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Parkinson disease, late-onset(PD)

MedGen UID:
463618
Concept ID:
C3160718
Disease or Syndrome
Synonyms: Hereditary late onset Parkinson disease; PARKINSON DISEASE, LATE-ONSET, SUSCEPTIBILITY TO; Parkinson disease, susceptibility to; Parkinson's disease; PD; Susceptibility to Parkinson's Disease
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Genes (locations): ADH1C (4q23); ATXN2 (12q24.12); ATXN3 (14q32.12); ATXN8OS (13q21.33); GBA1 (1q22); MAPT (17q21.31); MT-TT; NR4A2 (2q24.1); SNCAIP (5q23.2); TBP (6q27)
 
Monarch Initiative: MONDO:0008199
OMIM®: 168600
Orphanet: ORPHA411602

Definition

Generally, Parkinson's disease that begins after age 50 is called late-onset disease. The condition is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 are sometimes referred to as juvenile-onset Parkinson's disease.

Parkinson's disease can also affect emotions and thinking ability (cognition). Some affected individuals develop psychiatric conditions such as depression and visual hallucinations. People with Parkinson's disease also have an increased risk of developing dementia, which is a decline in intellectual functions including judgment and memory.

Often the first symptom of Parkinson's disease is trembling or shaking (tremor) of a limb, especially when the body is at rest. Typically, the tremor begins on one side of the body, usually in one hand. Tremors can also affect the arms, legs, feet, and face. Other characteristic symptoms of Parkinson's disease include rigidity or stiffness of the limbs and torso, slow movement (bradykinesia) or an inability to move (akinesia), and impaired balance and coordination (postural instability). These symptoms worsen slowly over time.

Parkinson's disease is a progressive disorder of the nervous system. The disorder affects several regions of the brain, especially an area called the substantia nigra that controls balance and movement. [from MedlinePlus Genetics]

Clinical features

From HPO
Urinary urgency
MedGen UID:
39315
Concept ID:
C0085606
Finding
Urge incontinence is the strong, sudden need to urinate.
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Abnormal autonomic nervous system physiology
MedGen UID:
8511
Concept ID:
C0013363
Disease or Syndrome
A functional abnormality of the autonomic nervous system.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Hallucinations
MedGen UID:
6709
Concept ID:
C0018524
Mental or Behavioral Dysfunction
Perceptions in a conscious and awake state that, in the absence of external stimuli, have qualities of real perception. These perceptions are vivid, substantial, and located in external objective space.
Sleep abnormality
MedGen UID:
52372
Concept ID:
C0037317
Finding
An abnormal pattern in the quality, quantity, or characteristics of sleep.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Lewy bodies
MedGen UID:
43126
Concept ID:
C0085200
Cell Component
Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of Lewy bodies is the histological marker of the degenerative changes in LEWY BODY DISEASE and PARKINSON DISEASE but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex.
Bradykinesia
MedGen UID:
115925
Concept ID:
C0233565
Sign or Symptom
Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement).
Resting tremor
MedGen UID:
66697
Concept ID:
C0234379
Sign or Symptom
A resting tremor occurs when muscles are at rest and becomes less noticeable or disappears when the affected muscles are moved. Resting tremors are often slow and coarse.
Micrographia
MedGen UID:
66806
Concept ID:
C0240341
Finding
Abnormally small-sized handwriting is formally defined as an impairment of fine motor skills, which mainly manifests as a progressive or stable reduction in amplitude during a writing task.
Personality changes
MedGen UID:
66817
Concept ID:
C0240735
Mental or Behavioral Dysfunction
An abnormal shift in patterns of thinking, acting, or feeling.
Parkinsonian disorder
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Postural instability
MedGen UID:
334529
Concept ID:
C1843921
Finding
A tendency to fall or the inability to keep oneself from falling; imbalance. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, Use of the retropulsion test includes a rapid balance perturbation in the backward direction, and the number of balance correcting steps (or total absence thereof) is used to rate the degree of postural instability. Healthy subjects correct such perturbations with either one or two large steps, or without taking any steps, hinging rapidly at the hips while swinging the arms forward as a counterweight. In patients with balance impairment, balance correcting steps are often too small, forcing patients to take more than two steps. Taking three or more steps is generally considered to be abnormal, and taking more than five steps is regarded as being clearly abnormal. Markedly affected patients continue to step backward without ever regaining their balance and must be caught by the examiner (this would be called true retropulsion). Even more severely affected patients fail to correct entirely, and fall backward like a pushed toy soldier, without taking any corrective steps.
Substantia nigra gliosis
MedGen UID:
337668
Concept ID:
C1846865
Finding
Focal proliferation of glial cells in the substantia nigra.
Neuronal loss in central nervous system
MedGen UID:
342515
Concept ID:
C1850496
Finding
Short stepped shuffling gait
MedGen UID:
812045
Concept ID:
C3805715
Finding
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Weak voice
MedGen UID:
66033
Concept ID:
C0241700
Finding
Reduced intensity (volume) of speech.
Mask-like facies
MedGen UID:
140860
Concept ID:
C0424448
Finding
A lack of facial expression often with staring eyes and a slightly open mouth.

