, Neuropsychiatry, Psychosomatics

Неврология, нейропсихиатрия, психосоматика

2074-27112310-1342

"IMA-Press", LLC

10.14412/2074-2711-2014-1-80-84

nnp-378

Research Article

REVIEWS

ОБЗОРЫ

Apathy in Parkinson's disease patients

Апатия при болезни Паркинсона

Нодель

М. Р.

Nodel

M. R.

1@ru.ru

Кафедра нервных болезней и нейрохирургии ГБОУ ВПО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России, Москва, РоссияРоссияDepartment of Nervous Diseases and Neurosurgery, Sechenov First Moscow State Medical University, the Ministry of Health of the Russian Federation, Moscow, RussiaRussian Federation

2014

05052014

618084

2014

Нодель М.Р.

Nodel M.R.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://nnp.ima-press.net/nnp/article/view/378

pathy in Parkinson's disease (PD) patients is one of the least studied manifestations of a broad range of neuropsychic disorders. According to numerous researchers, the rate of apathy in PD patients is 17–80%. The structural and neurochemical changes associated with PD have been considered to be the leading pathophysiological factors of apathy. The possible general pathophysiological mechanisms are discussed for apathy and hypokinesia, depression, executive (frontal) cognitive functions, and sleep disorders in PD patients. The pathophysiological commonality of apathy, hypokinesia, and executive functions is probably based on bilateral disorders of functional links of the striatum and dorsolateral, medial parts of the prefrontal cortex. A combination of apathy and depression in PD patients may be due to dysfunction of the structures of the limbic system and medial orbital prefrontal cortex, which are responsible for the motivationally driven behavior. Variability of relationships of apathy with hypokinesia, depression, cognitive impairments, sleep disorders at different stages of PD may be associated with the phenomenological heterogeneity of apathy. Apathy reduces quality of life, makes a significant contribution to disturbances of both everyday and social adaptation of PD patients. A study of the possibility for apathy correction using dopaminergic therapy is rather promising. Twenty patients with PD (the middle stage according to the Hoehn and Yahr scale, 2.5) received pramipexole (1.5–3.0 mg/day) to correct motor disorders. A statistically significant positive trend in the time course of apathy, according to the overall assessment by the Starkstein apathy scale (AS), was noted after 4–6 weeks of the therapy. Based on the results, no statistically significant correlation was observed between the dynamics of the overall apathy score and the dynamics of motor symptoms of PD on the unified rating scale for PD assessment («Motor functions»). We believe that this fact demonstrates the independent effect of pramipexole therapy against motivational disorders.

Апатия у пациентов с болезнью Паркинсона (БП) является одним из наименее изученных проявлений широкого спектра нервно-психических нарушений (НПН). Частота апатии при БП, по данным разных исследователей, составляет 17–80%. В качестве ведущих патофизиологических факторов апатии рассматриваются структурные и нейрохимические изменения, связанные с БП. Обсуждаются возможные общие патофизиологические механизмы апатии и гипокинезии, депрессии, управляющих (лобных) когнитивных функций, нарушений сна при БП. Основой патофизиологической общности апатии, гипокинезии, управляющих функций являются, вероятно, двусторонние нарушения функциональных связей стриатума и дорзолатеральных, медиальных отделов префронтальной коры. Сочетание апатии и депрессии при БП может быть обусловлено дисфункцией структур лимбической системы и медиоорбитальной префронтальной коры, ответственных за мотивационно обусловленное поведение. Вариабельность взаимоотношений апатии с гипокинезией, депрессией, когнитивными нарушениями, нарушениями сна на различных стадиях БП может быть связана с феноменологической неоднородностью апатии. Апатия ухудшает качество жизни, вносит значимый вклад в нарушения как бытовой, так и социальной адаптации пациентов с БП. Перспективно изучение возможности коррекции апатии с помощью дофаминергической терапии. На фоне назначения 20 пациентам с БП (средняя стадия по Хен–Яру – 2,5) прамипексола (1,5–3,0 мг/сут) с целью коррекции двигательных нарушений через 4–6 нед терапии была отмечена статистически значимая положительная динамика апатии по суммарной оценке шкалы апатии S.E. Starkstein (AS). В результате исследования статистически значимой корреляции динамики суммарного показателя апатии с динамикой двигательных симптомов БП по унифицированной рейтинговой шкале оценки БП («Двигательные функции») выявлено не было, что, полагаем, свидетельствует о самостоятельном эффекте терапии прамипексолом в отношении мотивационных расстройств.