Professional guidelines

PubMed

Falcone DC, Wood EM, Xie SX, Siderowf A, Van Deerlin VM
J Genet Couns 2011 Aug;20(4):384-95. Epub 2011 Apr 8 doi: 10.1007/s10897-011-9362-0. PMID: 21476119Free PMC Article

Recent clinical studies

Etiology

Fernández-Calle R, Konings SC, Frontiñán-Rubio J, García-Revilla J, Camprubí-Ferrer L, Svensson M, Martinson I, Boza-Serrano A, Venero JL, Nielsen HM, Gouras GK, Deierborg T
Mol Neurodegener 2022 Sep 24;17(1):62. doi: 10.1186/s13024-022-00566-4. PMID: 36153580Free PMC Article
Chen YP, Yu SH, Zhang GH, Hou YB, Gu XJ, Ou RW, Shen Y, Song W, Chen XP, Zhao B, Cao B, Zhang LY, Sun MM, Liu FF, Wei QQ, Liu KC, Lin JY, Yang TM, Yang J, Wu Y, Jiang Z, Liu J, Cheng YF, Xiao Y, Su WM, Feng F, Cai YY, Li SR, Hu T, Yuan XQ, Zhou QQ, Shao N, Ma S, Shang HF
Eur J Neurol 2022 Nov;29(11):3218-3228. Epub 2022 Aug 4 doi: 10.1111/ene.15509. PMID: 35861376
Weintraub D, Aarsland D, Chaudhuri KR, Dobkin RD, Leentjens AF, Rodriguez-Violante M, Schrag A
Lancet Neurol 2022 Jan;21(1):89-102. doi: 10.1016/S1474-4422(21)00330-6. PMID: 34942142Free PMC Article
Gialluisi A, Reccia MG, Modugno N, Nutile T, Lombardi A, Di Giovannantonio LG, Pietracupa S, Ruggiero D, Scala S, Gambardella S; International Parkinson’s Disease Genomics Consortium (IPDGC), Iacoviello L, Gianfrancesco F, Acampora D, D'Esposito M, Simeone A, Ciullo M, Esposito T
Mol Neurodegener 2021 Jun 21;16(1):35. doi: 10.1186/s13024-021-00455-2. PMID: 34148545Free PMC Article
Mehanna R, Jankovic J
Parkinsonism Relat Disord 2019 Aug;65:39-48. Epub 2019 Jun 1 doi: 10.1016/j.parkreldis.2019.06.001. PMID: 31176633

Diagnosis

Neri S, Mastroianni G, Gardella E, Aguglia U, Rubboli G
Epileptic Disord 2022 Apr 1;24(2):249-273. doi: 10.1684/epd.2021.1406. PMID: 35596580
Weintraub D, Aarsland D, Chaudhuri KR, Dobkin RD, Leentjens AF, Rodriguez-Violante M, Schrag A
Lancet Neurol 2022 Jan;21(1):89-102. doi: 10.1016/S1474-4422(21)00330-6. PMID: 34942142Free PMC Article
Riboldi GM, Frattini E, Monfrini E, Frucht SJ, Di Fonzo A
J Parkinsons Dis 2022;12(1):1-26. doi: 10.3233/JPD-212815. PMID: 34569973Free PMC Article
Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC, Boland A, Vronskaya M, van der Lee SJ, Amlie-Wolf A, Bellenguez C, Frizatti A, Chouraki V, Martin ER, Sleegers K, Badarinarayan N, Jakobsdottir J, Hamilton-Nelson KL, Moreno-Grau S, Olaso R, Raybould R, Chen Y, Kuzma AB, Hiltunen M, Morgan T, Ahmad S, Vardarajan BN, Epelbaum J, Hoffmann P, Boada M, Beecham GW, Garnier JG, Harold D, Fitzpatrick AL, Valladares O, Moutet ML, Gerrish A, Smith AV, Qu L, Bacq D, Denning N, Jian X, Zhao Y, Del Zompo M, Fox NC, Choi SH, Mateo I, Hughes JT, Adams HH, Malamon J, Sanchez-Garcia F, Patel Y, Brody JA, Dombroski BA, Naranjo MCD, Daniilidou M, Eiriksdottir G, Mukherjee S, Wallon D, Uphill J, Aspelund T, Cantwell LB, Garzia F, Galimberti D, Hofer E, Butkiewicz M, Fin B, Scarpini E, Sarnowski C, Bush WS, Meslage S, Kornhuber J, White CC, Song Y, Barber RC, Engelborghs S, Sordon S, Voijnovic D, Adams PM, Vandenberghe R, Mayhaus M, Cupples LA, Albert MS, De Deyn PP, Gu W, Himali JJ, Beekly D, 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Fratiglioni L, Germanou A, Apostolova LG, Keller L, Koutroumani M, Arnold SE, Panza F, Gkatzima O, Asthana S, Hannequin D, Whitehead P, Atwood CS, Caffarra P, Hampel H, Quintela I, Carracedo Á, Lannfelt L, Rubinsztein DC, Barnes LL, Pasquier F, Frölich L, Barral S, McGuinness B, Beach TG, Johnston JA, Becker JT, Passmore P, Bigio EH, Schott JM, Bird TD, Warren JD, Boeve BF, Lupton MK, Bowen JD, Proitsi P, Boxer A, Powell JF, Burke JR, Kauwe JSK, Burns JM, Mancuso M, Buxbaum JD, Bonuccelli U, Cairns NJ, McQuillin A, Cao C, Livingston G, Carlson CS, Bass NJ, Carlsson CM, Hardy J, Carney RM, Bras J, Carrasquillo MM, Guerreiro R, Allen M, Chui HC, Fisher E, Masullo C, Crocco EA, DeCarli C, Bisceglio G, Dick M, Ma L, Duara R, Graff-Radford NR, Evans DA, Hodges A, Faber KM, Scherer M, Fallon KB, Riemenschneider M, Fardo DW, Heun R, Farlow MR, Kölsch H, Ferris S, Leber M, Foroud TM, Heuser I, Galasko DR, Giegling I, Gearing M, Hüll M, Geschwind DH, Gilbert JR, Morris J, Green RC, Mayo K, 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S, Quinn JF, Sacchinelli E, Raj A, Spalletta G, Raskind M, Caltagirone C, Bossù P, Orfei MD, Reisberg B, Clarke R, Reitz C, Smith AD, Ringman JM, Warden D, Roberson ED, Wilcock G, Rogaeva E, Bruni AC, Rosen HJ, Gallo M, Rosenberg RN, Ben-Shlomo Y, Sager MA, Mecocci P, Saykin AJ, Pastor P, Cuccaro ML, Vance JM, Schneider JA, Schneider LS, Slifer S, Seeley WW, Smith AG, Sonnen JA, Spina S, Stern RA, Swerdlow RH, Tang M, Tanzi RE, Trojanowski JQ, Troncoso JC, Van Deerlin VM, Van Eldik LJ, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Wilhelmsen KC, Williamson J, Wingo TS, Woltjer RL, Wright CB, Yu CE, Yu L, Saba Y, Pilotto A, Bullido MJ, Peters O, Crane PK, Bennett D, Bosco P, Coto E, Boccardi V, De Jager PL, Lleo A, Warner N, Lopez OL, Ingelsson M, Deloukas P, Cruchaga C, Graff C, Gwilliam R, Fornage M, Goate AM, Sanchez-Juan P, Kehoe PG, Amin N, Ertekin-Taner N, Berr C, Debette S, Love S, Launer LJ, Younkin SG, Dartigues JF, Corcoran C, Ikram MA, Dickson DW, Nicolas G, Campion D, Tschanz J, Schmidt H, Hakonarson H, Clarimon J, Munger R, Schmidt R, Farrer LA, Van Broeckhoven C, C O'Donovan M, DeStefano AL, Jones L, Haines JL, Deleuze JF, Owen MJ, Gudnason V, Mayeux R, Escott-Price V, Psaty BM, Ramirez A, Wang LS, Ruiz A, van Duijn CM, Holmans PA, Seshadri S, Williams J, Amouyel P, Schellenberg GD, Lambert JC, Pericak-Vance MA; Alzheimer Disease Genetics Consortium (ADGC),; European Alzheimer’s Disease Initiative (EADI),; Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE),; Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium (GERAD/PERADES),
Nat Genet 2019 Mar;51(3):414-430. Epub 2019 Feb 28 doi: 10.1038/s41588-019-0358-2. PMID: 30820047Free PMC Article
Bandmann O, Weiss KH, Kaler SG
Lancet Neurol 2015 Jan;14(1):103-13. doi: 10.1016/S1474-4422(14)70190-5. PMID: 25496901Free PMC Article