болезнь Паркинсонаапатияпатофизиологиядофаминергическая терапияпрамипексол.

Parkinson's diseaseapathypathophysiologydopaminergic therapypramipexole.

References1

Aarsland D, Marsh L, Schrag A. Neuropsychiatric symptoms in Parkinsons disease. Mov Disord. 2009; 24(15):2175–86. DOI: 10.1002/mds.22589.

Scaravilli T, Gasparoli E, Rinaldi F, et al. Health-related quality of life and sleep disorders in Parkinson's disease. Neurol Sci. 2003 Oct;24(3):209–10. DOI: http://dx.doi.org/10.1007/s10072-003-0134-y.

Gallanger DA, Lees AJ, Shrag A. What are the most important nonmotor symptoms in patients with Parkinsons disease and are we missing them? Mov Disord. 2010;15(15):2493–500. DOI: 10.1002/mds.23394.

Нодель МР, Яхно НН. Нервно-психические нарушения болезни Паркинсона. Неврология, нейропсихиатрия, психосоматика. 2009;(2):3–8. [Nodel' MR, Yakhno NN. Nervous and mental disorders of parkinson's disease. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2009;(2):3–8. (In Russ.)]. DOI: http://dx.doi.org/10.14412/2074-2711-2009-30.

Левин ОС. Болезнь Паркинсона как нейропсихиатрическое заболевание. Руководство для врачей по материалам II Национального конгресса по болезни Паркинсона и расстройствам движений. Под. ред. С.Н. Иллариошкина, О.С. Левина. Москва: НЦН РАМН; 2011. C. 99–104. [Levin OS. Bolezn' Parkinsona kak neiropsikhiatricheskoe zabolevanie. Rukovodstvo dlya vrachei po materialam II Natsional'nogo kongressa po bolezni Parkinsona i rasstroistvam dvizhenii [Parkinson's illness as neuropsychiatric disease. The management for doctors on materials II of the National congress due to illness Parkinson and to disorders of movements]. Illarioshkina SN, Levina OS, editors. Moscow: NTsN RAMN; 2011. P. 99–104.]

Вознесенская ТГ. Синдром апатии. Неврологический журнал. 2013;18(3):4–10. [Voznesenskaya TG. Аpathy syndrome. Nevrologicheskii zhurnal. 2013;18(3):4–10. (In Russ.)]

Levy R, Dubois B. Apathy and functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb Cortex. 2006;16(7):916–28. DOI: http://dx.doi.org/10.1093/cercor/bhj043. Epub 2005 Oct 5.

Marin RS, Biedrzycki RC, Firinciogullari S. Reliability and validity of the Apathy Evaluation Scale. Psychiatry Res. 1991;38(2):143–62. DOI: http://dx.doi.org/10.1016/0165-1781(91)90040-V.

Starkstein SE, Jorge R, Mizrahi R, Robinson RG. A prospective longitudinal study of apathy in Alzheimers disease. J Neurol Neurosurg Psychiatr. 2006;77(1):8–11. DOI: http://dx.doi.org/10.1136/jnnp.2005.069575.

Robert P, Onyike CU, Leentjens AF, et al. Proposed diagnostic criteria for apathy in Alzheimer’s disease and other neuroposychiatric disorders. Eur Psychiatry. 2009;24(2):98–104. DOI: 10.1016/j.eurpsy.2008.09.001.

Epub 2009 Feb 7.