Therapy

Devanand DP, Jeste DV, Stroup TS, Goldberg TE
Int Psychogeriatr 2024 Jan;36(1):28-42. Epub 2023 Mar 3 doi: 10.1017/S1041610223000157. PMID: 36866576
Zhu H, Tonelli F, Turk M, Prescott A, Alessi DR, Sun J
Science 2023 Dec 22;382(6677):1404-1411. Epub 2023 Dec 21 doi: 10.1126/science.adi9926. PMID: 38127736Free PMC Article
Iglesias E, Pesini A, Garrido-Pérez N, Meade P, Bayona-Bafaluy MP, Montoya J, Ruiz-Pesini E
Ageing Res Rev 2018 Aug;45:24-32. Epub 2018 Apr 22 doi: 10.1016/j.arr.2018.04.006. PMID: 29689408
Sherer TB, Betarbet R, Greenamyre JT
ScientificWorldJournal 2001 May 1;1:207-8. doi: 10.1100/tsw.2001.35. PMID: 12805673Free PMC Article
Giovannini P, Piccolo I, Genitrini S, Soliveri P, Girotti F, Geminiani G, Scigliano G, Caraceni T
Mov Disord 1991;6(1):36-42. doi: 10.1002/mds.870060107. PMID: 2005920

Prognosis

Devanand DP, Jeste DV, Stroup TS, Goldberg TE
Int Psychogeriatr 2024 Jan;36(1):28-42. Epub 2023 Mar 3 doi: 10.1017/S1041610223000157. PMID: 36866576
Weintraub D, Aarsland D, Chaudhuri KR, Dobkin RD, Leentjens AF, Rodriguez-Violante M, Schrag A
Lancet Neurol 2022 Jan;21(1):89-102. doi: 10.1016/S1474-4422(21)00330-6. PMID: 34942142Free PMC Article
Deneubourg C, Ramm M, Smith LJ, Baron O, Singh K, Byrne SC, Duchen MR, Gautel M, Eskelinen EL, Fanto M, Jungbluth H
Autophagy 2022 Mar;18(3):496-517. Epub 2021 Aug 19 doi: 10.1080/15548627.2021.1943177. PMID: 34130600Free PMC Article
Gialluisi A, Reccia MG, Modugno N, Nutile T, Lombardi A, Di Giovannantonio LG, Pietracupa S, Ruggiero D, Scala S, Gambardella S; International Parkinson’s Disease Genomics Consortium (IPDGC), Iacoviello L, Gianfrancesco F, Acampora D, D'Esposito M, Simeone A, Ciullo M, Esposito T
Mol Neurodegener 2021 Jun 21;16(1):35. doi: 10.1186/s13024-021-00455-2. PMID: 34148545Free PMC Article
Bonifati V
Parkinsonism Relat Disord 2012 Jan;18 Suppl 1:S4-6. doi: 10.1016/S1353-8020(11)70004-9. PMID: 22166450

Clinical prediction guides

Guo P, Gong W, Li Y, Liu L, Yan R, Wang Y, Zhang Y, Yuan Z
BMC Med 2022 Jun 22;20(1):214. doi: 10.1186/s12916-022-02404-2. PMID: 35729600Free PMC Article
Gialluisi A, Reccia MG, Modugno N, Nutile T, Lombardi A, Di Giovannantonio LG, Pietracupa S, Ruggiero D, Scala S, Gambardella S; International Parkinson’s Disease Genomics Consortium (IPDGC), Iacoviello L, Gianfrancesco F, Acampora D, D'Esposito M, Simeone A, Ciullo M, Esposito T
Mol Neurodegener 2021 Jun 21;16(1):35. doi: 10.1186/s13024-021-00455-2. PMID: 34148545Free PMC Article
Ou R, Wei Q, Hou Y, Zhang L, Liu K, Kong X, Li S, Wang L, Xu X, Gu X, Lin J, Jiang Z, Liu J, Song W, Cao B, Shang H
J Neurol 2021 May;268(5):1876-1884. Epub 2021 Jan 4 doi: 10.1007/s00415-020-10333-4. PMID: 33392638
Hardy J, Escott-Price V
Hum Mol Genet 2019 Nov 21;28(R2):R235-R240. doi: 10.1093/hmg/ddz163. PMID: 31332445
Giovannini P, Piccolo I, Genitrini S, Soliveri P, Girotti F, Geminiani G, Scigliano G, Caraceni T
Mov Disord 1991;6(1):36-42. doi: 10.1002/mds.870060107. PMID: 2005920

Recent systematic reviews

Medina Escobar A, Pringsheim T, Gautreau S, Rivera-Duarte JD, Amorelli G, Cornejo-Olivas M, Rossi M
Mov Disord 2024 Nov;39(11):1907-1921. Epub 2024 Jul 23 doi: 10.1002/mds.29929. PMID: 39044616
Lee JM, Pak K
Medicine (Baltimore) 2023 Nov 3;102(44):e35861. doi: 10.1097/MD.0000000000035861. PMID: 37933060Free PMC Article
Sammartino-Arbour A, Dufour A, Frenette V, Forget MF, Bruneau MA, Ducharme S, Camicioli R, Nguyen QD, Desmarais P
Am J Geriatr Psychiatry 2023 Jan;31(1):33-43. Epub 2022 Jul 24 doi: 10.1016/j.jagp.2022.07.007. PMID: 35970734
Kilarski LL, Pearson JP, Newsway V, Majounie E, Knipe MD, Misbahuddin A, Chinnery PF, Burn DJ, Clarke CE, Marion MH, Lewthwaite AJ, Nicholl DJ, Wood NW, Morrison KE, Williams-Gray CH, Evans JR, Sawcer SJ, Barker RA, Wickremaratchi MM, Ben-Shlomo Y, Williams NM, Morris HR
Mov Disord 2012 Oct;27(12):1522-9. Epub 2012 Sep 6 doi: 10.1002/mds.25132. PMID: 22956510
Birks J, Flicker L
Cochrane Database Syst Rev 2003;(1):CD000442. doi: 10.1002/14651858.CD000442. PMID: 12535396

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