Sockeel P, Dujardin K, Devos D, et.al. The Lille apathy rating scale (LARS): a new instrument for detecting and quantifying apathy: validation in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2006;77(5):579–84. DOI: http://dx.doi.org/10.1136/jnnp.2005.075929.

Starkstein SE, Mayberg HS, Preziosi TJ, et.al. Reliability, validity, and clinical correlates of apathy in Parkinsons disease. J Neuropsychiatry Clin Neurosci. 1992;4(2):134–9.

Leroi I, David R, Robert PH. Apathy in Parkinsons disease. In: Psychiatry of in Parkinsons disease. Edmeier KP, O’Brien JT, Taylor J-P, editors. Basel: Karger; 2012. P. 27–40. DOI: http://dx.doi.org/10.1159/000331524.

Pedersen KF, Larsen JP, Alves G, Aarsland D. Prevalence and clinical correlates of apathy in Parkinsons disease: a community-based study. Parkinsonism Relat Disord. 2009 May;15(4):295–9. DOI: 10.1016/j.parkreldis.2008.07.006.

Epub 2008 Sep 17.

Mulin E, Leone E, Dujardin K, et al. Diagnostic criteria for apathy in clinical practice. Int J Geriatr Psychiatry. 2011;26(2):158–65. DOI: 10.1002/gps.2508.

Нодель МР, Яхно НН. Апатия при болезни Паркинсона. Неврологический журнал. 2014;1:9–15. [Nodel of MR, Yakhno NN. Apathy at Parkinson's illness. Nevrologicheskii zhurnal. 2014;1:9–15. (In Russ.)]

Bogart KR. Is apathy a valid and meaningful symptom or syndrome in Parkinsons disease? A critical review. Health Psychol. 2011;30(4):386–400. DOI: 10.1037/a0022851.

Jordan LL, Zahodne LB, Okun MS, Bowers D. Hedonistic and behavioral deficits associated with apathy in Parkinsons disease: potential treatment implications. Mov Disord. 2013;28(9):1301–04. DOI: 10.1002/mds.25496. Epub 2013 May 27.

Pluck GC, Brown RG. Apathy in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2002;73(6):636–42. DOI: http://dx.doi.org/10.1136/jnnp.73.6.636.

Czernecki V, Schupbach M, Yaici S, et al. Apathy following subthalamic stimulation in Parkinson disease: a dopamine responsive symptom. Mov Disord. 2008;23(7):964–9. DOI: 10.1002/mds.21949.

Robbins T, Evritt B. Neurobehavioral mechanism of reward and motivation.

Curr Opin Neurobiol. 1996;6(2):228–36. DOI: http://dx.doi.org/10.1016/S0959-4388(96)80077-8.

Reijnders JS, Scholtissen B, Weber WE, et al. Neuroanatomical correlates of apathy in Parkinson’s disease: a magnetic resonance imaging study using voxed-based morphometry. Mov Disord. 2010;25(14):2318–25. DOI: 10.1002/mds.23268. 23. Starkstein SE, Federoff JP, Price TR, et al. Apathy following cerebrovascular lesions. Stroke. 1993:24(11):1625–30. DOI: http://dx.doi.org/10.1161/01.STR.24.11.1625.

Levy ML, Cummings JL, Fairbanks LA, et al. Apathy is not depression. J Neuropsychiatr Clin Neuroscie.1998;10(3):314–9.

Reijnders J, Ehrt U, Lousberg R, et al. The association between motor subtypes and psychopatology in Parkinsons disease. Parkinsonism Relat Disord. 2009;15(5):379–82. DOI: 10.1016/j.parkreldis.2008.09.003. Epub 2008 Oct 31.

Pedersen KF, Alves G, Aarsland D, et al. Occurence and risk factors for apathy in Parkinsons disease:a 4-year prospective longitudinal study. J Neurol Neurosurg Psychiatry. 2009;80(11):1279–82. DOI: 10.1136/jnnp.2008.170043.

Нодель МР, Русакова ИМ, Яхно НН. Клиническая оценка нарушений сна и бодрствования при болезни Паркинсона. Неврологический журнал. 2010;(2):19–25. [Nodel' MR, Rusakova IM, Yakhno NN. Clinical assessment of violations of a dream and wakefulness at Parkinson's illness. Nevrologicheskii zhurnal. 2010;(2):19–25. (In Russ.)]

Vendette M, Gagnon JF, Decary A, et al. REM sleep behavior disorder predicts cognitive impairment in Parkinson disease without dementia. Neurology. 2007;69(19):1843–9. DOI: http://dx.doi.org/10.1212/01.wnl. 0000278114.14096.74.

Narabayashi H. Akinesia in parkinsonism. In: Movement disorders in Neurology and neuropsychiatry. Joseph AB, Young RR, editors. Oxford: Blackwell Science; 1999. P. 185–8.

Tekin S, Cummings JL. Frontal-subcortical neuronal circuits and clinical psychiatry: an update. J Psychosom Res. 2002;53(20:647–54.

Dujardin K, Sockeel P, Delliaux M, et al. Apathy may herald cognitive decline and dementia in Parkinsons disease. Mov Disord. 2009;24(16):2391–7. DOI: 10.1002/mds.22843.

Barone P, Antonini A, Colosimo C, et al. The Priamo Study : a multicenter assessement of nonmotor symptoms and their impact on quality of life in Parkinsons disease. Mov Disord. 2009;11(24):1641–9. DOI: http://dx.doi.org/10.1002/mds.23872.

Benito-Leon J, Cubo E, Coronell C, et al. Impact of apathy on health-related quality of life in recently diagnosed Parkinsons disease: the ANIMO study. Mov Disord. 2012;27(2):211–8. DOI: 10.1002/mds.23872. Epub 2011 Jul 20.

Mc Kinlay A, Grace RC, Dalrymple-Alford JC, et al. A profile of neuropsychiatric problems and their relationship to quality of life for Parkinsons disease. Parkinsonism Relat Disord. 2008;14(1):37–42. DOI: http://dx.doi.org/10.1016/j.parkreldis.2007.05.009. Epub 2007 Jul 12

Wangpakaran N, van Reekum R, Wangpakaran T, Clarke D. Selective serotonine reuptake ingibitor use associates with apathy among depressed elderly: a case control study. Ann Gen Psychiatry. 2007;6:7. DOI: http://dx.doi.org/10.1186/1744-859X-6-7.

Aarsland D, Mosimann UP, McKeith IG. Role of cholinesterase inhibitors in Parkinsons disease and dementia with Lewy bodies. J Geriatr Psychiatry. 2000;15(5):387–92.

Campbell JJ, Duffy JD. Treatment strategies in amotivated patients. Psychiatry Ann. 1997;27:44–9.

Czernecki V, Schupbach M, Levy R, et al. Apathy following subthalamic nucleus stimulation in Parkinsons disease is improved by treatment with a dopaminergic agonist. Mov Disord. 2006;21:652.

Thobois S, Lhommee E, Klinger H, et al. Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptors with piribedil. Brain. 2013;136 (Pt 5):1568–77. DOI: 10.1093/brain/awt067. Epub 2013 Mar 29.

Leentjens A, Koester J, Fruh B, et al. The effect of pramipexole on mood and motivotional symptoms in Parkinson disease: a meta-analysis of placebo-controlled studies. Clin Ther. 2009;31(1):89–92. DOI: 10.1016/j.clinthera.2009.01.012.

Нодель МР, Яхно НН. Мирапекс (прамипексол) в лечении недвигательных нарушений при болезни Паркинсона. Журнал неврологии и психиатрии им. С.С. Корсакова. 2008;108(5):32–8. [Nodel MR, Yakhno NN. Mirapex (pramipexole) in the treatment of nonmotor disturbances in Parkinson's disease. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2008;108(5):32–8. (In Russ.)]

The authors declare that there are no conflicts of interest present.